poor transition results, the genes here are the ones I'm browsing.¶

by u/Drwillpowers · 139 points · 98 comments · source

Posting this for two reasons. If you feel like poking around your own genome and seeing if anything weird is in there, this is where I start. Also, if someone is aware of a related gene that should be on one of these lists that I have overlooked, please comment it.

There are four lists here. Everything related to androgen signaling, estrogen signaling, progesterone signaling, and then lastly, genes that have had some reasonably decent study demonstrate mutations in them occur more often in people with gender dysphoria. Though it is unclear if any of these are actually "causative". For example, I would include MTHFR genes in that list, as I am absolutely certain that MTHFR mutations occur more often in Trans people than the genpop, (As well as VDR TAQ/BSM), but these havent been published in a study, so they are not included here. Obviously, some genes appear on multiple lists.

Androgen signaling gene list:

AR, FOXO1, MED1, NR3C4, NCOA1, NCOA2, NCOA3, SMAD3, ZBTB16, SHBG, SLCO1B1, SLCO1B3, ABCC2, HSD17B3, HSD17B6, HSD17B10, AKR1C2, AKR1C3, SRD5A1, SRD5A2, UGT2B17, UGT2B15, CYP19A1, MAPK1, MAPK3, PIK3CA, PTEN, RHOA, ROCK1, STAT3, WT1, DMRT1, SOX9, NR5A1, DHH, GATA4, ZFPM2, WNT4, RSPO1.

Estrogen Signaling Related Gene List

ESR1, ESR2, GPER1, CYP19A1, CYP17A1, CYP11A1, CYP1A1, CYP1B1, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B6, HSD17B7, HSD17B10, AKR1C1, AKR1C2, AKR1C3, SULT1E1, UGT1A1, UGT1A4, UGT2B7, UGT2B15, SHBG, NR5A1, NR0B1, NCOA1, NCOA2, NCOA3, NCOR1, NCOR2, MED1, FOXA1, CREBBP, EP300, STAT3, STAT5A, STAT5B, SOX9, WNT4, RSPO1, FST, FOXL2, BMP15, GATA4, ZFPM2, SMAD3, MAPK1, MAPK3, PIK3CA, PTEN, RHOA, ROCK1, IGF1, IGF1R, INSR, FGF2, FGFR1, FGFR2, FGFR3, FGFR4.

Progesterone signaling related gene list:

PGR, PGRMC1, PGRMC2, CYP11A1, CYP17A1, CYP21A2, HSD3B1, HSD3B2, HSD17B1, HSD17B2, HSD17B3, AKR1C1, AKR1C2, AKR1C3, STAR, NR5A1, NR0B1, NCOA1, NCOA2, NCOA3, NCOR1, NCOR2, FOXO1, CREBBP, EP300, STAT3, STAT5A, STAT5B, MAPK1, MAPK3, PIK3CA, PTEN, RHOA, ROCK1, IGF1, IGF1R, FGF2, FGFR1, FGFR2, FGFR3, FGFR4, SMAD3, ZBTB16, GATA4, ZFPM2, WNT4, RSPO1, SOX9, FOXL2, BMP15, FST, SHBG.

Gender Dysphoria Potentially Related Genes

AR, ESR1, ESR2, CYP19A1, CYP17A1, CYP11A1, CYP21A2, HSD17B3, HSD17B6, HSD17B10, HSD3B2, AKR1C2, AKR1C4, NR3C4, NR5A1, NR0B1, SHBG, SULT1E1, COMT, MAOA, MAOB, SRD5A2, FOXL2, SOX9, DMRT1, WT1, RSPO1, WNT4, FGF8, FGFR1, FGFR2, FGFR3, FGFR4, GNRH1, GNRHR, LH, LHCGR, FSHB, FSHR, AMH, AMHR2, DHH, NCOA1, NCOA2, NCOA3, NCOR1, NCOR2, CREBBP, EP300, GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GABRG3, SLC6A4, OXTR, AVPR1A, STAT3, STAT5A, STAT5B, MAPK1, MAPK3, PIK3CA, PTEN, RHOA, ROCK1, IGF1, IGF1R, ZBTB16, GATA4, ZFPM2, TSHR, NEGR1, CYP2D6

Hopefully you find this helpful as you explore your own whole genome sequence.

Do keep in mind, gender dysphoria is very very unlikely to be caused by a single off gene. In my experience, many related genes interact in such a way as to produce the outcome for the patient.

I have a high testosterone and a little bit high estradiol for a male (remember, both T and E masculinize while in utero as a fetus). I am extremely male. Not even a hint of dysphoria. However, I have two mutations in genes related to gender dysphoria. HOW CAN THIS BE?

I have:

SOX17 SNP chr8:54459229 C->T

EP300 SNP chr22:41117678 A->G

Both heterozygous mutations.

Do they matter for me? No.

Lets take a look at the EP300. That sounds like it could be a thing, but in my specific mutation:

17 alt of 152228 total genomes (This is very rare mutation)

0.000112 Allele frequency 0.000162 Population max allele frequency

Missense variant 0.198 REVEL

So here, we have a mutation that's fairly rare in the general population, however, its a missense, which means a single amino acid change. In terms of its likely clinical impact, its highly unlikely to have any, as the REVEL score is low. If the revel is under 0.5, its unlikely to matter. Revels over 0.5 are "possibly pathogenic". over .75 likely pathogenic, and 0.9 or higher extremely likely to be pathogenic.

In short, you are GUARANTEED to find mutations in the genes above, but if you're trying to find significant ones, look for ones that are fairly rare, but have a high revel score, then, see what those genes do.

Have fun!

PS: For the ease of those just looking to paste and go, here is the complete list of all genes above in one list:

AR, ESR1, ESR2, GPER1, CYP19A1, CYP17A1, CYP11A1, CYP1A1, CYP1B1, CYP21A2, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B6, HSD17B7, HSD17B10, HSD3B1, HSD3B2, AKR1C1, AKR1C2, AKR1C3, AKR1C4, SULT1E1, UGT1A1, UGT1A4, UGT2B7, UGT2B15, SHBG, NR5A1, NR0B1, NCOA1, NCOA2, NCOA3, NCOR1, NCOR2, FOXA1, FOXO1, CREBBP, EP300, STAT3, STAT5A, STAT5B, SOX9, WNT4, RSPO1, FST, FOXL2, BMP15, GATA4, ZFPM2, SMAD3, MAPK1, MAPK3, PIK3CA, PTEN, RHOA, ROCK1, IGF1, IGF1R, INSR, FGF2, FGFR1, FGFR2, FGFR3, FGFR4, PGR, PGRMC1, PGRMC2, STAR, COMT, MAOA, MAOB, SRD5A1, SRD5A2, FOXL2, DMRT1, WT1, RSPO1, DHH, GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GABRG3, SLC6A4, OXTR, AVPR1A, TSHR, NEGR1, CYP2D6, MED1, ZBTB16, FSHB, FSHR, AMH, AMHR2, LHCGR, LHB, GNRH1, GNRHR, ABCC2, SLCO1B1, SLCO1B3

Then, if you really really want to get into the weeds, this is the "super list" but some of the genes in this one are a bit of a reach. Mostly, they add in developmental signaling disruption, as the potential other pathway, but they are only "theoretical" there isn't actual research on how every one of these genes can cause dysphoria (the added ones at least)

GENDER DYSPHORIA GENE MASTER LIST:

ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ALDH1A2, AMH, AMHR2, ANOS1, AR, AREG, ATF1, AVPR1A, AKR1C1, AKR1C2, AKR1C3, AKR1C4, AKT1, BDNF, BMP15, BMP6, BMP7, BMPR1A, BMPR1B, BMPR2, BRCA1, CACNA1H, CACNB1, CALML5, CBX2, CCND1, CGA, CHD7, CIAO1, COMT, CREB1, CREBBP, CTNNB1, CXCL12, CYB5A, CYP11A1, CYP17A1, CYP19A1, CYP1A1, CYP1A2, CYP1B1, CYP21A2, CYP2C19, CYP2D6, CYP4F2, DHHS7C, DHH, DMRT1, DNMT3A, DNMT3B, EGR1, EGFR, EMX2, EP300, ESR1, ESR2, ESRRA, ESRRB, EZH2, FGF1, FGF2, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FKBP4, FKBP5, FOXL2, FOXA1, FOXO1, FSHB, FSHR, FST, GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GABRG3, GATA2, GATA4, GHR, GLI2, GLI3, GNAS, GNRH1, GNRHR, GPER1, H6PD, HDAC1, HMGCR, HNF1A, HNF1B, HOXA10, HOXA11, HOXA13, HOXD13, HSD11B1, HSD11B2, HSD17B1, HSD17B10, HSD17B2, HSD17B3, HSD17B4, HSD17B6, HSD17B7, HSD3B1, HSD3B2, HSP90AA1, HSP90AB1, IGF1, IGF1R, INHBA, INHBB, INSL3, INSR, ISL1, ITPR2, JUN, KDM1A, KDM6A, LDLR, LGR4, LGR5, LGR6, LHB, LHCGR, LHX1, LHX9, LRP5, LRP6, MAOA, MAOB, MAP3K1, MAPK1, MAPK3, MED1, MED12, MYB, MYC, NCOA1, NCOA2, NCOA3, NCOA4, NCOR1, NCOR2, NEGR1, NFKB1, NODAL, NR0B1, NR2C1, NR2F2, NR5A1, NR5A2, OXTR, PAK1, PCSK5, PGR, PGRMC1, PGRMC2, PIK3CA, PLAUR, POR, PORCN, PPP2CA, PRKACA, PRKACB, PRKACG, PROK2, PROKR2, PTEN, RAC1, RARA, RARG, RDH10, RHOA, RNF43, ROCK1, RPS6KB1, RSPO1, RXRA, SCARB1, SFRP1, SGTA, SHBG, SHH, SLC22A5, SLC6A4, SLCO1B1, SLCO1B3, SLCO2B1, SMAD1, SMAD2, SMAD3, SMAD4, SMAD6, SMO, SOX2, SOX8, SOX9, SOX17, SP1, SRD5A1, SRD5A2, SRD5A3, SRY, STAR, STAT3, STAT5A, STAT5B, STRA8, STUB1, SULT1E1, SULT2A1, TBX6, TBXA2R, TCF7L2, TET1, TET2, TGFB1, TGFB2, TGFBR1, TGFBR2, TP53, TSHR, TSPO, UGT1A1, UGT1A4, UGT1A8, UGT2B15, UGT2B17, UGT2B7, VEGFA, WDR11, WNT1, WNT3, WNT3A, WNT4, WNT5A, WNT7A, WNT8A, WNT16, WT1, WTIP, ZBTB16, ZFPM2, ZMIZ1, ZNRF3

(Master gene list updated as of March 1^st 2026 with everything Dr. Powers searches when browsing for causes of "why trans" in the MPS theory of how gender dysphoria arises).

Comments¶

u/desolatenature · 17 points

As much as I like to follow this subreddit, the people here sure do make me feel dumb. The trans community is overrepresented with brilliantly intelligent people.

u/doppelwurzel · 14 points

Is it gauche to ask what WGS service you tend to use?

u/Drwillpowers · 8 points

Nebula, but they have not exactly been forthright lately

u/doppelwurzel · 3 points

I appreciate the response and understand re nebula concerns !

u/foodmystery · 2 points

I use nucleus and they have been pretty good.

META10 is my 10% off referral discount code with them, but even if I didn’t get one I would still recommend them since they actually get results back in 2-6 weeks. A couple of friends have used them too. Only downside is you have to make the bam file yourself from the fastq file download but you do get a vcf option

u/2d4d_data · 5 points

Documented some options on the https://www.reddit.com/r/DrWillPowers/wiki/dna_basics/ page. If you use https://dnacomplete.com/ 30x (formally nebula), downloading the data and then canceling the subscription seems like it might be the current best option. (no doubt will be out of date advice in a year)

u/desolatenature · 1 points

So if I did a 23&me gene testing, it wouldn’t have enough info for me to determine anything from this list?

u/CaramelNo3420 · 2 points

23andme is extremely limited however it does list some genes of interest there most notably PCOS risk genes. If you go that route you can upload it into Promethease for more medically focused information.

u/2d4d_data · 1 points

You might. 23andme checks specific snps which may or may not cover what you are looking for. The particular 23andme chip that I had back in the day did notice my cah variant, but that was just luck.

u/desolatenature · 1 points

Can you explain to me how I would look into this, and how I could utilize it to gain information to benefit my transition?

u/2d4d_data · 2 points

Starting from the genetics and working up is going on hard mode. First go with symptoms. Read over the list and see what matches up. Do you have many symptoms of NCCAH for example? Do you have lab work? That might further result in your ability to guess. Maybe import your dna file into https://gene.iobio.io/ and see what it highlights/reports.

Combining symptoms, with lab work and genetics all together is the value.

u/TheImpermanentTao · 1 points

What website other than 23me is better for getting my dna mapped

u/2d4d_data · 1 points

I have a few different one listed on this page I keep updated https://www.reddit.com/r/DrWillPowers/wiki/dna_basics/

u/TheImpermanentTao · 3 points

Their heading towards bankruptcy shouldn’t be on this page https://www.reddit.com/r/DanteLabs/s/xzrvbFDKpi

u/TheImpermanentTao · 1 points

Smh 🤦‍♂️ I can’t navigate the wiki (it works I couldn’t find it before on my own)

u/TheImpermanentTao · 1 points

Dante 30x coverage is $400 while 30x coverage nebula dna complete is $1,000, why is nebula on there

u/2d4d_data · 1 points

Never seen nebula's not "on sale" for $500. Dante's was (now ny and dubai?) done out of Dubai and a number of folks didn't want their dna getting sent there.

u/Laura_Sandra · 1 points

> Dante

There is a sub /r/dantelabs and you may want to have a look there concerning reliability etc. Its not favorable.

There is also a sub for nebula and sequencing that may give further hints.

u/Siren_Nemesis · 2 points

i wanna know too

u/Meiguishui · 6 points

I ran my file through your snpeek and 8/16 estrogen signaling genes were pathogenic, and 4/6 folate cycle were pathogenic. I have no idea how to interpret these but does that sound average for a trans woman?

u/2d4d_data · 3 points

We don't have the data to say what is average or not, but yeah that tracks with what I often see that for many of us it isn't "one gene", but a half dozen variants that reduce the estrogen signaling. As for the folate the follow up question you could do would be what does your lab work say about b12 or Homocysteine?

u/Meiguishui · 1 points

With regards to estrogen signaling, would the ones labeled as pathogenic be pathogenic for both trans men or trans women or is it relative? For example, I am a trans woman and I want my estrogen signaling to be on point so from that perspective would genotypes that result in reduced estrogen signaling be labeled pathogenic? Would the same genotypes just be considered normal if I were viewed as a cis man?

u/2d4d_data · 2 points

They are simply associated with "lower estrogen", maybe conversion, maybe metabolization, maybe activation, etc.

u/Meiguishui · 1 points

Thanks. Maybe you’ve posted this elsewhere but do you provide more in depth genome analysis for your patients? Or non-patients?

u/[deleted] · 1 points

[removed]

u/TooLateForMeTF · 1 points

Sorry, this is kind of a random question from a very old thread, but do you have a link for the "snpeek" gene analysis tool you used?

I've heard multiple people reference it, but when I google "snpeek" all I get are hits for prenatal gender testing.

u/Laura_Sandra · 2 points

> a link

https://snpeek.com/meyer-powers/

Here was also more:

https://old.reddit.com/r/DrWillPowers/wiki/dna_basics#wiki_investigating_your_dna

https://snpedia.com/

u/Meiguishui · 1 points

Sorry, I no longer have it

u/Laura_Sandra · 1 points

> I no longer have it

You may want to have a look here.

u/EmeraldAlicorn · 6 points

I wonder if this is one of those problems that you could solve with a pattern recognition neural network. If anyone has the specific data set for it, it would be your practice.

u/Drwillpowers · 11 points

Yes. Yes it would be. But the files are each like 250 GB. So you'd be feeding an absolutely enormous amount of data into an AI to do this, and I don't have that level of tech available to me at the moment.

u/lilyrose629 · 18 points

I'm an AI engineer. I would be interested in volunteering and I suspect others in the community would be as well.

Obviously there are basic concerns around HIPPA and patient data, but if you could describe the problem precisely I think it would be possible for engineers to help you design a pipeline without having access to anyone's data.

Let me know if you're interested to discuss. Would love to provide whatever aid I can!

u/Eugregoria · 3 points

I hope you two have been in communication/having progress with this, it would be awesome to see results!

As for working with data, if you got your own genome done you could ethically use your own data for a test run, as well as the data of anyone willing to donate theirs. I'm sure plenty of people who've already gotten their genomes done would voluntarily contribute.

u/Muted_Will_2131 · 2 points

GitHub is a great place to find contributors. Although if you're an AI engineer, you already know about it...

u/4reddityo · 4 points

I’d like to be tested to see if my genetics explains my dysphoria

u/HiddenStill · 5 points

CYP2D6 can cause problems with some painkillers. Are trans people more likely to have problems with this? It’s quite important if you’re having surgery.

u/ShitdickMcGillicuddy · 1 points

Im trans and learned through an ER visit that I'm unfazed by Tramadol.

u/foodmystery · 4 points

A video of you going over a volunteer's genome how you would go over it for a patient would be pretty interesting.

u/[deleted] · 8 points

[deleted]

u/RuthAnnEsther · 12 points

I believe it is necessary to look into biology and to reveal unique traits and characteristics that can prove how naive an Executive Order is that asserts people start with XX or XY at conception, and after that sex/gender is set in concrete, develops the same for all XX vs XY and must be imposed in the absolute most heavy-handed manner by the government.

u/HiddenStill · 8 points

They don’t care about being correct, it’s all about gaining power.

u/jipax13855 · 3 points

history hard-to-find school grandfather subtract smart steer north terrific tidy

This post was mass deleted and anonymized with Redact

u/Drwillpowers · 10 points

Yes.

Except for the confirm about dysphoria, because there's literally no way to do that. That's like confirming that someone sees the color red properly.

There is one other benefit, someone's having transition problems, sometimes I can figure out why and do something about it.

u/2d4d_data · 5 points

This isn't a "I wonder what people will find and if there is any correlation" list. We are several years down this path at this point. My goal was simply to know and understand. And we have a very good understanding at this point. Every single day we improve on what we know, but is it in the details, filing in the gaps and cases that don't yet fit, not the broad understanding.

Many folks have difficulty on hrt, by understanding the underlying reasons one can look for what their specific causes are and Dr. Powers has been able to provide dramatically better care.

The community has a lot of medical comorbidities, and again knowing what to look for and the common reasons, and optimal treatment results in better care.

And yes for some folks that report gender dysphoria (not all gender dysphoria is the same) there are sometimes treatment options other than transitioning. Again only by understanding could Dr. Powers even give them more autonomy over what to do.

So the goal in this post is about helping others investigate their own genetics to match up with what we know. We are not blindly searching random genes like we once were. Yes there will still be interesting edge cases, but that is not what this list is. This is more the common list.

u/Anon374928 · 8 points

Knowledge and improved health.

u/lucy_chxn · 2 points

I've got anomalies, born male with a .7< whr and feminization at puberty. It's more than genetics, really, gender is beyond duality. I

u/LeopardSweet4697 · 2 points

Thank you for doing this!

u/Golurkcanfly · 2 points

I recently received some genetic testing results and ran through them with a friend of mine who has experience analyzing this kind of data. She informed me that I have an ESR1 gene that is associated with higher receptor activity, but an attenuated ESR2 gene.

What sort of implications does this carry? I have physically feminized very well in terms of breast growth and fat distribution (I had B cups within only a few months of Estradiol Monotherapy), which seems to correspond to ESR1, but my overall mental health has become more chaotic as well.

u/Drwillpowers · 1 points

Well, you're not wrong with your description there.

most transition effects are ESR1 mediated based on where that is in the tissues. But brain is primarily ESR2

u/Golurkcanfly · 1 points

Do you have any recommendations to improve mental health (and possible autonomic issues) that are a result of a poor ESR2 gene?

u/Drwillpowers · 2 points

Genestein, resveratrol, omega 3s, curcumin and cardiovascular exercise all boost esr2 expression, functioning or signaling.

If the ESR2 though is stone dead. Like a stop codon. Nothing will matter. These only work to upregulate. But they won't fix a completely silenced receptor. Which would be exceptionally rare but if that is your situation the only way to fix it would be a gene therapy.

u/Golurkcanfly · 1 points

Gotcha, thank you! Getting the exercise is hard because one of the unfortunate side effects I've had is some kind of autonomic dysfunction that affects my heart and lungs. On days where it's especially bad it feels like there's a hole in my chest and my anxiety gets especially bad. It disappeared for a while once I switched to injections but came back after introducing a low dose of Spiro (50mg) to improve skin/hair quality.

My sister had similar issues too, and all of the women in my family have weird hormonal issues (PCOS, endometriosis, breast cysts, etc.) as well, so it's been a long process trying to figure things out.

u/Willing_Section_2287 · 3 points

Aren’t you worried this will eventually have a negative effect on the community?

u/Drwillpowers · 35 points

No.

It is my personal belief, that if we are able to demonstrate, that transgender people are effectively all intersex, and that there are hard coded reasons for their existence, it's a lot harder to legislate away their existence.

If you are trans, I consider you basically no different than a redhead. If a redhead wants to let their head grow red hair, let it grow. If they want it to be blonde or black and dye it, that's fine too.

Trans people are that. If they want to transition, okay, if they don't and they want to treat their dysphoria in other ways, okay.

The choice should always be with the patient. Always. But the more knowledge we amass, the more choices they will have. 100 years ago they had few. Now they have more, in the future, even more. There is no reason to just "pause" where we are right now.

u/DeannaWilliams222 · 14 points

> It is my personal belief, that if we are able to demonstrate, that transgender people are effectively all intersex, and that there are hard coded reasons for their existence, it's a lot harder to legislate away their existence.

"intersex" is being ignored in the extreme push to eradicate trans people legally (and i'm sure they'd like to do it physically). unfortunately, your belief doesn't matter (in current politics) and will be ignored by the people you suggest you are trying to convince.

if you want proof, just go watch the intersex question from the Tennessee district 1 town hall meeting. this is reality. not what you portray it as.

these people are not taking scientific evidence into account when it goes against their beliefs. it's purely plato's cave.

u/Drwillpowers · 14 points

I'm never going to convince those people. I'm not even trying. It's the moderates that I'm trying to convince.

u/LessyLuLovesYou · 1 points

i know im late but if we could prove that every single trans person is intersex then wouldn't Intersexuality just skyrocket in awareness/importance to levels well above current transgender awareness has managed to reach?

It's one thing to talk about a nebulous LGBTQIA+ alliance of sexuality and identity divergences, it's another to talk about a specific mutation in humanity, one that encompasses everything we've learned so far about trans people but with a much stronger, more reliable scientific background that can be regulated according to reasonable transgender consensus.

If anything, I'm more worried about what that consensus would be. What will happen after we understand the biological basis for trans people? Will there be a push towards "curing transness"? Will discrimination increase because of the perception of "illness" associated with the mutation, or will it decrease because of an increased understanding in its causes and consequences?

In truth I understand that even if we as mankind are now able to "read" DNA to an increasing degree, CRISPR and other gene editing therapies are well in their infancy and very, very far from becoming widespread to the point one can actually effect any kind of worldwide gene protection/healing, but I do not think that will stop politicians and fearmongers from pushing the agenda of "fixing transness" even if it were still impossible.

Societal response to transness proves time and time again that the actual science and studies come a distant second to the masses' gut reaction to what's in front of their eyes, and so I really hope that as we advance in our understanding of the mutations humanity in this century is currently undergoing, we can also campaign for a more Darwinian understanding of "gene degradation" as something neutral and innocent, if not outright natural and harmless. Even if it's due to manmade artificial pollution, even if it does harm the human body in one way or another, the people who live such a life are not to blame and their lives (currently) are far more impacted by the public reaction to their condition than any advancement in the science to understand the reasons behind their identity.

u/DeannaWilliams222 · 2 points

I think your response is based upon an assumption that every person is willing to accept reason, logic and facts and set aside their unconscious bias and internalized opinions/fears.

u/desolatenature · 3 points

Dr Powers. Can you help me understand how I can use this list to aid my transition? I’ve been on HRT for 7 years now. My transition has gone decently, but it could’ve been much better. How would I use this list to understand what I could potentially do differently?

u/Drwillpowers · 9 points

Learn biochemistry, learn human physiology, learn genetics.

Get a whole genome sequence on yourself.

Understand it, browse it, look for defects and related genes, see how these impact you physically, see if there's any way to fix some of those problems. Sometimes there is and sometimes there isn't.

u/Bailey85 · 5 points

The transgender community is doing that on its own. Dr. Powers is actually doing science and medicine to help us, while some in the community did their best to disenfranchise us. Now, we’re stuck in a very difficult situation because of them. The accommodations that were given to us (not to be confused with rights) will hopefully be reinstated with the help of his research. You really need to take a step back and see what he’s doing to protect us.

u/[deleted] · 0 points

[deleted]

u/Bailey85 · 4 points

I didn’t blame tucutes, you did. I see this more as a death by a thousand cuts. There’s plenty of blame to go around — from doctors, therapists, politicians, parents, activists, transgender organizations, and those who claimed to represent us. The damage is done, as predicted, and we don’t have many options left to fix things. I believe what Dr. Powers is doing is one of the ways out of this mess.

u/[deleted] · 3 points

[deleted]

u/Bailey85 · 2 points

Make that 1,001 cuts. If you can’t see the mistakes that were made to get us to where we are now, then I don’t see how you can contribute to helping us in the future. We make up a very small minority in the world that isn’t transgender-dominant. There are actual genocides occurring on this planet right now. Screaming about transgender erasure will not tug at the heartstrings of the general public the way you think it will. You can see children’s hospitals in Palestine riddled with the bodies of children, yet the general public in America doesn’t seem to care about that. So why would they care if you get HRT or the correct gender marker on documents. Be smart about this, this is really the only advice I can give to someone in your current mindset.

u/[deleted] · 3 points

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u/Bailey85 · 2 points

There isn’t just one single person to blame for all this. It’s a combination of many factors. You’re fixated on the 20% of people who actually want us dead. There’s nothing you can do to appease those people—they want you dead. It’s the other 80% who don’t care about you because they’re busting their asses working, taking care of their kids, and just generally fighting to survive. Those are the people you need to convince. Law, medicine, and community are how we get through this until that time comes. Those are the three shields we use to protect ourselves. It sucks, but you represent the entire community with every action you take publicly. It’s not fair, but that’s just how it is.

Also, banning us publicly is banning freedom of expression, which is a keystone of what it means to be American. Our laws, which enshrine and implement that right, would collapse if that were to happen. Transgender people not being able to express themselves would be the least of my concerns if that were to happen.

u/[deleted] · 1 points

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u/Drwillpowers · 10 points

So while ChatGPT can be useful at times, It also sometimes infers things that it should not.

It's not like I just came up with these genes myself.

For example the CYP2D6 which it criticizes, is from a study. Where they found that gene had variants more commonly in transgender people.

Same goes for the other ones, so while this AI may think that it feels scattershot, hilariously, you can ask it about those genes and studies and it will give you the same answers that it would give me.

Never forget, that thing will confabulate whatever it can to make something that sounds legitimate. That doesn't make it true. You always have to verify it. If you do not have the medical knowledge to verify it, then don't trust it at all.

I use an AI every single day now. It's extremely useful. It's great for checking my work and seeing what I might have forgotten. It can't make a care plan for me though.

u/foodmystery · 2 points

AI really loses the plot, especially when you ask it broad things as you point out. You need to focus it constantly so it puts enough 'thought' into whatever you want.

u/[deleted] · 1 points

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u/Drwillpowers · 3 points

That doesn't say anything about what the environment was when you were a fetus. Which is when those values matter. Not when you were a teenager or adult.

u/Worried-Beach9078 · 1 points

A very comprehensive list! You have made so many progress recently!

If I can ask: 1-how many transgender data have you checked, and how many of them are not? 2-have you tried to create a sort of probability distribution? You have just 2 mutations, but in transgender population it is more common to have at least N mutations maybe. 3-A "cluster analysis" (https://en.m.wikipedia.org/wiki/Cluster_analysis) would be interesting to perform, to understand how many subpopulations there are in your data! You and Kate have already discovered some of the subpopulations. What if there is more? Have you tried it?

Well done!

u/CaramelNo3420 · 1 points

I'm going to look mine up on here already though for quick reference is there anything associated with genes listed on Promethease?

u/CaramelNo3420 · 1 points

Wow I already hit on having the variation of ESR1 that impacts the estrogen signalling pathway to increase estrogen levels overly in female assigned people. This is entirely in line with my circumstance!

u/Drwillpowers · 2 points

Well, if you're AMAB and not trans, then that's consistent with it. Increased estrogen signaling causes masculinization in utero.

u/CaramelNo3420 · 1 points

Hello! It's eating my posts probably since it thinks they are triple posts. One more try. AFAB with masculinizing medical conditions though somehow dangerously high estrogen levels as well. I'm also hitting on many rare SOX variations.

u/Drwillpowers · 2 points

Dangerously high estrogen? How high? Remember, pregnancy goes to like 25,000 so I don't know what you mean by dangerous.

u/CaramelNo3420 · 2 points

I can't take estrogen birth control without kidney damage. I also can't get pregnant safely so that even sounds potentially related.

u/Drwillpowers · 1 points

Why do you know these things? What do you mean by these? This is not something I've ever even heard mentioned before. I'm sort of confused about your whole situation so if you want to give me a better clinical history I will listen

u/CaramelNo3420 · 1 points

By doctors who did ultrasounds, xrays, urine samples (proteinuria suggesting kidney damage), blood samples, ekgs and even tilt table tests. The Yaz lawsuit for example really should have paid me out. I got diagnosed with severe adenomyosis with uterine fibroids initially which they thought ruled out PCOS. Then the xray said dramatically otherwise so I have that in addition to PCOS. I can definitely translate that into "uterine abnormality" myself. I'm myself more on the genetics side of things though I'm always enthused to look at my own issues especially on the medical side of things I understand less.

u/Drwillpowers · 1 points

Okay, so proteinuria does not mean your kidneys are damaged by birth control.

Honestly you kind of sound just like a regular old NCCAH case.

u/CaramelNo3420 · 1 points

Nope that was what was differentially diagnosed from the PCOS. I was having symptoms that started to suggest the beginning of multiple organ crisis with no clear explanation. They suspect early stage dysautonomia to this day. The trigger was two part though actually. The Yaz (which I had taken for years) plus there was this suspected viral infection of some mysterious provenance. The onset though for example of my hormonal issues though was very early in life.

They made the mistake in differentiating from NCCAH very early on then assuming the other issues were explained by some unicorn fully explanatory diagnosis thinking that PCOS was somehow also ruled out. They were right and wrong in that there are other issues at play though the regular (dangerous) symptoms are also features of more "regular" items like PCOS, severe muscle growth into my endometrium, early life prediabetes even.

u/dirt_devil_696 · 1 points

How is a genome analysis made?

u/[deleted] · 1 points

Doc, just wanted to share a funny story with you.

My friend is a health researcher, and he told me a recent story.
He got a client with unexplained dry mouth (almost no saliva), with ruined his quality of life - he suffers from multiple infections, dental caries and has sleep dificulty. No doctor was able to cure him, so my friend did a deep scientific research on his disease pathways, and identified several signaling pathways. They tried the acetylcholine, nitric oxide and aldosterone pathways - without any effects. as a last resort they tried 2mg estrogen transdermally, and his client's saliva production was restored! he never felt better.

now there is a choice between healthy feminization and being a man with poor dental health

u/Drwillpowers · 2 points

Yeah so why tho? I mean I can tell a patient to stick a vibrator up their ass to cure constipation but that doesn't explain or deal with why they are constipated or take stock of the fact that maybe not everyone is into rectal vibratory disempactions.

Sounds like your friends patient has sjogrens syndrome.

Also 2mg estrogen transdermally is like jumping into a pool of pure estrogen. That's 20x max dose patches. Feel like this could have been solved without massively overdosing on estrogen.

u/LividIndependence900 · 1 points

Let me add my experience.

I (AMAB, 42+, right now on EEn Injections) was totally coping throughout my life since puberty. I always naturally had good level of testosterone. But never had much beard or body hair. In 2021 a tragic failure of my political career made me so much depressed that I couldn't cope anymore. Started estrogen (oral tablet) and progesterone on my own (DIY). It literally saved me. Also, Interestingly my 6 years old left shoulder pain and 2 years old bicep ligament pain got cured within 15 days of starting the estrogen. Although I stopped HRT after the 18^th day due to rapid feminization and social fear. But those pain never returned. I started again and stopped, did this several times, now estrogen works very slowly on me, don't know whearher it's plateau or my estrogen receptors got less sensitive. But those almost forever pain got cure as a nice side effect. Nobody would believe, that was like a magic.

u/PhantomTF · 1 points

quick question Dr. P (or anyone who knows who sees this) I only have the rsid numbers from my ancestry file, how do I find out what a gene's corresponding rsid number is in order to take a look at it?

u/Drwillpowers · 1 points

It doesn't work that way. Those are just snps.

To look at whole genes like this you need a whole genome sequence. Not an ancestry. A WGS is like 300 GB of data and you have a file that's about 15 MB. It's not even remotely comparable.

u/hole-in-the-day · 1 points

Is there a reason why you include ABCC2 here but not any of the other ABC* genes that are included in your PFS/PSSD list?

From what I understand, a lot of them are involved in the intercellular transport and clearance of sex hormones, so if some of these genes are dysfunctional, you could have estrogens/androgens staying in certain tissues for longer than they "should," and then depending on whatever else is going on with hormone metabolism, you could either have a zombie apocalypse situation in ftm cases where metabolites marked for clearance can't leave so they eventually reactivate and bind, or in mtf cases if the person tends to make weaker metabolites and can't flush them out, this prevents stronger estrogens from binding.

Am I missing something here?

This may or may not be related, have you ever seen a ftm person with a passing voice pre-testosterone (sounding like a 16-18 year old boy) go on to take testosterone and experience no vocal changes even 5+ years in, even after DHT levels are corrected, where it's just stuck there? Is there some epigenetic thing that could explain this?

Along with ABC* mutations I have reduced function in several genes involved in the metabolism of strong estrogens/androgens into weaker/inactive forms, but I also have this

https://preview.redd.it/gmxoi3dr70wg1.png?width=1467&format=png&auto=webp&s=715b1902fe99dac3e782149f56cfb4471496fdcd

This mutation seems to be able to result in the full spectrum of sex phenotypes in XY, anything from mild hypospadias with normal fertility all the way over to ovotesticular disorder and female sex reversal. The handful of XX cases I can find information about aren't as thoroughly characterized, it's basically just "we assume this variant in this 46XY person was inherited maternally because both their mother and grandmother went through menopause in their 20s."

Maybe it's simply not as big of a deal in XX so it never gets diagnosed in the first place though. I just wonder whether it could be messing with hormone signalling, but if it is something significant then shouldn't it have prevented me from being ftm in the first place?

u/Drwillpowers · 2 points

This is a list of the stuff that's shown up when I've looked for it, but not necessarily the list of all possible things.

Admittedly I probably should update it with some of the things that I've encountered from PFS/PSSD but don't consider this an exhaustive list.

That being said there's like 10 genes in this list though that I actually routinely see. It's usually those. Like off the top of my head 21a2, 11bhsd, 17bhsd, esr1,esr2, essra, crebbp, ncor1, ncor2, 17ahsd, cyp19a1

It's one of those like ⅓ of the damn time.

u/hole-in-the-day · 1 points

Yes, NCOR1 and HSD17B2 get flagged too, reduced function in both which makes sense, and I actually have some of the same variants that were posted about here the other day in a stack in ESRRA. Nothing as weird as the NR5A1 mutation though.

I just wonder whether intercellular transport stuff might be important because it might easily explain why different tissues can be affected differently.

Like if you need a sufficient degree of prenatal androgen exposure/signalling to be attracted to women, you'd think that everyone born with a penis would be attracted to women, because that's the most obvious evidence of androgen exposure. You might be able to make sense of natal females who are a bit bisexual because of excess androgen exposure, but if there's a degree of androgen exposure/signalling that creates exclusive gynephilia, you'd think they couldn't be exclusively gynephilic, or they would all be born with penises except in rare cases where they have 5ard or are a chimera or something.

But if you have mutations in genes like ABCG2 that change how effectively sex hormones can be excreted from the brain, or in ABCC genes that trap androgens in other tissues so that they don't make it to the brain, or something that can cause/prevent high amounts of hormone exposure/signalling during the perinatal period only, that explains why this isn't the case. For transbians it might not matter, but it would make sense of other LGBT people.

u/Drwillpowers · 2 points

Actually a lot of penile development is driven by estrogen. But yes your understanding of the transporter glitches and then by extension how that could affect sexuality or gender matches my own at this time. You get it. Well done.

u/Total-Reference7212 · 1 points

I also have the ESRRA stack and am ftm, wondering what potential implications could it have ? It seems more like an mtf thing if it breaks estrogenic signalling in the brain, or marker for neurodivergence?

Also maybe it's not that uncommon to have it? Is it in the original .bam or VCF you got from the sequencing company?

u/[deleted] · -9 points

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u/DrWillPowers-ModTeam · 3 points

Your comment qualified for removal under the "don't be an asshole" rule.

u/9119343636 · -6 points

Just send it directly to Musk's grok while you're at it. Only you are making this available and even if some other autist somehow gathered thousands of trans patients together, who trusted them, (extremely unlikely because you're a unique case) and published a comprehensive account of all the gene markers it would be another couple of years off before it could be complete.

u/Anon374928 · 5 points

Can't stop the future, might as well fight for it.

u/9119343636 · -2 points

You can absolutely delay stuff. Everyone does it all the time.

u/Drwillpowers · 11 points

I'm sorry, are you asking me to deliberately obfuscate medical knowledge because you're afraid of what people are going to do with it?

What are you a Luddite?

The truth just is the truth friend. Nuclear power can be used to generate energy, or to destroy cities. But the knowledge was always going to come. The truth was always there, we just had to learn how to do it.

I think it'd be a lot better if the truth of this fell into the hands of somebody like me who basically has spent his life trying to help this population, rather than perhaps, be the side project of some TERF organization.

But, if you are rude like that again, you will be banned from the subreddit. You can say what you want within reason, but you can't act like that. Not like a petulant child that didn't get their way.

Archived 2026-04-20 from https://www.reddit.com/r/DrWillPowers/comments/1j1yv64/when_i_browse_patients_genomes_to_see_if_i_can/ via scrape-tools/social.