46,XY sex reversal 1
diseaseOn this page
Also known as 46,XY gonadal dysgenesis, complete, SRY-related46,XY sex reversal type 146,XY sex reversal, SRY-related46,XY true hermaphroditism, SRY-related46XY sex reversal 1, Y-linkedSRXY1
Summary
46,XY sex reversal 1 (MONDO:0020712) is a disease caused by SRY (GenCC Definitive), with 1 cohort gene.
At a glance
- Causal gene: SRY (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 56
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | 46,XY sex reversal 1 |
| Mondo ID | MONDO:0020712 |
| OMIM | 400044 |
| DOID | DOID:0111778 |
| NCIT | C128188 |
| UMLS | C2748896 |
| MedGen | 412662 |
| GARD | 0025219 |
| Is cancer (heuristic) | no |
Also known as: 46,XY gonadal dysgenesis, complete, SRY-related · 46,XY sex reversal 1 · 46,XY sex reversal type 1 · 46,XY sex reversal, SRY-related · 46,XY true hermaphroditism, SRY-related · 46XY sex reversal 1, Y-linked · SRXY1
Data availability: 56 ClinVar variants · 2 GenCC gene-disease records · 8 cell lines.
Disease family
Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › hypogonadism › gonadal dysgenesis › 46,XY complete gonadal dysgenesis › 46,XY sex reversal 1
Related subtypes (11): 46,XY sex reversal 4, 46,XY sex reversal 7, 46,XY sex reversal 2, 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome, 46,XY sex reversal 3, 46,XY sex reversal 5, 46,XY sex reversal 6, 46,XY disorder of sex development due to testicular 17,20-desmolase deficiency, 46,XY sex reversal 9, 46,XY sex reversal 10, 46,XY sex reversal 11
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
56 retrieved; paginated sample, class counts are floors:
32 pathogenic, 16 uncertain significance, 6 likely pathogenic, 1 benign, 1 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 3024128 | NC_000024.10:g.2792795A>G | Pathogenic | no assertion criteria provided | |
| 3024132 | NC_000024.10:g.2792798G>A | Pathogenic | no assertion criteria provided | |
| 2693711 | NM_003140.3(SRY):c.174_175insC (p.Arg59fs) | SRY | Pathogenic | criteria provided, single submitter |
| 2829588 | NM_003140.3(SRY):c.145G>T (p.Gly49Ter) | SRY | Pathogenic | criteria provided, single submitter |
| 3242611 | NC_000024.9:g.(?2654792)(2655895_?)del | SRY | Pathogenic | criteria provided, single submitter |
| 3652585 | NM_003140.3(SRY):c.22_23del (p.Met8fs) | SRY | Pathogenic | criteria provided, single submitter |
| 436871 | NM_003140.3(SRY):c.331C>T (p.Gln111Ter) | SRY | Pathogenic | criteria provided, single submitter |
| 470195 | NM_003140.3(SRY):c.264dup (p.Glu89fs) | SRY | Pathogenic | criteria provided, single submitter |
| 470196 | NM_003140.3(SRY):c.380A>G (p.Tyr127Cys) | SRY | Pathogenic | criteria provided, single submitter |
| 492908 | NM_003140.3(SRY):c.89G>T (p.Arg30Ile) | SRY | Pathogenic | no assertion criteria provided |
| 537738 | NM_003140.3(SRY):c.288C>G (p.Tyr96Ter) | SRY | Pathogenic | criteria provided, single submitter |
| 537739 | NM_003140.3(SRY):c.263C>A (p.Ser88Ter) | SRY | Pathogenic | criteria provided, single submitter |
| 664404 | NM_003140.3(SRY):c.169C>T (p.Gln57Ter) | SRY | Pathogenic | criteria provided, single submitter |
| 9737 | NM_003140.3(SRY):c.364_367del (p.Glu122fs) | SRY | Pathogenic | no assertion criteria provided |
| 9738 | NM_003140.3(SRY):c.326T>C (p.Phe109Ser) | SRY | Pathogenic | no assertion criteria provided |
| 9739 | NM_003140.3(SRY):c.178G>C (p.Val60Leu) | SRY | Pathogenic | criteria provided, single submitter |
| 9740 | NM_003140.3(SRY):c.277C>T (p.Gln93Ter) | SRY | Pathogenic | no assertion criteria provided |
| 9741 | NM_003140.3(SRY):c.270C>G (p.Ile90Met) | SRY | Pathogenic | no assertion criteria provided |
| 9742 | NM_003140.3(SRY):c.317A>T (p.Lys106Ile) | SRY | Pathogenic | no assertion criteria provided |
| 9743 | NM_003140.3(SRY):c.324del (p.Phe109fs) | SRY | Pathogenic | no assertion criteria provided |
| 9744 | NM_003140.3(SRY):c.337G>A (p.Ala113Thr) | SRY | Pathogenic | no assertion criteria provided |
| 9745 | NM_003140.3(SRY):c.320G>A (p.Trp107Ter) | SRY | Pathogenic | no assertion criteria provided |
| 9746 | NM_003140.3(SRY):c.203T>C (p.Ile68Thr) | SRY | Pathogenic | criteria provided, single submitter |
| 9748 | NM_003140.3(SRY):c.209G>A (p.Trp70Ter) | SRY | Pathogenic | no assertion criteria provided |
| 9749 | NM_003140.3(SRY):c.274A>T (p.Lys92Ter) | SRY | Pathogenic | no assertion criteria provided |
| 9750 | NM_003140.3(SRY):c.283G>C (p.Gly95Arg) | SRY | Pathogenic | no assertion criteria provided |
| 9751 | NM_003140.3(SRY):c.12T>A (p.Tyr4Ter) | SRY | Pathogenic | no assertion criteria provided |
| 9752 | NM_003140.3(SRY):c.397C>T (p.Arg133Trp) | SRY | Pathogenic | no assertion criteria provided |
| 9753 | NM_003140.3(SRY):c.4C>T (p.Gln2Ter) | SRY | Pathogenic | no assertion criteria provided |
| 9754 | NM_003140.3(SRY):c.53G>A (p.Ser18Asn) | SRY | Pathogenic | no assertion criteria provided |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 8 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| SRY | Definitive | X-linked | 46,XX sex reversal 1 | 8 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SRY | Orphanet:1772 | 45,X/46,XY mixed gonadal dysgenesis |
| SRY | Orphanet:2138 | 46,XX ovotesticular difference of sex development |
| SRY | Orphanet:242 | 46,XY complete gonadal dysgenesis |
| SRY | Orphanet:251510 | 46,XY partial gonadal dysgenesis |
| SRY | Orphanet:393 | 46,XX testicular difference of sex development |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| SRY | HGNC:11311 | ENSG00000184895 | Q05066 | Sex-determining region Y protein | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SRY | Sex-determining region Y protein | Transcriptional regulator that controls a genetic switch in male development. |
Protein-family classification
Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Transcription factor | 1 | 8.3× | 0.121 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| SRY | Transcription factor | no | HMG_box_dom, SRY, HMG_box_dom_sf |
Expression context
Cohort genes with no expression data: 0.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| primordial germ cell in gonad | 1 |
| right testis | 1 |
| tendon of biceps brachii | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SRY | 66 | tissue_specific | yes | primordial germ cell in gonad, tendon of biceps brachii, right testis |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| SRY | 2,835 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SRY | Q05066 | 10 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Transcriptional regulation of testis differentiation | 1 | 713.8× | 0.008 | SRY |
| Deactivation of the beta-catenin transactivating complex | 1 | 233.1× | 0.013 | SRY |
| TCF dependent signaling in response to WNT | 1 | 117.7× | 0.013 | SRY |
| Signaling by WNT | 1 | 112.0× | 0.013 | SRY |
| Developmental Biology | 1 | 14.5× | 0.083 | SRY |
| Signal Transduction | 1 | 10.2× | 0.098 | SRY |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| positive regulation of male gonad development | 1 | 1685.2× | 0.002 | SRY |
| male sex determination | 1 | 1404.3× | 0.002 | SRY |
| sex differentiation | 1 | 842.6× | 0.003 | SRY |
| positive regulation of gene expression | 1 | 38.7× | 0.042 | SRY |
| cell differentiation | 1 | 29.1× | 0.042 | SRY |
| positive regulation of DNA-templated transcription | 1 | 27.9× | 0.042 | SRY |
| positive regulation of transcription by RNA polymerase II | 1 | 14.9× | 0.067 | SRY |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| SRY | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | SRY |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| SRY | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: SRY