46,XY complete gonadal dysgenesis
diseaseOn this page
Also known as 46 XY gonadal dysgenesis46, XY CGD46, XY complete gonadal dysgenesis46, XY pure gonadal dysgenesis46,XY CGD46,XY gonadal dysgenesis46,XY pure gonadal dysgenesis46,XY SEX reversalgonadal dysgenesis, XY female typeSwyer syndrome
Summary
46,XY complete gonadal dysgenesis (MONDO:0010765) is a disease (an umbrella term covering 12 Mondo subtypes) with 11 cohort genes. The dominant Reactome pathway is Transcriptional regulation of testis differentiation (5 cohort genes).
At a glance
- Prevalence: Unknown (Worldwide) [Orphanet-validated]
- Umbrella term: 12 Mondo subtypes
- Cohort genes: 11
- ClinVar variants: 5
- Phenotypes (HPO): 4
Clinical features
Signs & symptoms
Clinical features (HPO)
4 HPO clinical features (Orphanet curated; top 4 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000037 | Male pseudohermaphroditism | Very frequent (80-99%) |
| HP:0000044 | Hypogonadotropic hypogonadism | Very frequent (80-99%) |
| HP:0000147 | Polycystic ovaries | Very frequent (80-99%) |
| HP:0008715 | Testicular dysgenesis | Very frequent (80-99%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | 46,XY complete gonadal dysgenesis |
| Mondo ID | MONDO:0010765 |
| MeSH | D006061 |
| OMIM | 400044 |
| Orphanet | 242 |
| DOID | DOID:14448 |
| NCIT | C120198 |
| SNOMED CT | 95218005 |
| UMLS | C2936694 |
| MedGen | 445380 |
| GARD | 0005068 |
| NORD | 1750 |
| Is cancer (heuristic) | no |
Also known as: 46 XY gonadal dysgenesis · 46, XY CGD · 46, XY complete gonadal dysgenesis · 46, XY pure gonadal dysgenesis · 46,XY CGD · 46,XY gonadal dysgenesis · 46,XY pure gonadal dysgenesis · 46,XY SEX reversal · gonadal dysgenesis, XY female type · Swyer syndrome
Data availability: 5 ClinVar variants · 7 GenCC gene-disease records · 29 cell lines.
Disease family
An umbrella term covering 12 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › hypogonadism › gonadal dysgenesis › 46,XY complete gonadal dysgenesis
Related subtypes (4): testicular dysgenesis syndrome, 46 XX gonadal dysgenesis, 45,X/46,XY mixed gonadal dysgenesis, Turner syndrome
Subtypes (12): 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 1, 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
5 retrieved; paginated sample, class counts are floors:
4 uncertain significance, 1 pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 988321 | NM_000044.6(AR):c.1462C>T (p.Gln488Ter) | AR | Pathogenic | criteria provided, single submitter |
| 2634053 | NM_005189.3(CBX2):c.288+52G>T | CBX2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3779001 | NM_005189.3(CBX2):c.629G>A (p.Gly210Asp) | CBX2 | Uncertain significance | criteria provided, single submitter |
| 1344532 | NM_017780.4(CHD7):c.4388T>C (p.Leu1463Pro) | CHD7 | Uncertain significance | criteria provided, single submitter |
| 988653 | NM_021951.3(DMRT1):c.967G>A (p.Val323Ile) | DMRT1 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 56 · Orphanet: 34 · 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 |
|---|---|---|---|---|
| DHH | Strong | Autosomal recessive | 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome | 4 |
| CBX2 | Supportive | Autosomal dominant | 46,XY complete gonadal dysgenesis | 3 |
| DHX37 | Supportive | Autosomal dominant | 46,XY complete gonadal dysgenesis | 9 |
| MAP3K1 | Supportive | Autosomal dominant | 46,XY complete gonadal dysgenesis | 7 |
| NR5A1 | Supportive | Autosomal dominant | 46,XY complete gonadal dysgenesis | 12 |
| SOX9 | Supportive | Autosomal dominant | 46,XY complete gonadal dysgenesis | 13 |
| SRY | Supportive | Autosomal dominant | 46,XY complete gonadal dysgenesis | 8 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| CBX2 | Orphanet:242 | 46,XY complete gonadal dysgenesis |
| SOX9 | Orphanet:140 | Campomelic dysplasia |
| SOX9 | Orphanet:2138 | 46,XX ovotesticular difference of sex development |
| SOX9 | Orphanet:242 | 46,XY complete gonadal dysgenesis |
| SOX9 | Orphanet:251510 | 46,XY partial gonadal dysgenesis |
| SOX9 | Orphanet:393 | 46,XX testicular difference of sex development |
| SOX9 | Orphanet:718 | Isolated Pierre Robin sequence |
| 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 |
| DHX37 | Orphanet:242 | 46,XY complete gonadal dysgenesis |
| DHX37 | Orphanet:251510 | 46,XY partial gonadal dysgenesis |
| DHX37 | Orphanet:983 | Testicular regression syndrome |
| DHH | Orphanet:168563 | 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome |
| DHH | Orphanet:242 | 46,XY complete gonadal dysgenesis |
| MAP3K1 | Orphanet:242 | 46,XY complete gonadal dysgenesis |
| MAP3K1 | Orphanet:251510 | 46,XY partial gonadal dysgenesis |
| NR5A1 | Orphanet:2138 | 46,XX ovotesticular difference of sex development |
| NR5A1 | Orphanet:242 | 46,XY complete gonadal dysgenesis |
| NR5A1 | Orphanet:243 | 46,XX gonadal dysgenesis |
| NR5A1 | Orphanet:251510 | 46,XY partial gonadal dysgenesis |
| NR5A1 | Orphanet:393 | 46,XX testicular difference of sex development |
| NR5A1 | Orphanet:399805 | Male infertility with azoospermia or oligozoospermia due to single gene mutation |
| CHD7 | Orphanet:138 | CHARGE syndrome |
| CHD7 | Orphanet:39041 | Omenn syndrome |
| CHD7 | Orphanet:432 | Normosmic congenital hypogonadotropic hypogonadism |
| CHD7 | Orphanet:478 | Kallmann syndrome |
| DMRT1 | Orphanet:242 | 46,XY complete gonadal dysgenesis |
| AR | Orphanet:481 | Kennedy disease |
| AR | Orphanet:90797 | Partial androgen insensitivity syndrome |
| AR | Orphanet:95706 | Non-syndromic posterior hypospadias |
| AR | Orphanet:99429 | Complete androgen insensitivity syndrome |
Cohort genes → proteins
11 cohort genes, 11 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 11 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| CBX2 | HGNC:1552 | ENSG00000173894 | Q14781 | Chromobox protein homolog 2 | gencc,clinvar |
| SOX9 | HGNC:11204 | ENSG00000125398 | P48436 | Transcription factor SOX-9 | gencc |
| SRY | HGNC:11311 | ENSG00000184895 | Q05066 | Sex-determining region Y protein | gencc |
| DHX37 | HGNC:17210 | ENSG00000150990 | Q8IY37 | Probable ATP-dependent RNA helicase DHX37 | gencc |
| DHH | HGNC:2865 | ENSG00000139549 | O43323 | Desert hedgehog protein | gencc |
| MAP3K1 | HGNC:6848 | ENSG00000095015 | Q13233 | Mitogen-activated protein kinase kinase kinase 1 | gencc |
| NR5A1 | HGNC:7983 | ENSG00000136931 | Q13285 | Steroidogenic factor 1 | gencc |
| CHD7 | HGNC:20626 | ENSG00000171316 | Q9P2D1 | ATP-dependent chromatin remodeler CHD7 | clinvar |
| DMRT1 | HGNC:2934 | ENSG00000137090 | Q9Y5R6 | Doublesex- and mab-3-related transcription factor 1 | clinvar |
| AR | HGNC:644 | ENSG00000169083 | P10275 | Androgen receptor | clinvar |
| AREG | HGNC:651 | ENSG00000109321 | P15514 | Amphiregulin | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| CBX2 | Chromobox protein homolog 2 | Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. |
| SOX9 | Transcription factor SOX-9 | Transcription factor that plays a key role in chondrocytes differentiation and skeletal development. |
| SRY | Sex-determining region Y protein | Transcriptional regulator that controls a genetic switch in male development. |
| DHX37 | Probable ATP-dependent RNA helicase DHX37 | ATP-binding RNA helicase that plays a role in maturation of the small ribosomal subunit in ribosome biogenesis. |
| DHH | Desert hedgehog protein | The C-terminal part of the desert hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity. |
| MAP3K1 | Mitogen-activated protein kinase kinase kinase 1 | Component of a protein kinase signal transduction cascade. |
| NR5A1 | Steroidogenic factor 1 | Transcriptional activator. |
| CHD7 | ATP-dependent chromatin remodeler CHD7 | ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP. |
| DMRT1 | Doublesex- and mab-3-related transcription factor 1 | Transcription factor that plays a key role in male sex determination and differentiation by controlling testis development and male germ cell proliferation. |
| AR | Androgen receptor | Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. |
| AREG | Amphiregulin | Ligand of the EGF receptor/EGFR. |
Protein-family classification
Druggable: 3 · Difficult: 2 · Unknown: 6 · Druggable fraction: 0.27
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 |
|---|---|---|---|
| Nuclear receptor | 2 | 70.2× | 0.001 |
| Kinase | 1 | 2.5× | 0.523 |
| Transcription factor | 2 | 1.5× | 0.523 |
| Other/Unknown | 6 | 1.0× | 0.654 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| CBX2 | Other/Unknown | no | Chromo/chromo_shadow_dom, Chromo-like_dom_sf, Chromodomain_CS | |
| SOX9 | Transcription factor | no | HMG_box_dom, Sox_N, HMG_box_dom_sf | |
| SRY | Transcription factor | no | HMG_box_dom, SRY, HMG_box_dom_sf | |
| DHX37 | Other/Unknown | no | Helicase_C-like, Helicase-assoc_dom, DEAD/DEAH_box_helicase_dom | |
| DHH | Other/Unknown | no | Hedgehog_signalling_dom, Hedgehog, Hedgehog_Hint | |
| MAP3K1 | Kinase | yes | 2.7.11.25 | Prot_kinase_dom, Znf_RING, Znf_SWIM |
| NR5A1 | Nuclear receptor | yes | Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt | |
| CHD7 | Other/Unknown | no | SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like | |
| DMRT1 | Other/Unknown | no | DM_DNA-bd, DMRT1-like, DMRT | |
| AR | Nuclear receptor | yes | Nucl_hrmn_rcpt_lig-bd, Andrgn_rcpt, Znf_hrmn_rcpt | |
| AREG | Other/Unknown | no | EGF |
Expression context
Cohort genes with no expression data: 0.
7 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 11 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| primordial germ cell in gonad | 3 |
| secondary oocyte | 2 |
| right testis | 2 |
| tendon of biceps brachii | 2 |
| buccal mucosa cell | 2 |
| oocyte | 1 |
| cranial nerve II | 1 |
| hair follicle | 1 |
| ventricular zone | 1 |
| medial globus pallidus | 1 |
| pancreatic ductal cell | 1 |
| left testis | 1 |
| tibial nerve | 1 |
| skin of hip | 1 |
| upper leg skin | 1 |
| left adrenal gland | 1 |
| right adrenal gland | 1 |
| right adrenal gland cortex | 1 |
| cerebellar vermis | 1 |
| sural nerve | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| CBX2 | 178 | ubiquitous | marker | secondary oocyte, oocyte, primordial germ cell in gonad |
| SOX9 | 274 | ubiquitous | marker | ventricular zone, cranial nerve II, hair follicle |
| SRY | 66 | tissue_specific | yes | primordial germ cell in gonad, tendon of biceps brachii, right testis |
| DHX37 | 236 | ubiquitous | yes | pancreatic ductal cell, tendon of biceps brachii, medial globus pallidus |
| DHH | 123 | tissue_specific | yes | tibial nerve, right testis, left testis |
| MAP3K1 | 264 | ubiquitous | marker | buccal mucosa cell, upper leg skin, skin of hip |
| NR5A1 | 77 | tissue_specific | yes | right adrenal gland cortex, right adrenal gland, left adrenal gland |
| CHD7 | 269 | ubiquitous | marker | secondary oocyte, cerebellar vermis, sural nerve |
| DMRT1 | 23 | tissue_specific | marker | primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell |
| AR | 250 | ubiquitous | marker | seminal vesicle, urethra, nipple |
| AREG | 216 | ubiquitous | marker | mucosa of urinary bladder, endometrium epithelium, right lung |
Protein interactions among cohort
Intra-cohort edges: 9.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| AR | 7,400 |
| SOX9 | 4,935 |
| CHD7 | 4,819 |
| MAP3K1 | 4,414 |
| DHX37 | 3,123 |
| SRY | 2,835 |
| AREG | 2,745 |
| NR5A1 | 2,146 |
| DHH | 1,849 |
| CBX2 | 1,609 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| CHD7 | SOX9 | string_interaction |
| DHH | NR5A1 | string_interaction |
| DHH | SOX9 | string_interaction |
| DHH | SRY | string_interaction |
| DMRT1 | NR5A1 | string_interaction |
| DMRT1 | SOX9 | string_interaction |
| DMRT1 | SRY | string_interaction |
| NR5A1 | SOX9 | biogrid_interaction, string_interaction |
| NR5A1 | SRY | string_interaction |
Structural data
PDB: 11 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| AR | P10275 | 95 |
| SRY | Q05066 | 10 |
| NR5A1 | Q13285 | 6 |
| DHH | O43323 | 5 |
| CBX2 | Q14781 | 3 |
| CHD7 | Q9P2D1 | 3 |
| SOX9 | P48436 | 1 |
| DHX37 | Q8IY37 | 1 |
| MAP3K1 | Q13233 | 1 |
| DMRT1 | Q9Y5R6 | 1 |
| AREG | P15514 | 1 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 116. Enrichment computed across 11 evidence-associated genes (11 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 11 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 | 5 | 324.4× | 1e-10 | SOX9, SRY, DHH, DMRT1, NR5A1 |
| SUMO E3 ligases SUMOylate target proteins | 3 | 48.7× | 0.001 | CBX2, AR, NR5A1 |
| SUMOylation | 3 | 44.5× | 0.001 | CBX2, AR, NR5A1 |
| SUMOylation of intracellular receptors | 2 | 61.1× | 0.013 | AR, NR5A1 |
| Transcriptional regulation by RUNX2 | 2 | 46.1× | 0.016 | SOX9, AR |
| Deactivation of the beta-catenin transactivating complex | 2 | 42.4× | 0.016 | SOX9, SRY |
| RNA Polymerase II Transcription | 4 | 8.2× | 0.016 | CBX2, SOX9, AR, NR5A1 |
| Nuclear Receptor transcription pathway | 2 | 36.4× | 0.019 | AR, NR5A1 |
| Post-translational protein modification | 4 | 7.0× | 0.023 | CBX2, AR, AREG, NR5A1 |
| Gene expression (Transcription) | 4 | 6.5× | 0.027 | CBX2, SOX9, AR, NR5A1 |
| Signal Transduction | 5 | 4.6× | 0.027 | CBX2, SOX9, SRY, AR, AREG |
| Cellular responses to stress | 3 | 10.1× | 0.027 | CBX2, AR, AREG |
| Signaling by Overexpressed Wild-Type EGFR in Cancer | 1 | 259.6× | 0.030 | AREG |
| TCF dependent signaling in response to WNT | 2 | 21.4× | 0.030 | SOX9, SRY |
| Signaling by WNT | 2 | 20.4× | 0.030 | SOX9, SRY |
| Cellular responses to stimuli | 3 | 8.6× | 0.030 | CBX2, AR, AREG |
| Generic Transcription Pathway | 4 | 5.5× | 0.030 | CBX2, SOX9, AR, NR5A1 |
| HHAT G278V doesn’t palmitoylate Hh-Np | 1 | 207.6× | 0.031 | DHH |
| Intracellular signaling by second messengers | 2 | 16.6× | 0.037 | CBX2, AREG |
| Release of Hh-Np from the secreting cell | 1 | 129.8× | 0.042 | DHH |
| Ligand-receptor interactions | 1 | 129.8× | 0.042 | DHH |
| Inhibition of Signaling by Overexpressed EGFR | 1 | 115.3× | 0.044 | AREG |
| Metabolism of proteins | 4 | 4.5× | 0.044 | CBX2, AR, AREG, NR5A1 |
| Signaling by EGFR in Cancer | 1 | 103.8× | 0.045 | AREG |
| EGFR interacts with phospholipase C-gamma | 1 | 103.8× | 0.045 | AREG |
| NFE2L2 regulating tumorigenic genes | 1 | 86.5× | 0.049 | AREG |
| PIP3 activates AKT signaling | 2 | 12.1× | 0.049 | CBX2, AREG |
| RUNX2 regulates bone development | 1 | 74.2× | 0.056 | AR |
| GRB2 events in EGFR signaling | 1 | 69.2× | 0.057 | AREG |
| SHC1 events in EGFR signaling | 1 | 64.9× | 0.059 | AREG |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 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 | 5 | 766.0× | 3e-12 | SOX9, SRY, DHX37, DMRT1, NR5A1 |
| male sex determination | 4 | 510.7× | 6e-09 | SRY, DHH, DMRT1, NR5A1 |
| Sertoli cell differentiation | 3 | 417.8× | 3e-06 | SOX9, DMRT1, NR5A1 |
| Leydig cell differentiation | 3 | 328.3× | 5e-06 | DHH, AR, NR5A1 |
| transcription by RNA polymerase II | 4 | 25.6× | 6e-04 | SOX9, CHD7, AR, NR5A1 |
| regulation of steroid biosynthetic process | 2 | 278.6× | 9e-04 | DHH, NR5A1 |
| positive regulation of transcription by RNA polymerase II | 6 | 8.1× | 0.001 | SOX9, SRY, CHD7, DMRT1, AR, NR5A1 |
| Sertoli cell development | 2 | 204.3× | 0.001 | SOX9, DMRT1 |
| male gonad development | 3 | 42.6× | 0.001 | SOX9, AR, NR5A1 |
| mammary gland alveolus development | 2 | 180.2× | 0.001 | AR, AREG |
| sex differentiation | 2 | 153.2× | 0.002 | SRY, DMRT1 |
| positive regulation of gene expression | 4 | 14.1× | 0.003 | SOX9, SRY, AR, NR5A1 |
| cell fate specification | 2 | 95.8× | 0.004 | SOX9, DHH |
| cell-cell signaling | 3 | 19.0× | 0.008 | DHH, AR, AREG |
| right ventricular compact myocardium morphogenesis | 1 | 1532.0× | 0.009 | CHD7 |
| male somatic sex determination | 1 | 1532.0× | 0.009 | AR |
| development of primary sexual characteristics | 1 | 1532.0× | 0.009 | CBX2 |
| prostate induction | 1 | 1532.0× | 0.009 | AR |
| negative regulation of osteoblast differentiation | 2 | 53.8× | 0.009 | SOX9, AREG |
| negative regulation of epithelial cell proliferation | 2 | 52.8× | 0.009 | SOX9, AR |
| negative regulation of immune system process | 1 | 766.0× | 0.010 | SOX9 |
| primary sex determination | 1 | 766.0× | 0.010 | NR5A1 |
| regulation of developmental growth | 1 | 766.0× | 0.010 | AR |
| epithelial cell proliferation involved in prostatic bud elongation | 1 | 766.0× | 0.010 | SOX9 |
| lateral sprouting involved in mammary gland duct morphogenesis | 1 | 766.0× | 0.010 | AR |
| regulation of cell proliferation involved in tissue homeostasis | 1 | 766.0× | 0.010 | SOX9 |
| positive regulation of meiosis I | 1 | 766.0× | 0.010 | DMRT1 |
| regulation of branching involved in lung morphogenesis | 1 | 766.0× | 0.010 | SOX9 |
| cell proliferation involved in heart morphogenesis | 1 | 766.0× | 0.010 | SOX9 |
| regulation of nodal signaling pathway | 1 | 766.0× | 0.010 | DMRT1 |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 9
Druggability breadth: 6 of 11 evidence-associated genes (55%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| MAP3K1 | PONATINIB |
| AR | PROGESTERONE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| AR | 116 | 4 |
| MAP3K1 | 31 | 4 |
| CBX2 | 0 | 0 |
| SOX9 | 0 | 0 |
| SRY | 0 | 0 |
| DHX37 | 0 | 0 |
| DHH | 0 | 0 |
| NR5A1 | 0 | 0 |
| CHD7 | 0 | 0 |
| DMRT1 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| PONATINIB | 4 | MAP3K1 |
| SORAFENIB | 4 | MAP3K1 |
| RUXOLITINIB | 4 | MAP3K1 |
| REGORAFENIB | 4 | MAP3K1 |
| BARICITINIB | 4 | MAP3K1 |
| BOSUTINIB | 4 | MAP3K1 |
| TOVORAFENIB | 4 | MAP3K1 |
| RIBOCICLIB | 4 | MAP3K1 |
| PAZOPANIB | 4 | MAP3K1 |
| DASATINIB | 4 | MAP3K1 |
| ERLOTINIB | 4 | MAP3K1 |
| CRIZOTINIB | 4 | MAP3K1 |
| PROGESTERONE | 4 | AR |
| ENZALUTAMIDE | 4 | AR |
| HYDROCORTISONE ACETATE | 4 | AR |
| EPLERENONE | 4 | AR |
| CHLORMADINONE ACETATE | 4 | AR |
| ARIPIPRAZOLE | 4 | AR |
| MOMETASONE FUROATE | 4 | AR |
| TESTOSTERONE PROPIONATE | 4 | AR |
| ESTRADIOL ACETATE | 4 | AR |
| OXANDROLONE | 4 | AR |
| BECLOMETHASONE DIPROPIONATE | 4 | AR |
| DIFLORASONE DIACETATE | 4 | AR |
| ETHYNODIOL DIACETATE | 4 | AR |
| HALCINONIDE | 4 | AR |
| DYDROGESTERONE | 4 | AR |
| FLUMETHASONE PIVALATE | 4 | AR |
| HALOBETASOL PROPIONATE | 4 | AR |
| ESTRADIOL CYPIONATE | 4 | AR |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| AR | 2,100 | Binding:1727, Functional:339, ADMET:33, Unclassified:1 |
| MAP3K1 | 167 | Binding:165, ADMET:1, Functional:1 |
| NR5A1 | 88 | Binding:84, Functional:4 |
| CBX2 | 12 | Binding:11, Functional:1 |
| SOX9 | 3 | Binding:3 |
| AREG | 1 | Functional:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| MAP3K1 | 2.7.11.25 | mitogen-activated protein kinase kinase kinase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| MAP3K1 | 167 |
| AR | 2,100 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
30 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| PONATINIB | 4 | MAP3K1 |
| SORAFENIB | 4 | MAP3K1 |
| RUXOLITINIB | 4 | MAP3K1 |
| REGORAFENIB | 4 | MAP3K1 |
| BARICITINIB | 4 | MAP3K1 |
| BOSUTINIB | 4 | MAP3K1 |
| TOVORAFENIB | 4 | MAP3K1 |
| RIBOCICLIB | 4 | MAP3K1 |
| PAZOPANIB | 4 | MAP3K1 |
| DASATINIB | 4 | MAP3K1 |
| ERLOTINIB | 4 | MAP3K1 |
| CRIZOTINIB | 4 | MAP3K1 |
| PROGESTERONE | 4 | AR |
| ENZALUTAMIDE | 4 | AR |
| HYDROCORTISONE ACETATE | 4 | AR |
| EPLERENONE | 4 | AR |
| CHLORMADINONE ACETATE | 4 | AR |
| ARIPIPRAZOLE | 4 | AR |
| MOMETASONE FUROATE | 4 | AR |
| TESTOSTERONE PROPIONATE | 4 | AR |
| ESTRADIOL ACETATE | 4 | AR |
| OXANDROLONE | 4 | AR |
| BECLOMETHASONE DIPROPIONATE | 4 | AR |
| DIFLORASONE DIACETATE | 4 | AR |
| ETHYNODIOL DIACETATE | 4 | AR |
| HALCINONIDE | 4 | AR |
| DYDROGESTERONE | 4 | AR |
| FLUMETHASONE PIVALATE | 4 | AR |
| HALOBETASOL PROPIONATE | 4 | AR |
| ESTRADIOL CYPIONATE | 4 | AR |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | MAP3K1, AR |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | NR5A1 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 8 | CBX2, SOX9, SRY, DHX37, DHH, CHD7, DMRT1, AREG |
Undrugged target profiles
9 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| CBX2 | 12 | — |
| SOX9 | 3 | — |
| SRY | 0 | — |
| DHX37 | 0 | — |
| DHH | 0 | — |
| NR5A1 | 88 | — |
| CHD7 | 0 | — |
| DMRT1 | 0 | — |
| AREG | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.