46,XY sex reversal 11

Summary

46,XY sex reversal 11 (MONDO:8000015) is a disease caused by DHX37 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Europe)
• Causal gene: DHX37 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 33
• Phenotypes (HPO): 11

Clinical features

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0010469	Absent testis	Very frequent (80-99%)
HP:0000008	Abnormal morphology of female internal genitalia	Very frequent (80-99%)
HP:0000022	Abnormality of male internal genitalia	Very frequent (80-99%)
HP:0000037	Male pseudohermaphroditism	Very frequent (80-99%)
HP:0000062	Ambiguous genitalia	Very frequent (80-99%)
HP:0000144	Decreased fertility	Very frequent (80-99%)
HP:0008633	Agonadism	Very frequent (80-99%)
HP:0008734	Decreased testicular size	Very frequent (80-99%)
HP:0008736	Hypoplasia of penis	Very frequent (80-99%)
HP:0010468	Aplasia/Hypoplasia of the testes	Very frequent (80-99%)
HP:0000271	Abnormality of the face	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	46,XY sex reversal 11
Mondo ID	MONDO:8000015
MeSH	C537770
OMIM	273250
Orphanet	983
SNOMED CT	53599007
UMLS	C0266427
MedGen	78602
GARD	0016552
MedDRA	10002641
Is cancer (heuristic)	no

Also known as: 46, XY sex reversal 11 · embryonic testicular regression syndrome · ETRS · SRXY11 · testicular regression syndrome · TRS · vanishing testes syndrome · vanishing testis syndrome

Data availability: 33 ClinVar variants · 2 GenCC gene-disease records.

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 11

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 1

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

33 retrieved; paginated sample, class counts are floors:

15 benign, 9 uncertain significance, 3 conflicting classifications of pathogenicity, 3 likely pathogenic, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
869419	NM_032656.4(DHX37):c.911C>T (p.Thr304Met)	DHX37	Pathogenic	no assertion criteria provided
869420	NM_032656.4(DHX37):c.923G>A (p.Arg308Gln)	DHX37	Pathogenic	criteria provided, multiple submitters, no conflicts
869422	NM_032656.4(DHX37):c.1784C>T (p.Ser595Phe)	DHX37	Pathogenic	no assertion criteria provided
1298360	NM_032656.4(DHX37):c.1877C>T (p.Ser626Leu)	DHX37	Likely pathogenic	criteria provided, single submitter
869421	NM_032656.4(DHX37):c.2020C>T (p.Arg674Trp)	DHX37	Likely pathogenic	criteria provided, multiple submitters, no conflicts
869423	NM_032656.4(DHX37):c.2021G>A (p.Arg674Gln)	DHX37	Likely pathogenic	criteria provided, single submitter
1030049	NM_032656.4(DHX37):c.985G>A (p.Val329Ile)	DHX37	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3376551	NM_032656.4(DHX37):c.1000C>T (p.Arg334Trp)	DHX37	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
402138	NM_032656.4(DHX37):c.1460G>A (p.Arg487His)	DHX37	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030047	NM_032656.4(DHX37):c.2956G>A (p.Val986Met)	DHX37	Uncertain significance	criteria provided, multiple submitters, no conflicts
1315592	NM_032656.4(DHX37):c.451C>T (p.Arg151Trp)	DHX37	Uncertain significance	criteria provided, multiple submitters, no conflicts
2057253	NM_032656.4(DHX37):c.1405G>T (p.Ala469Ser)	DHX37	Uncertain significance	criteria provided, multiple submitters, no conflicts
3067862	NM_032656.4(DHX37):c.1829C>T (p.Pro610Leu)	DHX37	Uncertain significance	criteria provided, multiple submitters, no conflicts
3376603	NM_032656.4(DHX37):c.994C>G (p.Gln332Glu)	DHX37	Uncertain significance	criteria provided, single submitter
3779568	NM_032656.4(DHX37):c.2776C>T (p.Arg926Ter)	DHX37	Uncertain significance	criteria provided, single submitter
4531387	NM_032656.4(DHX37):c.1050T>G (p.Asp350Glu)	DHX37	Uncertain significance	criteria provided, single submitter
4538445	NM_032656.4(DHX37):c.1879C>T (p.Leu627Phe)	DHX37	Uncertain significance	no assertion criteria provided
691928	NM_032656.4(DHX37):c.499_500inv (p.Glu167Ser)	DHX37	Uncertain significance	criteria provided, single submitter
1251560	NM_032656.4(DHX37):c.2793A>G (p.Ala931=)	DHX37	Benign	criteria provided, multiple submitters, no conflicts
1255483	NM_032656.4(DHX37):c.3242G>A (p.Arg1081Gln)	DHX37	Benign	criteria provided, multiple submitters, no conflicts
1255484	NM_032656.4(DHX37):c.3195C>T (p.Ala1065=)	DHX37	Benign	criteria provided, multiple submitters, no conflicts
1255485	NM_032656.4(DHX37):c.2869-38G>A	DHX37	Benign	criteria provided, multiple submitters, no conflicts
1255486	NM_032656.4(DHX37):c.2696-26G>A	DHX37	Benign	criteria provided, multiple submitters, no conflicts
1255487	NM_032656.4(DHX37):c.2695+12T>C	DHX37	Benign	criteria provided, multiple submitters, no conflicts
1255488	NM_032656.4(DHX37):c.2605A>G (p.Ser869Gly)	DHX37	Benign	criteria provided, multiple submitters, no conflicts
1255489	NM_032656.4(DHX37):c.2598G>A (p.Glu866=)	DHX37	Benign	criteria provided, multiple submitters, no conflicts
1255490	NM_032656.4(DHX37):c.2579-7T>C	DHX37	Benign	criteria provided, multiple submitters, no conflicts
1255491	NM_032656.4(DHX37):c.2578+17T>G	DHX37	Benign	criteria provided, multiple submitters, no conflicts
1255492	NM_032656.4(DHX37):c.2331A>G (p.Thr777=)	DHX37	Benign	criteria provided, multiple submitters, no conflicts
1255493	NM_032656.4(DHX37):c.2046-6A>G	DHX37	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · 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
DHX37	Strong	Autosomal dominant	46,XY sex reversal 11	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DHX37	Orphanet:242	46,XY complete gonadal dysgenesis
DHX37	Orphanet:251510	46,XY partial gonadal dysgenesis
DHX37	Orphanet:983	Testicular regression syndrome

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
DHX37	HGNC:17210	ENSG00000150990	Q8IY37	Probable ATP-dependent RNA helicase DHX37	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DHX37	Other/Unknown	no		Helicase_C-like, Helicase-assoc_dom, DEAD/DEAH_box_helicase_dom

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
medial globus pallidus	1
pancreatic ductal cell	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DHX37	236	ubiquitous	yes	pancreatic ductal cell, tendon of biceps brachii, medial globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DHX37	3,123

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DHX37	Q8IY37	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
rRNA modification in the nucleus and cytosol	1	187.2×	0.011	DHX37
Major pathway of rRNA processing in the nucleolus and cytosol	1	61.7×	0.016	DHX37

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
ribosome assembly	1	1872.4×	0.002	DHX37
positive regulation of male gonad development	1	1685.2×	0.002	DHX37
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1	674.1×	0.002	DHX37
ribosome biogenesis	1	624.1×	0.002	DHX37
ribosomal small subunit biogenesis	1	227.7×	0.005	DHX37
brain development	1	79.5×	0.013	DHX37

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
DHX37	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	DHX37

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)
DHX37	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.