46,XY sex reversal 7

Summary

46,XY sex reversal 7 (MONDO:0009301) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 71

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	46,XY sex reversal 7
Mondo ID	MONDO:0009301
MeSH	C565537
OMIM	233420
DOID	DOID:0111774
UMLS	C1856273
MedGen	383876
GARD	0015174
Is cancer (heuristic)	no

Also known as: 46,XY sex reversal 7 · 46,XY Sex reversal type 7 · 46XY sex reversal 7 · SRXY7

Data availability: 71 ClinVar variants.

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 7

Related subtypes (11): 46,XY sex reversal 4, 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

71 retrieved; paginated sample, class counts are floors:

39 uncertain significance, 13 likely benign, 8 benign, 6 pathogenic, 3 conflicting classifications of pathogenicity, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1685695	NM_021044.4(DHH):c.1004T>C (p.Leu335Pro)	DHH	Pathogenic	criteria provided, single submitter
5011	NM_021044.4(DHH):c.485T>C (p.Leu162Pro)	DHH	Pathogenic	no assertion criteria provided
5012	NM_021044.4(DHH):c.1086del (p.Leu363fs)	DHH	Pathogenic	no assertion criteria provided
561187	NM_021044.4(DHH):c.528C>A (p.Tyr176Ter)	DHH	Pathogenic	criteria provided, single submitter
561188	NM_021044.4(DHH):c.1011del (p.Asn337fs)	DHH	Pathogenic	criteria provided, single submitter
561189	NM_021044.4(DHH):c.528C>G (p.Tyr176Ter)	DHH	Pathogenic	no assertion criteria provided
265768	NM_021044.4(DHH):c.1027T>C (p.Cys343Arg)	DHH	Likely pathogenic	criteria provided, single submitter
561190	NM_021044.4(DHH):c.634G>A (p.Glu212Lys)	DHH	Likely pathogenic	no assertion criteria provided
309098	NM_021044.4(DHH):c.1134T>A (p.Thr378=)	DHH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
772189	NM_021044.4(DHH):c.228C>T (p.Asp76=)	DHH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
309105	NM_021044.4(DHH):c.234G>A (p.Val78=)	DHH-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1376380	NM_021044.4(DHH):c.286G>T (p.Asp96Tyr)	DHH	Uncertain significance	criteria provided, single submitter
1378694	NM_021044.4(DHH):c.799C>G (p.Leu267Val)	DHH	Uncertain significance	criteria provided, single submitter
1440085	NM_021044.4(DHH):c.605G>A (p.Gly202Glu)	DHH	Uncertain significance	criteria provided, single submitter
1490815	NM_021044.4(DHH):c.324C>A (p.Asn108Lys)	DHH	Uncertain significance	criteria provided, single submitter
1804932	NM_021044.4(DHH):c.434G>C (p.Arg145Pro)	DHH	Uncertain significance	criteria provided, single submitter
2037300	NM_021044.4(DHH):c.151G>A (p.Gly51Ser)	DHH	Uncertain significance	criteria provided, single submitter
2178846	NM_021044.4(DHH):c.121G>T (p.Val41Leu)	DHH	Uncertain significance	criteria provided, single submitter
2194081	NM_021044.4(DHH):c.566-8C>G	DHH	Uncertain significance	criteria provided, single submitter
2572517	NM_021044.4(DHH):c.119T>C (p.Leu40Pro)	DHH	Uncertain significance	criteria provided, single submitter
2966235	NM_021044.4(DHH):c.602C>A (p.Pro201Gln)	DHH	Uncertain significance	criteria provided, single submitter
309093	NM_021044.4(DHH):c.*401G>T	DHH	Uncertain significance	criteria provided, multiple submitters, no conflicts
309095	NM_021044.4(DHH):c.*159G>T	DHH	Uncertain significance	criteria provided, single submitter
309096	NM_021044.4(DHH):c.*110G>C	DHH	Uncertain significance	criteria provided, single submitter
309099	NM_021044.4(DHH):c.926G>T (p.Arg309Leu)	DHH	Uncertain significance	criteria provided, multiple submitters, no conflicts
309100	NM_021044.4(DHH):c.726C>T (p.Phe242=)	DHH	Uncertain significance	criteria provided, single submitter
309101	NM_021044.4(DHH):c.587C>A (p.Ala196Glu)	DHH	Uncertain significance	criteria provided, single submitter
309104	NM_021044.4(DHH):c.367C>T (p.Leu123=)	DHH	Uncertain significance	criteria provided, single submitter
309107	NM_021044.4(DHH):c.-254G>A	DHH	Uncertain significance	criteria provided, single submitter
309109	NM_021044.4(DHH):c.-256C>G	DHH	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DHH	Orphanet:168563	46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome
DHH	Orphanet:242	46,XY complete gonadal dysgenesis
FANCA	Orphanet:84	Fanconi anemia

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DHH	HGNC:2865	ENSG00000139549	O43323	Desert hedgehog protein	clinvar
FANCA	HGNC:3582	ENSG00000187741	O15360	Fanconi anemia group A protein	clinvar
DHH-AS1	HGNC:58445	ENSG00000257346		DHH antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DHH	Desert hedgehog protein	The C-terminal part of the desert hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity.
FANCA	Fanconi anemia group A protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DHH	Other/Unknown	no		Hedgehog_signalling_dom, Hedgehog, Hedgehog_Hint
FANCA	Other/Unknown	no		FANCA, Fanconi_A_N, Fanconi_A_C
DHH-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	3
right testis	2
tibial nerve	1
ventricular zone	1
sural nerve	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DHH	123	tissue_specific	yes	tibial nerve, right testis, left testis
FANCA	185	ubiquitous	marker	right testis, ventricular zone, left testis
DHH-AS1	104		yes	sural nerve, left testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FANCA	3,036
DHH	1,849
DHH-AS1	0

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FANCA	O15360	6
DHH	O43323	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
HHAT G278V doesn’t palmitoylate Hh-Np	1	1142.0×	0.005	DHH
Release of Hh-Np from the secreting cell	1	713.8×	0.005	DHH
Ligand-receptor interactions	1	713.8×	0.005	DHH
Transcriptional regulation of testis differentiation	1	356.9×	0.006	DHH
Activation of SMO	1	317.2×	0.006	DHH
Fanconi Anemia Pathway	1	139.3×	0.012	FANCA
Hedgehog ligand biogenesis	1	105.7×	0.013	DHH
Class B/2 (Secretin family receptors)	1	95.2×	0.013	DHH
Hedgehog ‘on’ state	1	79.3×	0.014	DHH
PKR-mediated signaling	1	70.5×	0.014	FANCA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of germ cell proliferation	1	4213.0×	0.006	FANCA
regulation of CD40 signaling pathway	1	2106.5×	0.006	FANCA
regulation of regulatory T cell differentiation	1	936.2×	0.006	FANCA
regulation of steroid biosynthetic process	1	766.0×	0.006	DHH
self proteolysis	1	766.0×	0.006	DHH
male sex determination	1	702.2×	0.006	DHH
Leydig cell differentiation	1	601.9×	0.006	DHH
female gonad development	1	401.2×	0.008	FANCA
protein autoprocessing	1	324.1×	0.009	DHH
male meiotic nuclear division	1	271.8×	0.009	FANCA
cell fate specification	1	263.3×	0.009	DHH
interstrand cross-link repair	1	216.1×	0.009	FANCA
positive regulation of smoothened signaling pathway	1	210.7×	0.009	DHH
response to estrogen	1	172.0×	0.010	DHH
myelination	1	125.8×	0.013	DHH
response to estradiol	1	99.1×	0.016	DHH
smoothened signaling pathway	1	90.6×	0.016	DHH
regulation of inflammatory response	1	84.3×	0.016	FANCA
male gonad development	1	78.0×	0.017	FANCA
spermatid development	1	72.6×	0.017	DHH
osteoblast differentiation	1	60.6×	0.020	DHH
protein-containing complex assembly	1	56.9×	0.020	FANCA
regulation of gene expression	1	41.7×	0.026	DHH
cell-cell signaling	1	34.8×	0.030	DHH
DNA repair	1	31.9×	0.031	FANCA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 0 of 3 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
DHH	0	0
FANCA	0	0
DHH-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	3	DHH, FANCA, DHH-AS1

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DHH	0	—
FANCA	0	—
DHH-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.