Pseudohermaphroditism

Summary

Pseudohermaphroditism (MONDO:0005518) is a disease with 2 cohort genes and 2 clinical trials.

At a glance

• Cohort genes: 2
• ClinVar variants: 14
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pseudohermaphroditism
Mondo ID	MONDO:0005518
EFO	EFO:0005579
DOID	DOID:3765
ICD-10-CM	Q56.3
NCIT	C124575
SNOMED CT	75164001
UMLS	C0033804
MedGen	10991
Is cancer (heuristic)	no

Data availability: 14 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › disorder of sexual differentiation › indeterminate sex and/or pseudohermaphroditism › pseudohermaphroditism

Subtypes (1): persistent Mullerian duct syndrome

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

14 retrieved; paginated sample, class counts are floors:

8 pathogenic, 3 pathogenic/likely pathogenic, 2 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
208587	NM_000197.2(HSD17B3):c.277+4A>T	HSD17B3	Pathogenic	criteria provided, multiple submitters, no conflicts
265484	NM_000197.2(HSD17B3):c.845C>T (p.Pro282Leu)	HSD17B3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4874	NM_000197.2(HSD17B3):c.239G>A (p.Arg80Gln)	HSD17B3	Pathogenic	criteria provided, multiple submitters, no conflicts
492760	NM_000197.2(HSD17B3):c.121_122del (p.Lys41fs)	HSD17B3	Pathogenic	criteria provided, single submitter
492761	NM_000197.2(HSD17B3):c.278-1G>C	HSD17B3	Pathogenic	criteria provided, multiple submitters, no conflicts
492765	NM_000197.2(HSD17B3):c.454-1G>A	HSD17B3	Pathogenic	no assertion criteria provided
492758	NM_000233.4(LHCGR):c.580T>G (p.Phe194Val)	LHCGR	Pathogenic	no assertion criteria provided
4875	NM_000197.2(HSD17B3):c.608C>T (p.Ala203Val)	SLC35D2-HSD17B3	Pathogenic	criteria provided, multiple submitters, no conflicts
4877	NM_000197.2(HSD17B3):c.238C>T (p.Arg80Trp)	SLC35D2-HSD17B3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
492763	NM_000197.2(HSD17B3):c.397G>A (p.Gly133Arg)	SLC35D2-HSD17B3	Pathogenic	no assertion criteria provided
492767	NM_000197.2(HSD17B3):c.614T>A (p.Val205Glu)	SLC35D2-HSD17B3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
492764	NM_000197.2(HSD17B3):c.414_416del (p.Leu139del)	HSD17B3	Likely pathogenic	criteria provided, single submitter
492766	NM_000197.2(HSD17B3):c.578C>A (p.Pro193His)	HSD17B3	Likely pathogenic	no assertion criteria provided
492762	NM_000197.2(HSD17B3):c.383T>C (p.Leu128Ser)	HSD17B3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HSD17B3	Orphanet:752	46,XY difference of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
LHCGR	Orphanet:3000	Familial peripheral male-limited precocious puberty
LHCGR	Orphanet:96265	Leydig cell hypoplasia due to complete LH resistance
LHCGR	Orphanet:96266	Leydig cell hypoplasia due to partial LH resistance

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HSD17B3	HGNC:5212	ENSG00000130948	P37058	17-beta-hydroxysteroid dehydrogenase type 3	clinvar
LHCGR	HGNC:6585	ENSG00000138039	P22888	Lutropin-choriogonadotropic hormone receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HSD17B3	17-beta-hydroxysteroid dehydrogenase type 3	Catalyzes the conversion of 17-oxosteroids to 17beta-hydroxysteroids.
LHCGR	Lutropin-choriogonadotropic hormone receptor	Receptor for lutropin-choriogonadotropic hormone.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
GPCR	1	12.0×	0.160
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HSD17B3	Enzyme (other)	yes	1.1.1.51	SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf
LHCGR	GPCR	yes		GPCR_Rhodpsn, Gphrmn_rcpt_fam, LSH_rcpt

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
right testis	1
testis	1
lower esophagus muscularis layer	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HSD17B3	129	tissue_specific	yes	right testis, left testis, testis
LHCGR	123	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, sural nerve, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HSD17B3	1,962
LHCGR	1,506

Intra-cohort edges

A	B	Sources
HSD17B3	LHCGR	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LHCGR	P22888	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HSD17B3	P37058	93.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 2 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
Androgen biosynthesis	1	519.1×	0.009	HSD17B3
Hormone ligand-binding receptors	1	475.8×	0.009	LHCGR
Synthesis of very long-chain fatty acyl-CoAs	1	228.4×	0.013	HSD17B3
Class A/1 (Rhodopsin-like receptors)	1	37.1×	0.046	LHCGR
G alpha (s) signalling events	1	36.6×	0.046	LHCGR
GPCR ligand binding	1	32.1×	0.046	LHCGR
GPCR downstream signalling	1	21.7×	0.055	LHCGR
Signaling by GPCR	1	20.0×	0.055	LHCGR
Signal Transduction	1	5.1×	0.187	LHCGR

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
male genitalia development	2	887.0×	3e-05	HSD17B3, LHCGR
regulation of steroid hormone biosynthetic process	1	8426.0×	0.001	LHCGR
ovulation cycle process	1	4213.0×	0.001	LHCGR
luteinizing hormone signaling pathway	1	4213.0×	0.001	LHCGR
development of animal secondary male sexual characteristics	1	2808.7×	0.002	LHCGR
positive regulation of inositol trisphosphate biosynthetic process	1	2106.5×	0.002	LHCGR
testosterone biosynthetic process	1	1404.3×	0.002	HSD17B3
cellular response to gonadotropin stimulus	1	1404.3×	0.002	LHCGR
cellular response to luteinizing hormone stimulus	1	1404.3×	0.002	LHCGR
androgen biosynthetic process	1	936.2×	0.002	HSD17B3
uterus development	1	401.2×	0.005	LHCGR
seminiferous tubule development	1	383.0×	0.005	LHCGR
steroid biosynthetic process	1	300.9×	0.006	HSD17B3
hormone-mediated signaling pathway	1	200.6×	0.007	LHCGR
ovarian follicle development	1	195.9×	0.007	LHCGR
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1	156.0×	0.009	LHCGR
cognition	1	142.8×	0.009	LHCGR
male gonad development	1	78.0×	0.016	LHCGR
phospholipase C-activating G protein-coupled receptor signaling pathway	1	65.8×	0.018	LHCGR
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	56.5×	0.019	LHCGR
G protein-coupled receptor signaling pathway	1	18.1×	0.056	LHCGR
spermatogenesis	1	17.6×	0.056	LHCGR

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HSD17B3	2	3
LHCGR	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CURCUMIN	3	HSD17B3
HYMECROMONE	2	HSD17B3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HSD17B3	64	Binding:62, ADMET:2
LHCGR	54	Binding:35, Functional:18, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HSD17B3	1.1.1.51, 1.1.1.64	3(or 17)beta-hydroxysteroid dehydrogenase, testosterone 17beta-dehydrogenase (NADP+)

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

2 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)
CURCUMIN	3	HSD17B3
HYMECROMONE	2	HSD17B3

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	1	HSD17B3
C	Druggable family + PDB, no drug	1	LHCGR
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
LHCGR	54	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00172510	Not specified	UNKNOWN	Mutation Analysis of 17α-Hydroxylase
NCT00173654	Not specified	UNKNOWN	Mutation Analysis of 17βhydroxysteroid Dehydrogenase 3 Deficiency