persistent Mullerian duct syndrome

Summary

persistent Mullerian duct syndrome (MONDO:0009857) is a disease caused by variants in AMHR2 and AMH, with 2 cohort genes.

At a glance

• Prevalence: (Worldwide) [Orphanet-validated]
• Causal genes: AMHR2 (GenCC Definitive), AMH (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 51
• Phenotypes (HPO): 3

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		300	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

3 HPO clinical features (Orphanet curated; top 3 by frequency):

HPO ID	Term	Frequency
HP:0000028	Cryptorchidism	Very frequent (80-99%)
HP:0000023	Inguinal hernia	Frequent (30-79%)
HP:0000037	Male pseudohermaphroditism	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	persistent Mullerian duct syndrome
Mondo ID	MONDO:0009857
MeSH	C536665
OMIM	261550
Orphanet	2856
DOID	DOID:0050791
ICD-11	697796373
NCIT	C120188
SNOMED CT	702358005
UMLS	C1849930
MedGen	342367
GARD	0008435
Is cancer (heuristic)	no

Also known as: female genital ducts in otherwise normal male · persistent Mullerian derivatives · persistent Mullerian duct syndrome · persistent mullerian duct syndrome, type I · persistent mullerian duct syndrome, type II · persistent mullerian duct syndrome, types 1 and 2 · persistent MULLERIAN duct syndrome, types I and II · persistent Müllerian derivatives · PMDS

Data availability: 51 ClinVar variants · 8 GenCC gene-disease records.

Disease family

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 › 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

51 retrieved; paginated sample, class counts are floors:

17 pathogenic, 13 likely pathogenic, 8 uncertain significance, 6 pathogenic/likely pathogenic, 3 benign/likely benign, 3 benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323119	NM_000479.5(AMH):c.151del (p.Gln51fs)	AMH	Pathogenic	criteria provided, single submitter
1344503	NM_000479.5(AMH):c.649C>T (p.Gln217Ter)	AMH	Pathogenic	criteria provided, multiple submitters, no conflicts
1804920	NM_000479.5(AMH):c.1165G>T (p.Glu389Ter)	AMH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3583552	NM_000479.5(AMH):c.118C>T (p.Arg40Ter)	AMH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3583553	NM_000479.5(AMH):c.209del (p.Leu70fs)	AMH	Pathogenic	criteria provided, multiple submitters, no conflicts
3583555	NM_000479.5(AMH):c.343_344del (p.Leu115fs)	AMH	Pathogenic	criteria provided, multiple submitters, no conflicts
3665082	NM_000479.5(AMH):c.451C>T (p.Pro151Ser)	AMH	Pathogenic	criteria provided, multiple submitters, no conflicts
8624	NM_000479.5(AMH):c.571C>T (p.Arg191Ter)	AMH	Pathogenic	criteria provided, single submitter
987678	NM_000479.5(AMH):c.563G>A (p.Cys188Tyr)	AMH	Pathogenic	no assertion criteria provided
1172834	NM_020547.3(AMHR2):c.649del (p.Val217fs)	AMHR2	Pathogenic	no assertion criteria provided
1256004	NM_020547.3(AMHR2):c.775C>T (p.Arg259Ter)	AMHR2	Pathogenic	criteria provided, single submitter
1338211	NM_020547.3(AMHR2):c.64C>T (p.Arg22Ter)	AMHR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705324	NM_020547.3(AMHR2):c.238C>T (p.Arg80Ter)	AMHR2	Pathogenic	criteria provided, single submitter
1707557	NM_020547.3(AMHR2):c.1340C>T (p.Thr447Ile)	AMHR2	Pathogenic	criteria provided, single submitter
2581234	NM_020547.3(AMHR2):c.1510C>T (p.Arg504Cys)	AMHR2	Pathogenic	criteria provided, single submitter
2884050	NM_020547.3(AMHR2):c.1412G>A (p.Arg471His)	AMHR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3336678	NM_020547.3(AMHR2):c.514C>T (p.Arg172Ter)	AMHR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3574976	NM_020547.3(AMHR2):c.78del (p.Phe27fs)	AMHR2	Pathogenic	criteria provided, single submitter
3574978	NM_020547.3(AMHR2):c.289C>T (p.Arg97Ter)	AMHR2	Pathogenic	criteria provided, single submitter
372896	NM_020547.3(AMHR2):c.1387C>T (p.Arg463Cys)	AMHR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3779441	NM_020547.3(AMHR2):c.1219C>T (p.Arg407Ter)	AMHR2	Pathogenic	criteria provided, single submitter
689555	NM_020547.3(AMHR2):c.994C>T (p.Arg332Ter)	AMHR2	Pathogenic	criteria provided, single submitter
8627	NM_020547.3(AMHR2):c.1332_1358del (p.Gly445_Leu453del)	AMHR2	Pathogenic	criteria provided, multiple submitters, no conflicts
3065466	NM_000479.5(AMH):c.1683A>T (p.Ter561Cys)	AMH	Likely pathogenic	criteria provided, single submitter
3583554	NM_000479.5(AMH):c.301G>A (p.Gly101Arg)	AMH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3583556	NM_000479.5(AMH):c.1015dup (p.Leu339fs)	AMH	Likely pathogenic	criteria provided, single submitter
3583557	NM_000479.5(AMH):c.1047_1056dup (p.Thr353fs)	AMH	Likely pathogenic	criteria provided, single submitter
3896650	NM_000479.5(AMH):c.1430T>C (p.Val477Ala)	AMH	Likely pathogenic	criteria provided, single submitter
4538452	NM_000479.5(AMH):c.992C>T (p.Ser331Leu)	AMH	Likely pathogenic	no assertion criteria provided
1120085	NM_020547.3(AMHR2):c.43del (p.Val15fs)	AMHR2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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
AMHR2	Definitive	Autosomal recessive	persistent Mullerian duct syndrome	5
AMH	Strong	Autosomal recessive	persistent Mullerian duct syndrome	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AMH	Orphanet:2856	Persistent Müllerian duct syndrome
AMHR2	Orphanet:2856	Persistent Müllerian duct syndrome

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
AMH	HGNC:464	ENSG00000104899	P03971	Anti-Muellerian hormone	gencc,clinvar
AMHR2	HGNC:465	ENSG00000135409	Q16671	Anti-Muellerian hormone type-2 receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AMH	Anti-Muellerian hormone	The anti-Muellerian hormone (AMH) plays an important role in several reproductive functions.
AMHR2	Anti-Muellerian hormone type-2 receptor	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AMH	Other/Unknown	no		TGF-b_C, AMH_N, TGFb_CS
AMHR2	Kinase	yes	2.7.10.2	TGFB_receptor, Prot_kinase_dom, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar hemisphere	1
male germ line stem cell (sensu Vertebrata) in testis	1
right hemisphere of cerebellum	1
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AMH	160	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, right hemisphere of cerebellum, cerebellar hemisphere
AMHR2	119	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AMHR2	1,576
AMH	1,556

Intra-cohort edges

A	B	Sources
AMH	AMHR2	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AMH	P03971	3
AMHR2	Q16671	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Signaling by BMP	2	356.9×	4e-05	AMH, AMHR2
Signaling by TGFB family members	2	115.3×	2e-04	AMH, AMHR2
Transcriptional regulation of testis differentiation	1	356.9×	0.005	AMH
Signal Transduction	2	10.2×	0.012	AMH, AMHR2
Developmental Biology	1	7.2×	0.134	AMH

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
Mullerian duct regression	2	3370.4×	1e-06	AMH, AMHR2
anti-Mullerian hormone receptor signaling pathway	2	2808.7×	1e-06	AMH, AMHR2
sex differentiation	2	842.6×	9e-06	AMH, AMHR2
development of primary male sexual characteristics	1	2808.7×	0.001	AMH
negative regulation of ovarian follicle development	1	2808.7×	0.001	AMH
preantral ovarian follicle growth	1	2106.5×	0.002	AMH
gonadal mesoderm development	1	842.6×	0.003	AMH
sex determination	1	842.6×	0.003	AMH
Leydig cell differentiation	1	601.9×	0.004	AMH
gonad development	1	561.7×	0.004	AMH
urogenital system development	1	495.6×	0.004	AMH
female gonad development	1	401.2×	0.004	AMHR2
ovarian follicle development	1	195.9×	0.008	AMH
positive regulation of SMAD protein signal transduction	1	191.5×	0.008	AMH
cellular response to growth factor stimulus	1	159.0×	0.009	AMHR2
BMP signaling pathway	1	100.3×	0.013	AMHR2
transforming growth factor beta receptor signaling pathway	1	79.5×	0.015	AMHR2
male gonad development	1	78.0×	0.015	AMHR2
cell-cell signaling	1	34.8×	0.030	AMH
response to xenobiotic stimulus	1	34.5×	0.030	AMH
positive regulation of gene expression	1	19.4×	0.051	AMH

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
AMH	0	0
AMHR2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AMHR2	2.7.10.2	non-specific protein-tyrosine kinase

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	1	AMHR2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	AMH

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
AMH	0	—
AMHR2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.