AMH

Summary

AMH (anti-Mullerian hormone, HGNC:464) is a protein-coding gene on chromosome 19p13.3, encoding Anti-Muellerian hormone (P03971). The anti-Muellerian hormone (AMH) plays an important role in several reproductive functions.

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate N- and C-terminal cleavage products that homodimerize and associate to form a biologically active noncovalent complex. This complex binds to the anti-Mullerian hormone receptor type 2 and causes the regression of Mullerian ducts in the male embryo that would otherwise differentiate into the uterus and fallopian tubes. This protein also plays a role in Leydig cell differentiation and function and follicular development in adult females. Mutations in this gene result in persistent Mullerian duct syndrome.

Source: NCBI Gene 268 — RefSeq curated summary.

At a glance

• Gene–disease (curated): persistent Mullerian duct syndrome (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 281 total — 19 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 63
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000479

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:464
Approved symbol	AMH
Name	anti-Mullerian hormone
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MIF, MIS
Ensembl gene	ENSG00000104899
Ensembl biotype	protein_coding
OMIM	600957
Entrez	268

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000221496, ENST00000589313, ENST00000592877

RefSeq mRNA: 1 — MANE Select: NM_000479 NM_000479

CCDS: CCDS12085

Canonical transcript exons

ENST00000221496 — 5 exons

Exon	Start	End
ENSE00000663838	2250337	2250479
ENSE00000663839	2250652	2250760
ENSE00000663841	2251099	2252073
ENSE00002805370	2249323	2249744
ENSE00003664705	2250849	2251008

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 91.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0385 / max 38.3422, expressed in 5 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173067	0.0239	3
173065	0.0086	5
173066	0.0060	3

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.97	silver quality
right hemisphere of cerebellum	UBERON:0014890	87.09	gold quality
cerebellar hemisphere	UBERON:0002245	85.93	gold quality
cerebellar cortex	UBERON:0002129	85.33	gold quality
right testis	UBERON:0004534	84.14	gold quality
left testis	UBERON:0004533	83.32	gold quality
adenohypophysis	UBERON:0002196	82.89	gold quality
cerebellum	UBERON:0002037	82.37	gold quality
pituitary gland	UBERON:0000007	81.56	gold quality
testis	UBERON:0000473	81.54	gold quality
right frontal lobe	UBERON:0002810	78.58	gold quality
nucleus accumbens	UBERON:0001882	76.88	gold quality
putamen	UBERON:0001874	74.84	gold quality
caudate nucleus	UBERON:0001873	74.77	gold quality
gastrocnemius	UBERON:0001388	74.26	gold quality
anterior cingulate cortex	UBERON:0009835	73.78	gold quality
cingulate cortex	UBERON:0003027	73.68	gold quality
cortical plate	UBERON:0005343	73.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	72.87	gold quality
ganglionic eminence	UBERON:0004023	72.55	gold quality
muscle of leg	UBERON:0001383	71.74	gold quality
body of pancreas	UBERON:0001150	70.95	gold quality
amygdala	UBERON:0001876	70.12	gold quality
ventricular zone	UBERON:0003053	69.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	69.56	gold quality
muscle layer of sigmoid colon	UBERON:0035805	69.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	68.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.45	gold quality
mucosa of transverse colon	UBERON:0004991	68.18	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	5555.97
E-GEOD-134144	yes	4051.06
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, ESR2, FOXL2, GATA4, GLI1, NFKB1, NFKB, NR0B1, NR5A1, RELA, SF1, SOX8, SOX9, SRY, VDR, WT1, ZNF354C

miRNA regulators (miRDB)

7 targeting AMH, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-3663-5P	97.01	64.84	713
HSA-MIR-3178	89.40	60.05	100
HSA-MIR-10394-3P	85.92	60.60	39

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Administration of MIS to male mice induced IEX-1S mRNA in the prostate in vivo, suggesting that MIS may function as an endogenous hormonal regulator of NF-kappaB signaling and growth in the prostate gland. (PMID:11773638)
• poor response in IVF, indicative of a diminished ovarian reserve, is associated with reduced baseline serum AMH concentrations (PMID:12456604)
• Review. The role of AMH in gonadal development and its mutation in the persistent Mullerian duct syndrome is discussed. (PMID:12462075)
• results indicate that serum AMH levels are strongly correlated with ovarian follicular status during the early follicular phase (PMID:12571168)
• Increase of anti-Mullerian hormone(AMH) serum level in polycystic ovary syndrome is consequence of androgen-induced excess in small antral follicle number, and each follicle produces normal amount of AMH. (PMID:14671196)
• Induction of p130 and p107 play an important role in the inhibition of growth of C33A cells by MIS. (PMID:14671316)
• serum anti-Mullerian hormone (AMH) concentrations are elevated in normogonadotropic anovulatory infertile women (WHO 2) women, especially in those patients exhibiting polycystic ovary syndrome (PMID:14715867)
• Anti-Mullerian hormone expression pattern in the human ovary follicle. (PMID:14742691)
• In XXY adolescents, AMH and INHB were undetectable (PMID:15070957)
• Serum AMH concentrations decrease over time both in women presenting with WHO 2 anovulatory infertility and in normal women. Decrease in WHO 2 patients is less pronounced despite distinctly elevated concentrations. May suggest retarded ovarian ageing. (PMID:15217995)
• Recombinant follitropin and chorionic gonadotropin stimulation of the testis dramatically suppresses the secretion of AMH in hypogonadism. (PMID:15536161)
• AMH promoter sequence variations or the previously proposed SF3a2-AMH fusion co-transcripts cannot be responsible for aberrant AMH expression leading to Mullerian duct degradation. (PMID:15550498)
• AMH is also a gonadal tumor suppressor which mediates its effects through a specific type II receptor and the bone morphogenetic protein (BMP)-specific Smad proteins. (PMID:15897891)
• a relative deficiency of AMH in primordial and transitional follicles in ovaries may contribute to disordered early follicle development in polycystic ovary syndrome (PMID:16030171)
• Aggressive granulosa cell tumors(GCTs) retain high GATA-4 expression, whereas larger tumors lose proliferation-suppressing anti-Mullerian hormone expression. High GATA-4 expression in GCTs may serve as marker of poor prognosis. (PMID:16159935)
• Increased MIS production in adolescent girls may represent an early manifestation of polycystic ovary syndrome (PMID:16213847)
• AMH could thus be used as a diagnostic criterion and incorporated as such in the Rotterdam definition of polycystic ovary syndrome. (PMID:16368745)
• MIS could potentially serve as a useful marker for identifying patients at risk for OHSS. (PMID:16566934)
• Mullerian inhibiting substance regulates androgen-induced gene expression and growth in prostate cancer cells through a nuclear factor-kappaB-dependent Smad-independent mechanism. (PMID:16740653)
• Its main physiological role is the induction of regression of Mullerian ducts in male fetuses but it also plays a role in Leydig cell steroidogenesis and in follicular development (PMID:16816803)
• Hence, AMH exhibits a relatively stable expression during the menstrual cycle, making it an attractive determinant of ovarian activity. (PMID:16923748)
• MIS in combination with selective targeted therapies might achieve greater activity against ovarian cancer than the use of each individual agent alone (PMID:17088539)
• serum anti-mullerian hormone (AMH) levels in Polysystic Ovary Syndrome patients were significantly higher than in healthy women (PMID:17335955)
• Polymorphisms in the AMH and AMHR2 genes are associated with follicular phase E(2) levels, suggesting a role for AMH in the regulation of FSH sensitivity in the human ovary. (PMID:17337470)
• Mullerian inhibiting substance has a role in response to ovarian stimulation (PMID:17425826)
• Serum AMH and inhibin B are significantly lower in the men with nonobstructive azoospermia compared to the controls. (PMID:17462637)
• anti-Mullerian hormone expression is stable during the menstrual cycle (PMID:17485437)
• AMH concentrations are increased in peripubertal daughters of polycystic ovary syndrome women (PMID:17488788)
• Oocytes are more likely to be fertilized when follicles are able to make high concentrations of AMH in the follicular fluid. AMH could be a prediction marker for fertilization. (PMID:17543956)
• MIS is the earliest marker to change with agem has it has least intercycle variabilityane has the least intracycle variability; and 4) it may be informative if randomly obtained during the menstrual cycle. {REVIEW] (PMID:17559842)
• Levels of AMH show a statistically significant change during the menstrual cycle and may influence the circulating gonadotropin and steroid hormone levels. (PMID:17603052)
• Infertile patients with endometriosis have a decreased serum anti-Mullerian hormone. (PMID:17624337)
• Granulosa cell production of AMH is augmented by pharmacologically induced increase in the intrafollicular androgen levels. (PMID:17628551)
• Serum anti-Mullerian hormone (AMH) levels differentiate control from subfertile men but not men with different causes of subfertility (PMID:17926161)
• Anti-Mullerian hormone levels in premature ovarian failure patients could identify women with persistent follicles. (PMID:18191888)
• Suggest that there is no significant difference in follicular microenvironment in terms of AMH secretion between GnRH agonist/antagonist protocols and that follicular fluid AMH is a marker that reflects ovarian reserve and response to ovarian stimulation. (PMID:18249372)
• Fluctuations observed are smaller than intercycle variability and thus are not clinically relevant as far as AMH measurements for clinical purposes are concerned. (PMID:18249391)
• The AMH and inhibin B levels on the day of oocyte retrieval are correlated to assisted reproductive outcome. (PMID:18291376)
• preliminary data suggest that AMH levels indicate early ovarian decline among women with longer FMR1 repeat alleles; moreover, AMH appears to be a better marker than FSH in identifying this early decline. (PMID:18310677)
• Review/Meta-Analysis: The role of antimullerian hormone in prediction of outcome after IVF: comparison with the antral follicle count. (PMID:18321493)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	amh	ENSDARG00000014357
mus_musculus	Amh	ENSMUSG00000035262
rattus_norvegicus	Amh	ENSRNOG00000019377

Protein

Protein identifiers

Anti-Muellerian hormone — P03971 (reviewed: P03971)

Alternative names: Muellerian-inhibiting factor, Muellerian-inhibiting substance

All UniProt accessions (1): P03971

UniProt curated annotations — full annotation on UniProt →

Function. The anti-Muellerian hormone (AMH) plays an important role in several reproductive functions. Anti-Muellerian hormone binds and activates AMHR2, its specific type-II receptor, that heterodimerizes with type-I receptors (ACVR1 and BMPR1A) to regulate target gene expression through downstream SMAD protein signal transduction. Produced and secreted by Sertoli cells of the male fetus, anti-Muellerian hormone induces Muellerian duct regression during male fetal sexual differentiation. In female, it is produced by granulosa cells of the preantral and small antral follicles and acts as a negative regulator of the primordial to primary follicle transition and decreases FSH sensitivity of growing follicles. Also plays a role in Leydig cell differentiation and function.

Subunit / interactions. Homodimer; disulfide-linked. Anti-Muellerian hormone (AMH) is secreted as part of a non-covalent heterotetrameric complex consisting of AMH prodomain and anti-Muellerian hormone homodimers. After proteolytic processing, the dimeric AMH prodomain remains non-covalently associated with the active homodimeric anti-Muellerian hormone, amplifying its biological activity. The AMH prodomain homodimer is displaced upon binding of anti-Muellerian hormone to its receptor.

Subcellular location. Secreted.

Tissue specificity. In ovaries, AMH is detected in granulosa cells of early growing follicles.

Post-translational modifications. The preproprotein is proteolytically processed to generate the AMH prodomain and the anti-Muellerian hormone. Both homodimerize covalently, and homodimers associate to form a non-covalent heterotetrameric complex.

Disease relevance. Persistent Muellerian duct syndrome 1 (PMDS1) [MIM:261550] A form of male pseudohermaphroditism characterized by a failure of Muellerian duct regression in otherwise normal males. The disease is caused by variants affecting the gene represented in this entry.

Induction. Plasma AMH levels in polycystic ovary syndrome (PCOS) patients are two- to threefold higher than in women with normal ovaries.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (1): NP_000470* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001839	TGF-b_C	Domain
IPR006799	AMH_N	Domain
IPR017948	TGFb_CS	Conserved_site
IPR021203	Muellerian-inhibiting_factor	Family
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00019, PF04709

UniProt features (56 total): sequence variant 13, mutagenesis site 13, disulfide bond 8, strand 8, region of interest 7, glycosylation site 2, signal peptide 1, propeptide 1, site 1, chain 1, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7L0J	X-RAY DIFFRACTION	2.6
9BAO	ELECTRON MICROSCOPY	3.2
9BAN	ELECTRON MICROSCOPY	3.39

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P03971-F1	69.40	0.16

Antibody-complex structures (SAbDab): 2 — 9BAN, 9BAO

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 451–452 (cleavage)

Disulfide bonds (8): 55, 103–188, 241, 411, 462–526, 488–557, 492–559, 525

Glycosylation sites (2): 64, 329

Mutagenesis-validated functional residues (13):

Position	Phenotype
55	reduced amh prodomain dimerization; when associated with s-241. impaired amh prodomain dimerization; when associated wit
103	loss of signaling activity.
188	loss of signaling activity.
241	reduced amh prodomain dimerization; when associated with s-55. impaired amh prodomain dimerization; when associated with
411	impaired amh prodomain dimerization; when associated with s-55 and s-241.
472	little effect on amh signaling.
478	abolishes amh signaling. does not induce regression of the muellerian duct.
481	shows a slight decrease in amh signaling. affects slightly mullerian duct regression.
481	decreases amh signaling.
484	little effect on amh signaling.
534	abolishes amh signaling.
535	little effect on amh signaling.
546	abolishes amh signaling.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-201451	Signaling by BMP
R-HSA-9690406	Transcriptional regulation of testis differentiation
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members

MSigDB gene sets: 691 (showing top): GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_ICOSANOID_SECRETION, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, GOBP_B_CELL_HOMEOSTASIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, HARRIS_HYPOXIA, GOBP_CELL_CHEMOTAXIS, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR, GOBP_REGULATION_OF_PROSTAGLANDIN_SECRETION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT

GO Biological Process (17): ovarian follicle development (GO:0001541), preantral ovarian follicle growth (GO:0001546), urogenital system development (GO:0001655), Mullerian duct regression (GO:0001880), cell-cell signaling (GO:0007267), gonadal mesoderm development (GO:0007506), sex determination (GO:0007530), sex differentiation (GO:0007548), gonad development (GO:0008406), response to xenobiotic stimulus (GO:0009410), positive regulation of gene expression (GO:0010628), Leydig cell differentiation (GO:0033327), development of primary male sexual characteristics (GO:0046546), positive regulation of SMAD protein signal transduction (GO:0060391), anti-Mullerian hormone receptor signaling pathway (GO:1990262), negative regulation of ovarian follicle development (GO:2000355), cell differentiation (GO:0030154)

GO Molecular Function (6): signaling receptor binding (GO:0005102), type II transforming growth factor beta receptor binding (GO:0005114), transforming growth factor beta receptor binding (GO:0005160), hormone activity (GO:0005179), growth factor activity (GO:0008083), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by TGFB family members	1
Developmental Biology	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	5
ovarian follicle development	2
male sex differentiation	2
development of primary sexual characteristics	2
receptor ligand activity	2
female gonad development	1
anatomical structure development	1
ovulation cycle process	1
multi-layer follicle stage	1
developmental growth	1
system development	1
renal system development	1
anatomical structure regression	1
cell communication	1
signaling	1
mesoderm development	1
gonad development	1
mesenchyme development	1
animal organ development	1
reproductive structure development	1
response to chemical	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
male gonad development	1
cell differentiation	1
regulation of SMAD protein signal transduction	1
SMAD protein signal transduction	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of intracellular signal transduction	1
cell surface receptor protein serine/threonine kinase signaling pathway	1
negative regulation of developmental process	1
regulation of ovarian follicle development	1
cellular developmental process	1
protein binding	1
transforming growth factor beta receptor binding	1
cytokine receptor binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMH	AMHR2	Q16671	999
AMH	GNRH1	P01148	918
AMH	NR5A1	Q13285	898
AMH	FSHR	P23945	882
AMH	INSL3	P51460	869
AMH	SRY	Q05066	855
AMH	SOX9	P48436	847
AMH	DMRT1	Q9Y5R6	847
AMH	CYP19A1	P11511	845
AMH	NR0B1	P51843	829
AMH	WT1	P19544	828
AMH	GDF9	O60383	818
AMH	BMP15	O95972	802
AMH	FOXL2	P58012	802
AMH	SHBG	P04278	792

IntAct

7 interactions, top by confidence:

A	B	Type	Score
PHACTR3	AMH	psi-mi:“MI:0915”(physical association)	0.400
AMH	ETV5	psi-mi:“MI:0915”(physical association)	0.370
AMH	ARL8B	psi-mi:“MI:0915”(physical association)	0.370
ZMAT2	AMH	psi-mi:“MI:0915”(physical association)	0.370
FHL3		psi-mi:“MI:0914”(association)	0.350
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (7): AMH (Affinity Capture-MS), AMH (Affinity Capture-MS), AMH (Affinity Capture-MS), AMH (Affinity Capture-Western), ETV5 (Two-hybrid), ARL8B (Two-hybrid), ZMAT2 (Two-hybrid)

ESM2 similar proteins: A0A0U1RQ45, A0A0U1RQS6, A0A286YF58, A0A2R8YCJ5, A0A7I2V3R4, A2A699, A2VDX9, A6NCS6, A6NGB7, A6NJG2, A6NKF7, A6NKL6, A6NLJ0, A8MVW0, B2RU40, B7Z1M9, B8ZZ34, C9JH25, C9JVW0, D4A9R4, J3QNX5, M0QZC1, P03971, P0CG09, P0DPE3, Q0PHV7, Q0VD38, Q14761, Q29RK8, Q29RM6, Q2KJ18, Q2M3G4, Q2M3V2, Q5T442, Q64697, Q69YZ2, Q6F5E0, Q6NY19, Q6UXK2, Q80XF7

Diamond homologs: P03971, P03972, P27106, P49000, P79295, P85857

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AMH	up-regulates	AMHR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

281 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	10
Uncertain significance	150
Likely benign	66
Benign	22

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
1323119	NM_000479.5(AMH):c.151del (p.Gln51fs)	Pathogenic
1344503	NM_000479.5(AMH):c.649C>T (p.Gln217Ter)	Pathogenic
2138185	NM_000479.5(AMH):c.1112G>A (p.Trp371Ter)	Pathogenic
2169606	NM_000479.5(AMH):c.555+1G>T	Pathogenic
2736758	NM_000479.5(AMH):c.500A>G (p.Tyr167Cys)	Pathogenic
3583553	NM_000479.5(AMH):c.209del (p.Leu70fs)	Pathogenic
3583555	NM_000479.5(AMH):c.343_344del (p.Leu115fs)	Pathogenic
3605417	NM_000479.5(AMH):c.649dup (p.Gln217fs)	Pathogenic
3611224	NM_000479.5(AMH):c.1150C>T (p.Gln384Ter)	Pathogenic
3665082	NM_000479.5(AMH):c.451C>T (p.Pro151Ser)	Pathogenic
3723227	NM_000479.5(AMH):c.412+3A>G	Pathogenic
372806	NM_000479.5(AMH):c.208dup (p.Leu70fs)	Pathogenic
4705424	NM_000479.5(AMH):c.1507T>C (p.Tyr503His)	Pathogenic
4708182	NM_000479.5(AMH):c.25del (p.Leu9fs)	Pathogenic
8622	NM_000479.5(AMH):c.1144G>T (p.Glu382Ter)	Pathogenic
8623	NM_000479.5(AMH):c.472_485del (p.Pro158fs)	Pathogenic
8624	NM_000479.5(AMH):c.571C>T (p.Arg191Ter)	Pathogenic
8625	NM_000479.5(AMH):c.1397_1419dup (p.Glu474delinsSerSerAlaTer)	Pathogenic
987678	NM_000479.5(AMH):c.563G>A (p.Cys188Tyr)	Pathogenic
1256034	NM_000479.5(AMH):c.1393C>T (p.Arg465Cys)	Likely pathogenic
1351018	NM_000479.5(AMH):c.1016T>C (p.Leu339Pro)	Likely pathogenic
3065466	NM_000479.5(AMH):c.1683A>T (p.Ter561Cys)	Likely pathogenic
3583554	NM_000479.5(AMH):c.301G>A (p.Gly101Arg)	Likely pathogenic
3583556	NM_000479.5(AMH):c.1015dup (p.Leu339fs)	Likely pathogenic
3583557	NM_000479.5(AMH):c.1047_1056dup (p.Thr353fs)	Likely pathogenic
3896650	NM_000479.5(AMH):c.1430T>C (p.Val477Ala)	Likely pathogenic
4082445	NM_000479.5(AMH):c.1414C>T (p.Arg472Cys)	Likely pathogenic
4538452	NM_000479.5(AMH):c.992C>T (p.Ser331Leu)	Likely pathogenic
4822774	NM_000479.5(AMH):c.1649C>T (p.Pro550Leu)	Likely pathogenic

SpliceAI

451 predictions. Top by Δscore:

Variant	Effect	Δscore
19:2251090:G:A	acceptor_gain	0.9900
19:2249742:A:T	donor_gain	0.9800
19:2250759:GG:G	donor_gain	0.9800
19:2250760:GG:G	donor_gain	0.9800
19:2251089:C:CA	acceptor_gain	0.9800
19:2249657:C:T	donor_gain	0.9700
19:2249741:G:GT	donor_gain	0.9700
19:2250487:G:GT	donor_gain	0.9700
19:2249743:AGGTA:A	donor_loss	0.9600
19:2249744:GGTA:G	donor_loss	0.9600
19:2249745:G:C	donor_loss	0.9600
19:2249746:T:G	donor_loss	0.9600
19:2250206:C:G	donor_gain	0.9500
19:2250473:TGCCC:T	donor_gain	0.9500
19:2250847:A:AG	acceptor_gain	0.9500
19:2250848:G:GG	acceptor_gain	0.9500
19:2251097:A:AG	acceptor_gain	0.9500
19:2251098:G:GG	acceptor_gain	0.9500
19:2249740:GGAAG:G	donor_gain	0.9300
19:2250202:GCAGC:G	donor_gain	0.9300
19:2250650:A:AG	acceptor_gain	0.9300
19:2250651:G:GG	acceptor_gain	0.9300
19:2250651:GA:G	acceptor_gain	0.9300
19:2250757:GAGG:G	donor_gain	0.9300
19:2250844:C:A	acceptor_gain	0.9300
19:2250848:GA:G	acceptor_gain	0.9300
19:2249503:G:GA	donor_gain	0.9200
19:2251098:GGCC:G	acceptor_gain	0.9200
19:2250758:AGGG:A	donor_loss	0.9100
19:2250759:GGGTA:G	donor_loss	0.9100

AlphaMissense

3464 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:2251735:T:A	N487K	0.997
19:2251735:T:G	N487K	0.997
19:2251736:T:A	C488S	0.997
19:2251737:G:C	C488S	0.997
19:2251857:C:A	P528H	0.997
19:2251738:C:G	C488W	0.996
19:2250367:T:C	F148S	0.995
19:2251737:G:A	C488Y	0.995
19:2251742:G:T	G490C	0.995
19:2251756:G:C	W494C	0.995
19:2251756:G:T	W494C	0.995
19:2251935:C:A	A554D	0.995
19:2251736:T:C	C488R	0.994
19:2251749:G:A	C492Y	0.994
19:2251851:G:A	C526Y	0.994
19:2251713:C:A	P480H	0.993
19:2251721:T:G	Y483D	0.993
19:2251737:G:T	C488F	0.993
19:2251748:T:A	C492S	0.993
19:2251749:G:C	C492S	0.993
19:2251850:T:A	C526S	0.993
19:2251850:T:C	C526R	0.993
19:2251851:G:C	C526S	0.993
19:2251943:T:A	C557S	0.993
19:2251944:G:C	C557S	0.993
19:2251748:T:C	C492R	0.992
19:2251852:C:G	C526W	0.992
19:2251884:T:C	I537T	0.992
19:2251949:T:A	C559S	0.992
19:2251950:G:C	C559S	0.992

dbSNP variants (sampled 300 via entrez): RS1000745528 (19:2250279 G>A,C), RS1001087147 (19:2251841 C>G,T), RS1001352207 (19:2249629 C>T), RS1002235757 (19:2252333 T>C), RS1002543989 (19:2252086 G>A,T), RS1003233694 (19:2251309 G>A,T), RS1004292558 (19:2250615 G>A,T), RS1005244332 (19:2249838 C>T), RS1005856129 (19:2250077 C>T), RS1005876499 (19:2249989 C>T), RS1005890364 (19:2249918 C>G,T), RS1007043302 (19:2251506 G>A,T), RS1007197280 (19:2248083 C>T), RS1007558765 (19:2249239 G>A,C), RS1008450940 (19:2251028 C>A,T)

Disease associations

OMIM: gene MIM:600957 | disease phenotypes: MIM:261550, MIM:157900

GenCC curated gene-disease

Disease	Classification	Inheritance
persistent Mullerian duct syndrome	Strong	Autosomal recessive

Mondo (2): persistent Mullerian duct syndrome (MONDO:0009857), Mobius syndrome (MONDO:0008006)

Orphanet (3): Persistent Müllerian duct syndrome (Orphanet:2856), Rare genetic premature ovarian failure (Orphanet:485382), Moebius syndrome (Orphanet:570)

HPO phenotypes

63 total (30 of 63 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000037	Male pseudohermaphroditism
HP:0000099	Glomerulonephritis
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000787	Nephrolithiasis
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000988	Skin rash
HP:0001369	Arthritis
HP:0001386	Joint swelling
HP:0001392	Abnormality of the liver
HP:0001394	Cirrhosis
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001701	Pericarditis
HP:0001738	Exocrine pancreatic insufficiency
HP:0001744	Splenomegaly
HP:0001945	Fever
HP:0002020	Gastroesophageal reflux
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002035	Rectal prolapse
HP:0002099	Asthma
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003274_10	Pulse pressure	3.000000e-15
GCST006022_13	Pulse pressure	3.000000e-08
GCST007705_84	Pulse pressure	2.000000e-11
GCST010796_4772	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D020331	Mobius Syndrome	C07.465.299.825; C10.292.319.825; C10.292.562.700.375.750; C11.590.436.400.750; C16.131.077.578; C16.614.595
C536665	Persistent Mullerian duct syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Rotenone	decreases expression, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
MOPP protocol	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
ferrous chloride	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
2-ethyl-5-carboxypentyl phthalate	decreases secretion	1
CD 437	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
pyrimidifen	increases expression	1
prothioconazole	decreases expression	1
monoethyl phthalate	increases secretion	1
Decitabine	decreases expression, affects reaction	1
Lamotrigine	affects cotreatment, increases secretion	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	increases expression, affects cotreatment, increases secretion, decreases expression	1
Carmustine	decreases expression	1
Cisplatin	decreases expression	1
Dust	decreases expression	1
Estradiol	increases expression	1
Ketoconazole	increases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies