AMHR2

Summary

AMHR2 (anti-Mullerian hormone receptor type 2, HGNC:465) is a protein-coding gene on chromosome 12q13.13, encoding Anti-Muellerian hormone type-2 receptor (Q16671). On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.

This gene encodes the receptor for the anti-Mullerian hormone (AMH) which, in addition to testosterone, results in male sex differentiation. AMH and testosterone are produced in the testes by different cells and have different effects. Testosterone promotes the development of male genitalia while the binding of AMH to the encoded receptor prevents the development of the mullerian ducts into uterus and Fallopian tubes. Mutations in this gene are associated with persistent Mullerian duct syndrome type II. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 269 — RefSeq curated summary.

At a glance

• Gene–disease (curated): persistent Mullerian duct syndrome (Definitive, GenCC)
• Clinical variants (ClinVar): 176 total — 22 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 8
• MANE Select transcript: NM_020547

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:465
Approved symbol	AMHR2
Name	anti-Mullerian hormone receptor type 2
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	MISR2, MISRII
Ensembl gene	ENSG00000135409
Ensembl biotype	protein_coding
OMIM	600956
Entrez	269

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 retained_intron

ENST00000257863, ENST00000379791, ENST00000548303, ENST00000550311, ENST00000550839, ENST00000552233, ENST00000553037, ENST00000963564, ENST00000963565, ENST00000963566

RefSeq mRNA: 3 — MANE Select: NM_020547 NM_001164690, NM_001164691, NM_020547

CCDS: CCDS53798, CCDS55829, CCDS8858

Canonical transcript exons

ENST00000257863 — 11 exons

Exon	Start	End
ENSE00000919968	53425455	53425573
ENSE00000919969	53425165	53425242
ENSE00000919970	53424709	53424900
ENSE00000919971	53424288	53424470
ENSE00001148959	53430146	53430282
ENSE00001148968	53429831	53429978
ENSE00001149025	53423855	53423983
ENSE00001308438	53429453	53429625
ENSE00001315925	53431177	53431672
ENSE00003534799	53428896	53429010
ENSE00003640106	53425689	53425919

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 95.61.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0203 / max 87.8103, expressed in 188 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125756	0.8766	157
125755	0.1437	72

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	95.61	gold quality
right adrenal gland	UBERON:0001233	95.49	gold quality
left adrenal gland	UBERON:0001234	94.18	gold quality
left adrenal gland cortex	UBERON:0035825	93.81	gold quality
adrenal cortex	UBERON:0001235	92.77	gold quality
adrenal tissue	UBERON:0018303	91.26	gold quality
adrenal gland	UBERON:0002369	91.04	gold quality
left ovary	UBERON:0002119	89.09	gold quality
right ovary	UBERON:0002118	87.93	gold quality
olfactory bulb	UBERON:0002264	86.77	gold quality
ovary	UBERON:0000992	86.25	gold quality
type B pancreatic cell	CL:0000169	86.17	gold quality
vastus lateralis	UBERON:0001379	82.34	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	82.30	gold quality
diaphragm	UBERON:0001103	81.56	gold quality
triceps brachii	UBERON:0001509	80.54	gold quality
left testis	UBERON:0004533	79.81	gold quality
gluteal muscle	UBERON:0002000	79.25	gold quality
tongue squamous epithelium	UBERON:0006919	78.86	gold quality
body of pancreas	UBERON:0001150	78.80	gold quality
testis	UBERON:0000473	78.69	gold quality
nasal cavity epithelium	UBERON:0005384	78.62	gold quality
right testis	UBERON:0004534	78.41	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.90	gold quality
biceps brachii	UBERON:0001507	76.29	gold quality
skeletal muscle tissue	UBERON:0001134	76.04	gold quality
vena cava	UBERON:0004087	75.36	gold quality
spleen	UBERON:0002106	75.35	gold quality
gingival epithelium	UBERON:0001949	74.70	gold quality
muscle tissue	UBERON:0002385	72.06	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APC, CTNNB1, NR5A1, TCF7L2, WT1

Literature-anchored findings (GeneRIF, showing 40)

• interacts with Mullerian inhibiting substance: an instructive developmental hormone with diagnostic and possible therapeutic applications. (PMID:11588147)
• Review. The role of AMHR2 in gonadal development and its mutation in the persistent Mullerian duct syndrome is discussed. (PMID:12462075)
• binding domains recognized by a monoclonal antibody and the natural ligand (PMID:14750901)
• 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)
• The observed association of the AMHR2 -482 A > G polymorphism with natural age at menopause suggests a role for AMH signaling in the usage of the primordial follicle pool in women. (PMID:17636279)
• MISIIR is highly expressed by a wide variety of gynecologic cancers, including cancers currently without effective systemic therapies. (PMID:17988723)
• Reduced AMH receptor type 2 is associated with Leydig cell tumours in multiple endocrine neoplasia type 1 (PMID:18310289)
• AMHR genes are overexpressed by granulosa cells from stimulated follicles of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation. (PMID:18697861)
• Non-epithelial malignant ovarian tumors showed stronger expression of anti-Mullerian hormone receptor type II than that of epithelial tumors. (PMID:19424576)
• Mutations of AMHR2 found in persistent Mullerian duct syndrome affect its ligand binding and cellular transport. (PMID:19457927)
• Genetic variants of AMH and AMHRII genes seem to be associated with infertility. (PMID:19539910)
• data demonstrate that polymorphisms in major folliculogenesis genes, GDF9, BMP15, AMH, and AMHR2, are not associated with polycystic ovary syndrome susceptibility. (PMID:20236105)
• Association studies of common variants of AMHRII suggests that antimullerian hormone may regulate the primordial graafian follicle recruitment. (PMID:20362961)
• AMH thus exemplifies a new mechanism for receptor engagement in which interaction with the type II receptor promotes pro-region dissociation to generate mature ligand. (PMID:20861221)
• the diversity of clinical symptoms within sibship and lack of correlation between development of Mullerian derivatives and severity of molecular defects suggest highly variable penetrance of abnormal alleles (PMID:22584735)
• The Mullerian inhibiting substance type 2 receptor suppresses tumorigenesis in testes with sustained beta-catenin signaling. (PMID:22962306)
• likely molecular etiology was found in eight patients with persistent Mullerian duct syndrome. Four mutations in AMH and two in AMHR2 were identified. Three of them are novel mutations, c.556-2A>G, and p.Arg502Leu in AMH; and p.Gly323Ser in AMHR2. (PMID:23295284)
• Data suggest that up-regulation of AMHR2 and AMH expression in luteal granulosa cells of anovulatory women with polycystic ovary syndrome is due to rising levels of luteinizing hormone (LH) and/or reversal of down-regulation by LH. (PMID:23321213)
• A statistically significant interaction between rs10407022 in AMH and rs11170547 in AMHR2 (p = 0.019) associated with age at natural menopause. (PMID:23544102)
• The role of the AMHR2 -482 A>G gene polymorphism in the pathogenesis of polycystic ovary syndrome was suggested by the association of the variant with risk. (PMID:23969185)
• Within primary ovarian insufficiency population, the AMH Ile(49)Ser and the AMHR2 -482A>G polymorphisms were not associated with age at the time of POI and (PMID:24146295)
• The possible involvement of AMHRII -482 A>G polymorphism on the malfunction of follicular development in Japanese women. (PMID:24271023)
• Antimullerian hormone receptor expression is increased in endometrium from patients with endometriosis. (PMID:24613539)
• These findings suggest that patients with primary ovarian insufficiency in China share AMH and AMHR2 genetic variants with those who go through menopause at a normal age. (PMID:24912417)
• Data indicate that Muellerian inhibiting substance type II receptor (MISRII) is a promising target for the control of ovarian granulosa cell tumors (GCT) and epithelial ovarian cancers (EOC). (PMID:25517316)
• There was evidence that in specific subgroups of women undergoing IVF/ICSI, AMH and AMHRII SNPs may be related to patients’ characteristics and controlled ovarian stimulation and pregnancy outcome (PMID:25542251)
• A significant portion of AMHRII was missing most of its extracellular domain (ECD) and was unfolded and retained in the endoplasmic reticulum. (PMID:25663701)
• AMHR2 rs11170555 and rs3741664 were positively associated with AMH, estradiol and FSH levels. (PMID:25790842)
• study demonstrated for the first time that human placenta and fetal membranes express and co-localize Anti-Mullerian hormone(AMH) and Anti-Mullerian hormone Receptor II (PMID:25972076)
• There is no association between single nucleotide polymorphisms in the AMH/AMHR2 signaling pathway and early ovarian hyperstimulation syndrome in Han Chinese women (PMID:26464718)
• -482A > G genotype not associated with estradiol levels, ovarian parameters, menstrual cycle length, or pregnancy outcomes in healthy Singapore women (PMID:26633196)
• A significant subset of GnRH neurons express the AMH receptor. (PMID:26753790)
• Neither AMH nor AMHR2 polymorphisms were related to age, BMI, hormone levels or ovarian parameters in the follicular phase in women of late reproductive stage. (PMID:26848671)
• AMHRII 1749C > T and -482A > G genetic variants are associated with the ovarian response to standard gonadotropin stimulation, affecting mainly the follicular growth in IVF. (PMID:26933946)
• a result of VEGF misregulation, AMHR2 overexpression increases AMH binding, which may attenuate follicular or oocyte maturation. (PMID:27109000)
• Genotyping of the AMH c.146G>T and AMHR2 -482A>G polymorphisms does not provide additional useful information as a predictor of ovarian reserve or ovarian response and treatment outcomes. (PMID:27142041)
• The aim of this study was to investigate the density and distribution of single nucleotide polymorphisms (SNPs) anti-Mullerian hormone (AMH) and AMHRII receptors in cryptorchid patients. (PMID:27162065)
• genetic variants of AMH or AMHR2 were not found to be associated with a higher risk for polycystic ovaries syndrome. (PMID:27664518)
• No evidence of significant associations of Ile49Ser and -482A>G with reproductive outcomes and polycystic ovary syndrome. (PMID:27832628)
• AMHR2 single nucleotide polymorphism is not associated with Endometriosis-associated infertility. (PMID:28831646)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Amhr2	ENSMUSG00000023047
rattus_norvegicus	Amhr2	ENSRNOG00000014850
drosophila_melanogaster	tkv	FBGN0003716
drosophila_melanogaster	babo	FBGN0011300
drosophila_melanogaster	wit	FBGN0024179
caenorhabditis_elegans		WBGENE00000897
caenorhabditis_elegans		WBGENE00004860

Paralogs (11): TGFBR1 (ENSG00000106799), BMPR1A (ENSG00000107779), ACVR2B (ENSG00000114739), ACVR1 (ENSG00000115170), ACVR2A (ENSG00000121989), ACVR1C (ENSG00000123612), ACVR1B (ENSG00000135503), BMPR1B (ENSG00000138696), ACVRL1 (ENSG00000139567), TGFBR2 (ENSG00000163513), BMPR2 (ENSG00000204217)

Protein

Protein identifiers

Anti-Muellerian hormone type-2 receptor — Q16671 (reviewed: Q16671)

Alternative names: Anti-Muellerian hormone type II receptor, MIS type II receptor

All UniProt accessions (2): Q16671, H3BPI9

UniProt curated annotations — full annotation on UniProt →

Function. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for anti-Muellerian hormone.

Subunit / interactions. Interacts with type I receptor ACVR1.

Subcellular location. Membrane.

Disease relevance. Persistent Muellerian duct syndrome 2 (PMDS2) [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.

Similarity. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q16671-1	1	yes
Q16671-2	2
Q16671-3	3

RefSeq proteins (3): NP_001158162, NP_001158163, NP_065434* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000333	TGFB_receptor	Family
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015771	Anti-muellerian_hrmn_rcpt_II	Family
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+) (RHEA:18673)
• L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+) (RHEA:44880)

UniProt features (38 total): sequence variant 10, strand 7, sequence conflict 3, glycosylation site 2, disulfide bond 2, splice variant 2, topological domain 2, turn 2, binding site 2, signal peptide 1, chain 1, helix 1, transmembrane region 1, domain 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7L0J	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16671-F1	78.34	0.46

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): 333 (proton acceptor)

Ligand- & substrate-binding residues (2): 209–217; 230

Disulfide bonds (2): 55–79, 92–109

Glycosylation sites (2): 119, 66

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-201451	Signaling by BMP
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members

MSigDB gene sets: 162 (showing top): EFC_Q6, GOBP_ANATOMICAL_STRUCTURE_REGRESSION, GATA3_01, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_FEMALE_SEX_DIFFERENTIATION, GATA1_04, GOBP_RESPONSE_TO_BMP, GOMF_TRANSMEMBRANE_RECEPTOR_PROTEIN_KINASE_ACTIVITY, GOBP_SEX_DIFFERENTIATION, GOBP_RESPONSE_TO_GROWTH_FACTOR, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GATA1_02

GO Biological Process (10): Mullerian duct regression (GO:0001880), transforming growth factor beta receptor signaling pathway (GO:0007179), sex differentiation (GO:0007548), male gonad development (GO:0008584), female gonad development (GO:0008585), BMP signaling pathway (GO:0030509), cellular response to growth factor stimulus (GO:0071363), anti-Mullerian hormone receptor signaling pathway (GO:1990262), protein phosphorylation (GO:0006468), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178)

GO Molecular Function (14): transforming growth factor beta receptor activity (GO:0005024), transforming growth factor beta receptor activity, type II (GO:0005026), ATP binding (GO:0005524), hormone binding (GO:0042562), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), anti-Mullerian hormone receptor activity (GO:1990272), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), transmembrane receptor protein serine/threonine kinase activity (GO:0004675), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by TGFB family members	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	2
transforming growth factor beta receptor superfamily signaling pathway	2
gonad development	2
cell surface receptor protein serine/threonine kinase signaling pathway	2
binding	2
male sex differentiation	1
anatomical structure regression	1
cellular response to transforming growth factor beta stimulus	1
development of primary male sexual characteristics	1
development of primary female sexual characteristics	1
cellular response to BMP stimulus	1
response to growth factor	1
cellular response to endogenous stimulus	1
phosphorylation	1
protein modification process	1
enzyme-linked receptor protein signaling pathway	1
transmembrane receptor protein serine/threonine kinase activity	1
transforming growth factor beta receptor activity	1
transforming growth factor beta binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
protein-hormone receptor activity	1
anti-Mullerian hormone receptor signaling pathway	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein kinase activity	1
protein serine/threonine kinase activity	1
transmembrane receptor protein kinase activity	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
membrane	1
cell periphery	1
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1510 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMHR2	AMH	P03971	999
AMHR2	CYREN	Q9BWK5	783
AMHR2	BMPR1B	P78366	775
AMHR2	FSHR	P23945	755
AMHR2	NR5A1	Q13285	715
AMHR2	LHCGR	P22888	697
AMHR2	ACVR1	Q04771	693
AMHR2	SRY	Q05066	685
AMHR2	FOXL2	P58012	655
AMHR2	GDF9	O60383	647
AMHR2	SOX9	P48436	617
AMHR2	BMP15	O95972	613
AMHR2	CYP19A1	P11511	604
AMHR2	DMRT1	Q9Y5R6	597
AMHR2	BMPR1A	P36894	577

IntAct

12 interactions, top by confidence:

A	B	Type	Score
CDC37	AMHR2	psi-mi:“MI:0915”(physical association)	0.670
HSP90AB1	AMHR2	psi-mi:“MI:0915”(physical association)	0.640
AMHR2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.640
MAL	AMHR2	psi-mi:“MI:0915”(physical association)	0.560
HSP90AA1	AMHR2	psi-mi:“MI:0915”(physical association)	0.560
AMHR2	FKBP5	psi-mi:“MI:0914”(association)	0.530
AMHR2	Hacd3	psi-mi:“MI:0915”(physical association)	0.400
AMHR2	ZFPL1	psi-mi:“MI:0914”(association)	0.350
AMHR2	ILVBL	psi-mi:“MI:0914”(association)	0.350
MAL	AMHR2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (54): LCK (Negative Genetic), AMHR2 (Negative Genetic), CIT (Negative Genetic), MAPK12 (Negative Genetic), PRKCZ (Negative Genetic), CDC25B (Negative Genetic), TST (Negative Genetic), INPP1 (Positive Genetic), GRM2 (Positive Genetic), MAL (Two-hybrid), AMHR2 (Negative Genetic), RPS6KA1 (Affinity Capture-MS), RPS6KA2 (Affinity Capture-MS), RPS6KA3 (Affinity Capture-MS), PIK3R3 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A0EQL2, D3YZF7, D7PDD4, O15533, O55237, O70394, O70540, O95866, P04278, P05111, P07994, P08689, P0C6B3, P0DP72, P15196, P17490, P18627, P40238, P55101, P60882, P97497, Q00657, Q08351, Q14393, Q14773, Q16671, Q3SWY4, Q5BK54, Q5NKT8, Q5TJE4, Q61790, Q61826, Q62588, Q6PZD2, Q6UVK1, Q6UWB1, Q7Z7M0, Q7Z7M1, Q86VR7

Diamond homologs: A0A0P0XII1, A0A0R0HPY5, A7J1T2, C0LGD6, C0LGD8, C0LGD9, C0LGG3, C0LGR6, C0LGV0, O00238, O00506, O04086, O35607, O46680, O64556, O65440, P04627, P09560, P0C5E2, P10398, P10533, P14056, P15056, P18161, P20792, P27037, P27038, P27039, P27040, P27041, P27966, P28028, P34908, P36894, P36895, P36896, P36897, P36898, P37023, P37172

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
AMHR2	up-regulates	ACVR1	binding
AMHR2	up-regulates	BMPR1B	binding
AMH	up-regulates	AMHR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	14
Uncertain significance	79
Likely benign	32
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1076254	NM_020547.3(AMHR2):c.128dup (p.Asp44fs)	Pathogenic
1172834	NM_020547.3(AMHR2):c.649del (p.Val217fs)	Pathogenic
1256004	NM_020547.3(AMHR2):c.775C>T (p.Arg259Ter)	Pathogenic
1338400	NM_020547.3(AMHR2):c.3G>A (p.Met1Ile)	Pathogenic
1338401	NM_020547.3(AMHR2):c.1216C>T (p.Arg406Ter)	Pathogenic
1524536	NM_020547.3(AMHR2):c.1504C>T (p.Gln502Ter)	Pathogenic
1705324	NM_020547.3(AMHR2):c.238C>T (p.Arg80Ter)	Pathogenic
1707557	NM_020547.3(AMHR2):c.1340C>T (p.Thr447Ile)	Pathogenic
2581234	NM_020547.3(AMHR2):c.1510C>T (p.Arg504Cys)	Pathogenic
2969058	NM_020547.3(AMHR2):c.118_119del (p.Gly40fs)	Pathogenic
3574976	NM_020547.3(AMHR2):c.78del (p.Phe27fs)	Pathogenic
3574978	NM_020547.3(AMHR2):c.289C>T (p.Arg97Ter)	Pathogenic
3621532	NM_020547.3(AMHR2):c.1106del (p.Pro369fs)	Pathogenic
3665562	NM_020547.3(AMHR2):c.261_262del (p.Cys87_Glu88delinsTer)	Pathogenic
3686415	NM_020547.3(AMHR2):c.175del (p.Arg59fs)	Pathogenic
3779441	NM_020547.3(AMHR2):c.1219C>T (p.Arg407Ter)	Pathogenic
4751051	NM_020547.3(AMHR2):c.1140+1G>A	Pathogenic
635875	Single allele	Pathogenic
689555	NM_020547.3(AMHR2):c.994C>T (p.Arg332Ter)	Pathogenic
8626	NM_020547.3(AMHR2):c.232+1G>A	Pathogenic
8627	NM_020547.3(AMHR2):c.1332_1358del (p.Gly445_Leu453del)	Pathogenic
8628	NM_020547.3(AMHR2):c.596del (p.Glu199fs)	Pathogenic
1120085	NM_020547.3(AMHR2):c.43del (p.Val15fs)	Likely pathogenic
1256005	NM_020547.3(AMHR2):c.515G>A (p.Arg172Gln)	Likely pathogenic
1256033	NM_020547.3(AMHR2):c.55C>G (p.Pro19Ala)	Likely pathogenic
1256035	NM_020547.3(AMHR2):c.355A>G (p.Asn119Asp)	Likely pathogenic
2169571	NM_020547.3(AMHR2):c.1511G>A (p.Arg504His)	Likely pathogenic
2985539	NM_020547.3(AMHR2):c.1140+6T>C	Likely pathogenic
3366389	NM_020547.3(AMHR2):c.160C>T (p.Arg54Cys)	Likely pathogenic
3574977	NM_020547.3(AMHR2):c.229C>T (p.Gln77Ter)	Likely pathogenic

SpliceAI

1697 predictions. Top by Δscore:

Variant	Effect	Δscore
12:53424856:G:GT	donor_gain	1.0000
12:53429623:G:GT	donor_gain	1.0000
12:53429829:A:AG	acceptor_gain	1.0000
12:53429829:AGGCT:A	acceptor_gain	1.0000
12:53429830:G:GG	acceptor_gain	1.0000
12:53429830:GGCT:G	acceptor_gain	1.0000
12:53429830:GGCTG:G	acceptor_gain	1.0000
12:53429974:GCCTG:G	donor_gain	1.0000
12:53429978:GGTA:G	donor_loss	1.0000
12:53429979:G:C	donor_loss	1.0000
12:53429979:G:GG	donor_gain	1.0000
12:53429980:T:G	donor_loss	1.0000
12:53423981:AAGG:A	donor_loss	0.9900
12:53423982:AGGTA:A	donor_loss	0.9900
12:53423983:GGT:G	donor_loss	0.9900
12:53423984:G:GA	donor_loss	0.9900
12:53423985:T:A	donor_loss	0.9900
12:53424274:ACCCT:A	acceptor_gain	0.9900
12:53424278:T:TA	acceptor_gain	0.9900
12:53424279:G:A	acceptor_gain	0.9900
12:53425559:C:G	donor_gain	0.9900
12:53425583:G:GT	donor_gain	0.9900
12:53425584:G:T	donor_gain	0.9900
12:53428885:C:CA	acceptor_gain	0.9900
12:53428890:CCCCA:C	acceptor_loss	0.9900
12:53428892:CCAGG:C	acceptor_loss	0.9900
12:53428893:CA:C	acceptor_loss	0.9900
12:53428894:AG:A	acceptor_gain	0.9900
12:53428895:G:GA	acceptor_loss	0.9900
12:53428895:GG:G	acceptor_gain	0.9900

AlphaMissense

3671 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:53424401:T:A	C55S	0.995
12:53424402:G:C	C55S	0.995
12:53424433:G:C	W65C	0.995
12:53424433:G:T	W65C	0.995
12:53424711:T:A	C79S	0.995
12:53424712:G:C	C79S	0.995
12:53429463:A:C	K326N	0.995
12:53429463:A:T	K326N	0.995
12:53431213:T:A	W488R	0.995
12:53431213:T:C	W488R	0.995
12:53425757:G:C	K230N	0.994
12:53425757:G:T	K230N	0.994
12:53429946:A:T	E419V	0.994
12:53424823:G:A	C116Y	0.993
12:53424827:T:A	N117K	0.993
12:53424827:T:G	N117K	0.993
12:53424401:T:C	C55R	0.992
12:53424421:C:G	C61W	0.992
12:53424822:T:A	C116S	0.992
12:53424823:G:C	C116S	0.992
12:53424403:C:G	C55W	0.991
12:53424711:T:C	C79R	0.991
12:53425747:T:A	V227D	0.991
12:53429474:C:A	A330D	0.991
12:53429491:A:C	S336R	0.991
12:53429493:C:A	S336R	0.991
12:53429493:C:G	S336R	0.991
12:53424308:T:A	C24S	0.990
12:53424309:G:A	C24Y	0.990
12:53424309:G:C	C24S	0.990

dbSNP variants (sampled 300 via entrez): RS1000365987 (12:53424990 C>A,G,T), RS1000801921 (12:53424298 C>G), RS1001028353 (12:53431230 A>G), RS1001067791 (12:53423754 C>T), RS1001258122 (12:53428579 G>C), RS1001575052 (12:53432103 G>A), RS1001704339 (12:53431690 C>G), RS1002137093 (12:53431950 T>C,G), RS1002142299 (12:53425011 T>C), RS1002628862 (12:53422146 A>G), RS1002788406 (12:53423386 T>G), RS1002808860 (12:53428239 C>T), RS1003028672 (12:53422015 G>A), RS1003196699 (12:53422102 G>A), RS1003743400 (12:53427001 A>T)

Disease associations

OMIM: gene MIM:600956 | disease phenotypes: MIM:261550

GenCC curated gene-disease

Disease	Classification	Inheritance
persistent Mullerian duct syndrome	Definitive	Autosomal recessive

Mondo (3): persistent Mullerian duct syndrome (MONDO:0009857), premature menopause (MONDO:0001119), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Persistent Müllerian duct syndrome (Orphanet:2856), Rare genetic premature ovarian failure (Orphanet:485382)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000037	Male pseudohermaphroditism
HP:0003251	Male infertility
HP:0003577	Congenital onset
HP:0008689	Bilateral cryptorchidism
HP:0031103	Decreased circulating antimullerian hormone circulation

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500
D065886	Neurodevelopmental Disorders	F03.625
C536665	Persistent Mullerian duct syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs784892	Efficacy,Metabolism/PK	3	metformin	Diabetes Mellitus

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs784888	AMHR2, SP1	3	2.50	1	metformin
rs784892	AMHR2	3	3.00	1	metformin

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type II receptor serine/threonine kinases

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, increases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
butyraldehyde	increases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
Chir 99021	increases expression, affects binding, affects cotreatment	1
abrine	increases expression	1
XAV939	affects binding, affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Aldehydes	increases expression	1
Ascorbic Acid	affects binding, affects cotreatment, increases expression	1
Vehicle Emissions	decreases methylation	1
Benzo(a)pyrene	decreases expression	1
Cycloheximide	decreases expression, decreases reaction	1
Diethylhexyl Phthalate	decreases expression	1
Dust	decreases expression	1
Hydrocortisone	affects cotreatment, increases expression	1
Niclosamide	increases expression	1
Nicotine	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Tetrachlorodibenzodioxin	decreases expression, decreases reaction	1
Tobacco Smoke Pollution	increases expression	1

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8Z3	Ubigene HEK293 AMHR2 KO	Transformed cell line	Female
CVCL_E6P2	Genomeditech CHO-K1 H_AMHR2	Spontaneously immortalized cell line	Female
CVCL_E6WA	Genomeditech MC-38 H_AMHR2	Cancer cell line	Female
CVCL_E6WP	Genomeditech RKO H_AMHR2	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary