GeneBe

AMHR2

protein-coding

anti-Mullerian hormone receptor type 2, the group of Type 2 receptor serine/threonine kinases

Gene summary

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. [provided by RefSeq, Sep 2009]

MANE transcript

NM_020547.3

Inheritance

AR

ClinVar variants

P:43U:79B:27

Top phenotype

Persistent Mullerian duct syndrome, type II

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr12:53,423,855-53,431,672

External References & Databases

Ensembl (ENSG00000135409)NCBI Gene (269)OMIM (600956)HGNC:465GenCCUniProt (Q16671)AlphaFoldClinVar (AMHR2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~7.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

persistent Mullerian duct syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009857

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

persistent Mullerian duct syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009857

Submitter: PanelApp Australia

persistent Mullerian duct syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009857

Submitter: Labcorp Genetics (formerly Invitae)

persistent Mullerian duct syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009857

Submitter: Ambry Genetics

persistent Mullerian duct syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009857

Submitter: Orphanet

Clinical Genomic Database (CGD)

Persistent Mullerian duct syndrome, type IIAR

Manifestation: Endocrine; Genitourinary; Oncologic

Intervention: Endocrine; Oncologic; Genitourinary

Rationale: In males, recognition can allow surveillance and surgical explorations to correct manifestations such as cryptorchdisim, which can be important to preserve fertility and decrease the chance of related sequelae (eg, testicular tumors)

Refs: 8162013; 7493017; 8872466; 8895659; 15878900; 19457927Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AMHR2 variants in ClinVar

10 Conditions Cataloged
not providedTotal: 70
Inborn genetic diseasesTotal: 66
Persistent Mullerian duct syndromeTotal: 24
not specifiedTotal: 13
AMHR2-related disorderTotal: 10
Persistent mullerian duct syndrome, type IITotal: 4
Genetic non-acquired premature ovarian failureTotal: 4
Male pseudohermaphroditismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020547.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
17
clinvar
2
clinvar
 20
missense
2
clinvar
12
clinvar
77
clinvar
8
clinvar
 99
nonsense
7
clinvar
4
clinvar
 11
start loss
1
clinvar
 1
frameshift
8
clinvar
5
clinvar
 13
splice donor/acceptor (+/-2bp)
2
clinvar
2
clinvar
1
clinvar
 5
Total202379252149

Highest pathogenic variant AF is 0.00038532782

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_020547.3RefSeqNP_065434.111MANE Select
ENST00000257863.9EnsemblENSP00000257863.311MANE Select
NM_001164690.2RefSeqNP_001158162.111Standard
NM_001164691.2RefSeqNP_001158163.19Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • TGF-beta signaling pathway - Homo sapiens (human)
  • Cytokine-cytokine receptor interaction - Homo sapiens (human)
  • TGF-Core
  • Signal Transduction
  • TGF-beta super family signaling pathway canonical

Biological Process

  • Mullerian duct regression
  • protein phosphorylation
  • transforming growth factor beta receptor signaling pathway
  • pattern specification process
  • sex differentiation

Molecular Function

  • transforming growth factor beta-activated receptor activity
  • transforming growth factor beta receptor activity, type II
  • protein binding
  • ATP binding
  • growth factor binding

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • receptor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000257863
Coding exons
11
Length
7680
Individuals with no LoFs
125683
Homozygous LoFs
0
Heterozygous LoFs
65
Defined
125748
p
0.000258
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.3942933130.9370.00001803651
Missense (PolyPhen)2738.0060.71041476
Synonymous1.051081230.8790.000005881243
Loss of Function1.852031.10.6430.00000218280

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000800.00080rare
Latino/Admixed American0.000350.00035rare
Ashkenazi Jewish0.000300.00030rare
East Asian0.000220.00022rare
Finnish0.0000990.000092rare
European (Non-Finnish)0.000240.00024rare
South Asian0.000130.00013rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
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.;
Disease
DISEASE: 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. {ECO:0000269|PubMed:11549681, ECO:0000269|PubMed:8872466}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.158

Intolerance Scores

LoFtool
0.206
RVIS EVS
-0.93
RVIS percentile EVS
9.47

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.964

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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