AMH
protein-codinganti-Mullerian hormone, the group of MicroRNA protein coding host genes|Receptor ligands|Transforming growth factor beta superfamily
Gene summary
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. [provided by RefSeq, Jul 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009857
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009857
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009857
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
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)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AMH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000479.5. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 52 | 3 | 55 | |||
| missense | 3 | 11 | 148 | 22 | 4 | 188 |
| nonsense | 4 | 4 | 8 | |||
| start loss | 0 | |||||
| frameshift | 9 | 5 | 1 | 15 | ||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 17 | 20 | 149 | 74 | 7 | 267 |
Highest pathogenic variant AF is 0.00033048063
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000470.3 | 5 | MANE Select | |
| Ensembl | ENSP00000221496.2 | 5 | MANE Select |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| amh | Danio rerio | Structure: spermatogonium Quality: increased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TGF-beta signaling pathway - Homo sapiens (human)
- Hippo signaling pathway - Homo sapiens (human)
- cAMP signaling pathway - Homo sapiens (human)
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- TGF-Core
Biological Process
- preantral ovarian follicle growth
- urogenital system development
- Mullerian duct regression
- cell-cell signaling
- gonadal mesoderm development
Molecular Function
- signaling receptor binding
- transforming growth factor beta receptor binding
- hormone activity
- growth factor activity
Cellular Component
- extracellular region
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000221496
- Coding exons
- 5
- Length
- 2765
- Individuals with no LoFs
- 124927
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 39
- Defined
- 124966
- p
- 0.000156
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.881 | 336 | 294 | 1.14 | 0.0000194 | 3296 |
| Missense (PolyPhen) | 143 | 124.41 | 1.1495 | 1462 | ||
| Synonymous | -1.32 | 163 | 143 | 1.14 | 0.00000982 | 1330 |
| Loss of Function | -0.701 | 16 | 13.2 | 1.21 | 7.45e-7 | 137 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00056 | 0.00037 | rare |
| Latino/Admixed American | 0.00022 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00015 | 0.00013 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This glycoprotein, produced by the Sertoli cells of the testis, causes regression of the Muellerian duct. It is also able to inhibit the growth of tumors derived from tissues of Muellerian duct origin.;
- Disease
- DISEASE: 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. {ECO:0000269|PubMed:8162013, ECO:0000269|PubMed:8872466}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.768
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |