On this page
AMH
anti-Mullerian hormone
The AMH gene provides instructions for producing anti-Müllerian hormone, a protein essential for male reproductive development by regulating the regression of Müllerian ducts. The AMH gene is crucial for male sex differentiation, encoding a hormone that causes the regression of structures that would otherwise develop into female reproductive organs in male foetuses.
AMH is located on the short (p) arm of chromosome 19, at band 19p13.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 19 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The AMH gene codes for anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting substance (MIS) or Müllerian-inhibiting factor (MIF). This hormone is fundamental in the sexual differentiation of male foetuses. Its primary function is to prevent the development of female reproductive structures, such as the uterus and fallopian tubes, in individuals who are chromosomally male.
What the gene does
During male foetal development, AMH is secreted by Sertoli cells in the testes. This protein then binds to specific receptors on the surface of Müllerian duct cells. In response to AMH binding, these cells undergo programmed cell death (apoptosis), leading to the breakdown and eventual disappearance of the Müllerian ducts. In the absence of AMH, such as in female foetuses, the Müllerian ducts persist and develop into the uterus, fallopian tubes, and upper part of the vagina. Therefore, AMH's action is critical for establishing the male reproductive anatomy by inhibiting the development of internal female structures.
Video: Genetics 101
Chromosome location
The AMH gene is situated on chromosome 19, specifically at position 19p13.3. This location refers to the short arm of chromosome 19, within band 13.3.
Protein structure
The AMH protein is composed of 560 amino acids. Key functional regions include a Disordered region (amino acids 259-287), multiple regions involved in Binding to Muellerian-inhibiting factor chain (amino acids 291-317 and 426-427), and regions for Binding to AMH prodomain (amino acids 468-482 and 536-549). The protein also features regions critical for Muellerian-inhibiting factor chain dimerization (amino acids 505-529 and 549-560).
Key variants
Genetic variations within the AMH gene can alter the production or function of anti-Müllerian hormone. These changes may range from small alterations in single DNA building blocks to larger deletions or insertions. Such variants can impact the gene's ability to produce a functional protein, potentially leading to disorders of sexual development.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1112G>A | p.Trp371Ter | Pathogenic | ★★☆☆ | not provided |
c.1165G>T | p.Glu389Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Persistent Mullerian duct syndrome |
c.118C>T | p.Arg40Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Persistent Mullerian duct syndrome |
c.208dup | p.Leu70fs | Pathogenic | ★★☆☆ | not provided |
c.209del | p.Leu70fs | Pathogenic | ★★☆☆ | Persistent Mullerian duct syndrome |
c.343_344del | p.Leu115fs | Pathogenic | ★★☆☆ | Persistent Mullerian duct syndrome |
c.451C>T | p.Pro151Ser | Pathogenic | ★★☆☆ | Persistent Mullerian duct syndrome |
c.500A>G | p.Tyr167Cys | Pathogenic | ★★☆☆ | not provided |
c.649C>T | p.Gln217Ter | Pathogenic | ★★☆☆ | Persistent Mullerian duct syndrome |
c.1507T>C | p.Tyr503His | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the AMH gene are associated with conditions such as Persistent Müllerian duct syndrome. This condition primarily affects males, causing them to develop internal female reproductive organs alongside their normal male reproductive structures, due to the failure of Müllerian duct regression.
- Persistent Müllerian duct syndrome Dedicated page coming soon
UK clinical status
The AMH gene is included in genetic testing panels within the NHS Genomic Medicine Service. It is currently listed as a 'green' gene on the Differences in sex development panel (R146), indicating that there is strong evidence for its association with this condition.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the AMH gene?
The AMH gene provides instructions for making anti-Müllerian hormone, which is essential for male sexual differentiation by causing the regression of the Müllerian ducts during foetal development, thus preventing the formation of female reproductive organs in males.
What happens if the AMH gene is not functional in males?
If the AMH gene is not functional in males, the Müllerian ducts will not regress during foetal development. This can lead to Persistent Müllerian duct syndrome, where males develop internal female reproductive organs alongside their normal male reproductive structures.
Is the AMH gene relevant for female reproductive development?
While AMH is crucial for inhibiting female organ development in males, its absence in females is normal and allows the Müllerian ducts to develop into the uterus, fallopian tubes, and upper vagina. Therefore, it plays an indirect but permissive role in female reproductive development.
References
- Josso N, Belville C, di Clemente N. AMH and AMH receptor defects in persistent Müllerian duct syndrome. Human reproduction update. 2005. PMID: 15878900
- Rey R. Anti-Müllerian hormone in disorders of sex determination and differentiation. Arquivos brasileiros de endocrinologia e metabologia. 2005. PMID: 16544032
- Belville C, Van Vlijmen H, Ehrenfels C. Mutations of the anti-mullerian hormone gene in patients with persistent mullerian duct syndrome: biosynthesis, secretion, and processing of the abnormal proteins and analysis using a three-dimensional model. Molecular endocrinology (Baltimore, Md.). 2004. PMID: 14673134
- Josso N, Picard JY, Imbeaud S. Clinical aspects and molecular genetics of the persistent müllerian duct syndrome. Clinical endocrinology. 1997. PMID: 9302384