On this page
AMH
anti-Mullerian hormone
The AMH gene provides instructions for producing anti-Müllerian hormone, a protein crucial for male reproductive development. The AMH gene encodes anti-Müllerian hormone (AMH), a protein that plays a key role in the development of male reproductive organs by preventing the formation of female reproductive structures during foetal development.
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 provides the genetic blueprint for anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting substance (MIS) or Müllerian-inhibiting factor (MIF). This hormone is fundamental in the process of sexual differentiation in humans, particularly in male foetal development.
AMH's primary role is to ensure the proper development of male reproductive organs by facilitating the regression of structures that would otherwise form female reproductive tracts. Dysregulation of AMH function can lead to developmental anomalies.
What the gene does
The anti-Müllerian hormone protein, encoded by the AMH gene, is a secreted glycoprotein that belongs to the transforming growth factor beta (TGF-β) superfamily. During early foetal development, specifically in male foetuses, AMH is produced by Sertoli cells in the testes. It acts as a signal to Müllerian duct cells, which are embryonic structures present in both male and female foetuses.
In males, the binding of AMH to its specific receptor on Müllerian duct cells initiates a cascade of events leading to the programmed self-destruction, or apoptosis, of these cells. This regression of the Müllerian ducts is essential for preventing the development of female internal reproductive organs, such as the uterus and fallopian tubes, in males. Conversely, in female foetuses, AMH is not produced in significant amounts during this critical developmental window, allowing the Müllerian ducts to develop into the female reproductive tract.
Video: Genetics 101
Chromosome location
The AMH gene is situated on the short arm of chromosome 19 at position 13.3, denoted as 19p13.3. This precise genomic location ensures its coordinated expression and function within the broader genetic landscape.
Protein structure
The AMH protein is composed of 560 amino acids. Key functional regions include a disordered region spanning amino acids 259-287. Several regions are involved in binding to the Müllerian-inhibiting factor chain, specifically amino acids 291-317 and 426-427. The protein also contains regions for binding to the AMH prodomain at amino acids 468-482 and 536-549. Additionally, two distinct regions, amino acids 505-529 and 549-560, are critical for Müllerian-inhibiting factor chain dimerization.
Key variants
Genetic variations within the AMH gene can alter the structure or function of the anti-Müllerian hormone protein. These changes may range from single nucleotide alterations to larger deletions or insertions, potentially impacting the protein's ability to bind to its receptor or to induce Müllerian duct regression. The clinical consequence of such variants depends on their specific effect on protein activity.
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/Likely pathogenic | ★★☆☆ | Persistent Mullerian duct syndrome |
c.500A>G | p.Tyr167Cys | Pathogenic | ★★☆☆ | not provided |
c.649C>T | p.Gln217Ter | Pathogenic/Likely pathogenic | ★★☆☆ | AMH-related disorder |
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
Pathogenic variants in the AMH gene are primarily associated with Persistent Müllerian duct syndrome (AR). This condition affects males, causing them to develop female reproductive organs, such as a uterus and fallopian tubes, in addition to their normal male reproductive anatomy. This occurs because the Müllerian ducts fail to regress during foetal development.
UK clinical status
The AMH gene is recognised in the UK for its clinical relevance within the NHS Genomic Medicine Service. It is listed on the 'Differences in sex development' Green list (R146) in PanelApp, indicating that there is strong evidence for its association with relevant conditions and it is routinely considered in diagnostic testing for these disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the AMH gene?
The AMH gene provides instructions for the anti-Müllerian hormone, which is critical for male foetal development. It signals the regression of Müllerian ducts, preventing the formation of female reproductive organs in male foetuses.
What condition is most commonly associated with AMH gene variants?
The condition most commonly associated with pathogenic variants in the AMH gene is Persistent Müllerian duct syndrome (AR). This syndrome results in males having both male and female internal reproductive organs.
Is the AMH gene part of UK genetic testing panels?
Yes, the AMH gene is included on the 'Differences in sex development' Green list (R146) in PanelApp, indicating its routine consideration in diagnostic testing within the NHS Genomic Medicine Service for related conditions.
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