Details for: AMH

Gene ID: 268

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: AMH

Ensembl ID: ENSG00000104899

Description: anti-Mullerian hormone

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • regulatory T cell CL0000815
    CSI 20.58
    rCSI 23.86%
    PRS 88.99
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 14.02
    rCSI 16.98%
    PRS 78.68
  • helper T cell CL0000912
    CSI 12.15
    rCSI 17.18%
    PRS 90.32
  • innate lymphoid cell CL0001065
    CSI 5.17
    rCSI 10.68%
    PRS 89.52
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 4.28
    rCSI 7.56%
    PRS 86.46
  • cytotoxic T cell CL0000910
    CSI 3.92
    rCSI 22.47%
    PRS 92.53
  • melanocyte of skin CL1000458
    CSI 3.87
    rCSI 5.28%
    PRS 71.21
  • epithelial cell CL0000066
    CSI 1.99
    rCSI 3.06%
    PRS 85.48

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [AMH](/details-gene/268) (anti-Mullerian hormone) is a protein-coding gene located on chromosome 19p13.3 that encodes a secreted glycoprotein belonging to the transforming growth factor-beta (TGF-beta) superfamily. Classically, [AMH](/details-gene/268) is known for its critical role in male sexual differentiation, where it induces the regression of the Müllerian ducts, the precursors to female reproductive organs [Link](https://doi.org/10.1016/0092-8674(86)90783-x). In females, it is produced by granulosa cells of ovarian follicles and is involved in regulating follicle development [Link](https://doi.org/10.1093/molehr/gah015). Mutations in [AMH](/details-gene/268) or its receptor are associated with Persistent Müllerian Duct Syndrome ([261550](https://omim.org/entry/261550), [600957](https://omim.org/entry/600957)), where males have normal external genitalia but also possess a uterus and fallopian tubes [Link](https://doi.org/10.1093/hmg/3.1.125). While its function in reproductive biology is well-established, expression data indicates a surprisingly significant presence in various T lymphocyte populations, suggesting a potential, less-characterized role in the immune system. ## Cellular Roles and Expression Landscape The expression profile of [AMH](/details-gene/268) reveals a significant role in adaptive immunity, particularly within T-cell lineages. **Overall**, the gene demonstrates its highest significance in several key T-cell subsets. It is a top marker in [regulatory T cell](/details-cell/CL0000815) (CSI: 20.58), suggesting a potential role in immune suppression and tolerance. Its high significance extends to memory and helper T-cell populations, including [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 14.02) and [helper T cell](/details-cell/CL0000912) (CSI: 12.15). Furthermore, notable expression in [cytotoxic T cell](/details-cell/CL0000910) (CSI: 3.92) and [innate lymphoid cell](/details-cell/CL0001065) (CSI: 5.17) reinforces its connection to both adaptive and innate lymphocyte biology. This strong and specific expression pattern within the immune compartment, especially in cells critical for regulating immune responses, points toward immunomodulatory functions that are distinct from its canonical role in developmental biology. Expression is also noted in non-immune cells such as [melanocyte of skin](/details-cell/CL1000458) and [epithelial cell](/details-cell/CL0000066), albeit with lower significance, indicating broader physiological involvement. ## Pathways and Molecular Function Functionally, [AMH](/details-gene/268) is a secreted growth factor that operates through the TGF-beta signaling cascade. Its molecular function includes [Growth factor activity](/details-go/GO:0008083) and binding to the [Type ii transforming growth factor beta receptor](/details-go/GO:0005114), which initiates the [Anti-mullerian hormone receptor signaling pathway](/details-go/GO:1990262) and leads to the [Positive regulation of smad protein signal transduction](/details-go/GO:0060391). The gene's involvement in the Reactome pathway [Signaling by tgfb family members](/details-reactome/R-HSA-9006936) is central to its well-documented roles in [Developmental biology](/details-reactome/R-HSA-1266738). Specifically, it is a key player in biological processes such as [Sex differentiation](/details-go/GO:0007548), driving [Mullerian duct regression](/details-go/GO:0001880) in males, and modulating [Ovarian follicle development](/details-go/GO:0001541) in females. The high expression of [AMH](/details-gene/268) in T-cell populations, particularly [regulatory T cell](/details-cell/CL0000815), suggests that its established TGF-beta signaling capacity may be co-opted for immunomodulatory purposes, as TGF-beta signaling is a cornerstone of regulatory T-cell function and peripheral tolerance. ## Research Directions The marked expression of [AMH](/details-gene/268) in T-lymphocytes, despite its classic association with reproductive development, opens up novel avenues for research in immunobiology. The disconnect between its established functional annotation and its observed cellular landscape suggests uncharacterized roles that warrant further investigation. **Proposed Hypotheses:** 1. Given its high significance in [regulatory T cell](/details-cell/CL0000815) and its function within the TGF-beta signaling family, [AMH](/details-gene/268) may act as a secreted factor that enhances the suppressive function and/or stability of regulatory T-cells, thereby contributing to the maintenance of immune homeostasis. 2. The high significance of [AMH](/details-gene/268) in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) suggests it may play a role in the long-term survival, maintenance, or recall response of memory T-cell populations following pathogen exposure or vaccination. **Experimental Approach:** To test the hypothesis that [AMH](/details-gene/268) enhances regulatory T-cell function, a series of experiments could be designed. Primary human naive T-cells could be cultured *in vitro* under conditions that promote differentiation into induced regulatory T-cells (iTregs) in the presence or absence of recombinant [AMH](/details-gene/268). The resulting iTreg populations could then be assessed for the expression of key transcription factors (e.g., FOXP3) by flow cytometry and for their suppressive capacity in co-culture assays with proliferating conventional T-cells. A parallel study using a T-cell-specific conditional knockout of the [AMH](/details-gene/268) receptor, AMHR2, in a mouse model of autoimmune disease (e.g., experimental autoimmune encephalomyelitis) would provide *in vivo* validation of its role in immune regulation. **Therapeutic Potential:** As a secreted hormone-like factor with immunomodulatory potential, [AMH](/details-gene/268) presents a compelling, though complex, therapeutic target. If it is shown to promote regulatory T-cell function and immune suppression, administration of recombinant [AMH](/details-gene/268) could represent a novel therapeutic strategy for treating autoimmune diseases by bolstering tolerance (an activation strategy). Conversely, in the context of oncology, where regulatory T-cells often inhibit anti-tumor immunity, targeting the [AMH](/details-gene/268)-AMHR2 signaling axis with monoclonal antibodies or small molecule inhibitors could serve as a novel immune checkpoint blockade, potentially synergizing with existing cancer immunotherapies (an inhibition strategy).

Genular Protein ID: 76971339

Symbol: MIS_HUMAN

Name: Muellerian-inhibiting factor

UniProtKB Accession Codes:

P03971 O75246 Q6GTN3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 GO 21 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PIRSF 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3754790

Title: Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells.

PubMed ID: 3754790

DOI: 10.1016/0092-8674(86)90783-x

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 2974034

Title: Proteolytic processing of mullerian inhibiting substance produces a transforming growth factor-beta-like fragment.

PubMed ID: 2974034

DOI: 10.1016/s0021-9258(18)37375-7

PubMed ID: 8469238

Title: Mullerian inhibiting substance requires its N-terminal domain for maintenance of biological activity, a novel finding within the transforming growth factor-beta superfamily.

PubMed ID: 8469238

DOI: 10.1210/mend.7.2.8469238

PubMed ID: 11779604

Title: Relationship between serum muellerian-inhibiting substance and other reproductive hormones in untreated women with polycystic ovary syndrome and normal women.

PubMed ID: 11779604

DOI: 10.1016/s0015-0282(01)02944-2

PubMed ID: 14742691

Title: Anti-Muellerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment.

PubMed ID: 14742691

DOI: 10.1093/molehr/gah015

PubMed ID: 20861221

Title: Processing of anti-mullerian hormone regulates receptor activation by a mechanism distinct from TGF-beta.

PubMed ID: 20861221

DOI: 10.1210/me.2010-0273

PubMed ID: 1483695

Title: Variants of the anti-Mullerian hormone gene in a compound heterozygote with the persistent Mullerian duct syndrome and his family.

PubMed ID: 1483695

DOI: 10.1007/bf00220465

PubMed ID: 8162013

Title: Molecular genetics of the persistent Mullerian duct syndrome: a study of 19 families.

PubMed ID: 8162013

DOI: 10.1093/hmg/3.1.125

PubMed ID: 8872466

Title: A 27 base-pair deletion of the anti-Muellerian type II receptor gene is the most common cause of the persistent Muellerian duct syndrome.

PubMed ID: 8872466

DOI: 10.1093/hmg/5.9.1269

PubMed ID: 34155118

Title: Structure of AMH bound to AMHR2 provides insight into a unique signaling pair in the TGF-beta family.

PubMed ID: 34155118

DOI: 10.1073/pnas.2104809118

Sequence Information:

  • Length: 560
  • Mass: 59195
  • Checksum: D05DCEE4FEDF94C2
  • Sequence:
    • MRDLPLTSLA LVLSALGALL GTEALRAEEP AVGTSGLIFR EDLDWPPGSP QEPLCLVALG 
GDSNGSSSPL RVVGALSAYE QAFLGAVQRA RWGPRDLATF GVCNTGDRQA ALPSLRRLGA 
WLRDPGGQRL VVLHLEEVTW EPTPSLRFQE PPPGGAGPPE LALLVLYPGP GPEVTVTRAG 
LPGAQSLCPS RDTRYLVLAV DRPAGAWRGS GLALTLQPRG EDSRLSTARL QALLFGDDHR 
CFTRMTPALL LLPRSEPAPL PAHGQLDTVP FPPPRPSAEL EESPPSADPF LETLTRLVRA 
LRVPPARASA PRLALDPDAL AGFPQGLVNL SDPAALERLL DGEEPLLLLL RPTAATTGDP 
APLHDPTSAP WATALARRVA AELQAAAAEL RSLPGLPPAT APLLARLLAL CPGGPGGLGD 
PLRALLLLKA LQGLRVEWRG RDPRGPGRAQ RSAGATAADG PCALRELSVD LRAERSVLIP 
ETYQANNCQG VCGWPQSDRN PRYGNHVVLL LKMQVRGAAL ARPPCCVPTA YAGKLLISLS 
EERISAHHVP NMVATECGCR