Details for: AMHR2

Gene ID: 269

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: AMHR2

Ensembl ID: ENSG00000135409

Description: anti-Mullerian hormone receptor type 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.78
    rCSI 2.51%
    PRS 99.01
  • mesothelial cell CL0000077
    CSI 1.25
    rCSI 4.89%
    PRS 95.24

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 The [AMHR2](/details-gene/269) gene encodes the anti-Müllerian hormone type-2 receptor, a transmembrane serine/threonine kinase that is a critical component of the transforming growth factor-beta (TGF-beta) signaling superfamily. Its primary and best-characterized function is mediating the effects of anti-Müllerian hormone (AMH), which leads to the regression of Müllerian ducts in male fetuses, a fundamental step in male sex differentiation. Mutations in [AMHR2](/details-gene/269) are a primary cause of Persistent Müllerian Duct Syndrome (PMDS) ([Link](https://doi.org/10.1093/hmg/5.9.1269)), a disorder of sex development in which male individuals have female reproductive structures. While its role in developmental biology is well-established, expression data from the **Overall** context suggests a broader functional landscape, with significant expression in cell types such as the '[megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)' and '[mesothelial cell](/details-cell/CL0000077)', indicating potential roles beyond canonical sex development. ## Cellular Roles and Expression Landscape The expression profile of [AMHR2](/details-gene/269) highlights its specialized function. **Overall**, the gene shows its most significant expression in '[megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)' (CSI: 2.78), a hematopoietic precursor cell, and '[mesothelial cell](/details-cell/CL0000077)' (CSI: 1.25), which form the lining of body cavities. This pattern suggests that in addition to its classical role in the gonads during embryonic development, [AMHR2](/details-gene/269) may participate in the regulation of hematopoiesis and the biology of serous membranes. Its expression has also been documented in ovarian cancer cells, where it appears to retain responsiveness to its ligand, AMH ([Link](https://pubmed.ncbi.nlm.nih.gov/10589763)). The highly specific expression pattern across these distinct cell lineages suggests that AMH-[AMHR2](/details-gene/269) signaling is leveraged in diverse biological contexts, from embryonic patterning to adult tissue homeostasis and pathology. ## Pathways and Molecular Function [AMHR2](/details-gene/269) functions as a type II receptor within the TGF-beta signaling family. Upon binding its ligand, anti-Müllerian hormone, it forms a complex with a type I receptor, which it then phosphorylates and activates. This initiates a downstream signaling cascade, primarily through SMAD proteins. This activity is annotated in its involvement in the '[Anti-mullerian hormone receptor signaling pathway](/details-cell/GO:1990262)' and the broader '[Transforming growth factor beta receptor signaling pathway](/details-cell/GO:0007179)'. The key biological outcome of this pathway is '[Mullerian duct regression](/details-cell/GO:0001880)', which is essential for '[Male gonad development](/details-cell/GO:0008584)' and overall '[Sex differentiation](/details-cell/GO:0007548)'. Genetic defects that disrupt '[Anti-mullerian hormone receptor activity](/details-cell/GO:1990272)' are clinically associated with Persistent Müllerian Duct Syndrome (PMDS) ([OMIM: 600956]), a condition where Müllerian derivatives persist in males ([Link](https://doi.org/10.1038/ng1295-382)). Furthermore, its participation in pathways like '[Signaling by bmp](/details-cell/R-HSA-201451)' and '[Blood vessel development](/details-cell/GO:0001568)' may help explain its significant expression in hematopoietic progenitors and other non-gonadal tissues. ## Research Directions The established role of [AMHR2](/details-gene/269) in developmental biology contrasts with its significant expression in adult hematopoietic progenitors, opening new avenues for investigation. While its function in Müllerian duct regression is well-defined, its purpose in other cell types is less understood and presents a compelling area for future research. Based on the available data, several testable hypotheses can be proposed: 1. The high significance of [AMHR2](/details-gene/269) in '[megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)' suggests that AMH signaling acts as a regulator of hematopoiesis, potentially by modulating the balance between proliferation and differentiation within the megakaryocyte and erythroid lineages. 2. Given its established growth-inhibitory effects and expression in ovarian tumors ([Link](https://pubmed.ncbi.nlm.nih.gov/10589763)), [AMHR2](/details-gene/269) activation by its ligand AMH may serve as a tumor-suppressive signaling axis in specific subtypes of gynecological cancers. To test the first hypothesis regarding its role in hematopoiesis, a key experiment would be to isolate primary human hematopoietic stem and progenitor cells (CD34+) and culture them under conditions that promote megakaryocyte-erythroid differentiation. Using a CRISPR-Cas9 or shRNA-based system to suppress [AMHR2](/details-gene/269) expression, researchers could then treat the cultures with recombinant AMH. The subsequent effects on cell fate decisions could be quantified using colony-forming unit assays (CFU-E, CFU-Mk) and flow cytometric analysis of lineage-specific markers (e.g., CD41, CD235a) to determine if [AMHR2](/details-gene/269) signaling influences progenitor cell expansion or commitment to a specific lineage. From a therapeutic standpoint, [AMHR2](/details-gene/269) holds potential, particularly in oncology. Its function as a receptor for a growth-inhibitory hormone makes it a candidate for therapies based on **activation**. For [AMHR2](/details-gene/269)-expressing tumors, such as certain ovarian cancers, treatment with recombinant AMH or a small molecule agonist could represent a targeted biological therapy to induce cell cycle arrest or apoptosis. This approach leverages the natural inhibitory function of the pathway and could offer a specific treatment modality for a defined patient population.

Genular Protein ID: 193977816

Symbol: AMHR2_HUMAN

Name: Anti-Muellerian hormone type-2 receptor

UniProtKB Accession Codes:

Q16671 A0AVE1 B9EGB7 E9PGD2 F8W1D2 Q13762 Q647K2

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 ChEBI 14 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 3 EMBL 19 Ensembl 3 ExpressionAtlas 1 GO 18 Gene3D 2 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 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 3 Rhea 6 SIGNOR 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 7493017

Title: Insensitivity to anti-Muellerian hormone due to a mutation in the human anti-Muellerian hormone receptor.

PubMed ID: 7493017

DOI: 10.1038/ng1295-382

PubMed ID: 7488027

Title: Structure and chromosomal localization of the human anti-Muellerian hormone type II receptor gene.

PubMed ID: 7488027

DOI: 10.1006/bbrc.1995.2567

PubMed ID: 10589763

Title: Human ovarian cancer, cell lines, and primary ascites cells express the human Muellerian inhibiting substance (MIS) type II receptor, bind, and are responsive to MIS.

PubMed ID: 10589763

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

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: 17911401

Title: Activin receptor-like kinase-2 inhibits activin signaling by blocking the binding of activin to its type II receptor.

PubMed ID: 17911401

DOI: 10.1677/joe-07-0281

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: 11549681

Title: Autosomal recessive segregation of a truncating mutation of anti-Muellerian type II receptor in a family affected by the persistent Muellerian duct syndrome contrasts with its dominant negative activity in vitro.

PubMed ID: 11549681

DOI: 10.1210/jcem.86.9.7839

Sequence Information:

  • Length: 573
  • Mass: 62750
  • Checksum: 1347C10C2942FDBA
  • Sequence:
    • MLGSLGLWAL LPTAVEAPPN RRTCVFFEAP GVRGSTKTLG ELLDTGTELP RAIRCLYSRC 
CFGIWNLTQD RAQVEMQGCR DSDEPGCESL HCDPSPRAHP SPGSTLFTCS CGTDFCNANY 
SHLPPPGSPG TPGSQGPQAA PGESIWMALV LLGLFLLLLL LLGSIILALL QRKNYRVRGE 
PVPEPRPDSG RDWSVELQEL PELCFSQVIR EGGHAVVWAG QLQGKLVAIK AFPPRSVAQF 
QAERALYELP GLQHDHIVRF ITASRGGPGR LLSGPLLVLE LHPKGSLCHY LTQYTSDWGS 
SLRMALSLAQ GLAFLHEERW QNGQYKPGIA HRDLSSQNVL IREDGSCAIG DLGLALVLPG 
LTQPPAWTPT QPQGPAAIME AGTQRYMAPE LLDKTLDLQD WGMALRRADI YSLALLLWEI 
LSRCPDLRPD SSPPPFQLAY EAELGNTPTS DELWALAVQE RRRPYIPSTW RCFATDPDGL 
RELLEDCWDA DPEARLTAEC VQQRLAALAH PQESHPFPES CPRGCPPLCP EDCTSIPAPT 
ILPCRPQRSA CHFSVQQGPC SRNPQPACTL SPV