AMHR2

anti-Mullerian hormone receptor type 2, the group of Type 2 receptor serine/threonine kinases

Basic information

Region (hg38): 12:53423855-53431672

Links

ENSG00000135409 ∙ NCBI:269 ∙ OMIM:600956 ∙ HGNC:465 ∙ Uniprot:Q16671 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• persistent Mullerian duct syndrome (Strong), mode of inheritance: AR
• persistent Mullerian duct syndrome (Definitive), mode of inheritance: AR
• persistent Mullerian duct syndrome (Supportive), mode of inheritance: AR
• persistent Mullerian duct syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Persistent Mullerian duct syndrome, type II	AR	Endocrine; Oncologic; Genitourinary	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)	Endocrine; Genitourinary; Oncologic	8162013; 7493017; 8872466; 8895659; 15878900; 19457927

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AMHR2 gene.

• not provided (8 variants)
• Persistent Mullerian duct syndrome (5 variants)
• Persistent mullerian duct syndrome, type II (1 variants)
• Male pseudohermaphroditism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AMHR2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				10	3	13
missense	3	4	37	6		50
nonsense	5		1			6
start loss	1					1
frameshift	2	1				3
inframe indel	1					1
splice donor/acceptor (+/-2bp)						0
splice region		1		1	1	3
non coding				7	12	19
Total	12	5	38	23	15

Highest pathogenic variant AF is 0.000374

Variants in AMHR2

This is a list of pathogenic ClinVar variants found in the AMHR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-53423937-G-A			Pathogenic (Apr 20, 2018)
12-53423957-G-C		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
12-53423976-TG-T		Persistent Mullerian duct syndrome	Likely pathogenic (Jun 11, 2020)
12-53423997-G-C			Likely benign (Jan 06, 2024)
12-53424132-T-A			Benign (Jun 18, 2021)
12-53424172-C-A			Benign (Oct 16, 2019)
12-53424293-C-G		Genetic non-acquired premature ovarian failure	Likely pathogenic (Oct 01, 2019)
12-53424302-C-T			Pathogenic (Dec 26, 2017)
12-53424335-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 12, 2023)
12-53424354-TGG-T			Pathogenic (Nov 06, 2022)
12-53424365-C-CT			Pathogenic (Mar 20, 2018)
12-53424398-C-T		Persistent Mullerian duct syndrome	Likely pathogenic (Aug 08, 2024)
12-53424399-G-A		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
12-53424408-A-G		not specified	Uncertain significance (Jun 01, 2020)
12-53424409-C-T			Benign (Oct 04, 2023)
12-53424414-G-A		not specified • Inborn genetic diseases	Likely benign (Oct 12, 2021)
12-53424441-C-A		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
12-53424443-C-G			Uncertain significance (Aug 13, 2022)
12-53424449-C-A			Likely benign (Dec 31, 2019)
12-53424450-G-A		Inborn genetic diseases	Likely benign (Aug 08, 2022)
12-53424457-G-A			Likely benign (Jul 01, 2022)
12-53424471-G-A		Persistent mullerian duct syndrome, type II	Pathogenic (Dec 01, 1995)
12-53424488-T-C			Likely benign (Oct 26, 2022)
12-53424503-A-G			Benign (Jun 19, 2021)
12-53424713-C-T			Likely benign (Dec 06, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AMHR2	protein_coding	protein_coding	ENST00000257863	11	7680

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.70e-10	0.895	125683	0	65	125748	0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.394	293	313	0.937	0.0000180	3651
Missense in Polyphen		27	38.006	0.71041		476
Synonymous	1.05	108	123	0.879	0.00000588	1243
Loss of Function	1.85	20	31.1	0.643	0.00000218	280

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00115	0.00115
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.000217	0.000217
Finnish	0.0000995	0.0000924
European (Non-Finnish)	0.000238	0.000237
Middle Eastern	0.000217	0.000217
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for anti-Muellerian hormone.
• Disease: DISEASE: Persistent Muellerian duct syndrome 2 (PMDS2) [MIM:261550]: A form of male pseudohermaphroditism characterized by a failure of Muellerian duct regression in otherwise normal males. {ECO:0000269|PubMed:11549681, ECO:0000269|PubMed:8872466}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: TGF-beta signaling pathway - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);TGF-Core;Signal Transduction;TGF-beta super family signaling pathway canonical;IL-7 signaling;JAK STAT pathway and regulation;EPO signaling;BMP2 signaling TGF-beta MV;VEGF;Signaling by BMP;Signaling by TGF-beta family members;ALK2 signaling events (Consensus)

Recessive Scores

• pRec: 0.158

Intolerance Scores

• loftool: 0.206
• rvis_EVS: -0.93
• rvis_percentile_EVS: 9.47

Haploinsufficiency Scores

• pHI: 0.329
• hipred: N
• hipred_score: 0.234
• ghis: 0.516

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.964

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Amhr2
• Phenotype: renal/urinary system phenotype; immune system phenotype; respiratory system phenotype; embryo phenotype; neoplasm; reproductive system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: Mullerian duct regression;protein phosphorylation;transforming growth factor beta receptor signaling pathway;pattern specification process;sex differentiation;male gonad development;female gonad development;BMP signaling pathway;anti-Mullerian hormone signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;receptor complex
• Molecular function: transforming growth factor beta-activated receptor activity;transforming growth factor beta receptor activity, type II;protein binding;ATP binding;growth factor binding;hormone binding;SMAD binding;metal ion binding;anti-Mullerian hormone receptor activity