MYH9

myosin heavy chain 9, the group of Myosin heavy chains, class II|MicroRNA protein coding host genes

Basic information

Region (hg38): 22:36281280-36388010

Previous symbols: [ "DFNA17" ]

Links

ENSG00000100345 ∙ NCBI:4627 ∙ OMIM:160775 ∙ HGNC:7579 ∙ Uniprot:P35579 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (Definitive), mode of inheritance: AD
• May-Hegglin anomaly (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (Supportive), mode of inheritance: AD
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 17 (Strong), mode of inheritance: AD
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss	AD	Hematologic	In active hemorrhage, DDAVP may decrease bleeding time; otherwise, platelet transfusion is necessary; Precautions related to bleeding risk may be beneficial	Audiologic/Otolaryngologic; Hematologic; Ophthalmologic; Renal	13940543; 1449176; 5011389; 2981587; 3232700; 2851314; 2176899; 1396928; 1319112; 8280620; 9390828; 9915977;10973260; 10973259; 11590545; 12533692; 12621333; 12792306; 15613099; 15667538; 16969870; 17241369; 18059020; 18284620; 19208103; 19285578; 19450438; 19860543; 20002731; 20174760; 20221761; 20301740; 20601875; 22541678; 23123319

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYH9 gene.

• Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (11 variants)
• not provided (10 variants)
• MYH9-related disorder (7 variants)
• Autosomal dominant nonsyndromic hearing loss 17 (2 variants)
• Thrombocytopenia;Abnormal bleeding (1 variants)
• Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss;Autosomal dominant nonsyndromic hearing loss 17 (1 variants)
• Abnormal bleeding;Thrombocytopenia (1 variants)
• Autosomal dominant nonsyndromic hearing loss 17;Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (1 variants)
• Rare genetic deafness (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYH9 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			14	243	40	297
missense	11	26	332	64	20	453
nonsense	1		3			4
start loss						0
frameshift	4	8	2			14
inframe indel			13			13
splice donor/acceptor (+/-2bp)	1		3			4
splice region			26	39	6	71
non coding			27	196	131	354
Total	17	34	394	503	191

Highest pathogenic variant AF is 0.00000658

Variants in MYH9

This is a list of pathogenic ClinVar variants found in the MYH9 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-36281338-T-C		Autosomal dominant nonsyndromic hearing loss 17 • MYH9-related disorder	Uncertain significance (Jan 13, 2018)
22-36281339-G-A		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Benign/Likely benign (May 01, 2023)
22-36281354-G-A		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Benign (Jan 12, 2018)
22-36281464-T-A		Autosomal dominant nonsyndromic hearing loss 17 • MYH9-related disorder	Uncertain significance (Jan 13, 2018)
22-36281475-T-C		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Uncertain significance (Jan 13, 2018)
22-36281507-TA-T		Nonsyndromic Hearing Loss, Dominant • MYH9-related disorder	Benign (Jun 14, 2016)
22-36281569-T-A		Autosomal dominant nonsyndromic hearing loss 17 • MYH9-related disorder	Uncertain significance (Jan 13, 2018)
22-36281642-G-C		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Uncertain significance (Jan 12, 2018)
22-36281690-T-C		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Uncertain significance (Jan 13, 2018)
22-36281693-T-C		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Uncertain significance (Jan 13, 2018)
22-36281762-C-A		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Benign (Jan 13, 2018)
22-36281866-A-C		Autosomal dominant nonsyndromic hearing loss 17 • MYH9-related disorder	Uncertain significance (Jan 13, 2018)
22-36281868-A-G		Autosomal dominant nonsyndromic hearing loss 17 • MYH9-related disorder	Benign (Jan 13, 2018)
22-36281920-T-C		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Uncertain significance (Jan 13, 2018)
22-36281936-G-A		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Benign (Oct 29, 2020)
22-36281982-G-A		Autosomal dominant nonsyndromic hearing loss 17 • MYH9-related disorder	Benign/Likely benign (May 14, 2021)
22-36282012-A-G		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Uncertain significance (Jan 13, 2018)
22-36282023-G-C		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Uncertain significance (Jan 13, 2018)
22-36282029-G-A		Autosomal dominant nonsyndromic hearing loss 17 • MYH9-related disorder	Uncertain significance (Jan 13, 2018)
22-36282072-C-T		Autosomal dominant nonsyndromic hearing loss 17 • MYH9-related disorder	Benign (May 13, 2021)
22-36282079-C-T			Likely benign (Sep 27, 2021)
22-36282129-C-T		MYH9-related disorder • Autosomal dominant nonsyndromic hearing loss 17	Uncertain significance (Jan 12, 2018)
22-36282194-G-A		Autosomal dominant nonsyndromic hearing loss 17 • MYH9-related disorder	Conflicting classifications of pathogenicity (Apr 01, 2022)
22-36282339-G-A		Autosomal dominant nonsyndromic hearing loss 17 • MYH9-related disorder	Benign/Likely benign (Jan 13, 2018)
22-36282343-G-A		Autosomal dominant nonsyndromic hearing loss 17 • MYH9-related disorder	Benign/Likely benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYH9	protein_coding	protein_coding	ENST00000216181	40	106737

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.44e-14	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.47	820	1.15e+3	0.712	0.0000835	12926
Missense in Polyphen		236	460.87	0.51207		5059
Synonymous	-3.16	594	504	1.18	0.0000382	3640
Loss of Function	9.11	4	104	0.0383	0.00000540	1253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000441	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. During cell spreading, plays an important role in cytoskeleton reorganization, focal contacts formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10. {ECO:0000269|PubMed:20052411}.
• Disease: DISEASE: Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (MATINS) [MIM:155100]: An autosomal dominant disorder characterized by thrombocytopenia, giant platelets and Dohle body-like inclusions in peripheral blood leukocytes with variable ultrastructural appearance. Some affected individuals lack leukocyte inclusion bodies on classic staining of peripheral blood smears. Alport syndrome-like features of nephritis, hearing loss, and eye abnormalities are present in some patients. {ECO:0000269|PubMed:10973259, ECO:0000269|PubMed:10973260, ECO:0000269|PubMed:11590545, ECO:0000269|PubMed:11752022, ECO:0000269|PubMed:11776386, ECO:0000269|PubMed:11935325, ECO:0000269|PubMed:12533692, ECO:0000269|PubMed:12621333, ECO:0000269|PubMed:12649151, ECO:0000269|PubMed:12792306, ECO:0000269|PubMed:16969870}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal dominant, 17 (DFNA17) [MIM:603622]: A form of deafness characterized by progressive high frequency hearing impairment and cochleosaccular degeneration. {ECO:0000269|PubMed:11023810}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Subjects with mutations in the motor domain of MYH9 present with severe thrombocytopenia and develop nephritis and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. The clinical course of patients with mutations in the four most frequently affected residues of MYH9 (responsible for 70% of MYH9- related cases) were evaluated. Mutations at residue 1933 do not induce kidney damage or cataracts and cause deafness only in the elderly, those in position 702 result in severe thrombocytopenia and produce nephritis and deafness at a juvenile age, while alterations at residue 1424 or 1841 result in intermediate clinical pictures.; DISEASE: Note=Genetic variations in MYH9 are associated with non- diabetic end stage renal disease (ESRD).
• Pathway: Salmonella infection - Homo sapiens (human);Tight junction - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Primary Focal Segmental Glomerulosclerosis FSGS;VEGFA-VEGFR2 Signaling Pathway;Developmental Biology;Signal Transduction;EPH-Ephrin signaling;EPHA-mediated growth cone collapse;RHO GTPases Activate ROCKs;RHO GTPases activate PAKs;RHO GTPases activate PKNs;RHO GTPases activate CIT;RHO GTPase Effectors;Signaling by Rho GTPases;EGFR1;Sema4D induced cell migration and growth-cone collapse;Sema4D in semaphorin signaling;Semaphorin interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.644

Intolerance Scores

• loftool: 0.00606
• rvis_EVS: -1.99
• rvis_percentile_EVS: 1.75

Haploinsufficiency Scores

• pHI: 0.306
• hipred: Y
• hipred_score: 0.825
• ghis: 0.543

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myh9
• Phenotype: renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; 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); embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: myh9b
• Affected structure: midbrain hindbrain boundary
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: meiotic spindle organization;angiogenesis;in utero embryonic development;establishment of T cell polarity;membrane protein ectodomain proteolysis;phagocytosis, engulfment;integrin-mediated signaling pathway;myoblast fusion;regulation of cell shape;protein transport;actin filament-based movement;platelet formation;monocyte differentiation;actomyosin structure organization;actin cytoskeleton reorganization;cytokinetic process;uropod organization;blood vessel endothelial cell migration;leukocyte migration;establishment of meiotic spindle localization;platelet aggregation;negative regulation of actin filament severing;positive regulation of protein processing in phagocytic vesicle
• Cellular component: stress fiber;ruffle;immunological synapse;uropod;nucleus;cytoplasm;spindle;actomyosin contractile ring;cytosol;plasma membrane;brush border;cell-cell adherens junction;focal adhesion;COP9 signalosome;actin cytoskeleton;membrane;myosin II complex;cell leading edge;neuromuscular junction;cleavage furrow;protein-containing complex;actomyosin;extracellular exosome;myosin II filament
• Molecular function: microfilament motor activity;RNA binding;motor activity;actin binding;integrin binding;protein binding;calmodulin binding;ATP binding;ATPase activity;protein domain specific binding;actin-dependent ATPase activity;protein homodimerization activity;protein membrane anchor;ADP binding;cadherin binding;actin filament binding