MYH9 (myosin, heavy polypeptide 9, non-muscle)

2003-08-01   Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC
LOCATION
22q12.3
LOCUSID
ALIAS
BDPLT6,DFNA17,EPSTS,FTNS,MATINS,MHA,NMHC-II-A,NMMHC-IIA,NMMHCA
FUSION GENES

DNA/RNA

Description

spans 107 kb; 40 exons

Transcription

alternate splicing; transcripts of 4.4, 5.3 and 5.9 kb

Proteins

Description

1960 amino acids; 227 kDa (and 1752 aa, 202 kDa, and 1486 aa, 172 kDa; globular head in N-term and a coiled-coil tail in C-term; actin binding site and light chains binding site are present in the globular domain. Myosin forms hexamers with 2 heavy chains, 2 essential (alkali) light chains, and 2 regulatory light chains

Expression

in platelets; upregulated during granulocyte differentiation (see below); also expressed in thymus, spleen, kidney, intestine, cochlea ....

Function

binds actin; protein of the cytoskeleton; role in cell shape and motility, and in cell division

Mutations

Germinal

in autosomal dominant giant-platelet disorders

Somatic

in non Hodgkin lymphomas

Implicated in

Disease
The autosomal dominant giant-platelet disorders, May-Hegglin anomaly (MHA), Fechtner syndrome (FTNS), and Sebastian syndrome (SBS), which share a triad of thrombocytopenia, large platelets (macrothrombocytopenia (MTCP)) and characteristic leukocyte inclusions (Dohle-like bodies), Epstein syndrome, which associates additional Alport-like clinical features (inherited sensorineural deafness, cataracts, nephritis), and MTCP without leukocyte inclusions, as well as a nonsyndromic hereditary hearing impairment are all caused by (germinal) mutations in MYH9. These disorders appear to represent a class of allelic disorders with variable phenotypic diversity. No clear no genotype-phenotype correlation was identified
Disease
ALCL are high grade non Hodgkin lymphomas; ALK+ ALCL are ALCL where ALK is involved in a fusion gene; ALK+ ALCL represent 50 to 60 % of ALCL cases (they are CD30+, ALK+;); belong to the "cytoplasmic ALK+" subset.
Prognosis
Althouth presenting as a high grade tumour, a 80% five yr survival is associated with this anomaly
Hybrid gene
5 MYH9 - 3 ALK
Fusion protein
NH2 MYH9 - COOH ALK

Bibliography

Pubmed IDLast YearTitleAuthors
109732602000Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly.Kelley MJ et al
117763862001Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions.Kunishima S et al
110238102000Human nonsyndromic hereditary deafness DFNA17 is due to a mutation in nonmuscle myosin MYH9.Lalwani AK et al
128001562003Non-muscle myosin heavy chain (MYH9): a new partner fused to ALK in anaplastic large cell lymphoma.Lamant L et al
122177982002Five (un)easy pieces: the MYH9-related giant platelet syndromes.Martignetti J et al
109732592000Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium.Seri M et al
127923062003MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness.Seri M et al

Other Information

Locus ID:

NCBI: 4627
MIM: 160775
HGNC: 7579
Ensembl: ENSG00000100345

Variants:

dbSNP: 4627
ClinVar: 4627
TCGA: ENSG00000100345
COSMIC: MYH9

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000100345ENST00000216181P35579
ENSG00000100345ENST00000216181A0A024R1N1
ENSG00000100345ENST00000401701Q5BKV1
ENSG00000100345ENST00000456729B1AH99

Expression (GTEx)

0
500
1000
1500
2000

Pathways

PathwaySourceExternal ID
Tight junctionKEGGko04530
Regulation of actin cytoskeletonKEGGko04810
Tight junctionKEGGhsa04530
Regulation of actin cytoskeletonKEGGhsa04810
Salmonella infectionKEGGko05132
Salmonella infectionKEGGhsa05132
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Fcgamma receptor (FCGR) dependent phagocytosisREACTOMER-HSA-2029480
Regulation of actin dynamics for phagocytic cup formationREACTOMER-HSA-2029482
Signal TransductionREACTOMER-HSA-162582
Signaling by Rho GTPasesREACTOMER-HSA-194315
RHO GTPase EffectorsREACTOMER-HSA-195258
RHO GTPases Activate ROCKsREACTOMER-HSA-5627117
RHO GTPases activate PAKsREACTOMER-HSA-5627123
RHO GTPases activate PKNsREACTOMER-HSA-5625740
RHO GTPases activate CITREACTOMER-HSA-5625900
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
Semaphorin interactionsREACTOMER-HSA-373755
Sema4D in semaphorin signalingREACTOMER-HSA-400685
Sema4D induced cell migration and growth-cone collapseREACTOMER-HSA-416572
EPH-Ephrin signalingREACTOMER-HSA-2682334
EPHA-mediated growth cone collapseREACTOMER-HSA-3928663

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
187948542008MYH9 is associated with nondiabetic end-stage renal disease in African Americans.318
187948562008MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis.316
187948562008MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis.316
206351882010Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene.274
173102412007Myosin IIA regulates cell motility and actomyosin-microtubule crosstalk.228
183322202008Inhibition of "self" engulfment through deactivation of myosin-II at the phagocytic synapse between human cells.136
231282392012Crawling from soft to stiff matrix polarizes the cytoskeleton and phosphoregulates myosin-II heavy chain.102
251272162014Matrix elasticity regulates lamin-A,C phosphorylation and turnover with feedback to actomyosin.98
209447482010Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1.97
244364212014Direct in vivo RNAi screen unveils myosin IIa as a tumor suppressor of squamous cell carcinomas.93

Citation

Jean-Loup Huret

MYH9 (myosin, heavy polypeptide 9, non-muscle)

Atlas Genet Cytogenet Oncol Haematol. 2003-08-01

Online version: http://atlasgeneticsoncology.org/gene/481/myh9-(myosin-heavy-polypeptide-9-non-muscle)