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
Phenotypes
GenCC
Source:
- 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
- autosomal dominant nonsyndromic hearing loss 17 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| 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
- not_provided (1241 variants)
- Autosomal_dominant_nonsyndromic_hearing_loss_17 (422 variants)
- Macrothrombocytopenia_and_granulocyte_inclusions_with_or_without_nephritis_or_sensorineural_hearing_loss (399 variants)
- MYH9-related_disorder (328 variants)
- not_specified (261 variants)
- Inborn_genetic_diseases (138 variants)
- Thrombocytopenia (7 variants)
- Macrothrombocytopenia (7 variants)
- Kidney_disorder (7 variants)
- Atypical_hemolytic-uremic_syndrome (6 variants)
- Nonsyndromic_Hearing_Loss,_Dominant (5 variants)
- Nephrotic_syndrome (5 variants)
- Focal_segmental_glomerulosclerosis (4 variants)
- Hearing_impairment (4 variants)
- Abnormal_bleeding (2 variants)
- Meniere_disease (2 variants)
- Proteinuria (2 variants)
- Glomerulonephritis (1 variants)
- Rare_genetic_deafness (1 variants)
- May-Hegglin_Disorder (1 variants)
- Abnormal_platelet_function (1 variants)
- Vitelliform_macular_dystrophy_1 (1 variants)
- Abnormal_platelet_morphology (1 variants)
- Increased_mean_platelet_volume (1 variants)
- Capillary_infantile_hemangioma (1 variants)
- Hearing_loss,_autosomal_recessive (1 variants)
- Type_1_diabetes_mellitus_17 (1 variants)
- Obesity (1 variants)
- Deafness (1 variants)
- Hypertensive_disorder (1 variants)
- Numerous_pigmented_freckles (1 variants)
- Cataract_35 (1 variants)
- Homocystinuria_due_to_methylene_tetrahydrofolate_reductase_deficiency (1 variants)
- Epistaxis (1 variants)
- Abnormal_facial_shape (1 variants)
- Kidney_failure (1 variants)
- Severe_X-linked_myotubular_myopathy (1 variants)
- Abnormal_platelet_shape (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. These statistics are base on transcript: NM_000002473.6. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 22 | 341 | 48 | 411 | ||
| missense | 12 | 41 | 541 | 203 | 22 | 819 |
| nonsense | 7 | |||||
| start loss | 0 | |||||
| frameshift | 16 | |||||
| splice donor/acceptor (+/-2bp) | 7 | |||||
| Total | 20 | 50 | 576 | 544 | 70 |
Highest pathogenic variant AF is 0.00066205394
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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