MYO1A
protein-codingmyosin IA, the group of Myosin heavy chains, class I
Gene summary
This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional skeletal muscle myosin-1 (MYH1). Unconventional myosins contain the basic domains characteristic of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with autosomal dominant deafness. Alternatively spliced variants have been found for this gene. [provided by RefSeq, Dec 2011]
- MYHL
- DFNA48
- BBMI
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0019497
Submitter: ClinGen
The MYO1A gene has been associated with autosomal dominant nonsyndromic hearing loss using the ClinGen Clinical Validity Framework as of 3/14/17. This association was made using case-level and case-control data. At least 11 variants (missense, in-frame indel, nonsense, frameshift) have been reported in humans. MYO1A was first associated with this disease in humans as early as 2003 (Donaudy et al.). Of the 11 published variants, one is supported by a functional study, and 10 are refuted by high frequency in gnomAD, nonsegregation with disease, or confirmed alternate cause of disease. A knock-out mouse model does not replicate the hearing loss phenotype. In summary, there is convincing evidence refuting the association between MYO1A and autosomal dominant nonsyndromic hearing loss, which significantly outweighs the evidence supporting the association. This classification was approved by the ClinGen Hearing Loss Working Group on 1/16/18.
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic
Intervention: Audiologic/Otolaryngologic
Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development
Comments: The condition has variable age of onset and severity
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MYO1A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005379.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 20 | 2 | 23 | ||
| missense | 1 | 149 | 36 | 3 | 189 | |
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 2 | 5 | |||
| Total | 0 | 1 | 154 | 59 | 6 | 220 |
Highest pathogenic variant AF is 0.000006815298
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005370.1 | 27 | MANE Select | |
| Ensembl | ENSP00000300119.3 | 27 | MANE Select | |
| RefSeq | NP_001242970.1 | 27 | Standard | |
| Ensembl | ENSP00000400991.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- sensory perception of sound
- microvillus assembly
- vesicle localization
Molecular Function
- motor activity
- calmodulin binding
- ATP binding
- actin filament binding
Cellular Component
- cytoplasm
- microvillus
- brush border
- basal plasma membrane
- basolateral plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000442789
- Coding exons
- 27
- Length
- 22682
- Individuals with no LoFs
- 124283
- Homozygous LoFs
- 7
- Heterozygous LoFs
- 1458
- Defined
- 125748
- p
- 0.00584
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.495 | 588 | 555 | 1.06 | 0.0000340 | 6804 |
| Missense (PolyPhen) | 236 | 210.32 | 1.1221 | 2618 | ||
| Synonymous | 0.333 | 216 | 222 | 0.972 | 0.0000130 | 2029 |
| Loss of Function | -0.578 | 66 | 61.1 | 1.08 | 0.00000375 | 710 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0026 | 0.0026 | notable |
| Latino/Admixed American | 0.0074 | 0.0074 | notable |
| Ashkenazi Jewish | 0.0064 | 0.0064 | notable |
| East Asian | 0.0052 | 0.0052 | notable |
| Finnish | 0.0034 | 0.0034 | notable |
| European (Non-Finnish) | 0.0062 | 0.0060 | notable |
| South Asian | 0.0069 | 0.0068 | notable |
| Other | 0.0072 | 0.0070 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in directing the movement of organelles along actin filaments. {ECO:0000305}.;
Recessive Scores
- pRec
- 0.0981
Intolerance Scores
- LoFtool
- 0.187
- RVIS EVS
- 0.79
- RVIS percentile EVS
- 87.31
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.899
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |