MYO9A
protein-codingmyosin IXA, the group of Myosin heavy chains, class IX
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 non-muscle myosin-9 (MYH9). Unconventional myosins contain the basic domains 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 Bardet-Biedl Syndrome. [provided by RefSeq, Dec 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~296.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0032597
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0032597
Submitter: Genomics England PanelApp
Inheritance Pattern: Unknown
Disease ID:MONDO:0015225
Submitter: ClinGen
Inheritance Pattern: AR
Disease ID:MONDO:0032597
Submitter: Laboratory for Molecular Medicine
This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.
Inheritance Pattern: Unknown
Disease ID:MONDO:0032597
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal; Neurologic
Intervention: Musculoskeletal; Neurologic
Rationale: Individuals have been described as benefiting from medical management (with pyridostigmine and 3,4-DAP)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MYO9A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006901.4. 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 | 3 | 45 | 7 | 55 | ||
| missense | 1 | 368 | 32 | 8 | 409 | |
| nonsense | 1 | 3 | 4 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 7 | 1 | 9 | ||
| Total | 0 | 3 | 382 | 78 | 15 | 478 |
Highest pathogenic variant AF is 0.0000013688542
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008832.2 | 41 | MANE Select | |
| Ensembl | ENSP00000348349.5 | 41 | MANE Select | |
| Ensembl | ENSP00000457945.1 | 19 | Standard | |
| Ensembl | ENSP00000456192.1 | 41 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Rho GTPase cycle
- Signaling by Rho GTPases
Biological Process
- visual perception
- bioluminescence
- cell junction assembly
- intracellular signal transduction
- positive regulation of GTPase activity
Molecular Function
- motor activity
- actin binding
- GTPase activator activity
- protein binding
- ATP binding
Cellular Component
- cytosol
- integral component of membrane
- unconventional myosin complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000356056
- Coding exons
- 41
- Length
- 296287
- Individuals with no LoFs
- 125569
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 178
- Defined
- 125748
- p
- 0.000712
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.74 | 1156 | 1.33e+3 | 0.866 | 0.0000709 | 16794 |
| Missense (PolyPhen) | 278 | 414.05 | 0.67141 | 5226 | ||
| Synonymous | -0.230 | 466 | 460 | 1.01 | 0.0000221 | 4745 |
| Loss of Function | 8.31 | 30 | 134 | 0.224 | 0.00000811 | 1606 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.00041 | 0.00040 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0053 | 0.0052 | notable |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00023 | 0.00023 | rare |
| South Asian | 0.00076 | 0.00072 | rare |
| Other | 0.0011 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Regulates Rho by stimulating it's GTPase activity in neurons, has a role in the regulation of neuronal morphology and function. {ECO:0000250|UniProtKB:Q9Z1N3}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- LoFtool
- 0.0452
- RVIS EVS
- -0.7
- RVIS percentile EVS
- 14.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.831
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |