MYO18A
protein-codingmyosin XVIIIA, the group of Myosin heavy chains, class XVIII|PDZ domain containing
Gene summary
The protein encoded by this gene can bind GOLPH3, linking the Golgi to the cytoskeleton and influencing Golgi membrane trafficking. The encoded protein is also part of a complex that assembles lamellar actomyosin bundles and may be required for cell migration. [provided by RefSeq, Oct 2016]
- TIAF1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~109.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MYO18A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_078471.4. 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 | 8 | 6 | 12 | 26 | ||
| missense | 320 | 13 | 2 | 335 | ||
| nonsense | 4 | 4 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 339 | 20 | 14 | 373 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_510880.2 | 41 | MANE Select | |
| Ensembl | ENSP00000437073.1 | 41 | MANE Select | |
| RefSeq | NP_001333694.1 | 42 | Standard | |
| RefSeq | NP_001333695.1 | 41 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| myo18aa | Danio rerio | Structure: muscle cell Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Disease
- Signaling by FGFR in disease
- Signaling by cytosolic FGFR1 fusion mutants
- FGFR1 mutant receptor activation
- Signaling by FGFR1 in disease
Biological Process
- DNA metabolic process
- Golgi organization
- cell migration
- actomyosin structure organization
- regulation of macrophage activation
Molecular Function
- DNA binding
- RNA binding
- protein binding
- ATP binding
- ATPase activity
Cellular Component
- Golgi membrane
- endoplasmic reticulum-Golgi intermediate compartment
- trans-Golgi network
- cell surface
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000527372
- Coding exons
- 41
- Length
- 106903
- Individuals with no LoFs
- 124978
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 125011
- p
- 0.000132
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.45 | 1000 | 1.24e+3 | 0.804 | 0.0000830 | 13298 |
| Missense (PolyPhen) | 386 | 524.63 | 0.73576 | 5592 | ||
| Synonymous | 1.89 | 449 | 503 | 0.893 | 0.0000319 | 3973 |
| Loss of Function | 7.49 | 20 | 101 | 0.197 | 0.00000530 | 1170 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00025 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035, PubMed:23345592). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (By similarity). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:16087679, PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (PubMed:27467939). {ECO:0000250|UniProtKB:Q9JMH9, ECO:0000269|PubMed:16087679, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:21123169, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:25965346, ECO:0000269|PubMed:27467939}.;
Recessive Scores
- pRec
- 0.144
Intolerance Scores
- LoFtool
- 0.118
- RVIS EVS
- -1.62
- RVIS percentile EVS
- 2.9
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.854
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |