RAB6A
protein-codingRAB6A, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases
Gene summary
This gene encodes a member of the RAB family, which belongs to the small GTPase superfamily. GTPases of the RAB family bind to various effectors to regulate the targeting and fusion of transport carriers to acceptor compartments. This protein is located at the Golgi apparatus, which regulates trafficking in both a retrograde (from early endosomes and Golgi to the endoplasmic reticulum) and an anterograde (from the Golgi to the plasma membrane) directions. Myosin II is an effector of this protein in these processes. This protein is also involved in assembly of human cytomegalovirus (HCMV) by interacting with the cellular protein Bicaudal D1, which interacts with the HCMV virion tegument protein, pp150. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
- RAB6
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~85.5 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 RAB6A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198896.2. 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 | 1 | 2 | |||
| missense | 6 | 1 | 7 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 7 | 1 | 1 | 9 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_942599.1 | 8 | MANE Select | |
| Ensembl | ENSP00000336850.3 | 8 | MANE Select | |
| RefSeq | NP_001230647.1 | 5 | Standard | |
| RefSeq | NP_001230648.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in leukocytes - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- Neutrophil degranulation
Biological Process
- intracellular protein transport
- retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
- intra-Golgi vesicle-mediated transport
- viral process
- peptidyl-cysteine methylation
Molecular Function
- GTPase activity
- protein binding
- GTP binding
- protein domain specific binding
- myosin V binding
Cellular Component
- Golgi membrane
- endoplasmic reticulum membrane
- Golgi apparatus
- trans-Golgi network
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000310653
- Coding exons
- 8
- Length
- 85500
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125743
- p
- 0.00000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.50 | 41 | 117 | 0.350 | 0.00000613 | 1376 |
| Missense (PolyPhen) | 7 | 29.634 | 0.23622 | 381 | ||
| Synonymous | 0.891 | 31 | 38.0 | 0.816 | 0.00000191 | 373 |
| Loss of Function | 3.22 | 1 | 14.0 | 0.0716 | 7.23e-7 | 159 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protein transport. Regulator of membrane traffic from the Golgi apparatus towards the endoplasmic reticulum (ER). Has a low GTPase activity. Involved in COPI-independent retrograde transport from the Golgi to the ER (PubMed:25962623). {ECO:0000269|PubMed:25962623}.;
Intolerance Scores
- LoFtool
- 0.286
- RVIS EVS
- 0.1
- RVIS percentile EVS
- 61.28
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.935
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |