RAB1A
protein-codingRAB1A, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases
Gene summary
This gene encodes a member of the Ras superfamily of GTPases. Members of the gene family cycle between inactive GDP-bound and active GTP-bound forms. This small GTPase controls vesicle traffic from the endoplasmic reticulum to the Golgi apparatus. Multiple alternatively spliced transcript variants have been identified for this gene which encode different protein isoforms. [provided by RefSeq, Oct 2008]
- RAB1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~59.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0100038
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RAB1A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004161.5. 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 | 0 | |||||
| missense | 12 | 1 | 13 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 12 | 0 | 1 | 14 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004152.1 | 6 | MANE Select | |
| Ensembl | ENSP00000387286.3 | 6 | MANE Select | |
| RefSeq | NP_056358.1 | 4 | Standard | |
| Ensembl | ENSP00000381540.3 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Legionellosis - Homo sapiens (human)
- Bisphosphonate Pathway, Pharmacodynamics
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
Biological Process
- autophagosome assembly
- intracellular protein transport
- endoplasmic reticulum to Golgi vesicle-mediated transport
- retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
- endocytosis
Molecular Function
- GTPase activity
- protein binding
- GTP binding
- cadherin binding
Cellular Component
- Golgi membrane
- early endosome
- endoplasmic reticulum membrane
- Golgi apparatus
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000409784
- Coding exons
- 6
- Length
- 59406
- Individuals with no LoFs
- 121784
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 121787
- p
- 0.0000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.31 | 37 | 103 | 0.360 | 0.00000524 | 1340 |
| Missense (PolyPhen) | 5 | 37.844 | 0.13212 | 547 | ||
| Synonymous | -0.794 | 43 | 36.9 | 1.17 | 0.00000203 | 378 |
| Loss of Function | 2.65 | 1 | 10.1 | 0.0992 | 5.07e-7 | 138 |
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 | 0.000059 | 0.000057 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000019 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB1A regulates vesicular protein transport from the endoplasmic reticulum (ER) to the Golgi compartment and on to the cell surface, and plays a role in IL-8 and growth hormone secretion. Regulates the level of CASR present at the cell membrane. Plays a role in cell adhesion and cell migration, via its role in protein trafficking. Plays a role in autophagosome assembly and cellular defense reactions against pathogenic bacteria. Plays a role in microtubule-dependent protein transport by early endosomes and in anterograde melanosome transport. {ECO:0000269|PubMed:20639577, ECO:0000269|PubMed:20861236, ECO:0000269|PubMed:21303926, ECO:0000269|PubMed:22939626}.;
Recessive Scores
- pRec
- 0.248
Intolerance Scores
- RVIS EVS
- 0.3
- RVIS percentile EVS
- 71.81
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.689
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |