RAB5A
protein-codingRAB5A, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases
Gene summary
Enables G protein activity; GDP binding activity; and GTP binding activity. Involved in several processes, including amyloid-beta clearance by transcytosis; early endosome to late endosome transport; and regulation of exocytosis. Located in several cellular components, including cytoplasmic side of early endosome membrane; somatodendritic compartment; and terminal bouton. Is active in early endosome membrane. [provided by Alliance of Genome Resources, Jun 2026]
- RAB5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~38.1 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 RAB5A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004162.5. 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 | 1 | 1 | 2 | |||
| missense | 25 | 25 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 30 | 0 | 1 | 31 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004153.2 | 5 | MANE Select | |
| Ensembl | ENSP00000273047.4 | 5 | MANE Select | |
| RefSeq | NP_001278977.1 | 5 | Standard | |
| Ensembl | ENSP00000403533.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rab5ab | Danio rerio | Structure: blastoderm Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Phagosome - Homo sapiens (human)
- Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)
- Vasopressin-regulated water reabsorption - Homo sapiens (human)
- Amoebiasis - Homo sapiens (human)
Biological Process
- phosphatidylinositol biosynthetic process
- intracellular protein transport
- endocytosis
- phagocytosis
- blood coagulation
Molecular Function
- GTPase activity
- protein binding
- GTP binding
- GDP binding
Cellular Component
- ruffle
- cytoplasm
- endosome
- early endosome
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000273047
- Coding exons
- 5
- Length
- 38097
- Individuals with no LoFs
- 125561
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125563
- p
- 0.00000796
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.851 | 92 | 118 | 0.780 | 0.00000591 | 1410 |
| Missense (PolyPhen) | 11 | 35.773 | 0.30749 | 451 | ||
| Synonymous | -0.599 | 48 | 43.0 | 1.12 | 0.00000251 | 407 |
| Loss of Function | 2.63 | 2 | 11.7 | 0.170 | 6.62e-7 | 128 |
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) | 0.000018 | 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. RAB5A is required for the fusion of plasma membranes and early endosomes (PubMed:10818110, PubMed:14617813, PubMed:16410077, PubMed:15378032). Contributes to the regulation of filopodia extension (PubMed:14978216). Required for the exosomal release of SDCBP, CD63, PDCD6IP and syndecan (PubMed:22660413). Regulates maturation of apoptotic cell- containing phagosomes, probably downstream of DYN2 and PIK3C3 (By similarity). {ECO:0000250|UniProtKB:Q9CQD1, ECO:0000269|PubMed:10818110, ECO:0000269|PubMed:14617813, ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:15378032, ECO:0000269|PubMed:16410077, ECO:0000269|PubMed:22660413}.;
Recessive Scores
- pRec
- 0.460
Intolerance Scores
- LoFtool
- 0.314
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.706
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |