RAB35
protein-codingRAB35, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases
Gene summary
Enables G protein activity and anion binding activity. Involved in several processes, including endosomal transport; plasma membrane to endosome transport; and protein localization to endosome. Located in several cellular components, including clathrin-coated endocytic vesicle; clathrin-coated pit; and intercellular bridge. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0005439
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RAB35 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006861.7. 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 | 3 | ||||
| missense | 7 | 7 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 8 | 3 | 0 | 11 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006852.1 | 6 | MANE Select | |
| Ensembl | ENSP00000229340.5 | 6 | MANE Select | |
| RefSeq | NP_001161078.1 | 5 | Standard | |
| Ensembl | ENSP00000441883.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Vesicle-mediated transport
- TBC/RABGAPs
- Membrane Trafficking
- Post-translational protein modification
Biological Process
- mitotic cytokinesis
- intracellular protein transport
- protein localization
- endosomal transport
- antigen processing and presentation
Molecular Function
- GTPase activity
- protein binding
- GTP binding
- phosphatidylinositol-4,5-bisphosphate binding
- GDP binding
Cellular Component
- Golgi membrane
- cytosol
- plasma membrane
- clathrin-coated pit
- endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000229340
- Coding exons
- 6
- Length
- 22408
- Individuals with no LoFs
- 124745
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124746
- p
- 0.00000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.36 | 53 | 128 | 0.413 | 0.00000883 | 1335 |
| Missense (PolyPhen) | 12 | 63.522 | 0.18891 | 577 | ||
| Synonymous | 0.0424 | 53 | 53.4 | 0.993 | 0.00000413 | 361 |
| Loss of Function | 3.18 | 0 | 11.8 | 0.00 | 6.73e-7 | 127 |
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 | 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. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth. Together with TBC1D13 may be involved in regulation of insulin-induced glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes. {ECO:0000250|UniProtKB:Q6PHN9, ECO:0000269|PubMed:16950109, ECO:0000269|PubMed:21951725}.;
Intolerance Scores
- LoFtool
- 0.280
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.969
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |