RAB12
protein-codingRAB12, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases
Gene summary
Enables GDP binding activity. Predicted to be involved in several processes, including endocytic recycling; endosome to lysosome transport; and positive regulation of macroautophagy. Predicted to act upstream of or within cellular response to type II interferon. Predicted to be located in lysosome; phagocytic vesicle; and recycling endosome membrane. Predicted to be active in cytoplasmic vesicle and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.9 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 RAB12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001025300.3. 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 | 2 | 2 | ||||
| missense | 27 | 27 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 29 | 2 | 0 | 31 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001020471.3 | 6 | MANE Select | |
| Ensembl | ENSP00000497886.1 | 6 | MANE Select | |
| Ensembl | ENSP00000797837.1 | 3 | Standard | |
| Ensembl | ENSP00000815159.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
- Metabolism of proteins
- Rab regulation of trafficking
Biological Process
- intracellular protein transport
- endoplasmic reticulum to Golgi vesicle-mediated transport
- autophagy
- endosome to lysosome transport
- positive regulation of macroautophagy
Molecular Function
- GTPase activity
- protein binding
- GTP binding
- GDP binding
Cellular Component
- Golgi membrane
- lysosome
- lysosomal membrane
- autophagosome
- endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000329286
- Coding exons
- 6
- Length
- 29937
- Individuals with no LoFs
- 124754
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 25
- Defined
- 124779
- p
- 0.000100
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.69 | 70 | 123 | 0.570 | 0.00000598 | 1595 |
| Missense (PolyPhen) | 12 | 35.342 | 0.33954 | 450 | ||
| Synonymous | -1.11 | 57 | 47.3 | 1.21 | 0.00000249 | 458 |
| Loss of Function | 1.95 | 4 | 10.9 | 0.365 | 4.60e-7 | 149 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00080 | 0.00078 | rare |
| Latino/Admixed American | 0.00030 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00018 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000028 | 0.000018 | rare |
| South Asian | 0.000074 | 0.000033 | rare |
| 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 set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab may play a role in protein transport from recycling endosomes to lysosomes regulating, for instance, the degradation of the transferrin receptor. Involved in autophagy (By similarity). {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.106
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.508
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |