RAB21
protein-codingRAB21, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases
Gene summary
This gene belongs to the Rab family of monomeric GTPases, which are involved in the control of cellular membrane traffic. The encoded protein plays a role in the targeted trafficking of integrins via its association with integrin alpha tails. As a consequence, the encoded protein is involved in the regulation of cell adhesion and migration. Expression of this gene is associated with a poor prognosis for glioma patients. This gene is downregulated by the tumor suppressor miR-200b, and miRNA-200b is itself downregulated in glioma tissues. [provided by RefSeq, Nov 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.4 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 RAB21 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014999.4. 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 | 19 | 19 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 19 | 1 | 1 | 21 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055814.1 | 7 | MANE Select | |
| Ensembl | ENSP00000261263.3 | 7 | MANE Select | |
| Ensembl | ENSP00000637077.1 | 7 | Standard | |
| Ensembl | ENSP00000637077.1 | 7 | 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
- anterograde axonal transport
- regulation of exocytosis
- regulation of axon extension
- Rab protein signal transduction
Molecular Function
- GTPase activity
- protein binding
- GTP binding
- GDP binding
Cellular Component
- endosome
- early endosome
- endoplasmic reticulum membrane
- trans-Golgi network
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261263
- Coding exons
- 7
- Length
- 36046
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125747
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.25 | 72 | 109 | 0.662 | 0.00000529 | 1440 |
| Missense (PolyPhen) | 10 | 36.826 | 0.27154 | 476 | ||
| Synonymous | 1.11 | 30 | 38.8 | 0.773 | 0.00000197 | 420 |
| Loss of Function | 2.42 | 4 | 13.6 | 0.293 | 7.63e-7 | 169 |
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 | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates integrin internalization and recycling, but does not influence the traffic of endosomally translocated receptors in general. As a result, may regulate cell adhesion and migration (By similarity). During the mitosis of adherent cells, controls the endosomal trafficking of integrins which is required for the successful completion of cytokinesis. Involved in neurite growth (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q6AXT5, ECO:0000269|PubMed:18804435}.;
Recessive Scores
- pRec
- 0.125
Intolerance Scores
- LoFtool
- 0.395
- RVIS EVS
- 0.33
- RVIS percentile EVS
- 73.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.581
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |