RAB13
protein-codingRAB13, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases
Gene summary
This gene is a member of the Rab family of small G proteins and plays a role in regulating membrane trafficking between trans-Golgi network (TGN) and recycling endosomes (RE). The encoded protein is involved in the assembly of tight junctions, which are components of the apical junctional complex (AJC) of epithelial cells. The AJC plays a role in forming a barrier between luminal contents and the underlying tissue. Additional functions associated with the protein include endocytic recycling of occludin, regulation of epithelial cell scattering, neuronal regeneration and regulation of neurite outgrowth. Alternately spliced transcript variants have been observed for this gene. A pseudogene associated with this gene is located on chromosome 12. [provided by RefSeq, Jan 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.7 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 RAB13 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002870.5. 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 | ||||
| missense | 21 | 21 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 27 | 1 | 0 | 28 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002861.1 | 8 | MANE Select | |
| Ensembl | ENSP00000357564.3 | 8 | MANE Select | |
| RefSeq | NP_001258967.1 | 6 | Standard | |
| Ensembl | ENSP00000480103.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rab13 | Danio rerio | Structure: dorsal longitudinal anastomotic vessel Quality: aplastic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tight junction - Homo sapiens (human)
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
- Metabolism of proteins
Biological Process
- intracellular protein transport
- protein kinase A signaling
- endosomal transport
- cortical actin cytoskeleton organization
- neuron projection development
Molecular Function
- GTPase activity
- protein binding
- GTP binding
Cellular Component
- Golgi apparatus
- trans-Golgi network
- cytosol
- plasma membrane
- bicellular tight junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368575
- Coding exons
- 8
- Length
- 4708
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125748
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.07 | 86 | 119 | 0.723 | 0.00000677 | 1342 |
| Missense (PolyPhen) | 38 | 63.778 | 0.59582 | 704 | ||
| Synonymous | 0.575 | 41 | 46.0 | 0.892 | 0.00000269 | 370 |
| Loss of Function | 2.20 | 5 | 13.8 | 0.362 | 7.40e-7 | 152 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0.000066 | 0.000065 | 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 sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in endocytic recycling and regulates the transport to the plasma membrane of transmembrane proteins like the tight junction protein OCLN/occludin. Thereby, it regulates the assembly and the activity of tight junctions. Moreover, it may also regulate tight junction assembly by activating the PKA signaling pathway and by reorganizing the actin cytoskeleton through the activation of the downstream effectors PRKACA and MICALL2 respectively. Through its role in tight junction assembly, may play a role in the establishment of Sertoli cell barrier. Plays also a role in angiogenesis through regulation of endothelial cells chemotaxis. Also involved in neurite outgrowth. Has also been proposed to play a role in post-Golgi membrane trafficking from the TGN to the recycling endosome. Finally, it has been involved in insulin- induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore may play a role in glucose homeostasis. {ECO:0000269|PubMed:12058051, ECO:0000269|PubMed:15096524, ECO:0000269|PubMed:15528189, ECO:0000269|PubMed:16525024, ECO:0000269|PubMed:18779367, ECO:0000269|PubMed:20008558}.;
Recessive Scores
- pRec
- 0.149
Intolerance Scores
- LoFtool
- 0.353
- RVIS EVS
- 0.22
- RVIS percentile EVS
- 67.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.942
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |