ARL2
protein-codingADP ribosylation factor like GTPase 2, the group of ARF GTPase family|MicroRNA protein coding host genes
Gene summary
This gene encodes a small GTP-binding protein of the RAS superfamily which functions as an ADP-ribosylation factor (ARF). The encoded protein is one of a functionally distinct group of ARF-like genes. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0033644
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0033644
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0033644
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ARL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001667.4. 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 | 4 | 4 | ||||
| missense | 25 | 3 | 28 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 25 | 8 | 0 | 33 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001658.2 | 5 | MANE Select | |
| Ensembl | ENSP00000246747.4 | 5 | MANE Select | |
| RefSeq | NP_001186674.1 | 4 | Standard | |
| Ensembl | ENSP00000436021.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of proteins
- Metabolism
- Regulation of insulin secretion
- Protein folding
- Post-chaperonin tubulin folding pathway
Biological Process
- tubulin complex assembly
- centrosome cycle
- positive regulation of cell-substrate adhesion
- regulation of microtubule polymerization
- positive regulation of microtubule polymerization
Molecular Function
- GTPase activity
- GTPase inhibitor activity
- protein binding
- GTP binding
Cellular Component
- nucleus
- nucleolus
- mitochondrial intermembrane space
- mitochondrial matrix
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000246747
- Coding exons
- 5
- Length
- 8072
- Individuals with no LoFs
- 125686
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125694
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.05 | 82 | 113 | 0.723 | 0.00000722 | 1176 |
| Missense (PolyPhen) | 22 | 42.918 | 0.51261 | 507 | ||
| Synonymous | -0.422 | 50 | 46.3 | 1.08 | 0.00000285 | 363 |
| Loss of Function | 1.58 | 4 | 9.15 | 0.437 | 4.75e-7 | 97 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000063 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. Regulates formation of new microtubules and centrosome integrity. Prevents the TBCD-induced microtubule destruction. Participates in association with TBCD, in the disassembly of the apical junction complexes. Antagonizes the effect of TBCD on epithelial cell detachment and tight and adherens junctions disassembly. Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. Component of a regulated secretory pathway involved in Ca(2+)-dependent release of acetylcholine. Required for normal progress through the cell cycle. {ECO:0000269|PubMed:10831612, ECO:0000269|PubMed:16525022, ECO:0000269|PubMed:18234692, ECO:0000269|PubMed:18588884, ECO:0000269|PubMed:20740604}.;
Intolerance Scores
- LoFtool
- 0.423
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.12
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.926
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | High | Medium | High |