ARL1
protein-codingADP ribosylation factor like GTPase 1, the group of ARF GTPase family
Gene summary
The protein encoded by this gene belongs to the ARL (ADP-ribosylation factor-like) family of proteins, which are structurally related to ADP-ribosylation factors (ARFs). ARFs, described as activators of cholera toxin (CT) ADP-ribosyltransferase activity, regulate intracellular vesicular membrane trafficking, and stimulate a phospholipase D (PLD) isoform. Although, ARL proteins were initially thought not to activate CT or PLD, later work showed that they are weak stimulators of PLD and CT in a phospholipid dependent manner. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.7 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 ARL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001177.6. 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 | 6 | 6 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 7 | 0 | 0 | 7 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001168.1 | 6 | MANE Select | |
| Ensembl | ENSP00000261636.8 | 6 | MANE Select | |
| RefSeq | NP_001287997.1 | 5 | Standard | |
| Ensembl | ENSP00000441808.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Retrograde transport at the Trans-Golgi-Network
- Intra-Golgi and retrograde Golgi-to-ER traffic
Biological Process
- intracellular protein transport
- Golgi organization
- toxin metabolic process
- vesicle-mediated transport
- activation of phospholipase D activity
Molecular Function
- GTPase activity
- GTP binding
- enzyme activator activity
- protein domain specific binding
- metal ion binding
Cellular Component
- cytoplasm
- Golgi apparatus
- trans-Golgi network
- cytosol
- trans-Golgi network membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261636
- Coding exons
- 6
- Length
- 14701
- Individuals with no LoFs
- 124630
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 124636
- p
- 0.0000241
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.18 | 33 | 91.8 | 0.360 | 0.00000455 | 1158 |
| Missense (PolyPhen) | 5 | 37.232 | 0.13429 | 464 | ||
| Synonymous | 0.929 | 26 | 32.8 | 0.794 | 0.00000178 | 336 |
| Loss of Function | 2.34 | 4 | 13.1 | 0.304 | 8.13e-7 | 149 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: GTP-binding protein that has very low efficiency as allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Can activate phospholipase D with very low efficiency. Important for normal function of the Golgi apparatus. {ECO:0000269|PubMed:9624189}.;
Recessive Scores
- pRec
- 0.285
Intolerance Scores
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |