ARFGAP1
protein-codingADP ribosylation factor GTPase activating protein 1, the group of ArfGAPs|MicroRNA protein coding host genes
Gene summary
The protein encoded by this gene is a GTPase-activating protein, which associates with the Golgi apparatus and which interacts with ADP-ribosylation factor 1. The encoded protein promotes hydrolysis of ADP-ribosylation factor 1-bound GTP and is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. The activity of this protein is stimulated by phosphoinosides and inhibited by phosphatidylcholine. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
- ARF1GAP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.0 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 ARFGAP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018209.4. 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 | 3 | 2 | 5 | |||
| missense | 72 | 6 | 78 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 80 | 8 | 0 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060679.1 | 12 | MANE Select | |
| Ensembl | ENSP00000359306.4 | 12 | MANE Select | |
| RefSeq | NP_001268411.1 | 13 | Standard | |
| RefSeq | NP_001268412.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- XBP1(S) activates chaperone genes
- Vesicle-mediated transport
- rho cell motility signaling pathway
- t cell receptor signaling pathway
Biological Process
- endoplasmic reticulum to Golgi vesicle-mediated transport
- retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
- protein transport
- regulation of endocytosis
- regulation of ARF protein signal transduction
Molecular Function
- GTPase activator activity
- protein binding
- metal ion binding
Cellular Component
- Golgi membrane
- cytosol
- postsynaptic density
- synapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000353546
- Coding exons
- 13
- Length
- 17006
- Individuals with no LoFs
- 125685
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125708
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.423 | 238 | 257 | 0.926 | 0.0000158 | 2736 |
| Missense (PolyPhen) | 65 | 91.782 | 0.7082 | 998 | ||
| Synonymous | -1.82 | 138 | 113 | 1.22 | 0.00000877 | 738 |
| Loss of Function | 3.19 | 10 | 28.3 | 0.353 | 0.00000148 | 281 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00039 | 0.00039 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: GTPase-activating protein (GAP) for the ADP ribosylation factor 1 (ARF1). Involved in membrane trafficking and /or vesicle transport. Promotes hydrolysis of the ARF1-bound GTP and thus, is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles, a prerequisite for vesicle's fusion with target compartment. Probably regulates ARF1-mediated transport via its interaction with the KDELR proteins and TMED2. Overexpression induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, as when ARF1 is deactivated. Its activity is stimulated by phosphoinosides and inhibited by phosphatidylcholine (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.630
- RVIS EVS
- -0.11
- RVIS percentile EVS
- 45.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.637
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |