ARL6IP5
protein-codingADP ribosylation factor like GTPase 6 interacting protein 5, the group of YIP family
Gene summary
Expression of this gene is affected by vitamin A. The encoded protein of this gene may be associated with the cytoskeleton. A similar protein in rats may play a role in the regulation of cell differentiation. The rat protein binds and inhibits the cell membrane glutamate transporter EAAC1. The expression of the rat gene is upregulated by retinoic acid, which results in a specific reduction in EAAC1-mediated glutamate transport. [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 ~21.2 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 ARL6IP5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006407.4. 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 | 0 | |||||
| missense | 31 | 2 | 33 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 32 | 2 | 0 | 34 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006398.1 | 3 | MANE Select | |
| Ensembl | ENSP00000273258.3 | 3 | MANE Select | |
| Ensembl | ENSP00000420138.1 | 3 | Standard | |
| Ensembl | ENSP00000420138.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuronal System
- Glutamate Neurotransmitter Release Cycle
- Neurotransmitter release cycle
- Transmission across Chemical Synapses
Biological Process
- negative regulation of L-glutamate import across plasma membrane
- intrinsic apoptotic signaling pathway in response to oxidative stress
- negative regulation of mitochondrial membrane potential
- L-glutamate transmembrane transport
- positive regulation of stress-activated MAPK cascade
Molecular Function
- molecular_function
- protein binding
Cellular Component
- endoplasmic reticulum membrane
- cytoskeleton
- plasma membrane
- membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000273258
- Coding exons
- 3
- Length
- 21123
- Individuals with no LoFs
- 125745
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125748
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.374 | 104 | 115 | 0.902 | 0.00000634 | 1253 |
| Missense (PolyPhen) | 37 | 42.57 | 0.86915 | 510 | ||
| Synonymous | 0.194 | 43 | 44.7 | 0.963 | 0.00000263 | 364 |
| Loss of Function | 1.23 | 2 | 4.96 | 0.403 | 2.09e-7 | 63 |
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 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000065 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates intracellular concentrations of taurine and glutamate. Negatively modulates SLC1A1/EAAC1 glutamate transport activity by decreasing its affinity for glutamate in a PKC activity-dependent manner. May be involved in membrane traffic. {ECO:0000250|UniProtKB:Q8R5J9, ECO:0000250|UniProtKB:Q9ES40}.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.406
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.975
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |