ARRDC4
protein-codingarrestin domain containing 4, the group of Alpha arrestins
Gene summary
Enables ubiquitin-like ligase-substrate adaptor activity. Involved in positive regulation of interferon-beta production and protein K63-linked ubiquitination. Acts upstream of or within positive regulation of ubiquitin-protein transferase activity. Located in endosome and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.1 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 ARRDC4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_183376.3. 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 | 66 | 1 | 1 | 68 | ||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 67 | 1 | 1 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_899232.2 | 8 | MANE Select | |
| Ensembl | ENSP00000268042.6 | 8 | MANE Select | |
| Ensembl | ENSP00000555094.1 | 8 | Standard | |
| Ensembl | ENSP00000555095.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein transport
- protein ubiquitination
- positive regulation of ubiquitin-protein transferase activity
- extracellular vesicle biogenesis
Molecular Function
- protein binding
- protein binding, bridging involved in substrate recognition for ubiquitination
Cellular Component
- endosome
- early endosome
- plasma membrane
- extracellular vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000268042
- Coding exons
- 8
- Length
- 54285
- Individuals with no LoFs
- 125687
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 60
- Defined
- 125747
- p
- 0.000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.617 | 177 | 202 | 0.878 | 0.0000104 | 2625 |
| Missense (PolyPhen) | 60 | 87.835 | 0.6831 | 1011 | ||
| Synonymous | -0.593 | 84 | 77.4 | 1.09 | 0.00000423 | 839 |
| Loss of Function | 1.15 | 13 | 18.3 | 0.709 | 0.00000102 | 230 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0017 | 0.0017 | notable |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.000067 | 0.000065 | rare |
| Other | 0.00065 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as an adapter recruiting ubiquitin-protein ligases to their specific substrates (By similarity). Plays a role in endocytosis of activated G protein-coupled receptors (GPCRs) (Probable). Through an ubiquitination-dependent mechanism plays also a role in the incorporation of SLC11A2 into extracellular vesicles (By similarity). May play a role in glucose uptake (PubMed:19605364). {ECO:0000250|UniProtKB:A0A0B4J1F4, ECO:0000269|PubMed:19605364, ECO:0000305}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.717
- RVIS EVS
- 0.46
- RVIS percentile EVS
- 78.59
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.977
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |