ARRDC1

protein-coding

arrestin domain containing 1, the group of Alpha arrestins

Gene summary

Enables several functions, including arrestin family protein binding activity; ubiquitin protein ligase binding activity; and ubiquitin-like ligase-substrate adaptor activity. Involved in several processes, including extracellular transport; extracellular vesicle biogenesis; and negative regulation of Notch signaling pathway. Located in cytoplasmic vesicle; extracellular vesicle; and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_152285.4

Inheritance

—

ClinVar variants

U:103B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr9:137,605,685-137,615,360

External References & Databases

Ensembl (ENSG00000197070)

Transcript & Mutation Effects

hg38 • Region Span ~9.7 kb

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GenCC 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 ARRDC1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 101

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152285.4. 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			97 clinvar	6 clinvar		103
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	103	6	0	109

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152285.4	RefSeq	NP_689498.1	8	MANE Select
ENST00000371421.9	Ensembl	ENSP00000360475.4	8	MANE Select
NM_001317968.2	RefSeq	NP_001304897.1	7	Standard
ENST00000419386.1	Ensembl	ENSP00000406833.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ubiquitin-dependent protein catabolic process
extracellular transport
protein transport
protein ubiquitination
negative regulation of Notch signaling pathway

Molecular Function

protein binding
ubiquitin protein ligase binding
identical protein binding
protein binding, bridging involved in substrate recognition for ubiquitination
arrestin family protein binding

Cellular Component

plasma membrane
cytoplasmic vesicle
extracellular exosome
extracellular vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371421
Coding exons: 8
Length: 9707
Individuals with no LoFs: 125686
Homozygous LoFs: 0
Heterozygous LoFs: 59
Defined: 125745
p: 0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.116	267	262	1.02	0.0000162	2752
Missense (PolyPhen)		83	84.242	0.98525		898
Synonymous	-0.913	138	125	1.10	0.00000902	948
Loss of Function	0.997	11	15.2	0.724	6.47e-7	187

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00030	0.00029	rare
South Asian	0.00033	0.00033	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as an adapter recruiting ubiquitin-protein ligases to their specific substrates (PubMed:23886940, PubMed:27462458). Through an ubiquitination-dependent mechanism plays for instance a role in the incorporation of SLC11A2 into extracellular vesicles (PubMed:27462458). More generally, plays a role in the extracellular transport of proteins between cells through the release in the extracellular space of microvesicles (PubMed:22315426). By participating to the ITCH-mediated ubiquitination and subsequent degradation of NOTCH1, negatively regulates the NOTCH signaling pathway (PubMed:23886940). {ECO:0000269|PubMed:22315426, ECO:0000269|PubMed:23886940, ECO:0000269|PubMed:27462458}.;

Intolerance Scores

LoFtool: 0.757
RVIS EVS: 0.11
RVIS percentile EVS: 62.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium