ARRDC3

Chr 5

arrestin domain containing 3

Also known as: TLIMP

NCBI Gene: 57561ENSG00000113369UniProt: Q96B67

This gene encodes a member of the arrestin family of proteins, which regulate G protein-mediated signaling. The encoded protein is thought to act as a regulator of breast cancer growth and progression by binding to a phosphorylated form of integrin beta4, a tumor-related antigen, targeting the integrin for internalization and degradation. [provided by RefSeq, Jul 2016]

76
ClinVar variants
27
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ARRDC3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 47 VUS of 76 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.29LOEUF
pLI 0.987
Z-score 3.95
OE 0.09 (0.04–0.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.87Z-score
OE missense 0.65 (0.57–0.75)
150 obs / 229.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.09 (0.04–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.57–0.75)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 2 / 22.0Missense obs/exp: 150 / 229.6Syn Z: 0.28

ClinVar Variant Classifications

76 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic5
VUS47
Likely Benign1
Benign1
22
Pathogenic
5
Likely Pathogenic
47
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
5
0
5
VUS
0
43
4
0
47
Likely Benign
0
0
0
1
1
Benign
0
0
0
1
1
Total04331276

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ARRDC3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ARRDC3 promotes lysosome-mediated YAP degradation to inhibit enterovirus replication.
Huang X et al.·Virol Sin
2025
Single-cell/spatial integration reveals an MES2-like glioblastoma program orchestrated by immune communication and regulatory networks.
Zhang C et al.·Front Immunol
2025
ARRDC3 Inhibits the Progression of Human Prostate Cancer Through ARRDC3-ITGβ4 Pathway.
Zheng Y et al.·Curr Mol Med
2017
Identification of Ferroptosis-related potential biomarkers and immunocyte characteristics in Chronic Thromboembolic Pulmonary Hypertension via bioinformatics analysis.
Lin J et al.·BMC Cardiovasc Disord
2023
Possible association of arrestin domain-containing protein 3 and progression of non-alcoholic fatty liver disease.
Ogawa M et al.·Int J Med Sci
2019
Assessment of the role of copy-number variants in 150 patients with congenital heart defects.
Derwińska K et al.·Med Wieku Rozwoj
2012Cohort
Genetic polymorphisms in androgen receptor-binding sites predict survival in prostate cancer patients receiving androgen-deprivation therapy.
Huang CN et al.·Ann Oncol
2012Cohort
Comprehensive molecular profiling of UV-induced metastatic melanoma in Nme1/Nme2-deficient mice reveals novel markers of survival in human patients.
Leonard MK et al.·Oncogene
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools