ARVCF

Chr 22

ARVCF delta catenin family member

NCBI Gene: 421ENSG00000099889UniProt: O00192

Armadillo Repeat gene deleted in Velo-Cardio-Facial syndrome (ARVCF) is a member of the catenin family. This family plays an important role in the formation of adherens junction complexes, which are thought to facilitate communication between the inside and outside environments of a cell. The ARVCF gene was isolated in the search for the genetic defect responsible for the autosomal dominant Velo-Cardio-Facial syndrome (VCFS), a relatively common human disorder with phenotypic features including cleft palate, conotruncal heart defects and facial dysmorphology. The ARVCF gene encodes a protein containing two motifs, a coiled coil domain in the N-terminus and a 10 armadillo repeat sequence in the midregion. Since these sequences can facilitate protein-protein interactions ARVCF is thought to function in a protein complex. In addition, ARVCF contains a predicted nuclear-targeting sequence suggesting that it may have a function as a nuclear protein. [provided by RefSeq, Jun 2010]

492
ClinVar variants
183
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ARVCF
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
183 Pathogenic / Likely Pathogenic· 229 VUS of 492 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.82LOEUF
pLI 0.000
Z-score 2.44
OE 0.58 (0.42–0.82)
Tolerant

Typical tolerance to LoF variation

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.
-0.27Z-score
OE missense 1.03 (0.97–1.10)
674 obs / 654.6 exp
Tolerant

Tolerant to missense variation

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.0.58 (0.42–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.97–1.10)
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.0.95
0≤1.21.6
LoF obs/exp: 23 / 39.6Missense obs/exp: 674 / 654.6Syn Z: 0.66

ClinVar Variant Classifications

492 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic176
Likely Pathogenic7
VUS229
Likely Benign21
Benign58
Conflicting1
176
Pathogenic
7
Likely Pathogenic
229
VUS
21
Likely Benign
58
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
176
0
176
Likely Pathogenic
0
0
7
0
7
VUS
4
218
7
0
229
Likely Benign
0
6
3
12
21
Benign
0
9
41
8
58
Conflicting
—1
Total423323420492

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

View in ClinVar →

Protein Context — Lollipop Plot

ARVCF · 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
Integrating RNA-seq and scRNA-seq to explore the prognostic features and immune landscape of exosome-related genes in breast cancer metastasis.
Huang G et al.·Ann Med
2025
Analysis of genetic profiling, pathomics signature, and prognostic features of primary lymphoepithelioma-like carcinoma of the renal pelvis.
Fan B et al.·Mol Oncol
2022
Patterns of Antinuclear Antibodies in a New Variant of Endemic Pemphigus in El Bagre, Colombia, Colocalizing with Antigens against MIZAP, ARVCF, p0071, and Desmoplakins I and II.
Abreu-Velez AM et al.·J Appl Lab Med
2022
ARVCF localizes to the nucleus and adherens junction and is mutually exclusive with p120(ctn) in E-cadherin complexes.
Mariner DJ et al.·J Cell Sci
2000
ARVCF expression is significantly correlated with the malignant phenotype of non-small cell lung cancer.
Zhang D et al.·Mol Carcinog
2015
Coronary artery disease-associated variants regulate vascular smooth muscle cell gene expression.
Barbera N et al.·Nat Cardiovasc Res
2025
Type 2 Diabetes Modifies the Association of CAD Genomic Risk Variants With Subclinical Atherosclerosis.
Hasbani NR et al.·Circ Genom Precis Med
2023
Exome-Wide Association Study Identified New Risk Loci for Hirschsprung's Disease.
Tang W et al.·Mol Neurobiol
2017
A functional variant provided further evidence for the association of ARVCF with schizophrenia.
Mas S et al.·Am J Med Genet B Neuropsychiatr Genet
2010Functional
Haplotypic association spanning the 22q11.21 genes COMT and ARVCF with schizophrenia.
Sanders AR et al.·Mol Psychiatry
2005Clinical trial
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Single-Cell Profiling Identifies Reward Behavior-Related Neurons and Alterations in the Ventral Tegmental Area Based on Arvcf-Knockout Mouse Model.
Zhang M et al.·Research (Wash D C)
2025🔓 Open AccessFunctional
Vimentin Regulates Alternative Polyadenylation and mTOR Signaling via ARVCF to Promote B Cell Lymphoma Progression.
Shao L et al.·Hum Mutat
2025🔓 Open Access
Investigating the effect of Arvcf reveals an essential role on regulating the mesolimbic dopamine signaling-mediated nicotine reward.
Wang Y et al.·Commun Biol
2025🔓 Open Access
Identification and validation of a novel gene ARVCF associated with alcohol dependence among Chinese population.
Shi X et al.·iScience
2024🔓 Open Access
Single nucleotide polymorphisms rs148582811 regulates its host gene ARVCF expression to affect nicotine-associated hippocampus-dependent memory.
Yang Z et al.·iScience
2023🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools