ARV1

Chr 1AR

ARV1 fatty acid homeostasis modulator

Also known as: DEE38, EIEE38

NCBI Gene: 64801ENSG00000173409UniProt: Q9H2C2

this gene encodes a transmembrane protein that contains a conserved zinc ribbon motif at the N- terminus. A similar protein in mouse is thought to function in fatty acid homeostasis. Mutations in this gene are associated with early infantile epileptic encephalopathy 38. [provided by RefSeq, Nov 2016]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 38MIM #617020
AR
123
ClinVar variants
54
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ARV1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
54 Pathogenic / Likely Pathogenic· 55 VUS of 123 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.
1.25LOEUF
pLI 0.000
Z-score 0.89
OE 0.74 (0.46–1.25)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.19Z-score
OE missense 0.96 (0.83–1.10)
139 obs / 145.5 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.0.74 (0.46–1.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.83–1.10)
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.0.93
0≤1.21.6
LoF obs/exp: 10 / 13.5Missense obs/exp: 139 / 145.5Syn Z: 0.39

ClinVar Variant Classifications

123 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic13
VUS55
Likely Benign10
Benign3
Conflicting1
41
Pathogenic
13
Likely Pathogenic
55
VUS
10
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
36
0
41
Likely Pathogenic
9
2
2
0
13
VUS
2
40
13
0
55
Likely Benign
0
4
1
5
10
Benign
0
1
1
1
3
Conflicting
—1
Total1647536123

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

View in ClinVar →

Protein Context — Lollipop Plot

ARV1 · 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

Developmental and epileptic encephalopathy 38

MIM #617020

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.
Alazami AM et al.·Cell Rep
2015
The sterol-regulating human ARV1 binds cholesterol and phospholipids through its conserved ARV1 homology domain.
Cunningham JL et al.·J Biol Chem
2025
Dilated cardiomyopathy is a part of the ARV1-associated phenotype: a case report.
Karabinos A et al.·J Med Case Rep
2022Case report
Epileptic encephalopathy caused by ARV1 deficiency: Refinement of the genotype-phenotype spectrum and functional impact on GPI-anchored proteins.
Salian S et al.·Clin Genet
2021Case report
Arv1 interacts with and regulates the first step of GPI biosynthesis in Candida albicans.
Bharati M et al.·FEBS J
2025
ARV1 Gene: A Novel Cause of Autosomal Recessive Cerebellar Ataxia with Elevated Alpha Fetoprotein.
Kamate M et al.·Cerebellum
2024Case report
Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy.
Palmer EE et al.·Hum Mol Genet
2016Case report
A defect in GPI synthesis as a suggested mechanism for the role of ARV1 in intellectual disability and seizures.
Segel R et al.·Neurogenetics
2020Case report
Human placental androgen receptor variants: Potential regulators of male fetal growth.
Meakin AS et al.·Placenta
2019
Interplay between Cytoplasmic and Nuclear Androgen Receptor Splice Variants Mediates Castration Resistance.
Zhan Y et al.·Mol Cancer Res
2017
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