ARV1

Chr 1AR

ARV1 fatty acid homeostasis modulator

Also known as: DEE38, EIEE38

NCBI Gene: 64801 ENSG00000173409 UniProt: Q9H2C2 OMIM: 611647

The protein mediates endoplasmic reticulum cholesterol and bile acid homeostasis and participates in sterol transport from the ER to plasma membranes. Autosomal recessive mutations cause developmental and epileptic encephalopathy 38, which presents in early infancy with seizures and developmental delays. The gene is highly constrained against loss-of-function variants (pLI near 1), indicating intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 38MIM #617020

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Developmental and epileptic encephalopathy 38; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.25

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.19Z-score

OE missense 0.96 (0.83–1.10)

139 obs / 145.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.46–1.25)

0≤0.351.4

Missense OE?0.96 (0.83–1.10)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 10 / 13.5Missense obs/exp: 139 / 145.5Syn Z: 0.39

Background carrier burden — how many people carry a rare variant somewhere in ARV1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

348 rare PASS variants

Rare truncating (LoF)

1 in 400

69 rare PASS variants

Rare synonymous (reference)

1 in 610

133 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ARV1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 340
South Asian	~43k	1 in 180	1 in 690
Remaining (unassigned)	~30k	1 in 180	1 in 430
European (Finnish)	~27k	1 in 280	1 in 3,900
Admixed American	~22k	1 in 130	1 in 960
African / African American	~21k	1 in 130	1 in 650
East Asian	~20k	1 in 150	1 in 410
Ashkenazi Jewish	~13k	1 in 550	≈ 1 in 2,900
Middle Eastern	~2,884	1 in 86	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 5.? see exons ↓