ELOVL4
Chr 6ARADELOVL fatty acid elongase 4
Also known as: ADMD, CT118, ISQMR, SCA34, STGD2, STGD3
The protein catalyzes the rate-limiting step in very long-chain fatty acid elongation, synthesizing saturated and polyunsaturated fatty acids that serve as precursors for membrane lipids critical in early brain and skin development. Mutations cause autosomal dominant Stargardt disease 3 (retinal dystrophy), autosomal recessive spinocerebellar ataxia 34, and autosomal recessive ichthyosis with spastic quadriplegia and intellectual disability. The gene is highly constrained against loss-of-function variants, reflecting its essential role in neurodevelopment and retinal function.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, dominant-negative and gain-of-function). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
379 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 14 | 2 | 15 | 0 | 31 |
Likely Pathogenic | 7 | 3 | 1 | 0 | 11 |
VUS | 3 | 132 | 50 | 2 | 187 |
Likely Benign | 0 | 3 | 37 | 63 | 103 |
Benign | 0 | 1 | 33 | 0 | 34 |
Conflicting | — | 11 | |||
| Total | 24 | 141 | 136 | 65 | 377 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ELOVL4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools