ELOVL4

Chr 6ARAD

ELOVL fatty acid elongase 4

ENSG00000118402UniProt: Q9GZR5

Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that catalyzes the synthesis of very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty acids that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May play a critical role in early brain and skin development

Primary Disease Associations & Inheritance

Ichthyosis, spastic quadriplegia, and impaired intellectual developmentMIM #614457
AR
Spinocerebellar ataxia 34MIM #133190
AD
Stargardt disease 3MIM #600110
AD
0
ClinVar variants
0
Pathogenic / LP
0.83
pLI score
1
Active trials
Clinical Summary— ELOVL4
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Gene-Disease Validity (ClinGen)
ELOVL4-related maculopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.41LOEUF
pLI 0.832
Z-score 3.41
OE 0.16 (0.07–0.41)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.19Z-score
OE missense 0.74 (0.64–0.86)
126 obs / 169.4 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.0.16 (0.07–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.64–0.86)
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.1.05
0≤1.21.6
LoF obs/exp: 3 / 19.1Missense obs/exp: 126 / 169.4Syn Z: -0.28

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Gene2Phenotype Curations

ELOVL4-related ichthyosis, spastic quadriplegia, and intellectual developmental disorder

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

ELOVL4-related Stargardt disease

definitive
ADLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ichthyosis, spastic quadriplegia, and impaired intellectual development

MIM #614457

Molecular basis of disorder known

Autosomal recessive

Spinocerebellar ataxia 34

MIM #133190

Molecular basis of disorder known

Autosomal dominant

Stargardt disease 3

MIM #600110

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Two New Families and a Literature Review of ELOVL4-Associated Spinocerebellar Ataxia Type 34.
Nishide M et al.·Cerebellum
2024Review
A novel ELOVL4 variant, L168S, causes early childhood-onset Spinocerebellar ataxia-34 and retinal dysfunction: a case report.
Gyening YK et al.·Acta Neuropathol Commun
2023Case report
ELOVL4 Mutations That Cause Spinocerebellar Ataxia-34 Differentially Alter Very Long Chain Fatty Acid Biosynthesis.
Gyening YK et al.·J Lipid Res
2023
The expression of ELOVL4, repressed by MYCN, defines neuroblastoma patients with good outcome.
Rugolo F et al.·Oncogene
2021Cohort
Genome-wide association study of brain arteriolosclerosis.
Shade LM et al.·J Cereb Blood Flow Metab
2022
Genetics and molecular pathology of Stargardt-like macular degeneration.
Vasireddy V et al.·Prog Retin Eye Res
2010Review
Generation of novel lipid metabolism-based signatures to predict prognosis and immunotherapy response for colorectal adenocarcinoma.
Wang Y et al.·Sci Rep
2024
Expanding the allelic spectrum of ELOVL4-related autosomal recessive neuro-ichthyosis.
Alabdulrazzaq F et al.·Mol Genet Genomic Med
2023
The bisretinoids of retinal pigment epithelium.
Sparrow JR et al.·Prog Retin Eye Res
2012Review
Dengue virus is particularly sensitive to interference with long-chain fatty acid elongation and desaturation.
Hehner J et al.·J Biol Chem
2025
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
Stargardt-Like Macular Dystrophy

Stargardt-like Macular Dystrophy (STDG3) Secondary to Mutations in ELOVL4

RECRUITING
NCT04591483National Eye Institute (NEI)Started 2022-04-19

External Resources

Links to major genomics databases and tools