ERLIN1

Chr 10

ER lipid raft associated 1

Also known as: C10orf69, Erlin-1, KE04, KEO4, SPFH1, SPG62

NCBI Gene: 10613ENSG00000107566UniProt: O75477

The protein encoded by this gene is part of a protein complex that mediates degradation of inositol 1,4,5-trisphosphate receptors in the endoplasmic reticulum. The encoded protein also binds cholesterol and regulates the SREBP signaling pathway, which promotes cellular cholesterol homeostasis. Defects in this gene have been associated with spastic paraplegia 62. [provided by RefSeq, Dec 2016]

Primary Disease Associations & Inheritance

UniProtSpastic paraplegia 62, autosomal recessive
0
ClinVar variants
0
Pathogenic / LP
0.18
pLI score
0
Active trials
Clinical Summary— ERLIN1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
Some data sources returned errors (2)

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

omim: Error: OMIM fetch failed: 429

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.
0.54LOEUF
pLI 0.178
Z-score 3.04
OE 0.26 (0.13–0.54)
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.
1.79Z-score
OE missense 0.63 (0.54–0.73)
115 obs / 183.1 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.0.26 (0.13–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.63 (0.54–0.73)
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.0.96
0≤1.21.6
LoF obs/exp: 5 / 19.5Missense obs/exp: 115 / 183.1Syn Z: 0.24

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ERLIN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The common p.Ile291Val variant of ERLIN1 enhances TM6SF2 function and is associated with protection against MASLD.
Rendel MD et al.·Med
2024
A novel homozygous mutation in ERLIN1 gene causing spastic paraplegia 62 and literature review.
Zhu ZY et al.·Eur J Med Genet
2022Review
The ERLIN1-CHUK-CWF19L1 gene cluster influences liver fat deposition and hepatic inflammation in the NHLBI Family Heart Study.
Feitosa MF et al.·Atherosclerosis
2013Meta-analysis
A Retrospective Review of 18 Patients With Childhood-Onset Hereditary Spastic Paraplegia, Nine With Novel Variants.
Kilic MA et al.·Pediatr Neurol
2024Review
Usp25-Erlin1/2 activity limits cholesterol flux to restrict virus infection.
Teo QW et al.·Dev Cell
2023
Biallelic variants in ERLIN1: a series of 13 individuals with spastic paraparesis.
Cogan G et al.·Hum Genet
2024Cohort
Expanding the Phenotypic Spectrum of ERLIN1-Related SPG62: Report of Two Siblings With Behavioral Features and Hyperacusis.
Ozkose GS et al.·Clin Genet
2026Case report
Validating a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program.
Serper M et al.·PLoS One
2020
Autophagy Promotes Enrichment of Raft Components within Extracellular Vesicles Secreted by Human 2FTGH Cells.
Manganelli V et al.·Int J Mol Sci
2024
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.

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External Resources

Links to major genomics databases and tools