ERLIN2

Chr 8ADAR

ER lipid raft associated 2

Also known as: C8orf2, Erlin-2, NET32, SPFH2, SPG18, SPG18A, SPG18B

This protein localizes to endoplasmic reticulum lipid rafts and mediates ER-associated degradation of inositol 1,4,5-trisphosphate receptors, playing a critical role in IP3 signaling and cellular cholesterol homeostasis. Mutations cause spastic paraplegia type 18, which can be inherited in either autosomal dominant (SPG18A) or autosomal recessive (SPG18B) patterns. The gene is not highly constrained against loss-of-function variants, suggesting that different types of mutations may underlie the distinct inheritance patterns.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismAD/ARLOEUF 0.832 OMIM phenotypes
Clinical SummaryERLIN2
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Gene-Disease Validity (ClinGen)
hereditary spastic paraplegia 18 · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.001
Z-score 2.08
OE 0.46 (0.270.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.88Z-score
OE missense 0.60 (0.520.71)
108 obs / 178.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.46 (0.270.83)
00.351.4
Missense OE0.60 (0.520.71)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 8 / 17.3Missense obs/exp: 108 / 178.6Syn Z: 0.35
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedERLIN2-related intellectual developmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.82top 10%
GOF
0.6346th %ile
LOF
0.2484th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ERLIN2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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