ERLIN2

Chr 8

ER lipid raft associated 2

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

NCBI Gene: 11160 ENSG00000147475 UniProt: O94905

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the SPFH domain-containing family of lipid raft-associated proteins. The encoded protein is localized to lipid rafts of the endoplasmic reticulum and plays a critical role in inositol 1,4,5-trisphosphate (IP3) signaling by mediating ER-associated degradation of activated IP3 receptors. Mutations in this gene are a cause of spastic paraplegia-18 (SPG18). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpastic paraplegia 18B, autosomal recessive

UniProtSpastic paraplegia 18A, autosomal dominant

Clinical highlights

Gene-disease validity (ClinGen)

hereditary spastic paraplegia 18 · ADLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.83

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ERLIN2