REEP2

Chr 5ARAD

receptor accessory protein 2

Also known as: C5orf19, SGC32445, SPG72, SPG72A, SPG72B, Yip2d

The REEP2 protein is required for endoplasmic reticulum network formation, shaping and remodeling, and may enhance cell surface expression of odorant receptors. Mutations cause spastic paraplegia 72, which can follow either autosomal dominant or autosomal recessive inheritance patterns. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.549), suggesting some tolerance to protein-truncating mutations.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAR/ADLOEUF 0.552 OMIM phenotypes
Clinical SummaryREEP2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
📖
GeneReview available — REEP2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.439
Z-score 2.74
OE 0.21 (0.100.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.64Z-score
OE missense 0.64 (0.540.75)
103 obs / 161.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.100.55)
00.351.4
Missense OE0.64 (0.540.75)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 3 / 14.1Missense obs/exp: 103 / 161.5Syn Z: 0.52
DN
0.7132th %ile
GOF
0.6833th %ile
LOF
0.4726th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNIn vitro functional expression studies showed that the V36E mutant protein inhibited the normal binding of wildtype REEP2 to cellular membranes, thus acting in a dominant-negative manner.PMID:24388663

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

REEP2 · 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
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗