REEP5

Chr 5

receptor accessory protein 5

Also known as: C5orf18, D5S346, DP1, POB16, TB2, YOP1, Yip2e

NCBI Gene: 7905 ENSG00000129625 UniProt: Q00765

Predicted to be involved in endoplasmic reticulum membrane organization and regulation of intracellular transport. Located in endoplasmic reticulum tubular network. [provided by Alliance of Genome Resources, Apr 2025]

Research

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.27

Clinical Summary— REEP5

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Population Constraint (gnomAD)

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

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 17 VUS of 29 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.001

Z-score 1.00

OE 0.65 (0.35–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.08Z-score

OE missense 0.98 (0.83–1.16)

100 obs / 102.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.35–1.27)

0≤0.351.4

Missense OE?0.98 (0.83–1.16)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 6 / 9.3Missense obs/exp: 100 / 102.2Syn Z: -0.82

This gene — mechanism propensity

0.81top 10%

GOF

0.79top 25%

LOF

0.2483th %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

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.

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

ClinVar Variant Classifications

29 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS17

Likely Benign2

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	3	3
Likely Pathogenic	0	0	0
VUS	16	1	17
Likely Benign	2	0	2
Benign	1	0	1
Total	19	4	23

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

30 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap REEP5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →