REPS2

Chr X

RALBP1 associated Eps domain containing 2

Also known as: POB1

The REPS2 protein regulates endocytosis of growth factor receptors including EGF and insulin receptors, controlling receptor internalization and downstream signaling pathways that affect cell survival, adhesion, and migration. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. The gene is moderately constrained against loss-of-function variants (LOEUF 0.486), suggesting some intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 0.49
Clinical SummaryREPS2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.203
Z-score 3.45
OE 0.25 (0.130.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.31Z-score
OE missense 0.76 (0.670.86)
174 obs / 230.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.130.49)
00.351.4
Missense OE0.76 (0.670.86)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 6 / 24.4Missense obs/exp: 174 / 230.0Syn Z: -0.55
DN
0.5869th %ile
GOF
0.6542th %ile
LOF
0.51top 25%

The highest-scoring mechanism for this gene is gain-of-function.

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

REPS2 · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC