REPS2

Chr X

RALBP1 associated Eps domain containing 2

NCBI Gene: 9185ENSG00000169891UniProt: Q8NFH8

Involved in ligand-dependent receptor mediated endocytosis of the EGF and insulin receptors as part of the Ral signaling pathway (PubMed:10393179, PubMed:12771942, PubMed:9422736). By controlling growth factor receptors endocytosis may regulate cell survival (PubMed:12771942). Through ASAP1 may regulate cell adhesion and migration (PubMed:12149250)

0
ClinVar variants
0
Pathogenic / LP
0.20
pLI score
0
Active trials
Clinical Summary— REPS2
⚡
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

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.49LOEUF
pLI 0.203
Z-score 3.45
OE 0.25 (0.13–0.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.31Z-score
OE missense 0.76 (0.67–0.86)
174 obs / 230.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.13–0.49)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.67–0.86)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 6 / 24.4Missense obs/exp: 174 / 230.0Syn Z: -0.55

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Reps2: a cellular signaling and molecular trafficking nexus.
Badway JA et al.·Int J Biochem Cell Biol
2011Review
Expression and clinical significance of REPS2 in human esophageal squamous cell carcinoma.
Zhang H et al.·Asian Pac J Cancer Prev
2013
Liver X receptor agonists exert antitumor effects against hepatocellular carcinoma via inducing REPS2 expression.
He XY et al.·Acta Pharmacol Sin
2023
Identification of coagulation-related hub genes in ischemic stroke based on bioinformatics integration analysis and investigation of their immune regulatory mechanisms.
Li H et al.·Eur J Med Res
2025Functional
Nance-Horan syndrome pedigree due to a novel microdeletion and skewed X chromosome inactivation.
Huang Y et al.·Mol Genet Genomic Med
2023
Identification of a novel microdeletion causative of Nance-Horan syndrome.
Lopez Martinolich M et al.·Mol Genet Genomic Med
2022Case report
Nuclear DICKKOPF-1 as a biomarker of chemoresistance and poor clinical outcome in colorectal cancer.
Aguilera Ó et al.·Oncotarget
2015
Recurrent and novel SS18-SSX fusion transcripts in synovial sarcoma: description of three new cases.
Przybyl J et al.·Tumour Biol
2012Cohort
Identification of a microdeletion at Xp22.13 in a Taiwanese family presenting with Nance-Horan syndrome.
Liao HM et al.·J Hum Genet
2011Case report
Copy-number variations on the X chromosome in Japanese patients with mental retardation detected by array-based comparative genomic hybridization analysis.
Honda S et al.·J Hum Genet
2010Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools