RABEP1

Chr 17

rabaptin, RAB GTPase binding effector protein 1

Also known as: RAB5EP, RABPT5

NCBI Gene: 9135ENSG00000029725UniProt: Q15276

Enables protein domain specific binding activity and protein homodimerization activity. Involved in vesicle-mediated transport. Located in cytosol; endocytic vesicle; and endosome. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jul 2025]

120
ClinVar variants
22
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RABEP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 88 VUS of 120 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.27LOEUF
pLI 0.999
Z-score 5.82
OE 0.15 (0.09–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
1.86Z-score
OE missense 0.75 (0.69–0.82)
330 obs / 439.4 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.0.15 (0.09–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.69–0.82)
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.0.95
0≤1.21.6
LoF obs/exp: 8 / 54.2Missense obs/exp: 330 / 439.4Syn Z: 0.49

ClinVar Variant Classifications

120 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS88
Likely Benign8
Benign2
21
Pathogenic
1
Likely Pathogenic
88
VUS
8
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
80
8
0
88
Likely Benign
0
3
1
4
8
Benign
0
0
1
1
2
Total083325120

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

View in ClinVar →

Protein Context — Lollipop Plot

RABEP1 · 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
Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes.
Novikova G et al.·Nat Commun
2021
The Rabep1-Mediated Endocytosis and Activation of Trypsinogen to Promote Pancreatic Stellate Cell Activation.
Yao W et al.·Biomolecules
2022
Integrating rare pathogenic variant prioritization with gene-based association analysis to identify novel genes and relevant multimodal traits for Alzheimer's disease.
Cao J et al.·Alzheimers Dement
2025
Identification and genomic analysis of pedigrees with exceptional longevity identifies candidate rare variants.
Miller JB et al.·Neurobiol Dis
2020
Interrogating differences in expression of targeted gene sets to predict breast cancer outcome.
Andres SA et al.·BMC Cancer
2013
5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Diagnostic Biomarkers for Late-Onset Alzheimer's Disease.
Chen L et al.·J Alzheimers Dis
2022
Abnormalities in endothelial form of nitric oxide synthase is pathogenic in limited cutaneous systemic sclerosis.
Jia XJ et al.·J Cosmet Dermatol
2019
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.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools