RABEP1

Chr 17

rabaptin, RAB GTPase binding effector protein 1

Also known as: RAB5EP, RABPT5

NCBI Gene: 9135 ENSG00000029725 UniProt: Q15276 OMIM: 603616

The protein acts as a Rab effector that links gamma-adaptin with RAB4A and RAB5A to facilitate endocytic membrane fusion, recycling endosome trafficking, and transport of protein complexes including ion channels and polycystin proteins to the cilium. Biallelic pathogenic variants cause Martsolf syndrome, an autosomal recessive disorder characterized by congenital cataracts, intellectual disability, hypogonadism, and distinctive facial features. This gene is highly constrained against loss-of-function variants (pLI 0.998, LOEUF 0.266), indicating that complete protein loss is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.27

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

80 VUS of 113 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

1.86Z-score

OE missense 0.75 (0.69–0.82)

330 obs / 439.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.09–0.27)

0≤0.351.4

Missense OE?0.75 (0.69–0.82)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 8 / 54.2Missense obs/exp: 330 / 439.4Syn Z: 0.49

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

VUS80

Likely Benign7

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	80	0	0	80
Likely Benign	3	0	4	7
Benign	0	1	1	2
Total	83	1	5	89

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap RABEP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →