RGP1

Chr 9

RGP1 partner of RAB6A GEF complex

Also known as: KIAA0258

RGP1 encodes a protein that forms a complex with RIC1 to function as a guanine nucleotide exchange factor, activating RAB6A to facilitate fusion of endosome-derived vesicles with the Golgi and participate in mannose-6-phosphate receptor recycling. Mutations cause autosomal recessive developmental delay with seizures, microcephaly, and movement abnormalities, typically presenting in early childhood. The gene is highly intolerant to loss-of-function variants, indicating that both functional copies are required for normal development.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.13
Clinical SummaryRGP1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
74 unique Pathogenic / Likely Pathogenic· 79 VUS of 168 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 1.12
OE 0.74 (0.501.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.72Z-score
OE missense 0.87 (0.770.97)
196 obs / 226.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.74 (0.501.13)
00.351.4
Missense OE0.87 (0.770.97)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 16 / 21.6Missense obs/exp: 196 / 226.4Syn Z: 0.08

ClinVar Variant Classifications

168 submitted variants in ClinVar

Classification Summary

Pathogenic65
Likely Pathogenic9
VUS79
Likely Benign2
Benign2
65
Pathogenic
9
Likely Pathogenic
79
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
65
0
65
Likely Pathogenic
0
0
9
0
9
VUS
0
70
9
0
79
Likely Benign
0
1
1
0
2
Benign
0
0
2
0
2
Total071860157

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

View in ClinVar →

Protein Context — Lollipop Plot

RGP1 · 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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