RGP1

Chr 9

RGP1 partner of RAB6A GEF complex

Also known as: KIAA0258

NCBI Gene: 9827 ENSG00000107185 UniProt: Q92546 OMIM: 615742

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in negative regulation of protein catabolic process; positive regulation of GTPase activity; and retrograde transport, endosome to Golgi. Located in cytosol and membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.13

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.000

Z-score 1.12

OE 0.74 (0.50–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.72Z-score

OE missense 0.87 (0.77–0.97)

196 obs / 226.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.50–1.13)

0≤0.351.4

Missense OE?0.87 (0.77–0.97)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 16 / 21.6Missense obs/exp: 196 / 226.4Syn Z: 0.08

Background carrier burden — how many people carry a rare variant somewhere in RGP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

454 rare PASS variants

Rare truncating (LoF)

1 in 2,600

71 rare PASS variants

Rare synonymous (reference)

1 in 310

220 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RGP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 2,700
South Asian	~43k	1 in 110	1 in 5,400
Remaining (unassigned)	~30k	1 in 90	1 in 3,000
European (Finnish)	~27k	1 in 760	≈ 1 in 13,000
Admixed American	~22k	1 in 90	1 in 1,900
African / African American	~21k	1 in 160	1 in 1,500
East Asian	~20k	1 in 160	1 in 560
Ashkenazi Jewish	~13k	1 in 340	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 87	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓