RPGRIP1

Chr 14

RPGR interacting protein 1

Also known as: CORD13, LCA6, RGI1, RGRIP, RPGRIP, RPGRIP1d

NCBI Gene: 57096 ENSG00000092200 UniProt: Q96KN7

The protein functions as a scaffolding protein required for normal localization of RPGR at the connecting cilium of photoreceptor cells and is essential for disk morphogenesis and organization in the outer segment of photoreceptor cells. Mutations cause autosomal recessive Leber congenital amaurosis 6 and cone-rod dystrophy 13, both leading to severe visual impairment affecting the retina. The gene shows tolerance to loss-of-function variants (low constraint), consistent with its recessive inheritance pattern where biallelic mutations are required for disease.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a photoreceptor protein that interacts with retinitis pigmentosa GTPase regulator protein and is a key component of cone and rod photoreceptor cells. Mutations in this gene lead to autosomal recessive congenital blindness. [provided by RefSeq, Oct 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeber congenital amaurosis 6

UniProtCone-rod dystrophy 13

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · inherited retinal dystrophy · AR · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.88

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — RPGRIP1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.000

Z-score 2.40

OE 0.69 (0.54–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.25Z-score

OE missense 0.97 (0.91–1.04)

636 obs / 653.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.54–0.88)

0≤0.351.4

Missense OE?0.97 (0.91–1.04)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 47 / 68.4Missense obs/exp: 636 / 653.9Syn Z: -0.22

Background carrier burden — how many people carry a rare variant somewhere in RPGRIP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 36

1,651 rare PASS variants

Rare truncating (LoF)

1 in 510

309 rare PASS variants

Rare synonymous (reference)

1 in 59

606 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RPGRIP1. 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 53	1 in 590
South Asian	~43k	1 in 31	1 in 210
Remaining (unassigned)	~30k	1 in 32	1 in 490
European (Finnish)	~27k	1 in 190	1 in 1,000
Admixed American	~22k	1 in 36	1 in 390
African / African American	~21k	1 in 39	1 in 370
East Asian	~20k	1 in 32	1 in 270
Ashkenazi Jewish	~13k	1 in 150	1 in 720
Middle Eastern	~2,884	1 in 34	1 in 210

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 18 of 24 coding exons well covered in gnomAD exomes; exons 5, 7, 8, 10, 20, 24 marginal. Genomes: 23 of 24 (exon 21 below).? see exons ↓