RLBP1

Chr 15

retinaldehyde binding protein 1

Also known as: CRALBP

NCBI Gene: 6017 ENSG00000140522 UniProt: P12271

The encoded protein is a soluble retinoid carrier that transports 11-cis-retinaldehyde and participates in the visual cycle, which regenerates active retinoids essential for both rod and cone photoreceptor function. Mutations cause autosomal recessive retinal dystrophies including Bothnia retinal dystrophy, fundus albipunctatus, Newfoundland rod-cone dystrophy, and retinitis punctata albescens. The gene shows tolerance to loss-of-function variants (pLI near zero), and rare autosomal dominant inheritance has also been reported.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a 36-kD water-soluble protein which carries 11-cis-retinaldehyde or 11-cis-retinal as physiologic ligands. It may be a functional component of the visual cycle. Mutations of this gene have been associated with severe rod-cone dystrophy, Bothnia dystrophy (nonsyndromic autosomal recessive retinitis pigmentosa) and retinitis punctata albescens. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBothnia retinal dystrophy

UniProtRod-cone dystrophy Newfoundland

UniProtRetinitis punctata albescens

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · RLBP1-related retinopathy · AR · ClinGen 2021

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

1.08

LOEUF

LOF

Mechanism· G2P

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GeneReview available — RLBP1

Authoritative clinical overview · Recommended first read

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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?

1.08LOEUF

pLI 0.000

Z-score 1.33

OE 0.64 (0.39–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.31Z-score

OE missense 1.06 (0.95–1.20)

195 obs / 183.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.64 (0.39–1.08)

0≤0.351.4

Missense OE?1.06 (0.95–1.20)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 10 / 15.7Missense obs/exp: 195 / 183.3Syn Z: 0.33

Background carrier burden — how many people carry a rare variant somewhere in RLBP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

437 rare PASS variants

Rare truncating (LoF)

1 in 2,200

60 rare PASS variants

Rare synonymous (reference)

1 in 140

163 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RLBP1. 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 150	1 in 2,200
South Asian	~43k	1 in 120	1 in 4,800
Remaining (unassigned)	~30k	1 in 71	1 in 1,200
European (Finnish)	~27k	1 in 620	≈ 1 in 27,000
Admixed American	~22k	1 in 120	1 in 1,700
African / African American	~21k	1 in 130	≈ 1 in 6,000
East Asian	~20k	1 in 230	1 in 990
Ashkenazi Jewish	~13k	1 in 300	none seen
Middle Eastern	~2,884	1 in 160	none seen

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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓