RLBP1

Chr 15ARAD

retinaldehyde binding protein 1

Also known as: CRALBP

NCBI Gene: 6017 ENSG00000140522 UniProt: P12271 OMIM: 180090

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 OMIM 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 OMIM ResearchGenerating clinical summary…

LOFmechanismAR/ADLOEUF 1.084 OMIM phenotypes

Clinical Summary— RLBP1

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Gene-Disease Validity (ClinGen)

RLBP1-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

57 unique Pathogenic / Likely Pathogenic· 152 VUS of 431 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — RLBP1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveRLBP1-related Bothnia retinal dystrophyOTHERAR

strongRLBP1-related Newfoundland rod-cone dystrophyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.5967th %ile

GOF

0.7028th %ile

LOF

0.2190th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

431 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36

Likely Pathogenic21

VUS152

Likely Benign179

Benign17

Conflicting25

Pathogenic

Likely Pathogenic

152

VUS

179

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	26	4	5	1	36
Likely Pathogenic	13	7	1	0	21
VUS	4	121	23	4	152
Likely Benign	0	5	74	100	179
Benign	0	0	15	2	17
Conflicting	—				25
Total	43	137	118	107	430

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

View in ClinVar →

36 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap RLBP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →