GeneBe

RLBP1

protein-coding

retinaldehyde binding protein 1

Gene summary

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]

MANE transcript

NM_000326.5

Inheritance

AD, AR

ClinVar variants

P:58U:142B:123

Top phenotype

Newfoundland rod-cone dystrophy; Bothnia retinal dystrophy; Retinitis punctata albescens; Fundus albipunctatus

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr15:89,209,869-89,221,614

External References & Databases

Ensembl (ENSG00000140522)NCBI Gene (6017)OMIM (180090)HGNC:10024GenCCUniProt (P12271)AlphaFoldClinVar (RLBP1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~11.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

retinitis pigmentosaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019200

Submitter: Orphanet

Newfoundland cone-rod dystrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011839

Submitter: G2P

retinitis punctata albescensSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018877

Submitter: Orphanet

RLBP1-related retinopathyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0100444

Submitter: ClinGen

RLBP1 has been reported in the literature in association with multiple retinopathy conditions including Retinitis punctata albescens (RPA), Fundus albipunctatus (FA), Bothnia retinal dystrophy, and Newfoundland rod-cone dystrophy (PMIDs: 14718298, 25429852, 10102298, 11868161). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference/ in molecular mechanism, inheritance pattern, or phenotypic variability. Therefore, the disease entities have been lumped under RLBP1-related retinopathy. At least 8 unique variants (missense, nonsense, frameshift etc.) have been reported in probands. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease relationship is also supported by animal models and expression studies. In summary, RLBP1 is definitively associated with autosomal recessive RLBP1-related retinopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Retina Expert Panel on 6/3/2021 (SOP Version 8).

Bothnia retinal dystrophyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011838

Submitter: G2P

fundus albipunctatusSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007639

Submitter: Orphanet

fundus albipunctatusSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007639

Submitter: Labcorp Genetics (formerly Invitae)

Bothnia retinal dystrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011838

Submitter: Labcorp Genetics (formerly Invitae)

Newfoundland cone-rod dystrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011839

Submitter: Labcorp Genetics (formerly Invitae)

Bothnia retinal dystrophySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011838

Submitter: Orphanet

RLBP1-related retinopathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100444

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Newfoundland rod-cone dystrophy; Bothnia retinal dystrophy; Retinitis punctata albescens; Fundus albipunctatusAR

Manifestation: Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 10102298; 11176989; 11868161; 14718298; 18344446; 20301590; 21447491; 22551409Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RLBP1 variants in ClinVar

17 Conditions Cataloged
not providedTotal: 367
RLBP1-related disorderTotal: 68
not specifiedTotal: 62
Pigmentary retinal dystrophyTotal: 46
Retinitis pigmentosaTotal: 42
Newfoundland cone-rod dystrophyTotal: 40
Inborn genetic diseasesTotal: 32
Retinal dystrophyTotal: 21

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000326.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
4
clinvar
111
clinvar
 116
missense
4
clinvar
8
clinvar
134
clinvar
12
clinvar
 158
nonsense
10
clinvar
6
clinvar
2
clinvar
 18
start loss
1
clinvar
 1
frameshift
10
clinvar
6
clinvar
1
clinvar
 17
splice donor/acceptor (+/-2bp)
4
clinvar
8
clinvar
1
clinvar
 13
Total29291421230323

Highest pathogenic variant AF is 0.00008427492

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000326.5RefSeqNP_000317.17MANE Select
ENST00000268125.10EnsemblENSP00000268125.57MANE Select
ENST00000563254.1EnsemblENSP00000454740.13Standard
ENST00000567787.1EnsemblENSP00000457251.14Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
rlbp1bDanio rerio

Structure: pigmentation

Quality: decreased intensity

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Vitamin A and Carotenoid Metabolism
  • Signaling by GPCR
  • Signal Transduction
  • The canonical retinoid cycle in rods (twilight vision)
  • The retinoid cycle in cones (daylight vision)

Biological Process

  • retinoid metabolic process
  • vitamin A metabolic process
  • visual perception
  • response to stimulus

Molecular Function

  • 11-cis retinal binding
  • retinol binding

Cellular Component

  • cellular_component
  • cytosol
  • cell body

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000268125
Coding exons
7
Length
11883
Individuals with no LoFs
125701
Homozygous LoFs
0
Heterozygous LoFs
47
Defined
125748
p
0.000187
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.3081951831.060.00001212081
Missense (PolyPhen)7978.1341.0111821
Synonymous0.3267073.60.9520.00000487596
Loss of Function1.331015.70.6378.55e-7171

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000140.00012rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.00140.0014notable
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000970.000097rare
South Asian0.000130.00013rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors. Participates in the regeneration of active 11-cis-retinol and 11-cis-retinaldehyde, from the inactive 11-trans products of the rhodopsin photocycle and in the de novo synthesis of these retinoids from 11-trans metabolic precursors. The cycling of retinoids between photoreceptor and adjacent pigment epithelium cells is known as the 'visual cycle'. {ECO:0000269|PubMed:19846785}.;
Disease
DISEASE: Rod-cone dystrophy Newfoundland (NFRCD) [MIM:607476]: A rod-cone dystrophy reminiscent of retinitis punctata albescens but with a substantially lower age at onset and more-rapid and distinctive progression. Rod-cone dystrophies results from initial loss of rod photoreceptors, later followed by cone photoreceptors loss. {ECO:0000269|PubMed:11868161}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis punctata albescens (RPA) [MIM:136880]: A form of fleck retina disease characterized by aggregation of white flecks posteriorly in the retina, causing night blindness and delayed dark adaptation. It differs from fundus albipunctatus in being progressive and evolving to generalized atrophy of the retina. {ECO:0000269|PubMed:10102299, ECO:0000269|PubMed:11453974, ECO:0000269|PubMed:9326942}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.216

Intolerance Scores

LoFtool
0.332
RVIS EVS
0.17
RVIS percentile EVS
65.96

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.502

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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