RLBP1

Summary

RLBP1 (retinaldehyde binding protein 1, HGNC:10024) is a protein-coding gene on chromosome 15q26.1, encoding Retinaldehyde-binding protein 1 (P12271). Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors.

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.

Source: NCBI Gene 6017 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RLBP1-related retinopathy (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 428 total — 34 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 65
• MANE Select transcript: NM_000326

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10024
Approved symbol	RLBP1
Name	retinaldehyde binding protein 1
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	CRALBP
Ensembl gene	ENSG00000140522
Ensembl biotype	protein_coding
OMIM	180090
Entrez	6017

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000268125, ENST00000563254, ENST00000564388, ENST00000567787, ENST00000873617, ENST00000873618, ENST00000873619

RefSeq mRNA: 1 — MANE Select: NM_000326 NM_000326

CCDS: CCDS32324

Canonical transcript exons

ENST00000268125 — 9 exons

Exon	Start	End
ENSE00000943552	89218565	89218693
ENSE00000943553	89217120	89217324
ENSE00000943554	89215060	89215238
ENSE00000943556	89210699	89210809
ENSE00000943557	89209869	89210443
ENSE00001375615	89219737	89219859
ENSE00001386450	89218964	89219075
ENSE00001391768	89221535	89221579
ENSE00003506619	89211743	89211901

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 98.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8750 / max 799.4700, expressed in 162 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151433	0.6309	92
151437	0.0837	47
151435	0.0815	9
151430	0.0356	15
151436	0.0175	5
151434	0.0123	5
151429	0.0069	3
151432	0.0041	1
151431	0.0025	1

Top tissues by expression

245 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	98.78	gold quality
retina	UBERON:0000966	98.76	gold quality
optic choroid	UBERON:0001776	90.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.38	gold quality
caudate nucleus	UBERON:0001873	82.07	gold quality
putamen	UBERON:0001874	82.00	gold quality
right frontal lobe	UBERON:0002810	80.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.30	gold quality
anterior cingulate cortex	UBERON:0009835	78.05	gold quality
amygdala	UBERON:0001876	77.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.65	silver quality
prefrontal cortex	UBERON:0000451	76.60	gold quality
endometrium epithelium	UBERON:0004811	75.49	gold quality
nucleus accumbens	UBERON:0001882	75.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.20	gold quality
ventricular zone	UBERON:0003053	73.84	gold quality
ganglionic eminence	UBERON:0004023	72.57	gold quality
neocortex	UBERON:0001950	72.47	gold quality
frontal cortex	UBERON:0001870	72.27	gold quality
forebrain	UBERON:0001890	69.74	gold quality
Brodmann (1909) area 10	UBERON:0013541	69.16	gold quality
cerebral cortex	UBERON:0000956	69.13	gold quality
cranial nerve II	UBERON:0000941	68.05	silver quality
brain	UBERON:0000955	67.62	gold quality
central nervous system	UBERON:0001017	67.31	gold quality
adenohypophysis	UBERON:0002196	66.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	64.89	gold quality
frontal pole	UBERON:0002795	64.77	gold quality
middle frontal gyrus	UBERON:0002702	64.47	gold quality
hypothalamus	UBERON:0001898	64.46	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	2970.09
E-GEOD-135922	yes	2738.14
E-GEOD-137537	yes	47.31
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): LHX2, NR2E3, OTX2, PAX6, RARA, SOX9

miRNA regulators (miRDB)

29 targeting RLBP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-3136-5P	98.53	67.68	793
HSA-MIR-4439	98.53	67.53	793
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-3664-5P	96.74	66.56	770
HSA-MIR-6857-3P	96.70	65.43	915
HSA-MIR-6760-3P	96.35	68.31	1001
HSA-MIR-3162-5P	95.67	67.53	794
HSA-MIR-1237-5P	95.38	62.21	451
HSA-MIR-4488	95.38	62.00	443
HSA-MIR-4697-5P	95.38	61.72	457
HSA-MIR-4278	95.28	65.49	351
HSA-MIR-1915-5P	95.25	65.78	571

Literature-anchored findings (GeneRIF, showing 31)

• Newfoundland rod-cone dystrophy, an early-onset retinal dystrophy, is caused by splice-junction mutations in RLBP1 (PMID:11868161)
• the M225K mutation abolishes and the R233W mutation tightens retinoid binding and both impair CRALBP function in the visual cycle as an 11-cis-retinol acceptor and as a substrate carrier. (PMID:12536144)
• Trp-165, Met-208, Met-222, Met-225, and Trp-244 are components of the CRALBP ligand binding cavity. (PMID:12536149)
• Patients with a clinical presentation of RPA (retinitis punctata albescens) can have genetically different mutations. (PMID:14718298)
• Only eight RLBP1 mutations have been reported to date, and here we describe two novel mutations. (PMID:15234312)
• Cellular retinaldehyde binding protein 1 (CRALBP) inhibits the reduction of 11-cis-retinal stronger than the oxidation of 11-cis-retinol, in accord with its higher affinity for 11-cis-retinal. (PMID:15865448)
• A novel mutation in RLBP1 gene was found in a Japanese patient with retinitis punctata albescens. Degenerative changes of the outer retina were detected by optical coherence tomography (PMID:15953459)
• Because of the high density of Alu elements in RLBP1, a systematic search should be made for deletions in this gene when one or both alleles lack point mutations, in the case of RPA or flecked retinal dystrophy. (PMID:17065479)
• analysis of CRALBP ligand and protein interactions (PMID:17249612)
• CRALBP transcripts in retinal pigment epithelium cells contain a noncoding exon in addition to a newly described promoter and, by definition, an additional intron (PMID:17652763)
• The presence of CRALBP autoantibodies in 54% of tested uveitis patients supports CRALBP as a possible autoantigen in human autoimmune uveitis (PMID:18317528)
• Bothnia dystrophy is caused by the loss of CRALBP function due to changed physical features and impaired activity of retinoid binding. (PMID:18344446)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia (PMID:19165527)
• These results reveal an unanticipated domino-like structural transition causing Bothnia-type retinal dystrophy by the impaired release of 11-cis-retinal from R234W. (PMID:19846785)
• In the RLBP1-Bothnia dystrophy phenotype, a loss of function and thinning of the central macula are found, indicating early damage of the cone photoreceptors in this disease of the visual cycle. (PMID:20696998)
• mutations in RLBP1 are responsible for fundus albipunctatus in the affected individuals of these consanguineous Pakistani families. (PMID:21447491)
• Identification of autoantibodies specific for two retinal antigens (CRALBP and S-Ag) supports the concept of an autoimmunological origin of the disease. (PMID:21904838)
• The clinical characteristics of a Japanese patient with a homozygous R234W mutation in RLBP1 are very similar to that of Swedish patients with Bothnia dystrophy. (PMID:22171637)
• The R234W mutation reveals impaired 11-cis-retinal release through stabilization of the ligand complex. (PMID:22183382)
• The two RLBP1 genotypes presented a phenotypical and electrophysiological expression of progressive retinal disease similar to that previously described in homozygotes for the c.700C>T (p.R234W) RLBP1 mutation. (PMID:22551409)
• Patients with retinitis punctata albescens (RPA) show variable degrees of foveal cone death, even at an early stage. This finding has implications for future treatment. (PMID:23929416)
• RLBP1 gene is upregulated in patients with reactive retinal astrocytic tumors. (PMID:24921169)
• Different mutations in RLBP1 are correlated with quite different morphological and functional characteristics outlines the complexity of the protein. (PMID:25429852)
• We conclude that the expression of Rlbp1 and Rdh5 critically depends on functional Mitf in the RPE and suggest that MITF has an important role in controlling retinoid processing in the RPE. (PMID:26876013)
• we provide evidence for an allosteric modulation of the enzymatic activity by 11-cis retinoids. This regulation is independent from cellular retinaldehyde-binding protein (CRALBP), the major cis-retinoid binding protein. (PMID:28096191)
• RLBP1 gene geographical area-related mutation is associated with retinitis punctata albescens. (PMID:28764803)
• These results show that joint tests of main effects and gene-gene interaction reveal associations at some novel loci that were missed when considering main effects alone. (PMID:28813576)
• Effects of deficiency in the RLBP1-encoded visual cycle protein CRALBP on visual dysfunction in humans and mice. (PMID:32188692)
• Clinical heterogeneity in retinitis pigmentosa caused by variants in RP1 and RLBP1 in five extended consanguineous pedigrees. (PMID:32587456)
• Shared Features in Retinal Disorders With Involvement of Retinal Pigment Epithelium. (PMID:34115091)
• Variants of Uncertain Significance: Twins With Identical Pathogenic Gene Mutations in Retinitis Punctata Albescens. (PMID:34410188)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	rlbp1a	ENSDARG00000012504
danio_rerio	rlbp1b	ENSDARG00000045808
mus_musculus	Rlbp1	ENSMUSG00000039194
rattus_norvegicus	Rlbp1	ENSRNOG00000016897
drosophila_melanogaster	CG3191	FBGN0023525
drosophila_melanogaster	CG3091	FBGN0029608
drosophila_melanogaster	CG3823	FBGN0029863
drosophila_melanogaster	CG1902	FBGN0033434
drosophila_melanogaster	CG12926	FBGN0033437
drosophila_melanogaster	CG10301	FBGN0039106
drosophila_melanogaster	CG10300	FBGN0039107
drosophila_melanogaster	CG30339	FBGN0050339
drosophila_melanogaster	CG31636	FBGN0051636
drosophila_melanogaster	CG32485	FBGN0052485
drosophila_melanogaster	CG33514	FBGN0053514
drosophila_melanogaster	CG33965	FBGN0053965
drosophila_melanogaster	CG33966	FBGN0053966

Paralogs (3): TTPAL (ENSG00000124120), CLVS2 (ENSG00000146352), CLVS1 (ENSG00000177182)

Protein

Protein identifiers

Retinaldehyde-binding protein 1 — P12271 (reviewed: P12271)

Alternative names: Cellular retinaldehyde-binding protein

All UniProt accessions (3): P12271, H3BN92, H3BTN3

UniProt curated annotations — full annotation on UniProt →

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’.

Subunit / interactions. Interacts with DEGS1; the interaction increases synthesis of chromophore-precursors by DEGS1.

Subcellular location. Cytoplasm.

Tissue specificity. Retina and pineal gland. Not present in photoreceptor cells but is expressed abundantly in the adjacent retinal pigment epithelium (RPE) and in the Mueller glial cells of the retina.

Disease relevance. Bothnia retinal dystrophy (BRD) [MIM:607475] A type of retinitis punctata albescens. Affected individuals show night blindness from early childhood with features consistent with retinitis punctata albescens and macular degeneration. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_000317* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001251	CRAL-TRIO_dom	Domain
IPR011074	CRAL/TRIO_N_dom	Domain
IPR036273	CRAL/TRIO_N_dom_sf	Homologous_superfamily
IPR036865	CRAL-TRIO_dom_sf	Homologous_superfamily

Pfam: PF00650, PF03765

UniProt features (44 total): helix 19, turn 9, strand 7, sequence variant 3, binding site 2, initiator methionine 1, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3HX3	X-RAY DIFFRACTION	1.69
4CJ6	X-RAY DIFFRACTION	1.9
3HY5	X-RAY DIFFRACTION	3.04
4CIZ	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12271-F1	91.75	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 180; 202

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2187335	The retinoid cycle in cones (daylight vision)
R-HSA-2453902	The canonical retinoid cycle in rods (twilight vision)
R-HSA-9918438	Defective visual phototransduction due to RDH5 loss of function

MSigDB gene sets: 165 (showing top): MODULE_404, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, TGCTGAY_UNKNOWN, GOBP_LIPID_METABOLIC_PROCESS, GOBP_SENSORY_PERCEPTION, GOBP_ISOPRENOID_METABOLIC_PROCESS, MODULE_573, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOCC_CELL_BODY, ZHENG_GLIOBLASTOMA_PLASTICITY_UP, GOMF_PHOSPHATIDYLINOSITOL_PHOSPHATE_BINDING, GOMF_ALCOHOL_BINDING, GOMF_PHOSPHATIDYLINOSITOL_BINDING, GOMF_RETINAL_BINDING

GO Biological Process (2): vitamin A metabolic process (GO:0006776), visual perception (GO:0007601)

GO Molecular Function (4): 11-cis retinal binding (GO:0005502), retinol binding (GO:0019841), phosphatidylinositol bisphosphate binding (GO:1902936), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), cell body (GO:0044297), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Visual phototransduction	2
Retinoid cycle disease events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
retinoid metabolic process	1
sensory perception of light stimulus	1
retinal binding	1
retinoid binding	1
vitamin binding	1
alcohol binding	1
anion binding	1
binding	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1064 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RLBP1	RDH5	Q92781	957
RLBP1	RPE65	Q16518	925
RLBP1	RDH11	Q8TC12	904
RLBP1	RDH8	Q9NYR8	891
RLBP1	RBP1	P09455	862
RLBP1	RHO	P08100	858
RLBP1	RDH12	Q96NR8	857
RLBP1	BEST1	O76090	782
RLBP1	PRPH2	P23942	754
RLBP1	LRAT	O95237	737
RLBP1	VSX2	P58304	683
RLBP1	RCVRN	P35243	682
RLBP1	RGR	P47804	682
RLBP1	RBP3	P10745	680
RLBP1	GLUL	P15104	643

IntAct

7 interactions, top by confidence:

A	B	Type	Score
RLBP1	KLHL8	psi-mi:“MI:0915”(physical association)	0.560
OR10H1	NRP1	psi-mi:“MI:0914”(association)	0.350
EMB	RLBP1	psi-mi:“MI:0914”(association)	0.350
RLBP1	INPPL1	psi-mi:“MI:0914”(association)	0.350
RLBP1	KLHL8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): KLHL8 (Two-hybrid), RDH5 (Reconstituted Complex), RLBP1 (Affinity Capture-MS), RLBP1 (Affinity Capture-MS), VPS11 (Affinity Capture-MS), INPPL1 (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A7T167, A8Y5H7, B4JLU7, B4L529, B5MCN3, E1C1U1, O17907, O35239, O76054, P10123, P11541, P12271, P16499, P16586, P23440, P24280, P24859, P27664, P35913, P43378, P46250, P49193, P51160, P53989, P58875, Q03606, Q09270, Q0V9N0, Q16KN5, Q19895, Q28263, Q29JQ0, Q5RFR0, Q641Z2, Q6CXS7, Q6DNF4, Q75BM4, Q75DK1, Q8R0F9, Q91ZQ1

Diamond homologs: A6JFQ6, A6JUQ6, E1C1U1, P10123, P12271, P41034, P49638, Q19895, Q5M7E1, Q5RCA6, Q5RFR0, Q5SPP0, Q5SYC1, Q8BG92, Q8BWP5, Q8IUQ0, Q95KF7, Q9BTX7, Q9D3D0, Q9D4C9, Q9Z275, P53989, P49193, O76054, P45816, Q99J08, Q99MS0, A8Y5H7, B5MCN3, F4HP88, F4IHJ0, F4JLE5, F4JVA6, F4JVA9, O43304, P58875, Q03606, Q0V9N0, Q10137, Q29JQ0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

428 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	10
Uncertain significance	152
Likely benign	174
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074473	NM_000326.5(RLBP1):c.466C>T (p.Arg156Ter)	Pathogenic
13097	NM_000326.5(RLBP1):c.452G>A (p.Arg151Gln)	Pathogenic
13099	NM_000326.5(RLBP1):c.141G>A (p.Lys47=)	Pathogenic
1345386	NM_000326.5(RLBP1):c.1A>T (p.Met1Leu)	Pathogenic
1400422	NM_000326.5(RLBP1):c.250del (p.Val84fs)	Pathogenic
1457901	NM_000326.5(RLBP1):c.202G>T (p.Glu68Ter)	Pathogenic
1458059	NM_000326.5(RLBP1):c.508G>T (p.Glu170Ter)	Pathogenic
1489065	NM_000326.5(RLBP1):c.827del (p.Phe276fs)	Pathogenic
2422890	NC_000015.9:g.(?89758271)(89758489_?)del	Pathogenic
2769329	NM_000326.5(RLBP1):c.735G>A (p.Trp245Ter)	Pathogenic
2793624	NM_000326.5(RLBP1):c.5C>G (p.Ser2Ter)	Pathogenic
2831163	NM_000326.5(RLBP1):c.333T>A (p.Tyr111Ter)	Pathogenic
2846223	NM_000326.5(RLBP1):c.130_131del (p.Thr44fs)	Pathogenic
2848932	NM_000326.5(RLBP1):c.631_638del (p.Gln210_Gln211insTer)	Pathogenic
2861745	NM_000326.5(RLBP1):c.61C>T (p.Gln21Ter)	Pathogenic
2873431	NM_000326.5(RLBP1):c.446_447del (p.Leu148_Ser149insTer)	Pathogenic
2876674	NM_000326.5(RLBP1):c.505C>T (p.Gln169Ter)	Pathogenic
2972776	NM_000326.5(RLBP1):c.346+2T>G	Pathogenic
2995933	NM_000326.5(RLBP1):c.163del (p.Arg55fs)	Pathogenic
3243856	NC_000015.9:g.(?89753516)(89755152_?)del	Pathogenic
3250289	NC_000015.10:g.(?89210284)(89211902_89215059)del	Pathogenic
3641145	NM_000326.5(RLBP1):c.167_168dup (p.Glu57fs)	Pathogenic
3644722	NM_000326.5(RLBP1):c.498G>A (p.Trp166Ter)	Pathogenic
3647188	NM_000326.5(RLBP1):c.141+1G>C	Pathogenic
3704469	NM_000326.5(RLBP1):c.811del (p.Asp271fs)	Pathogenic
4277810	NM_000326.5(RLBP1):c.12+1G>A	Pathogenic
4727667	NM_000326.5(RLBP1):c.795+1G>A	Pathogenic
4733689	NM_000326.5(RLBP1):c.141+2T>G	Pathogenic
635160	NM_000326.5(RLBP1):c.79del (p.Thr27fs)	Pathogenic
636197	NM_000326.5(RLBP1):c.346G>C (p.Gly116Arg)	Pathogenic

SpliceAI

1335 predictions. Top by Δscore:

Variant	Effect	Δscore
15:89210693:A:AC	donor_gain	1.0000
15:89210694:C:CC	donor_gain	1.0000
15:89210696:CA:C	donor_loss	1.0000
15:89210697:A:AC	donor_gain	1.0000
15:89210697:AC:A	donor_gain	1.0000
15:89210698:C:CC	donor_gain	1.0000
15:89210698:CC:C	donor_gain	1.0000
15:89210698:CCCT:C	donor_gain	1.0000
15:89210808:TC:T	acceptor_gain	1.0000
15:89210809:CC:C	acceptor_gain	1.0000
15:89211737:CCTCA:C	donor_loss	1.0000
15:89211738:CTCA:C	donor_loss	1.0000
15:89211739:TCA:T	donor_loss	1.0000
15:89211740:CA:C	donor_loss	1.0000
15:89211741:ACCTG:A	donor_loss	1.0000
15:89211742:C:CT	donor_loss	1.0000
15:89211763:T:TA	donor_gain	1.0000
15:89211899:GAT:G	acceptor_gain	1.0000
15:89211902:C:CA	acceptor_loss	1.0000
15:89211902:C:CC	acceptor_gain	1.0000
15:89211903:T:C	acceptor_gain	1.0000
15:89211903:T:TC	acceptor_gain	1.0000
15:89215056:TAACC:T	donor_loss	1.0000
15:89215057:AAC:A	donor_loss	1.0000
15:89215058:A:AG	donor_loss	1.0000
15:89215059:CCT:C	donor_gain	1.0000
15:89215235:TAGC:T	acceptor_gain	1.0000
15:89215236:AGC:A	acceptor_gain	1.0000
15:89215237:GC:G	acceptor_gain	1.0000
15:89215238:CC:C	acceptor_gain	1.0000

AlphaMissense

2099 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:89215118:C:G	R156P	0.999
15:89210699:C:A	R265S	0.998
15:89210699:C:G	R265S	0.998
15:89210733:A:T	V254D	0.998
15:89210796:G:T	A233D	0.998
15:89210799:G:T	P232Q	0.998
15:89211837:C:A	G197V	0.998
15:89211837:C:T	G197D	0.998
15:89211838:C:G	G197R	0.998
15:89217128:A:G	L113P	0.998
15:89217165:G:T	R101S	0.998
15:89217169:G:C	F99L	0.998
15:89217169:G:T	F99L	0.998
15:89217171:A:G	F99L	0.998
15:89210700:C:A	R265M	0.997
15:89211747:A:G	L227P	0.997
15:89215121:C:A	G155V	0.997
15:89217158:C:G	R103P	0.997
15:89217164:C:G	R101P	0.997
15:89210700:C:G	R265T	0.996
15:89210709:A:G	L262P	0.996
15:89210799:G:C	P232R	0.996
15:89210785:C:G	A237P	0.995
15:89210790:A:G	F235S	0.995
15:89211743:C:A	Q228H	0.995
15:89211743:C:G	Q228H	0.995
15:89211747:A:T	L227H	0.995
15:89211838:C:A	G197C	0.995
15:89211845:T:A	Q194H	0.995
15:89211845:T:G	Q194H	0.995

dbSNP variants (sampled 300 via entrez): RS1000039936 (15:89220082 T>C), RS1000064967 (15:89210029 C>T), RS1000118159 (15:89213736 A>G,T), RS1000506230 (15:89216907 G>A), RS1000618858 (15:89216634 A>G), RS1001181220 (15:89211104 C>A,T), RS1001296387 (15:89216141 G>A), RS1001643237 (15:89221923 C>A,G), RS1001801103 (15:89212190 A>G), RS1001844933 (15:89211569 G>A), RS1001874744 (15:89211131 T>A), RS1001939444 (15:89212610 G>A,T), RS1002144872 (15:89222663 G>A), RS1002246134 (15:89222930 C>A,G,T), RS1002355871 (15:89217804 AT>A,ATT)

Disease associations

OMIM: gene MIM:180090 | disease phenotypes: MIM:136880, MIM:607475, MIM:607476, MIM:268000, MIM:310500

GenCC curated gene-disease

Disease	Classification	Inheritance
Bothnia retinal dystrophy	Definitive	Autosomal recessive
fundus albipunctatus	Strong	Autosomal recessive
Newfoundland cone-rod dystrophy	Strong	Autosomal recessive
RLBP1-related retinopathy	Strong	Autosomal recessive
retinitis punctata albescens	Supportive	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
RLBP1-related retinopathy	Definitive	AR

Mondo (10): inherited retinal dystrophy (MONDO:0019118), optic atrophy (MONDO:0003608), fundus albipunctatus (MONDO:0007639), Bothnia retinal dystrophy (MONDO:0011838), Newfoundland cone-rod dystrophy (MONDO:0011839), retinitis punctata albescens (MONDO:0018877), retinitis pigmentosa (MONDO:0019200), retinal disorder (MONDO:0005283), congenital stationary night blindness (MONDO:0016293), RLBP1-related retinopathy (MONDO:0100444)

Orphanet (6): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Fundus albipunctatus (Orphanet:227796), Retinitis punctata albescens (Orphanet:52427), Bothnia retinal dystrophy (Orphanet:85128), Retinitis pigmentosa (Orphanet:791), Congenital stationary night blindness (Orphanet:215)

HPO phenotypes

65 total (30 of 65 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000493	Abnormal foveal morphology
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000529	Progressive visual loss
HP:0000539	Abnormality of refraction
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000556	Retinal dystrophy
HP:0000563	Keratoconus
HP:0000575	Scotoma
HP:0000580	Pigmentary retinopathy
HP:0000602	Ophthalmoplegia
HP:0000603	Central scotoma
HP:0000608	Macular degeneration
HP:0000610	Abnormal choroid morphology
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001123	Visual field defect

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004868_2	Advanced age-related macular degeneration	1.000000e-07
GCST004871_1	Age-related macular degeneration (SNP x mitochondrial G12771A interaction)	2.000000e-08
GCST004946_120	Schizophrenia	3.000000e-08

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C564392	Bothnia Retinal Dystrophy (supp.)
C562733	Fundus Albipunctatus (supp.)
C564391	Newfoundland Rod-Cone Dystrophy (supp.)
C536122	Night blindness, congenital stationary (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Fatty acid-binding proteins

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
beta-lapachone	increases expression	1
(+)-JQ1 compound	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1

Clinical trials (associated diseases)

266 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa