RDH5

Summary

RDH5 (retinol dehydrogenase 5, HGNC:9940) is a protein-coding gene on chromosome 12q13.2, encoding Retinol dehydrogenase 5 (Q92781). Catalyzes the oxidation of cis-isomers of retinol, including 11-cis-, 9-cis-, and 13-cis-retinol in an NAD-dependent manner.

This gene encodes an enzyme belonging to the short-chain dehydrogenases/reductases (SDR) family. This retinol dehydrogenase functions to catalyze the final step in the biosynthesis of 11-cis retinaldehyde, which is the universal chromophore of visual pigments. Mutations in this gene cause autosomal recessive fundus albipunctatus, a rare form of night blindness that is characterized by a delay in the regeneration of cone and rod photopigments. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S1 (biogenesis of lysosomal organelles complex-1, subunit 1) gene.

Source: NCBI Gene 5959 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RDH5-related retinopathy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 51 total — 5 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 23
• MANE Select transcript: NM_002905

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9940
Approved symbol	RDH5
Name	retinol dehydrogenase 5
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Aliases	HSD17B9, SDR9C5
Ensembl gene	ENSG00000135437
Ensembl biotype	protein_coding
OMIM	601617
Entrez	5959

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000257895, ENST00000547072, ENST00000547301, ENST00000548082, ENST00000548123, ENST00000548486, ENST00000550608, ENST00000551444, ENST00000552930, ENST00000553160, ENST00000553187, ENST00000866859, ENST00000866860, ENST00000866861, ENST00000866862

RefSeq mRNA: 2 — MANE Select: NM_002905 NM_001199771, NM_002905

CCDS: CCDS31829

Canonical transcript exons

ENST00000257895 — 5 exons

Exon	Start	End
ENSE00000920086	55721689	55721947
ENSE00003605848	55721153	55721494
ENSE00003618525	55723886	55724049
ENSE00003899933	55724322	55724705
ENSE00003902243	55720393	55720517

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 95.32.

FANTOM5 (CAGE): breadth broad, TPM avg 6.3120 / max 477.5487, expressed in 652 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125976	4.7211	579
125977	0.6659	244
125979	0.3245	136
125978	0.3066	108
125980	0.1498	36
206739	0.1440	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
subcutaneous adipose tissue	UBERON:0002190	95.32	gold quality
right lobe of liver	UBERON:0001114	94.72	gold quality
adipose tissue	UBERON:0001013	94.61	gold quality
mucosa of transverse colon	UBERON:0004991	94.59	gold quality
omental fat pad	UBERON:0010414	93.74	gold quality
liver	UBERON:0002107	92.83	gold quality
right atrium auricular region	UBERON:0006631	92.19	gold quality
duodenum	UBERON:0002114	91.21	gold quality
transverse colon	UBERON:0001157	90.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.28	gold quality
left coronary artery	UBERON:0001626	90.14	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.96	gold quality
colon	UBERON:0001155	89.74	gold quality
heart left ventricle	UBERON:0002084	89.73	gold quality
heart	UBERON:0000948	89.66	gold quality
small intestine	UBERON:0002108	89.44	gold quality
intestine	UBERON:0000160	89.42	gold quality
mammary gland	UBERON:0001911	89.38	gold quality
thoracic mammary gland	UBERON:0005200	89.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.26	gold quality
lower esophagus	UBERON:0013473	89.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.25	gold quality
right coronary artery	UBERON:0001625	88.86	gold quality
popliteal artery	UBERON:0002250	88.82	gold quality
tibial artery	UBERON:0007610	88.80	gold quality
apex of heart	UBERON:0002098	88.73	gold quality
right uterine tube	UBERON:0001302	88.60	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.21	gold quality
ascending aorta	UBERON:0001496	88.18	gold quality
thoracic aorta	UBERON:0001515	88.14	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	18.37
E-MTAB-5061	no	2.12
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting RDH5, 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-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4473	98.89	69.10	652
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-4715-5P	97.62	67.47	506
HSA-MIR-6753-5P	94.70	64.08	470

Literature-anchored findings (GeneRIF, showing 24)

• Macular dystrophy is caused by the RDH5 mutation as a phenotype variation in fundus albipunctus. (PMID:11812441)
• Macular dystrophy is caused by the RDH5 gene mutation as a phenotype variation in fundus albipunctatus. (PMID:12788147)
• Fundus changes due to Fundus albipunctatus associated with mutations in the RDH5 gene. (PMID:12860821)
• RDH5 gene mutations cause a progressive cone dystrophy or macular dystrophy as well as night blindness. The clinical phenotype including electrophysiological responses varied among patients with the RDH5 gene mutations. (PMID:12906118)
• A homozygous G490T (Val164Phe) missense RDH5 gene mutation was detected. (PMID:12967826)
• Homozygous Gly107Arg mutation in the RDH5 gene in two unrelated Japanese families with fundus albipunctatus. (PMID:15007239)
• Cone dystrophy can be present in patients with fundus albipunctatus, not only elderly men but also young women. (PMID:15302662)
• Our study indicates that different mutations in the RDH5 gene can cause phenotypic variations of either fundus albipunctatus or familial fleck retina with night blindness. (PMID:16637847)
• study describes an unusual family which included a mother with fundus albipunctatus and three children with typical retinitis pigmentosa; a novel RDH5 mutation was found (PMID:18363170)
• An amino acid important for steroid/retinoid discrimination was identified and its significance was highlighted by the results of molecular modeling studies. (PMID:20382160)
• Mutations in RDH5 associated with fundus albipunctatus seem to prevent normal lipofuscin accumulation. (PMID:20829743)
• The clinical and electrophysiologic phenotype of patients with RDH5 retinopathy is variable. (PMID:21529959)
• The proband had a compound heterozygotic missense mutation of Cys59Ser (TGC –> AGC) and a nonsense mutation of Trp95ter (TGG –> TGA) in the RDH5 gene. (PMID:22669287)
• RDH5 sequence analysis revealed a novel five base pair deletion, c.913_917delGTGCT (p.Val305Hisfs*29), in family A, and a novel missense mutation, c.758T>G (p.Met253Arg), in family B with fundus albipunctatus. (PMID:22736946)
• Four novel RDH5 gene mutations were identified in fundus albipunctatus Israeli patients. Of them, the null mutations c.343C>T (p.R54X) and c. 242delTGCC were the most prevalent. (PMID:22815624)
• Macular cone density is lower and the regularity of the macular cone mosaic spatial arrangement is disrupted in eyes with fundus albipunctatus. (PMID:24246574)
• A novel c.832C>T (p.Arg278Ter) nonsense mutation in RDH5 was identified. Preserved rod function was observed in one young subject in this study. (PMID:25170858)
• 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)
• a novel homozygous missense mutation, (c.602 C > T) in exon 4 of the RDH5 gene (MIM: 601617) was identified. This mutation resulted in substitution of phenyl alanine for serine at amino acid 201 (p.Ser201Phe) of the RDH5 gene. Identification of this mutation reveals the allelic heterogeneity of RDH5 in patients with retinitis pigmentosa phenotype. (PMID:29892959)
• A founder RDH5 splice site mutation leads to retinitis punctata albescens in two inbred Pakistani kindreds. (PMID:31933420)
• Multimodal imaging and electroretinography of RDH5-related fundus albipunctatus (FAP) revealed high frequencies of macular involvement in older patients and decreased cone responses. (PMID:32232344)
• Retinal dehydrogenase 5 (RHD5) attenuates metastasis via regulating HIPPO/YAP signaling pathway in Hepatocellular Carcinoma. (PMID:32788868)
• Shared Features in Retinal Disorders With Involvement of Retinal Pigment Epithelium. (PMID:34115091)
• Novel variants in the RDH5 Gene in a Chinese Han family with fundus albipunctatus. (PMID:35148716)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rdh5	ENSDARG00000008306
mus_musculus	Rdh5	ENSMUSG00000025350
rattus_norvegicus	Rdh5	ENSRNOG00000007784

Paralogs (25): HSD17B6 (ENSG00000025423), RDH11 (ENSG00000072042), HSD17B10 (ENSG00000072506), DHRS9 (ENSG00000073737), HSD17B2 (ENSG00000086696), HSD17B14 (ENSG00000087076), DHRS12 (ENSG00000102796), HSDL1 (ENSG00000103160), HSD17B1 (ENSG00000108786), RDH10 (ENSG00000121039), HSD17B3 (ENSG00000130948), HSD17B7 (ENSG00000132196), HSD17B4 (ENSG00000133835), RDH16 (ENSG00000139547), RDH12 (ENSG00000139988), HSD17B12 (ENSG00000149084), BDH1 (ENSG00000161267), DHRS3 (ENSG00000162496), SDR9C7 (ENSG00000170426), HSD17B13 (ENSG00000170509), SDR16C5 (ENSG00000170786), HSD11B2 (ENSG00000176387), WWOX (ENSG00000186153), HSD17B11 (ENSG00000198189), HSD17B8 (ENSG00000204228)

Protein

Protein identifiers

Retinol dehydrogenase 5 — Q92781 (reviewed: Q92781)

Alternative names: 11-cis retinol dehydrogenase, 9-cis retinol dehydrogenase, Short chain dehydrogenase/reductase family 9C member 5

All UniProt accessions (4): Q92781, F8VUB9, F8VVC7, H0YHP7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidation of cis-isomers of retinol, including 11-cis-, 9-cis-, and 13-cis-retinol in an NAD-dependent manner. Has no activity towards all-trans retinal. Plays a significant role in 11-cis retinol oxidation in the retinal pigment epithelium cells (RPE). Also recognizes steroids (androsterone, androstanediol) as its substrates.

Subunit / interactions. Homodimer.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed. In the eye, abundant in the retinal pigment epithelium.

Disease relevance. Fundus albipunctatus (FALBI) [MIM:136880] A form of fleck retina disease characterized by discrete uniform white dots over the entire fundus with greatest density in the mid-periphery and no macular involvement. Night blindness occurs. Inheritance can be autosomal dominant or autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by 9-cis-, 13-cis- and all-trans-retinoic acids, with the most potent inhibitor being 13-cis-retinoic acid. Weakly inhibited by oleic acid.

Domain organisation. The last 8 amino acids of the C-terminal tail are important for a proper localization as well as for the in vivo enzymatic activity.

Pathway. Cofactor metabolism; retinol metabolism.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family.

RefSeq proteins (2): NP_001186700, NP_002896* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00106

Enzyme classification (BRENDA):

• EC 1.1.1.300 — NADP-retinol dehydrogenase (BRENDA: 11 organisms, 101 substrates, 7 inhibitors, 67 Km, 12 kcat entries)
• EC 1.1.1.315 — 11-cis-retinol dehydrogenase (BRENDA: 3 organisms, 59 substrates, 4 inhibitors, 26 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

25 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ALL-TRANS-RETINAL	0.0001–0.5	19
NADPH	0.0005–0.23	10
NADP+	0.0004–0.8	9
ALL-TRANS-RETINOL	0.0006–1.3	6
NADH	2.22–1300	4
NAD+	0.002–0.1	4
ALL-TRANS-3-HYDROXYRETINAL	0.0032–0.0044	3
ESTRONE	0.0096–0.0307	3
NAD+	0.004–680	3
11-CIS-RETINOL-[CELLULAR RETINALDEHYDE BINDING P	0.0025–0.0067	3
9-CIS-RETINOL	0.0066–6	3
ALL-TRANS RETINOL	0.0002–0.0041	3
9-CIS-RETINAL	0.0001–0.19	2
RETINAL	0.007–0.13	2
11-CIS-RETINOL	0.0063–0.06	2

Catalyzed reactions (Rhea), 5 shown:

• androsterone + NAD(+) = 5alpha-androstan-3,17-dione + NADH + H(+) (RHEA:20381)
• 5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta-hydroxy-5alpha-androstan-3-one + NADH + H(+) (RHEA:42004)
• 9-cis-retinol + NAD(+) = 9-cis-retinal + NADH + H(+) (RHEA:42052)
• 13-cis-retinol + NAD(+) = 13-cis-retinal + NADH + H(+) (RHEA:42056)
• 11-cis-retinol + NAD(+) = 11-cis-retinal + NADH + H(+) (RHEA:42060)

UniProt features (37 total): sequence variant 22, sequence conflict 5, transmembrane region 2, topological domain 2, binding site 2, chain 1, mutagenesis site 1, active site 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92781-F1	96.02	0.94

Functional residue map

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

Catalytic / active sites (1): 175 (proton acceptor)

Ligand- & substrate-binding residues (2): 32–56; 163

Glycosylation sites (1): 160

Mutagenesis-validated functional residues (1):

Position	Phenotype
175–179	decreases androsterone dehydrogenase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2453902	The canonical retinoid cycle in rods (twilight vision)
R-HSA-5365859	RA biosynthesis pathway
R-HSA-9918438	Defective visual phototransduction due to RDH5 loss of function

MSigDB gene sets: 181 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_RETINOL_METABOLIC_PROCESS, PID_CONE_PATHWAY, GOMF_STEROID_DEHYDROGENASE_ACTIVITY_ACTING_ON_THE_CH_OH_GROUP_OF_DONORS_NAD_OR_NADP_AS_ACCEPTOR, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, BROWNE_HCMV_INFECTION_24HR_DN, GOBP_LIPID_METABOLIC_PROCESS, NRF2_Q4, SANSOM_APC_TARGETS_DN, GOBP_SENSORY_PERCEPTION, KANG_IMMORTALIZED_BY_TERT_DN, AML1_01, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS

GO Biological Process (5): retinoid metabolic process (GO:0001523), visual perception (GO:0007601), steroid metabolic process (GO:0008202), retinol metabolic process (GO:0042572), lipid metabolic process (GO:0006629)

GO Molecular Function (7): all-trans-retinol dehydrogenase (NAD+) activity (GO:0004745), protein homodimerization activity (GO:0042803), androsterone dehydrogenase [NAD(P)+] activity (GO:0047023), androstan-3-alpha,17-beta-diol dehydrogenase (NAD+) activity (GO:0047044), 11-cis-retinol dehydrogenase (NAD+) activity (GO:0106429), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616)

GO Cellular Component (5): endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), cell body (GO:0044297), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Visual phototransduction	1
Signaling by Retinoic Acid	1
Retinoid cycle disease events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
alcohol dehydrogenase (NAD+) activity	2
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
cellular anatomical structure	2
diterpenoid metabolic process	1
sensory perception of light stimulus	1
lipid metabolic process	1
retinoid metabolic process	1
primary alcohol metabolic process	1
hormone metabolic process	1
olefinic compound metabolic process	1
primary metabolic process	1
identical protein binding	1
protein dimerization activity	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
endoplasmic reticulum	1
intracellular organelle lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

890 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RDH5	RLBP1	P12271	957
RDH5	RGR	P47804	871
RDH5	RPE65	Q16518	844
RDH5	LRAT	O95237	762
RDH5	RHO	P08100	758
RDH5	ABCA4	P78363	717
RDH5	PRPH2	P23942	666
RDH5	RBP1	P09455	635
RDH5	CABP4	P57796	626
RDH5	DHRS11	Q6UWP2	601
RDH5	PRSS56	P0CW18	600
RDH5	ALDH1A3	P47895	572
RDH5	STRA6	Q9BX79	556
RDH5	RBP3	P10745	542
RDH5	CYP26A1	O43174	534

IntAct

5 interactions, top by confidence:

A	B	Type	Score
RDH5	NME2P1	psi-mi:“MI:0914”(association)	0.530
ORC4	RDH5	psi-mi:“MI:0915”(physical association)	0.490

BioGRID (12): UBE2G1 (Affinity Capture-MS), DDI2 (Affinity Capture-MS), NME2P1 (Affinity Capture-MS), HERC3 (Affinity Capture-MS), NME2P1 (Affinity Capture-MS), DDI2 (Affinity Capture-MS), GNPNAT1 (Affinity Capture-MS), RDH5 (Two-hybrid), RDH5 (Reconstituted Complex), NME2P1 (Affinity Capture-MS), DDI2 (Affinity Capture-MS), RDH5 (Affinity Capture-RNA)

ESM2 similar proteins: A2AI05, D3ZDK7, E1BNQ4, O55240, O70249, P21139, P24298, P25409, P50336, P51175, P56602, P97849, Q03426, Q1JPJ0, Q27979, Q2KJF7, Q3T0A0, Q3ZKN0, Q498R1, Q4JIJ2, Q5E9M9, Q5E9T8, Q5R7A2, Q5RK23, Q60714, Q60HD5, Q6AYG0, Q6NRG5, Q6P1M0, Q6P3E7, Q6PCB7, Q6PFP6, Q7TSA0, Q8BNV1, Q8BZG5, Q8C1A3, Q8CHP8, Q8IXI1, Q8JZN7, Q8QZR5

Diamond homologs: A0A017SE81, A0A0E3D8L9, A0A0U1LQE2, A0A140JWS5, A0A2G0QDN4, A0A3R5XUE6, A0A5B8YU68, A0A8F5XX49, A7LB60, D2WKD9, F1QLP1, G4N286, G9N4A9, N4WE73, O05730, O14756, O16881, O54753, O55240, O67610, O74628, O75452, P0A2D1, P0A2D2, P0AFP4, P0AFP5, P0CU71, P0DKC5, P0DKC6, P15047, P16152, P25970, P29147, P37059, P37959, P39577, P40471, P50170, P54554, P66778

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RDH5	“down-regulates quantity”	retinol	“chemical modification”
RDH5	“up-regulates quantity”	retinal	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	5
Uncertain significance	24
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1323522	NM_002905.5(RDH5):c.625del (p.Arg209fs)	Pathogenic
1458154	NM_002905.5(RDH5):c.284G>A (p.Trp95Ter)	Pathogenic
236445	NM_002905.5(RDH5):c.536A>G (p.Lys179Arg)	Pathogenic
812391	NM_002905.5(RDH5):c.71_74del (p.Leu24fs)	Pathogenic
812393	NM_002905.5(RDH5):c.547G>T (p.Glu183Ter)	Pathogenic
2765616	NM_002905.5(RDH5):c.569+1G>A	Likely pathogenic
3574983	NM_002905.5(RDH5):c.55_56del (p.Arg19fs)	Likely pathogenic
3574985	NM_002905.5(RDH5):c.148C>T (p.Gln50Ter)	Likely pathogenic
623474	NM_002905.5(RDH5):c.-33+2dup	Likely pathogenic
930528	NM_002905.5(RDH5):c.248dup (p.Thr84fs)	Likely pathogenic

SpliceAI

891 predictions. Top by Δscore:

Variant	Effect	Δscore
12:55721286:C:A	acceptor_gain	1.0000
12:55721315:T:TA	acceptor_gain	1.0000
12:55721491:GCAG:G	donor_gain	1.0000
12:55721492:CAGG:C	donor_loss	1.0000
12:55721494:GGT:G	donor_loss	1.0000
12:55721495:G:GA	donor_loss	1.0000
12:55721683:CCACA:C	acceptor_loss	1.0000
12:55721684:CACA:C	acceptor_loss	1.0000
12:55721684:CACAG:C	acceptor_loss	1.0000
12:55721686:CA:C	acceptor_loss	1.0000
12:55721687:A:AG	acceptor_gain	1.0000
12:55721687:AG:A	acceptor_gain	1.0000
12:55721687:AGG:A	acceptor_gain	1.0000
12:55721688:G:GT	acceptor_gain	1.0000
12:55721688:GG:G	acceptor_gain	1.0000
12:55721688:GGG:G	acceptor_gain	1.0000
12:55721688:GGGC:G	acceptor_gain	1.0000
12:55720514:GGAG:G	donor_gain	0.9900
12:55720515:GAG:G	donor_gain	0.9900
12:55720515:GAGG:G	donor_gain	0.9900
12:55720518:G:GA	donor_loss	0.9900
12:55721284:ACC:A	acceptor_gain	0.9900
12:55721287:G:A	acceptor_gain	0.9900
12:55721490:AGCAG:A	donor_gain	0.9900
12:55721491:GCAGG:G	donor_gain	0.9900
12:55721492:CAG:C	donor_gain	0.9900
12:55721494:GGTA:G	donor_loss	0.9900
12:55721495:G:GG	donor_gain	0.9900
12:55721496:T:A	donor_loss	0.9900
12:55721685:A:AG	acceptor_gain	0.9900

AlphaMissense

2016 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:55721865:A:C	S163R	0.996
12:55721867:C:A	S163R	0.996
12:55721867:C:G	S163R	0.996
12:55721708:T:A	N110K	0.995
12:55721708:T:G	N110K	0.995
12:55721911:C:T	S178F	0.995
12:55721914:A:T	K179I	0.995
12:55721866:G:T	S163I	0.992
12:55721911:C:A	S178Y	0.992
12:55723938:T:C	F208L	0.992
12:55723940:C:A	F208L	0.992
12:55723940:C:G	F208L	0.992
12:55721858:C:A	N160K	0.991
12:55721858:C:G	N160K	0.991
12:55721901:T:C	Y175H	0.991
12:55721916:T:C	F180L	0.991
12:55721918:T:A	F180L	0.991
12:55721918:T:G	F180L	0.991
12:55721356:A:C	S58R	0.990
12:55721358:C:A	S58R	0.990
12:55721358:C:G	S58R	0.990
12:55721934:T:C	S186P	0.989
12:55721947:G:T	R190M	0.989
12:55721292:T:G	C36W	0.988
12:55721291:G:A	C36Y	0.987
12:55721935:C:T	S186F	0.987
12:55721947:G:C	R190T	0.987
12:55721276:T:A	V31D	0.985
12:55721786:C:A	N136K	0.985
12:55721786:C:G	N136K	0.985

dbSNP variants (sampled 300 via entrez): RS1001008131 (12:55722729 A>G), RS1001100029 (12:55722536 T>G), RS1001887070 (12:55722471 A>C), RS1001913268 (12:55724899 T>C), RS1001995245 (12:55725166 G>A,T), RS1002603694 (12:55719753 A>G), RS1002657866 (12:55719440 G>A,C), RS1002770957 (12:55719981 A>G), RS1003100626 (12:55719673 A>G,T), RS1003851537 (12:55722211 G>A,T), RS1004896999 (12:55723096 G>A), RS1005040363 (12:55718622 G>T), RS1005238107 (12:55725185 G>A), RS1005250211 (12:55723268 C>T), RS1005497782 (12:55724951 G>A)

Disease associations

OMIM: gene MIM:601617 | disease phenotypes: MIM:136880, MIM:310500

GenCC curated gene-disease

Disease	Classification	Inheritance
fundus albipunctatus	Definitive	Semidominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
RDH5-related retinopathy	Definitive	AR

Mondo (3): fundus albipunctatus (MONDO:0007639), inherited retinal dystrophy (MONDO:0019118), congenital stationary night blindness (MONDO:0016293)

Orphanet (4): Fundus albipunctatus (Orphanet:227796), Retinitis punctata albescens (Orphanet:52427), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Congenital stationary night blindness (Orphanet:215)

HPO phenotypes

23 total (24 of 23 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000529	Progressive visual loss
HP:0000580	Pigmentary retinopathy
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000662	Nyctalopia
HP:0001105	Retinal atrophy
HP:0001142	Lenticonus
HP:0007401	Macular atrophy
HP:0007675	Progressive night blindness
HP:0007814	Retinal pigment epithelial mottling
HP:0007843	Attenuation of retinal blood vessels
HP:0007987	Progressive visual field defects
HP:0007994	Peripheral visual field loss
HP:0008323	Abnormal light- and dark-adapted electroretinogram
HP:0008527	Congenital sensorineural hearing impairment
HP:0011505	Cystoid macular edema
HP:0012045	Retinal flecks
HP:0030506	Yellow/white retinal lesion
HP:0030642	Fundus albipunctatus
HP:0030825	Absent foveal reflex
HP:0031605	Abnormal fundus pigmentation
HP:0000556	Retinal dystrophy

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001858_16	Refractive error	4.000000e-12
GCST003219_5	Advanced age-related macular degeneration	4.000000e-09
GCST003455_28	Spherical equivalent (joint analysis main effects and education interaction)	1.000000e-08
GCST003455_29	Spherical equivalent (joint analysis main effects and education interaction)	4.000000e-08
GCST003997_20	Myopia	2.000000e-51
GCST006291_131	Spherical equivalent or myopia (age of diagnosis)	2.000000e-43
GCST006976_3	Macular thickness	9.000000e-105
GCST009962_15	High myopia	7.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0004784	self reported educational attainment
EFO:0004847	age at onset

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
C562733	Fundus Albipunctatus (supp.)
C536122	Night blindness, congenital stationary (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
Dexamethasone	increases expression, affects cotreatment	2
pirinixic acid	affects binding, decreases expression, increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
heptylparaben	decreases activity	1
ICG 001	decreases expression	1
abrine	decreases expression	1
palbociclib	increases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
Rosiglitazone	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Cadmium	increases expression, increases abundance	1
Estradiol	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
NAD	increases activity, affects binding	1
Nickel	decreases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
NCT07502664	Not specified	RECRUITING	Development and Evaluation of Functional Visual Field and Navigation Endpoints in Moderate to Profound Inherited Retinal Disease (DEFINE-IRD)
NCT07529041	Not specified	ENROLLING_BY_INVITATION	Real-time Acoustic Biofeedback for Enhancing Fixation Stability: A Proof-of-concept Study to Improve Ophthalmic Imaging Diagnostic Quality