CDHR1

Summary

CDHR1 (cadherin related family member 1, HGNC:14550) is a protein-coding gene on chromosome 10q23.1, encoding Cadherin-related family member 1 (Q96JP9). Potential calcium-dependent cell-adhesion protein.

This gene belongs to the cadherin superfamily of calcium-dependent cell adhesion molecules. The encoded protein is a photoreceptor-specific cadherin that plays a role in outer segment disc morphogenesis. Mutations in this gene are associated with inherited retinal dystrophies. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 92211 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa 65 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1,011 total — 68 pathogenic, 30 likely-pathogenic
• Phenotypes (HPO): 39
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_033100

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14550
Approved symbol	CDHR1
Name	cadherin related family member 1
Location	10q23.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1775, CORD15, RP65
Ensembl gene	ENSG00000148600
Ensembl biotype	protein_coding
OMIM	609502
Entrez	92211

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000332904, ENST00000372117, ENST00000459673, ENST00000622973, ENST00000623399, ENST00000623527, ENST00000624091, ENST00000852959, ENST00000926453, ENST00000926454

RefSeq mRNA: 2 — MANE Select: NM_033100 NM_001171971, NM_033100

CCDS: CCDS53548, CCDS7372

Canonical transcript exons

ENST00000623527 — 17 exons

Exon	Start	End
ENSE00000986126	84204527	84204605
ENSE00000986127	84205827	84205927
ENSE00000986128	84208174	84208377
ENSE00000986129	84208729	84208881
ENSE00000986130	84211001	84211165
ENSE00000986132	84212179	84212407
ENSE00000986136	84213091	84213348
ENSE00001377098	84211648	84211715
ENSE00001630108	84194537	84194815
ENSE00001633353	84200601	84200687
ENSE00001718948	84201807	84201920
ENSE00001741865	84195494	84195589
ENSE00001747895	84197786	84197836
ENSE00001751523	84199032	84199121
ENSE00001767877	84196505	84196650
ENSE00003474491	84202980	84203123
ENSE00003755314	84214082	84218694

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 97.40.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2021 / max 362.0044, expressed in 475 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105929	1.3910	280
105932	1.1189	291
105930	0.3919	143
105933	0.1139	34
105928	0.1114	51
105931	0.0750	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	97.40	gold quality
skin of leg	UBERON:0001511	97.24	gold quality
skin of abdomen	UBERON:0001416	96.89	gold quality
rectum	UBERON:0001052	96.32	gold quality
zone of skin	UBERON:0000014	95.73	gold quality
mucosa of transverse colon	UBERON:0004991	95.73	gold quality
upper leg skin	UBERON:0004262	95.10	gold quality
skin of hip	UBERON:0001554	91.71	gold quality
transverse colon	UBERON:0001157	87.92	gold quality
lower esophagus mucosa	UBERON:0035834	87.76	gold quality
nucleus accumbens	UBERON:0001882	86.93	gold quality
caudate nucleus	UBERON:0001873	85.65	gold quality
putamen	UBERON:0001874	84.78	gold quality
colonic epithelium	UBERON:0000397	83.69	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.54	gold quality
ileal mucosa	UBERON:0000331	83.49	gold quality
colonic mucosa	UBERON:0000317	83.45	gold quality
middle frontal gyrus	UBERON:0002702	83.35	gold quality
esophagus mucosa	UBERON:0002469	83.01	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.54	gold quality
ganglionic eminence	UBERON:0004023	82.43	gold quality
cingulate cortex	UBERON:0003027	80.39	gold quality
anterior cingulate cortex	UBERON:0009835	80.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.08	silver quality
pigmented layer of retina	UBERON:0001782	79.96	gold quality
Brodmann (1909) area 10	UBERON:0013541	79.93	silver quality
prefrontal cortex	UBERON:0000451	79.73	gold quality
nipple	UBERON:0002030	79.04	gold quality
right frontal lobe	UBERON:0002810	78.53	gold quality
small intestine	UBERON:0002108	77.65	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	23.29
E-MTAB-7316	yes	19.70
E-GEOD-137537	yes	3.88
E-GEOD-110499	no	62.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

113 targeting CDHR1, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-130B-5P	99.83	68.50	1888

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 17)

• PCDH21 mutations are not a major cause of the retinal diseases investigated herein, and the corresponding human phenotype remains to be determined. (PMID:16288196)
• Biallelic mutations in the photoreceptor-specific gene PCDH21 cause recessive retinal degeneration in humans. (PMID:20087419)
• To our knowledge, this is the first report of mutations in PCDH21 as a cause of human disease, autosomal recessive cone-rod dystrophy. (PMID:20805371)
• High-resolution retinal imaging revealed outer retinal changes suggesting that CDHR1 is important for normal photoreceptor structure and survival. (PMID:23044944)
• A novel splice site mutation of CDHR1, c.1485+2T>G, underlying autosomal recessive cone-rod dystrophy has been described in a consanguineous Israeli Christian Arab family. (PMID:23233793)
• Lack of CDHR1 in the human retina causes symptoms related to cone photoreceptor dysfunction. (PMID:24265541)
• we delineate the retinal pathology of two families segregating autosomal recessive retinal dystrophy due to two previously undescribed mutations in CDHR1. (PMID:26350383)
• the recessive retinal disorder previously reported to be due to homozygous mutation in RGR is, at least in part, due to variants in CDHR1 and that the true consequences of RGR knock-out on human retinal structure and function are yet to be determined. (PMID:27623334)
• Mutations in CDHR1 are a rare cause of retinal dystrophy. This study further expands the mutational spectrum of this gene and the associated clinical presentation. (PMID:28765526)
• CDHR1-related retinal dystrophy should be considered in adult patients with a retinal dystrophy who present with symptoms of cone-and-rod dysfunction and macular atrophy on ophthalmoscopic examination. (PMID:28885867)
• our study is the first to indicate that the novel homozygous variant c.T1641A (p.Y547*) in the CHDR1 gene might be the disease-causing mutation for retinal dystrophy in our patient, extending its mutation spectrums. (PMID:30160356)
• Patients with biallelic c.783G>A CDHR1 mutations demonstrate a retinal phenotype consistent with autosomal recessive central areolar choroidal dystrophy (CACD). (PMID:31387115)
• Identification of a novel homozygous nonsense mutation in the CDHR1 gene in a Chinese family with autosomal recessive retinitis pigmentosa. (PMID:32277948)
• A clinical study of patients with novel CDHR1 genotypes associated with late-onset macular dystrophy. (PMID:32681094)
• Deep phenotyping of the Cdhr1(-/-) mouse validates its use in pre-clinical studies for human CDHR1-associated retinal degeneration. (PMID:33964272)
• A rare case of RGR/CDHR1 haplotype identified in Bulgarian patient with cone-rod dystrophy. (PMID:34229535)
• Clinical Phenotypes of CDHR1-Associated Retinal Dystrophies. (PMID:35627310)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdhr1a	ENSDARG00000004643
danio_rerio	CDHR1	ENSDARG00000104756
mus_musculus	Cdhr1	ENSMUSG00000021803
rattus_norvegicus	Cdhr1	ENSRNOG00000013330

Paralogs (33): CDH1 (ENSG00000039068), CDH10 (ENSG00000040731), CDH3 (ENSG00000062038), CDH19 (ENSG00000071991), CDHR2 (ENSG00000074276), CDH17 (ENSG00000079112), CDH7 (ENSG00000081138), PCDH11Y (ENSG00000099715), CDHR5 (ENSG00000099834), CDH20 (ENSG00000101542), PCDH11X (ENSG00000102290), CDH23 (ENSG00000107736), CDH9 (ENSG00000113100), CDH6 (ENSG00000113361), CDH26 (ENSG00000124215), CDHR3 (ENSG00000128536), CDH15 (ENSG00000129910), CDH24 (ENSG00000139880), CDH11 (ENSG00000140937), CDH13 (ENSG00000140945), CDH18 (ENSG00000145526), CDH22 (ENSG00000149654), CDH8 (ENSG00000150394), CDH12 (ENSG00000154162), PCDH1 (ENSG00000156453), DCHS1 (ENSG00000166341), PCDH7 (ENSG00000169851), CDH2 (ENSG00000170558), CDH4 (ENSG00000179242), CDH5 (ENSG00000179776), PCDH9 (ENSG00000184226), DCHS2 (ENSG00000197410), PCDH20 (ENSG00000280165)

Protein

Protein identifiers

Cadherin-related family member 1 — Q96JP9 (reviewed: Q96JP9)

Alternative names: Photoreceptor cadherin, Protocadherin-21

All UniProt accessions (6): Q96JP9, A0A096LNP9, A0A096LNV6, A0A096LP91, A0A0A6YYA3, F1T0L2

UniProt curated annotations — full annotation on UniProt →

Function. Potential calcium-dependent cell-adhesion protein. May be required for the structural integrity of the outer segment (OS) of photoreceptor cells.

Subunit / interactions. Interacts with PROM1.

Subcellular location. Cell membrane.

Post-translational modifications. Undergoes proteolytic cleavage; produces a soluble 95 kDa N-terminal fragment and a 25 kDa cell-associated C-terminal fragment.

Disease relevance. Cone-rod dystrophy 15 (CORD15) [MIM:613660] An autosomal recessive retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96JP9-1	1	yes
Q96JP9-2	2

RefSeq proteins (2): NP_001165442, NP_149091* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR039808	Cadherin	Family

Pfam: PF00028

UniProt features (25 total): sequence variant 7, domain 6, glycosylation site 3, splice variant 2, topological domain 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JP9-F1	78.79	0.46

Functional residue map

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

Glycosylation sites (3): 58, 89, 296

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 177 (showing top): RORA1_01, JAEGER_METASTASIS_DN, GOBP_NEUROGENESIS, GOBP_CELL_CELL_ADHESION, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_PHOTORECEPTOR_CELL_DEVELOPMENT, GOBP_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOCC_NEURON_PROJECTION, GOBP_RETINA_HOMEOSTASIS, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_PHOTORECEPTOR_OUTER_SEGMENT_MEMBRANE, GOBP_HOMEOSTATIC_PROCESS, GOCC_PLASMA_MEMBRANE_REGION, GOCC_CILIARY_MEMBRANE

GO Biological Process (6): cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), photoreceptor cell morphogenesis (GO:0008594), photoreceptor cell outer segment organization (GO:0035845), photoreceptor cell maintenance (GO:0045494), cell-cell adhesion (GO:0098609)

GO Molecular Function (2): calcium ion binding (GO:0005509), cell adhesion molecule binding (GO:0050839)

GO Cellular Component (3): plasma membrane (GO:0005886), photoreceptor outer segment membrane (GO:0042622), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
photoreceptor cell development	2
cellular process	1
cell-cell adhesion	1
cell morphogenesis involved in neuron differentiation	1
cellular component organization	1
retina homeostasis	1
multicellular organismal process	1
cell adhesion	1
metal ion binding	1
protein binding	1
membrane	1
cell periphery	1
photoreceptor outer segment	1
ciliary membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDHR1	PROM1	O43490	888
CDHR1	TM4SF5	O14894	781
CDHR1	RPGRIP1	Q96KN7	754
CDHR1	ABCA4	P78363	750
CDHR1	GUCY2D	Q02846	747
CDHR1	MINPP1	Q9UNW1	743
CDHR1	AIPL1	Q9NZN9	743
CDHR1	RAX2	Q96IS3	737
CDHR1	PITPNM3	Q9BZ71	727
CDHR1	CERKL	Q49MI3	687
CDHR1	SEMA4A	Q9H3S1	667
CDHR1	PRPH2	P23942	659
CDHR1	CFAP418	Q96NL8	657
CDHR1	UNC119	Q13432	649
CDHR1	RIMS1	Q86UR5	626

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
CDHR1	ATP5PO	psi-mi:“MI:0915”(physical association)	0.400
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
RYK	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): CDHR1 (Affinity Capture-MS), CDHR1 (Proximity Label-MS), CDHR1 (Affinity Capture-MS), CDHR1 (Affinity Capture-MS), CDHR1 (Affinity Capture-MS), CDHR1 (Affinity Capture-MS), PROM1 (Affinity Capture-Western), CDHR1 (Affinity Capture-Western)

ESM2 similar proteins: O02840, O93319, O94985, P08641, P09803, P19535, P33151, P33152, P55280, P55284, P55285, P55287, P55288, P70408, P79883, P79995, P97326, Q08DJ5, Q12864, Q13634, Q3SWX5, Q5DWV1, Q5DWV2, Q63315, Q6B3P0, Q6B457, Q6Q0N0, Q6URK6, Q8AYD0, Q8BM92, Q8IXH8, Q8QGH3, Q8UVJ7, Q8VHP6, Q8WN91, Q90762, Q90763, Q90Z37, Q91838, Q91XU7

Diamond homologs: B2KI42, E9Q7P9, O18926, O54800, O55075, O93319, P08641, P20310, P30944, P33147, P55280, P55284, P55286, P55287, P55288, P58365, P97291, P97326, Q2PZL6, Q3SWX5, Q63418, Q6B457, Q6PB90, Q6PFX6, Q767I8, Q86UP0, Q8AYD0, Q8UVJ7, Q8VHP6, Q8WN91, Q90762, Q90Z37, Q91XU7, Q91XZ4, Q96JP9, Q99PF4, Q9BYE9, Q9H251, Q9QYP2, A0A8M2BIB6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1011 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	68
Likely pathogenic	30
Uncertain significance	490
Likely benign	310
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068893	NM_033100.4(CDHR1):c.355G>T (p.Glu119Ter)	Pathogenic
1069264	NM_033100.4(CDHR1):c.1463dup (p.Ser489fs)	Pathogenic
1070985	NM_033100.4(CDHR1):c.413del (p.Glu138fs)	Pathogenic
1071089	NM_033100.4(CDHR1):c.1000C>T (p.Gln334Ter)	Pathogenic
1076765	NC_000010.10:g.(?85954517)(85960443_?)del	Pathogenic
1184878	NM_033100.4(CDHR1):c.768C>G (p.Tyr256Ter)	Pathogenic
1213966	NM_033100.4(CDHR1):c.1219C>T (p.Arg407Ter)	Pathogenic
1297570	NM_033100.4(CDHR1):c.523C>T (p.Gln175Ter)	Pathogenic
1361262	NM_033100.4(CDHR1):c.1503_1507del (p.Gly502fs)	Pathogenic
1371750	NM_033100.4(CDHR1):c.1516G>T (p.Glu506Ter)	Pathogenic
1417137	NM_033100.4(CDHR1):c.257del (p.Thr86fs)	Pathogenic
1435934	NM_033100.4(CDHR1):c.580del (p.Ala194fs)	Pathogenic
1451292	NM_033100.4(CDHR1):c.1220del (p.Arg407fs)	Pathogenic
1453319	NM_033100.4(CDHR1):c.1511G>A (p.Trp504Ter)	Pathogenic
1454909	NM_033100.4(CDHR1):c.2108del (p.Gly703fs)	Pathogenic
1455858	NM_033100.4(CDHR1):c.525+1G>T	Pathogenic
1457085	NM_033100.4(CDHR1):c.610del (p.Arg204fs)	Pathogenic
1460364	NM_033100.4(CDHR1):c.18G>A (p.Trp6Ter)	Pathogenic
18416	NM_033100.4(CDHR1):c.524dup (p.Asn176fs)	Pathogenic
1941911	NM_033100.4(CDHR1):c.1956del (p.Trp652fs)	Pathogenic
1949981	NM_033100.4(CDHR1):c.121_122del (p.Leu41fs)	Pathogenic
1962540	NM_033100.4(CDHR1):c.1040del (p.Asn347fs)	Pathogenic
2008868	NM_033100.4(CDHR1):c.2038G>T (p.Glu680Ter)	Pathogenic
2012350	NM_033100.4(CDHR1):c.1991del (p.Pro664fs)	Pathogenic
2028607	NM_033100.4(CDHR1):c.850del (p.Ser284fs)	Pathogenic
2030498	NM_033100.4(CDHR1):c.1305del (p.Val436fs)	Pathogenic
2070853	NM_033100.4(CDHR1):c.1632C>A (p.Tyr544Ter)	Pathogenic
2092326	NM_033100.4(CDHR1):c.1405del (p.Val469fs)	Pathogenic
2101859	NM_033100.4(CDHR1):c.1709del (p.Asn570fs)	Pathogenic
2107487	NM_033100.4(CDHR1):c.1233del (p.Thr412fs)	Pathogenic

SpliceAI

2757 predictions. Top by Δscore:

Variant	Effect	Δscore
10:84194814:GG:G	donor_gain	1.0000
10:84194814:GGGT:G	donor_loss	1.0000
10:84194815:GG:G	donor_gain	1.0000
10:84194815:GGTG:G	donor_loss	1.0000
10:84194816:G:GG	donor_gain	1.0000
10:84194816:G:T	donor_loss	1.0000
10:84194817:T:A	donor_loss	1.0000
10:84195492:A:AG	acceptor_gain	1.0000
10:84195493:G:GT	acceptor_gain	1.0000
10:84195493:GC:G	acceptor_gain	1.0000
10:84195493:GCT:G	acceptor_gain	1.0000
10:84195493:GCTC:G	acceptor_gain	1.0000
10:84195493:GCTCA:G	acceptor_gain	1.0000
10:84195586:GTAG:G	donor_gain	1.0000
10:84195587:TAG:T	donor_gain	1.0000
10:84195588:AG:A	donor_gain	1.0000
10:84195588:AGG:A	donor_loss	1.0000
10:84195589:GG:G	donor_gain	1.0000
10:84195589:GGTG:G	donor_loss	1.0000
10:84195590:G:GG	donor_gain	1.0000
10:84195590:GTGA:G	donor_loss	1.0000
10:84196499:TTCCA:T	acceptor_loss	1.0000
10:84196500:TCCA:T	acceptor_loss	1.0000
10:84196503:A:AG	acceptor_gain	1.0000
10:84196503:AGGCT:A	acceptor_loss	1.0000
10:84196504:G:GA	acceptor_gain	1.0000
10:84196631:TTG:T	donor_gain	1.0000
10:84196646:GAGAG:G	donor_gain	1.0000
10:84196648:G:GT	donor_gain	1.0000
10:84196648:GAG:G	donor_gain	1.0000

AlphaMissense

5641 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:84208361:T:A	V384D	0.998
10:84211008:C:A	A443D	0.997
10:84211046:G:C	A456P	0.997
10:84208367:A:C	D386A	0.996
10:84211089:C:A	P470H	0.996
10:84208268:T:C	F353S	0.995
10:84208744:T:C	F395L	0.994
10:84208746:C:A	F395L	0.994
10:84208746:C:G	F395L	0.994
10:84208367:A:T	D386V	0.993
10:84208368:C:A	D386E	0.993
10:84208368:C:G	D386E	0.993
10:84208373:A:C	D388A	0.993
10:84208745:T:C	F395S	0.993
10:84211002:T:C	L441P	0.993
10:84212181:T:C	F519S	0.993
10:84212201:G:T	G526W	0.993
10:84208262:C:A	P351Q	0.992
10:84208267:T:C	F353L	0.992
10:84208269:C:A	F353L	0.992
10:84208269:C:G	F353L	0.992
10:84208297:T:C	F363L	0.992
10:84208298:T:C	F363S	0.992
10:84208299:T:A	F363L	0.992
10:84208299:T:G	F363L	0.992
10:84208367:A:G	D386G	0.992
10:84211059:T:A	I460N	0.992
10:84211649:C:A	A496D	0.992
10:84212273:G:C	A550P	0.992
10:84213103:G:C	D599H	0.992

dbSNP variants (sampled 300 via entrez): RS1000011701 (10:84215248 G>A,C), RS1000042033 (10:84207988 A>G), RS1000225016 (10:84193477 G>A), RS1000243263 (10:84204147 C>A,T), RS1000249251 (10:84210116 A>G), RS1000271175 (10:84203189 T>C), RS1000631732 (10:84194431 C>T), RS1000635606 (10:84199469 T>C), RS1000688050 (10:84199766 C>G,T), RS1000700071 (10:84193316 A>G), RS1000716422 (10:84194430 C>A), RS1000803984 (10:84204393 G>A,C), RS1000908975 (10:84219488 A>C,G), RS1000964610 (10:84194570 A>G), RS1000983442 (10:84219584 A>G)

Disease associations

OMIM: gene MIM:609502 | disease phenotypes: MIM:613660, MIM:268000, MIM:120970, MIM:204000, MIM:612657

GenCC curated gene-disease

Disease	Classification	Inheritance
cone-rod dystrophy 15	Definitive	Autosomal recessive
cone-rod dystrophy	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
retinitis pigmentosa 65	Definitive	AR

Mondo (11): inherited retinal dystrophy (MONDO:0019118), cone-rod dystrophy 15 (MONDO:0013348), retinitis pigmentosa (MONDO:0019200), macular dystrophy, retinal, 5 (MONDO:0700381), cone-rod dystrophy (MONDO:0015993), Leber congenital amaurosis (MONDO:0018998), cone dystrophy (MONDO:0000455), retinitis pigmentosa 65 (MONDO:0800352), optic atrophy (MONDO:0003608), retinal disorder (MONDO:0005283), cone-rod dystrophy 12 (MONDO:0012983)

Orphanet (5): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Cone rod dystrophy (Orphanet:1872), Leber congenital amaurosis (Orphanet:65), Progressive cone dystrophy (Orphanet:1871)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000529	Progressive visual loss
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000602	Ophthalmoplegia
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001133	Constriction of peripheral visual field
HP:0007641	Dyschromatopsia
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007722	Retinal pigment epithelial atrophy
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract
HP:0007843	Attenuation of retinal blood vessels

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_293	Refractive error	1.000000e-70

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D000077765	Cone Dystrophy	C11.270.151; C11.768.216
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
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
C567206	Cone-Rod Dystrophy 12 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	3
triphenyl phosphate	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
terbufos	increases methylation	1
sodium arsenite	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
quinocetone	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	decreases methylation	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Diethylhexyl Phthalate	decreases expression	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Formaldehyde	decreases expression	1
Niclosamide	increases expression	1
Parathion	increases methylation	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Serpentine	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

263 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
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
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