PRPH2

Summary

PRPH2 (peripherin 2, HGNC:9942) is a protein-coding gene on chromosome 6p21.1, encoding Peripherin-2 (P23942). Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure.

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein found in the outer segment of both rod and cone photoreceptor cells. It may function as an adhesion molecule involved in stabilization and compaction of outer segment disks or in the maintenance of the curvature of the rim. This protein is essential for disk morphogenesis. Defects in this gene are associated with both central and peripheral retinal degenerations. Some of the various phenotypically different disorders are autosomal dominant retinitis pigmentosa, progressive macular degeneration, macular dystrophy and retinitis pigmentosa digenic.

Source: NCBI Gene 5961 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PRPH2-related retinopathy (Definitive, ClinGen) — +14 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 846 total — 218 pathogenic, 87 likely-pathogenic
• Phenotypes (HPO): 86
• MANE Select transcript: NM_000322

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9942
Approved symbol	PRPH2
Name	peripherin 2
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	TSPAN22, rd2, CACD2
Ensembl gene	ENSG00000112619
Ensembl biotype	protein_coding
OMIM	179605
Entrez	5961

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000230381

RefSeq mRNA: 1 — MANE Select: NM_000322 NM_000322

CCDS: CCDS4871

Canonical transcript exons

ENST00000230381 — 3 exons

Exon	Start	End
ENSE00000751440	42704365	42704611
ENSE00000849981	42721754	42722597
ENSE00001035135	42696598	42698507

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 79.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5326 / max 333.5554, expressed in 10 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73627	0.4508	9
73628	0.0604	7
73626	0.0214	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
quadriceps femoris	UBERON:0001377	79.27	silver quality
vastus lateralis	UBERON:0001379	79.08	silver quality
hindlimb stylopod muscle	UBERON:0004252	78.33	gold quality
deltoid	UBERON:0001476	78.12	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.49	gold quality
muscle organ	UBERON:0001630	76.21	gold quality
skeletal muscle tissue	UBERON:0001134	75.79	gold quality
muscle of leg	UBERON:0001383	75.66	gold quality
gastrocnemius	UBERON:0001388	75.20	gold quality
triceps brachii	UBERON:0001509	75.15	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.01	gold quality
biceps brachii	UBERON:0001507	74.76	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	74.36	silver quality
gluteal muscle	UBERON:0002000	73.92	gold quality
prefrontal cortex	UBERON:0000451	73.77	gold quality
muscle tissue	UBERON:0002385	73.46	gold quality
diaphragm	UBERON:0001103	70.08	gold quality
cortical plate	UBERON:0005343	69.17	gold quality
frontal cortex	UBERON:0001870	68.31	gold quality
left ovary	UBERON:0002119	67.79	gold quality
ventricular zone	UBERON:0003053	67.67	gold quality
tendon of biceps brachii	UBERON:0008188	67.67	gold quality
smooth muscle tissue	UBERON:0001135	67.62	gold quality
ovary	UBERON:0000992	67.32	gold quality
neocortex	UBERON:0001950	66.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	66.78	silver quality
right ovary	UBERON:0002118	66.46	gold quality
ganglionic eminence	UBERON:0004023	66.28	gold quality
muscle layer of sigmoid colon	UBERON:0035805	66.25	gold quality
right frontal lobe	UBERON:0002810	66.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	1377.05
E-MTAB-7316	yes	59.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ATOH7, CRX, HES1, HIF1A, NEUROD1, NR2E3, PITX2, POU4F1, PRDM1, RARA

miRNA regulators (miRDB)

74 targeting PRPH2, 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-186-5P	99.99	70.83	3707
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4310	99.59	68.84	2527

Literature-anchored findings (GeneRIF, showing 40)

• This study describes a new RDS/peripherin mutation for BPD and provides the first combined genetic-pathological study of this condition. (PMID:11934323)
• This review describes the role of peripherin in vision, specifically, disk morphogenesis. (PMID:12019563)
• A frameshift null mutation in the RDS/Peripherin gene associated with a relatively severe manifestation of adult-onset foveomacular dystrophy in affected family members. (PMID:12566026)
• Autosomal dominant macular dystrophy is described in a large family with an Arg172Trp mutation in the RDS gene. (PMID:12608515)
• This study reveals that genetic heterogeneity for BSMD (butterfly-shaped macular dystrophy) is not associated with a mutation in the peripherin/RDS gene nor with any other known non-syndromic retinal disease gene. (PMID:12724643)
• The RDS mutation in codon 141 is associated with an unusual age-related macular degeneration-like late-onset maculopathy. (PMID:12882809)
• Peptide mass-signature genotyping applied to the RDS/peripherin gene of 16 individuals from a family exhibiting autosomal dominant macular degeneration revealed an A–>T transversion in the 5’ splice site of intron 2 that is the likely cause of disease. (PMID:12902384)
• A deletion of Asn169 in the peripherin/RDS protein causes a peculiar form of autosomal dominant macular dystrophy in a large family from the Netherlands. (PMID:14557182)
• Autosomal dominant central areolar choroidal dystrophy and a novel Arg195Leu mutation in the peripherin/RDS gene. (PMID:14557183)
• Peripherin gene mutation associated with diverse macular phenotypes (PMID:15370544)
• Proline at position 296 is necessary for optimal function. (PMID:15591062)
• This is the first report describing marked intrafamilial variation associated with Arg172Trp (R172W) peripherin/RDS mutation, including nonpenetrance. (PMID:16019073)
• A three-generation family with an autosomal dominant pattern dystrophy arising from a previously unreported splice site mutation in the RDS gene is described. (PMID:16340530)
• Age of onset, progression of the disease, and characteristic fundus abnormalities share similarities to previous reports on families with central areolar choroidal dystrophy associated with peripherin/RDS gene mutations (PMID:16832026)
• Although RDS and VMD2 are the only known genes with mutations contributing to adult-onset vitelliform macular dystropht, our series demonstrates that most patients have mutations in genes that have yet to be discovered. (PMID:16885924)
• To our knowledge, we report the first complex mutation in the peripherin/RDS gene as the cause of a mild macular phenotype, supporting the importance of molecular diagnosis in genetic counseling. (PMID:17031298)
• The two siblings underwent genetic testing and were found to be carriers of a heterozygous frame-shift mutation 920delT affecting codon 307 of the peripherin/RDS gene (PMID:17148040)
• mutations in the RDS/peripherin gene cause choroidal neovascularization in patients with adult-onset foveomacular dystrophy (PMID:17249552)
• RDS gene is unlikely to be involved in the pathogenesis of age-related macular degeneration. (PMID:17362467)
• Mutations in the peripherin/RDS gene are the major cause of multifocal pattern dystrophy simulating STGD1/fundus flavimaculatus. (PMID:17504850)
• Different macular dystrophy phenotypes according to the mutations in peripherin/RDS. Limited phenotype variation was observed for these mutations within the family. (PMID:17653047)
• Peripherin is demonstrated in rectal well-differentiated endocrine neoplasms without metastases and reflects the phenotype of epithelial cells. (PMID:17671712)
• Patient without a VMD2 mutation carried a sequence variant in the 5’ untranslated region of the peripherin/RDS gene. (PMID:17698758)
• Novel C165R mutation of retinal degeneration slow/peripherin gene in family affected by different patterns of retinal dystrophy. (PMID:17851265)
• two separate phenotypes (retinitis pigmentosa and adult onset vitelliform macular dystrophy) are associated with an identical mutation (S212G) in the peripherin/RDS gene. (PMID:18050133)
• characteristics of the peripherin/RDS gene & its protein product; overview of spectrum of clinical phenotypes caused by peripherin mutations, ranging from macular dystrophies to widespread forms of retinal dystrophy such as retinitis pigmentosa [review] (PMID:18328765)
• This series describes the broad spectrum of phenotypes associated with PRPH2 mutations. (PMID:19038374)
• When caused by a p.Arg142Trp mutation in the peripherin/RDS gene, CACD (central areolar choroidal dystrophy) causes a central cone dystrophy phenotype. (PMID:19243827)
• visual prognosis in macular dystrophies associated with peripherin/RDS may be mutation specific and, for the Arg172Trp substitution, worse than the Arg142Trp and Arg172Gln substitutions. (PMID:19262438)
• Mutations in PRPF31, RHO, and PRPH2 were found in low frequencies (1 of 9 autosomal dominant RP families) in Chinese patients, and the PRPF31 and PRPH2 truncating mutations were novel. (PMID:19506198)
• The structure of peripherin/RDS and of a pathogenic mutant is assessed spectroscopically for the first time. (PMID:19921174)
• Five novel rhodopsin mutations were c.365A>G in exon 2 (Glu122Gly), and c.233A> in exon 1 (Asn78Ile). The other three RHO mutations were Phe45Leu, Arg135Trp, and Ser186Trp. No peripherin/RDS gene mutations were demonstrated in the remaining 23 probands. (PMID:19958124)
• Four mutations of the PRPH2 gene were found in 3 sporadic cases and 3 families (n = 11). A p.R46X mutation, previously described in CACD, was found in 3 members of a family with AOFVD and in a sporadic case with DMD. (PMID:20213611)
• Families showing a variable macular dystrophy phenotype caused by mutations in PRPH2 should be tested for additional mutations in ABCA4 and ROM1, as they may alter the progression of the PRPH2 phenotype. (PMID:20335603)
• The patient’s DNA contained a mutation within the peripherin/RDS gene (CAG>TAG nucleotide substitution) in the coding sequence of exon 3, resulting in the diagnosis of pattern dystrophy. (PMID:20458258)
• peripherin/RDS mutations produced diffuse AF abnormalities, disruption of the photoreceptor/RPE junction, and increased cone spacing, consistent with cone loss in the macula. (PMID:21071739)
• PRPH2 screening should be recommended to patients with an age of onset more than 40 years. For an onset between 30 and 40 years, PRPH2 can be screened if no mutation has been detected in BEST1. (PMID:21269699)
• Molecular screening of the candidate genes BEST1 and PRPH2 revealed no mutations. (PMID:22174098)
• This is the first report of marked intrafamilial variation of pattern dystrophy because of peripherin/RDS Y141C mutation. Intravitreal ranibizumab injections might be a valuable treatment for associated subfoveal choroidal neovascularization. (PMID:22466463)
• Novel mutation c.389T > C (p.Leu130Pro) in PRPH2 was found in patients with retinitis pigmentosa and hearing loss. (PMID:22842402)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	prph2b	ENSDARG00000014840
danio_rerio	prph2a	ENSDARG00000038018
mus_musculus	Prph2	ENSMUSG00000023978
rattus_norvegicus	Prph2	ENSRNOG00000068377

Paralogs (32): TSPAN6 (ENSG00000000003), CD9 (ENSG00000010278), TSPAN9 (ENSG00000011105), TSPAN17 (ENSG00000048140), TSPAN32 (ENSG00000064201), CD82 (ENSG00000085117), TSPAN15 (ENSG00000099282), CD37 (ENSG00000104894), UPK1A (ENSG00000105668), TSPAN12 (ENSG00000106025), TSPAN13 (ENSG00000106537), TSPAN14 (ENSG00000108219), CD81 (ENSG00000110651), TSPAN11 (ENSG00000110900), UPK1B (ENSG00000114638), TSPAN1 (ENSG00000117472), TSPAN8 (ENSG00000127324), TSPAN16 (ENSG00000130167), TSPAN2 (ENSG00000134198), CD63 (ENSG00000135404), TSPAN31 (ENSG00000135452), TSPAN3 (ENSG00000140391), CD53 (ENSG00000143119), ROM1 (ENSG00000149489), TSPAN7 (ENSG00000156298), TSPAN18 (ENSG00000157570), TSPAN33 (ENSG00000158457), TSPAN5 (ENSG00000168785), CD151 (ENSG00000177697), TSPAN10 (ENSG00000182612), TSPAN4 (ENSG00000214063), TSPAN19 (ENSG00000231738)

Protein

Protein identifiers

Peripherin-2 — P23942 (reviewed: P23942)

Alternative names: Retinal degeneration slow protein, Tetraspanin-22

All UniProt accessions (1): P23942

UniProt curated annotations — full annotation on UniProt →

Function. Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure. Required for the maintenance of retinal outer nuclear layer thickness. Required for the correct development and organization of the photoreceptor inner segment.

Subunit / interactions. Homodimer; disulfide-linked. Forms a homotetramer. Forms a heterotetramer with ROM1. Homotetramer and heterotetramer core complexes go on to form higher order complexes by formation of intermolecular disulfide bonds. Interacts with MREG. Interacts with STX3. Interacts with SNAP25.

Subcellular location. Membrane. Cell projection. Cilium. Photoreceptor outer segment. Photoreceptor inner segment.

Tissue specificity. Retina (photoreceptor). In rim region of ROS (rod outer segment) disks.

Disease relevance. Retinitis pigmentosa 7 (RP7) [MIM:608133] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. 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. Macular dystrophy, vitelliform, 3 (VMD3) [MIM:608161] A form of vitelliform macular dystrophy, a retinal disease characterized by yellow, lipofuscin-containing deposits, usually localized at the center of the macula. Patients usually become symptomatic in the fourth or fifth decade of life with a protracted disease of decreased visual acuity. The disease is caused by variants affecting the gene represented in this entry. Macular dystrophy, patterned, 1 (MDPT1) [MIM:169150] A form of retinal patterned dystrophy, a heterogeneous group of macular disorders that includes reticular (fishnet-like) dystrophy, macroreticular (spider-shaped) dystrophy and butterfly-shaped pigment dystrophy. The disease is caused by variants affecting the gene represented in this entry. Choroidal dystrophy, central areolar 2 (CACD2) [MIM:613105] A form of central areolar choroidal dystrophy, a retinal disease that affects the macula and results in a well-demarcated circumscribed area of atrophy of the pigment epithelium and choriocapillaris. The disease is caused by variants affecting the gene represented in this entry. Defects in PRPH2 are found in different retinal diseases including cone-rod dystrophy, retinitis pigmentosa, macular degeneration. The mutations underlying autosomal dominant retinitis pigmentosa and severe macular degeneration are largely missense or small in-frame deletions in a large intradiscal loop between the third and fourth transmembrane domains. In contrast, those associated with the milder pattern phenotypes or with digenic RP are scattered more evenly through the gene and are often nonsense mutations. This observation correlates with the hypothesis that the large loop is an important site of interaction between PRPH2 molecules and other protein components in the disk.

Similarity. Belongs to the PRPH2/ROM1 family.

RefSeq proteins (1): NP_000313* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000830	Peripherin/rom-1	Family
IPR008952	Tetraspanin_EC2_sf	Homologous_superfamily
IPR018498	Peripherin/rom-1_CS	Conserved_site
IPR018499	Tetraspanin/Peripherin	Family
IPR042026	Peripherin_LEL	Domain

Pfam: PF00335

UniProt features (74 total): sequence variant 59, topological domain 5, transmembrane region 4, glycosylation site 2, chain 1, region of interest 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7ZW1	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23942-F1	87.56	0.67

Antibody-complex structures (SAbDab): 1 — 7ZW1

Functional residue map

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

Disulfide bonds (1): 150

Glycosylation sites (2): 53, 229

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, MODULE_64, GOBP_NEUROGENESIS, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_PROTEIN_MATURATION, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_PHOTORECEPTOR_CELL_DEVELOPMENT, MODULE_99, GOBP_RESPONSE_TO_RADIATION, GOBP_DETECTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, GOBP_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION

GO Biological Process (10): cell adhesion (GO:0007155), visual perception (GO:0007601), response to low light intensity stimulus (GO:0009645), photoreceptor cell outer segment organization (GO:0035845), detection of light stimulus involved in visual perception (GO:0050908), protein homooligomerization (GO:0051260), protein heterooligomerization (GO:0051291), protein maturation (GO:0051604), retina development in camera-type eye (GO:0060041), protein localization to plasma membrane (GO:0072659)

GO Molecular Function (2): protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (5): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein complex oligomerization	2
cellular process	1
sensory perception of light stimulus	1
response to light intensity	1
cellular component organization	1
photoreceptor cell development	1
visual perception	1
detection of light stimulus involved in sensory perception	1
gene expression	1
protein metabolic process	1
camera-type eye development	1
anatomical structure development	1
protein localization to membrane	1
protein localization to cell periphery	1
identical protein binding	1
protein dimerization activity	1
binding	1
photoreceptor cell cilium	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPH2	PDE6B	P35913	968
PRPH2	ROM1	Q03395	949
PRPH2	RHO	P08100	927
PRPH2	ABCA4	P78363	889
PRPH2	GUCY2D	Q02846	887
PRPH2	RD3	Q7Z3Z2	885
PRPH2	IMPG1	Q17R60	874
PRPH2	BEST1	O76090	868
PRPH2	ELOVL4	Q9GZR5	837
PRPH2	CNGB1	Q14028	832
PRPH2	RP9	Q8TA86	825
PRPH2	RPGR	Q92834	816
PRPH2	TULP1	O00294	809
PRPH2	CRX	O43186	805
PRPH2	PRPF31	Q8WWY3	800

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CCK	PRPH2	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	PRPH2	psi-mi:“MI:0915”(physical association)	0.560
SH3GLB1	PRPH2	psi-mi:“MI:0915”(physical association)	0.560
PRPF40A	PRPH2	psi-mi:“MI:0915”(physical association)	0.560
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
PRPH2	TOR1A	psi-mi:“MI:0914”(association)	0.350
HSPE1	LYPLA2	psi-mi:“MI:0914”(association)	0.350
PRPH2	NHERF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): SRSF5 (Affinity Capture-Western), LAMP2 (Co-localization), SLMAP (Affinity Capture-MS), NUP35 (Affinity Capture-MS), UBB (Affinity Capture-MS), RAET1L (Affinity Capture-MS), EXTL2 (Affinity Capture-MS), CSTF3 (Affinity Capture-MS), SLC9A3R1 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), PCYT1A (Affinity Capture-MS), ACSL6 (Affinity Capture-MS), TOR1A (Affinity Capture-MS), HMOX2 (Affinity Capture-MS), RAB9B (Affinity Capture-MS)

ESM2 similar proteins: O00322, O42281, O42282, O42581, O42582, O42583, O46101, O60635, O70352, O95859, P15499, P17438, P17810, P23942, P27701, P35906, P38572, P40237, P52204, P58418, Q11098, Q29RH7, Q2KIS9, Q3T0S3, Q4R7W6, Q4V922, Q504G0, Q569A2, Q5CZV0, Q5M962, Q5R8B5, Q5RC27, Q6AYR9, Q6GPA5, Q6NUZ2, Q6NWG0, Q6P1U2, Q6ZUX7, Q7T392, Q7TQI0

Diamond homologs: O42281, O42282, O42581, O42582, O42583, P15499, P17438, P17810, P23942, P32958, P35906, P52204, P52205, Q03395, Q5PPM7, Q9QZA6, Q3ZBH3, O95858, P48509, P61170, P61171

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	218
Likely pathogenic	87
Uncertain significance	262
Likely benign	93
Benign	40

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1004420	NM_000322.5(PRPH2):c.603_620del (p.Arg203_Gly208del)	Pathogenic
1006733	NM_000322.5(PRPH2):c.695C>A (p.Ala232Glu)	Pathogenic
1026875	NM_000322.5(PRPH2):c.641_652del (p.Cys214_Ser217del)	Pathogenic
1053626	NM_000322.5(PRPH2):c.991del (p.Gln331fs)	Pathogenic
1067912	NM_000322.5(PRPH2):c.628C>G (p.Pro210Ala)	Pathogenic
1069377	NM_000322.5(PRPH2):c.522G>A (p.Trp174Ter)	Pathogenic
1069629	NM_000322.5(PRPH2):c.810_828+9del	Pathogenic
1071016	NC_000006.11:g.(?42689492)(42690072_?)del	Pathogenic
1072932	NM_000322.5(PRPH2):c.440dup (p.Gly148fs)	Pathogenic
1073033	NM_000322.5(PRPH2):c.205dup (p.Val69fs)	Pathogenic
1073894	NM_000322.5(PRPH2):c.702C>A (p.Tyr234Ter)	Pathogenic
1074169	NM_000322.5(PRPH2):c.282_286dup (p.Pro96fs)	Pathogenic
1074234	NM_000322.5(PRPH2):c.52del (p.Gln18fs)	Pathogenic
1074608	NM_000322.5(PRPH2):c.208_217dup (p.Val73fs)	Pathogenic
1075134	NM_000322.5(PRPH2):c.537G>A (p.Trp179Ter)	Pathogenic
1075684	NM_000322.5(PRPH2):c.302del (p.Tyr101fs)	Pathogenic
1076115	NM_000322.5(PRPH2):c.633_658del (p.Phe211fs)	Pathogenic
1175212	NM_000322.5(PRPH2):c.265_268delinsAGGGCC (p.Ala89fs)	Pathogenic
1175214	NM_000322.5(PRPH2):c.281G>A (p.Trp94Ter)	Pathogenic
1175216	NM_000322.5(PRPH2):c.513dup (p.Arg172fs)	Pathogenic
1175217	NM_000322.5(PRPH2):c.516G>T (p.Arg172=)	Pathogenic
1175218	NM_000322.5(PRPH2):c.520T>A (p.Trp174Arg)	Pathogenic
1175220	NM_000322.5(PRPH2):c.599T>G (p.Val200Gly)	Pathogenic
1175221	NM_000322.5(PRPH2):c.610_623del (p.Tyr204fs)	Pathogenic
1175223	NM_000322.5(PRPH2):c.654_655del (p.Pro219fs)	Pathogenic
1175225	NM_000322.5(PRPH2):c.658del (p.Arg220fs)	Pathogenic
1175230	NM_000322.5(PRPH2):c.824_828+3delinsCATTTGGGCTCCTCATTTGG	Pathogenic
1175231	NM_000322.5(PRPH2):c.826G>T (p.Glu276Ter)	Pathogenic
1175234	NC_000006.11:g.(42672350_42689491)(42690353?)del	Pathogenic
1175236	NM_000322.5(PRPH2):c.1A>T (p.Met1Leu)	Pathogenic

SpliceAI

396 predictions. Top by Δscore:

Variant	Effect	Δscore
6:42704609:CGA:C	acceptor_gain	1.0000
6:42704612:C:CC	acceptor_gain	1.0000
6:42704613:T:C	acceptor_gain	1.0000
6:42704613:T:TC	acceptor_gain	1.0000
6:42721752:A:AC	donor_gain	1.0000
6:42721752:ACT:A	donor_gain	1.0000
6:42721753:C:CC	donor_gain	1.0000
6:42721753:CT:C	donor_gain	1.0000
6:42721753:CTC:C	donor_gain	1.0000
6:42721763:T:TA	donor_gain	1.0000
6:42698505:CAC:C	acceptor_gain	0.9900
6:42698506:ACC:A	acceptor_loss	0.9900
6:42698508:CT:C	acceptor_loss	0.9900
6:42704360:CCTA:C	donor_loss	0.9900
6:42704362:TAC:T	donor_loss	0.9900
6:42704363:AC:A	donor_loss	0.9900
6:42704364:C:CG	donor_loss	0.9900
6:42704607:TTCGA:T	acceptor_gain	0.9900
6:42704609:CGACT:C	acceptor_gain	0.9900
6:42721749:CT:C	donor_loss	0.9900
6:42721750:TCA:T	donor_loss	0.9900
6:42721751:CA:C	donor_loss	0.9900
6:42721752:AC:A	donor_loss	0.9900
6:42721753:CTCT:C	donor_gain	0.9900
6:42721755:CTTTG:C	donor_gain	0.9900
6:42698506:AC:A	acceptor_gain	0.9800
6:42698507:CC:C	acceptor_gain	0.9800
6:42698508:C:CC	acceptor_gain	0.9800
6:42698511:G:GC	acceptor_gain	0.9800
6:42704608:TCGA:T	acceptor_gain	0.9800

AlphaMissense

2286 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002737 (6:42715613 G>A), RS1000097195 (6:42715434 G>A,T), RS1000147493 (6:42700327 G>A), RS1000148371 (6:42722531 G>A), RS1000345100 (6:42709729 C>T), RS1000513777 (6:42720472 G>C), RS1000797380 (6:42707056 T>G), RS1000860538 (6:42706571 ACT>A), RS1000935642 (6:42698118 A>G), RS1001028004 (6:42704333 T>C), RS1001150591 (6:42698826 C>A), RS1001163510 (6:42713984 G>C), RS1001239599 (6:42704758 C>A,G,T), RS1001402878 (6:42705480 T>C,G), RS1001608234 (6:42722968 G>A)

Disease associations

OMIM: gene MIM:179605 | disease phenotypes: MIM:169150, MIM:608133, MIM:136880, MIM:608161, MIM:613105, MIM:268000, MIM:248200, MIM:153700, MIM:120970, MIM:276900, MIM:215500, MIM:303100, MIM:611809, MIM:126600

GenCC curated gene-disease

Disease	Classification	Inheritance
PRPH2-related retinopathy	Definitive	Autosomal dominant
retinitis pigmentosa 7	Definitive	Semidominant
Leber congenital amaurosis	Definitive	Autosomal recessive
hereditary macular dystrophy	Definitive	Autosomal dominant
choroidal dystrophy, central areolar 2	Strong	Autosomal dominant
fundus albipunctatus	Strong	Autosomal dominant
vitelliform macular dystrophy 3	Strong	Autosomal dominant
inherited retinal dystrophy	Moderate	Autosomal recessive
cone-rod dystrophy	Supportive	Autosomal dominant
retinitis punctata albescens	Supportive	Autosomal dominant
central areolar choroidal dystrophy	Supportive	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant
adult-onset foveomacular vitelliform dystrophy	Supportive	Autosomal dominant
patterned macular dystrophy	Supportive	Autosomal dominant
multifocal pattern dystrophy simulating fundus flavimaculatus	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
PRPH2-related retinopathy	Definitive	SD

Mondo (31): patterned macular dystrophy 1 (MONDO:0008210), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa 7 (MONDO:0011974), retinal disorder (MONDO:0005283), fundus albipunctatus (MONDO:0007639), vitelliform macular dystrophy 3 (MONDO:0024561), choroidal dystrophy, central areolar 2 (MONDO:0013137), multifocal pattern dystrophy simulating fundus flavimaculatus (MONDO:0020382), patterned dystrophy of the retinal pigment epithelium (MONDO:0018973), retinitis pigmentosa (MONDO:0019200), retinitis pigmentosa 7, digenic (MONDO:1060144), Leber congenital amaurosis 18 (MONDO:1060145), Stargardt disease (MONDO:0019353), vitelliform macular dystrophy 2 (MONDO:0007931), cone-rod dystrophy (MONDO:0015993)

Orphanet (19): Butterfly-shaped pigment dystrophy (Orphanet:99001), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Fundus albipunctatus (Orphanet:227796), Retinitis punctata albescens (Orphanet:52427), Central areolar choroidal dystrophy (Orphanet:75377), Multifocal pattern dystrophy simulating fundus flavimaculatus (Orphanet:99003), Pattern dystrophy (Orphanet:63454), Stargardt disease (Orphanet:827), Best vitelliform macular dystrophy (Orphanet:1243), Cone rod dystrophy (Orphanet:1872), Progressive cone dystrophy (Orphanet:1871), Adult-onset foveomacular vitelliform dystrophy (Orphanet:99000), Familial prostate cancer (Orphanet:1331), Usher syndrome (Orphanet:886)

HPO phenotypes

86 total (30 of 86 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:0000478	Abnormality of the eye
HP:0000493	Abnormal foveal morphology
HP:0000501	Glaucoma
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000529	Progressive visual loss
HP:0000533	Chorioretinal atrophy
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000572	Visual loss
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:0000649	Abnormality of visual evoked potentials
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007096_39	Pulse pressure	1.000000e-08
GCST007097_57	Pulse pressure	4.000000e-06
GCST007097_58	Pulse pressure	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

MeSH disease descriptors (16)

Descriptor	Name	Tree numbers
D015794	Choroideremia	C11.270.142; C11.941.160.300; C16.320.290.142; C16.320.322.092
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
D008268	Macular Degeneration	C11.768.585.439
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
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
D000080362	Stargardt Disease	C11.270.872; C11.768.585.439.339; C16.320.290.724
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886
C567518	Bestrophinopathy (supp.)
C567750	Choroidal Dystrophy, Central Areolar 2 (supp.)
C562733	Fundus Albipunctatus (supp.)
C536309	Patterned dystrophy of retinal pigment epithelium (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_QX13	P101M3	Induced pluripotent stem cell	Female
CVCL_QX14	P101M6	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

303 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
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
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
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
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
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
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]
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
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
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