PRPH2

peripherin 2, the group of Tetraspanins

Basic information

Region (hg38): 6:42696598-42722597

Previous symbols: [ "RP7", "RDS" ]

Links

ENSG00000112619 ∙ NCBI:5961 ∙ OMIM:179605 ∙ HGNC:9942 ∙ Uniprot:P23942 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• choroidal dystrophy, central areolar 2 (Moderate), mode of inheritance: AD
• retinitis pigmentosa 7 (Definitive), mode of inheritance: Semidominant
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• retinitis punctata albescens (Supportive), mode of inheritance: AD
• central areolar choroidal dystrophy (Supportive), mode of inheritance: AD
• adult-onset foveomacular vitelliform dystrophy (Supportive), mode of inheritance: AD
• patterned macular dystrophy (Supportive), mode of inheritance: AD
• multifocal pattern dystrophy simulating fundus flavimaculatus (Supportive), mode of inheritance: AD
• Leber congenital amaurosis 9 (Definitive), mode of inheritance: AR
• retinitis pigmentosa 7 (Definitive), mode of inheritance: AR
• choroidal dystrophy, central areolar 2 (Strong), mode of inheritance: AD
• retinitis pigmentosa 7 (Strong), mode of inheritance: AR
• vitelliform macular dystrophy 3 (Strong), mode of inheritance: AD
• retinitis pigmentosa 7 (Strong), mode of inheritance: AD
• fundus albipunctatus (Strong), mode of inheritance: AD
• inherited retinal dystrophy (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Choriodal dystrophy, central areolar 2; Retinitis punctata albescens; Macular dystrophy, vitelliform 3; Macula dystrophy, patterned 1; Retinitis pigmentosa 7	AD/Digenic	General	Digenic inheritance (with ROM1) has been reported; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	13410569; 900215; 7115165; 6984500; 3718916; 1749427; 1684223; 8485575; 8251014; 8485574; 8485572; 8485576; 7519821; 8202715; 8302543; 7493155; 8689482; 8644804; 9010868; 9443872; 10532447; 14557183; 19262438; 19243827; 20213611; 22842402; 22863181; 23847139

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRPH2 gene.

• PRPH2-related disorder (129 variants)
• not provided (71 variants)
• Retinal dystrophy (15 variants)
• Stargardt disease (12 variants)
• Retinitis pigmentosa (10 variants)
• Patterned dystrophy of the retinal pigment epithelium (7 variants)
• Patterned macular dystrophy 1 (7 variants)
• Vitelliform macular dystrophy 3 (5 variants)
• Retinitis pigmentosa 7 (4 variants)
• Macular dystrophy (3 variants)
• Pigmentary retinal dystrophy (3 variants)
• Choroidal dystrophy, central areolar 2 (3 variants)
• Cone-rod dystrophy (3 variants)
• Vitelliform macular dystrophy 2 (3 variants)
• Multifocal pattern dystrophy simulating fundus flavimaculatus (2 variants)
• Central areolar choroidal dystrophy (1 variants)
• Cone dystrophy (1 variants)
• Adult-onset foveomacular vitelliform dystrophy (1 variants)
• Leber congenital amaurosis 18 (1 variants)
• Choroideremia (1 variants)
• Doyne honeycomb retinal dystrophy (1 variants)
• maculopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRPH2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	67	1	70
missense	31	71	153	5	4	264
nonsense	34	16	1			51
start loss	3					3
frameshift	67	15	3			85
inframe indel	6		10			16
splice donor/acceptor (+/-2bp)	7	3	2			12
splice region	2	1	9	3		15
non coding			23	20	29	72
Total	148	105	194	92	34

Highest pathogenic variant AF is 0.00000657

Variants in PRPH2

This is a list of pathogenic ClinVar variants found in the PRPH2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-42696608-G-A		Cone-rod dystrophy • Patterned macular dystrophy 1 • Retinitis pigmentosa • Adult-onset foveomacular vitelliform dystrophy • Choroidal dystrophy, central areolar 2 • Pigmentary retinal dystrophy	Conflicting classifications of pathogenicity (Jan 12, 2018)
6-42696715-G-C		Cone-rod dystrophy • Choroidal dystrophy, central areolar 2 • Pigmentary retinal dystrophy • Retinitis pigmentosa • Adult-onset foveomacular vitelliform dystrophy • Patterned macular dystrophy 1	Uncertain significance (Jan 13, 2018)
6-42696730-C-T		Adult-onset foveomacular vitelliform dystrophy • Cone-rod dystrophy • Retinitis pigmentosa • Choroidal dystrophy, central areolar 2 • Patterned macular dystrophy 1 • Pigmentary retinal dystrophy	Conflicting classifications of pathogenicity (Apr 01, 2023)
6-42696761-A-G		Patterned macular dystrophy 1 • Pigmentary retinal dystrophy • Cone-rod dystrophy • Adult-onset foveomacular vitelliform dystrophy • Retinitis pigmentosa • Choroidal dystrophy, central areolar 2	Benign/Likely benign (Jan 13, 2018)
6-42696762-T-C		Cone-rod dystrophy • Retinitis pigmentosa • Pigmentary retinal dystrophy • Choroidal dystrophy, central areolar 2 • Patterned macular dystrophy 1 • Adult-onset foveomacular vitelliform dystrophy	Uncertain significance (Apr 27, 2017)
6-42696771-C-G		Retinitis pigmentosa • Cone-rod dystrophy • Choroidal dystrophy, central areolar 2 • Adult-onset foveomacular vitelliform dystrophy • Patterned macular dystrophy 1 • Pigmentary retinal dystrophy	Benign/Likely benign (Jan 13, 2018)
6-42696887-C-G		Retinitis pigmentosa • Choroidal dystrophy, central areolar 2 • Adult-onset foveomacular vitelliform dystrophy • Pigmentary retinal dystrophy • Cone-rod dystrophy • Patterned macular dystrophy 1	Uncertain significance (Jan 13, 2018)
6-42696920-G-A		Adult-onset foveomacular vitelliform dystrophy • Retinitis pigmentosa • Patterned macular dystrophy 1 • Cone-rod dystrophy • Choroidal dystrophy, central areolar 2 • Pigmentary retinal dystrophy	Benign (May 14, 2021)
6-42696923-G-T		Retinitis pigmentosa • Cone-rod dystrophy • Adult-onset foveomacular vitelliform dystrophy • Choroidal dystrophy, central areolar 2 • Patterned macular dystrophy 1 • Pigmentary retinal dystrophy	Benign/Likely benign (Jan 12, 2018)
6-42696925-T-A			Benign (May 24, 2021)
6-42696938-G-A		Choroidal dystrophy, central areolar 2 • Pigmentary retinal dystrophy • Cone-rod dystrophy • Patterned macular dystrophy 1 • Retinitis pigmentosa • Adult-onset foveomacular vitelliform dystrophy	Benign (May 14, 2021)
6-42696982-C-T		Adult-onset foveomacular vitelliform dystrophy • Pigmentary retinal dystrophy • Retinitis pigmentosa • Cone-rod dystrophy • Patterned macular dystrophy 1 • Choroidal dystrophy, central areolar 2	Benign/Likely benign (Jan 12, 2018)
6-42696996-G-A		Patterned macular dystrophy 1 • Pigmentary retinal dystrophy • Cone-rod dystrophy • Choroidal dystrophy, central areolar 2 • Retinitis pigmentosa • Adult-onset foveomacular vitelliform dystrophy	Uncertain significance (Jan 13, 2018)
6-42697065-G-A		Choroidal dystrophy, central areolar 2 • Retinitis pigmentosa • Patterned macular dystrophy 1 • Adult-onset foveomacular vitelliform dystrophy • Pigmentary retinal dystrophy • Cone-rod dystrophy	Benign/Likely benign (Jan 12, 2018)
6-42697174-T-G		Patterned macular dystrophy 1 • Adult-onset foveomacular vitelliform dystrophy • Retinitis pigmentosa • Pigmentary retinal dystrophy • Choroidal dystrophy, central areolar 2 • Cone-rod dystrophy	Benign/Likely benign (Jan 13, 2018)
6-42697216-C-T		Cone-rod dystrophy • Pigmentary retinal dystrophy • Adult-onset foveomacular vitelliform dystrophy • Choroidal dystrophy, central areolar 2 • Retinitis pigmentosa • Patterned macular dystrophy 1	Conflicting classifications of pathogenicity (Jan 13, 2018)
6-42697288-G-T		Adult-onset foveomacular vitelliform dystrophy • Choroidal dystrophy, central areolar 2 • Pigmentary retinal dystrophy • Patterned macular dystrophy 1 • Cone-rod dystrophy • Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
6-42697294-G-T		Adult-onset foveomacular vitelliform dystrophy • Retinitis pigmentosa • Patterned macular dystrophy 1 • Pigmentary retinal dystrophy • Cone-rod dystrophy • Choroidal dystrophy, central areolar 2	Benign (May 14, 2021)
6-42697295-G-C		Pigmentary retinal dystrophy • Adult-onset foveomacular vitelliform dystrophy • Retinitis pigmentosa • Choroidal dystrophy, central areolar 2 • Patterned macular dystrophy 1 • Cone-rod dystrophy	Uncertain significance (Apr 27, 2017)
6-42697306-C-T		Retinitis pigmentosa • Choroidal dystrophy, central areolar 2 • Adult-onset foveomacular vitelliform dystrophy • Patterned macular dystrophy 1 • Cone-rod dystrophy • Pigmentary retinal dystrophy	Benign/Likely benign (Jan 13, 2018)
6-42697378-C-T		Choroidal dystrophy, central areolar 2 • Adult-onset foveomacular vitelliform dystrophy • Retinitis pigmentosa • Cone-rod dystrophy • Patterned macular dystrophy 1 • Pigmentary retinal dystrophy	Uncertain significance (Jan 13, 2018)
6-42697397-G-T		Choroidal dystrophy, central areolar 2 • Adult-onset foveomacular vitelliform dystrophy • Pigmentary retinal dystrophy • Patterned macular dystrophy 1 • Cone-rod dystrophy • Retinitis pigmentosa	Benign (May 14, 2021)
6-42697440-ATGTC-A			not provided (-)
6-42697444-CTGAT-C			Uncertain significance (May 27, 2021)
6-42697456-C-T		Cone-rod dystrophy • Adult-onset foveomacular vitelliform dystrophy • Choroidal dystrophy, central areolar 2 • Patterned macular dystrophy 1 • Pigmentary retinal dystrophy • Retinitis pigmentosa	Benign (May 24, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRPH2	protein_coding	protein_coding	ENST00000230381	3	25973

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.116	0.879	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.102	189	193	0.979	0.0000127	2273
Missense in Polyphen		39	49.852	0.78232		561
Synonymous	-0.392	92	87.3	1.05	0.00000656	681
Loss of Function	2.44	4	13.8	0.291	7.39e-7	145

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000792	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. It is essential for disk morphogenesis.
• Disease: DISEASE: Retinitis punctata albescens (RPA) [MIM:136880]: A form of fleck retina disease characterized by aggregation of white flecks posteriorly in the retina, causing night blindness and delayed dark adaptation. It differs from fundus albipunctatus in being progressive and evolving to generalized atrophy of the retina. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:15370544, ECO:0000269|PubMed:17653047, ECO:0000269|PubMed:20213611, ECO:0000269|PubMed:26796962, ECO:0000269|PubMed:9338584}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:16024869, ECO:0000269|PubMed:26796962, ECO:0000269|PubMed:8485574, ECO:0000269|PubMed:9443872}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:16832026, ECO:0000269|PubMed:19038374, ECO:0000269|PubMed:20213611, ECO:0000269|PubMed:26796962}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=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.

Recessive Scores

• pRec: 0.214

Intolerance Scores

• loftool: 0.171
• rvis_EVS: 0.46
• rvis_percentile_EVS: 78.59

Haploinsufficiency Scores

• pHI: 0.367
• hipred: Y
• hipred_score: 0.553
• ghis: 0.405

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.134

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Prph2
• Phenotype: cellular phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; pigmentation phenotype

Gene ontology

• Biological process: cell adhesion;cell surface receptor signaling pathway;visual perception;retina development in camera-type eye
• Cellular component: photoreceptor outer segment;integral component of plasma membrane;integral component of membrane