Menu
GeneBe

PRPH2

peripherin 2, the group of Tetraspanins

Basic information

Region (hg38): 6:42696597-42722597

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Choriodal dystrophy, central areolar 2; Retinitis punctata albescens; Macular dystrophy, vitelliform 3; Macula dystrophy, patterned 1; Retinitis pigmentosa 7AD/DigenicGeneralDigenic 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 testingOphthalmologic13410569; 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 Disorders (445 variants)
  • not provided (251 variants)
  • Retinitis pigmentosa (114 variants)
  • Patterned macular dystrophy 1 (102 variants)
  • Pigmentary retinal dystrophy (88 variants)
  • Cone-rod dystrophy (87 variants)
  • Choroidal dystrophy, central areolar 2 (81 variants)
  • Adult-onset foveomacular vitelliform dystrophy (79 variants)
  • Retinal dystrophy (62 variants)
  • Stargardt disease (46 variants)
  • Patterned dystrophy of the retinal pigment epithelium (30 variants)
  • Retinitis pigmentosa 7 (18 variants)
  • not specified (16 variants)
  • Vitelliform macular dystrophy 3 (16 variants)
  • Vitelliform macular dystrophy 2 (12 variants)
  • Macular dystrophy (6 variants)
  • Inborn genetic diseases (4 variants)
  • Choroidal Dystrophy (4 variants)
  • Vitelliform macular dystrophy (4 variants)
  • Retinitis Pigmentosa, Dominant (4 variants)
  • Cone-Rod Dystrophy, Dominant (4 variants)
  • maculopathy (3 variants)
  • Cone dystrophy (2 variants)
  • Leber congenital amaurosis 18 (2 variants)
  • Multifocal pattern dystrophy simulating fundus flavimaculatus (2 variants)
  • Isolated macular dystrophy (2 variants)
  • Retinitis pigmentosa 7, digenic (1 variants)
  • Central areolar choroidal dystrophy (1 variants)
  • PRPH2-related condition (1 variants)
  • Usher syndrome (1 variants)
  • Choroideremia (1 variants)
  • Progressive cone dystrophy (without rod involvement) (1 variants)
  • Patterned macular dystrophy 1;Pigmentary retinal dystrophy;Choroidal dystrophy, central areolar 2;Retinitis pigmentosa 7;Vitelliform macular dystrophy 3 (1 variants)
  • Macular degeneration;Pigmentary retinopathy;Abnormality of retinal pigmentation;Blurred vision (1 variants)
  • Doyne honeycomb retinal dystrophy (1 variants)
  • Autosomal recessive bestrophinopathy (1 variants)
  • Adult onset vitelliform dystrophy (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
1
clinvar
63
clinvar
1
clinvar
 65
missense
24
clinvar
66
clinvar
138
clinvar
5
clinvar
4
clinvar
 237
nonsense
30
clinvar
16
clinvar
1
clinvar
 47
start loss
3
clinvar
1
clinvar
 4
frameshift
65
clinvar
14
clinvar
4
clinvar
 83
inframe indel
4
clinvar
10
clinvar
 14
splice donor/acceptor (+/-2bp)
7
clinvar
3
clinvar
2
clinvar
 12
splice region
?
    Intron variants in splice region, excluding donor/acceptor (+/-2bp)
2
1
8
2
 13
non coding
?
    UTR, intron and other, non coding variants
23
clinvar
19
clinvar
29
clinvar
 71
Total 133 100 179 87 34

Highest pathogenic variant AF is 0.0000197

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)356743
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)356744
6-42696730-C-T Cone-rod dystrophy • Adult-onset foveomacular vitelliform dystrophy • Retinitis pigmentosa • Choroidal dystrophy, central areolar 2 • Patterned macular dystrophy 1 • Pigmentary retinal dystrophy Conflicting classifications of pathogenicity (Apr 01, 2023)356745
6-42696761-A-G Pigmentary retinal dystrophy • Patterned macular dystrophy 1 • Cone-rod dystrophy • Adult-onset foveomacular vitelliform dystrophy • Retinitis pigmentosa • Choroidal dystrophy, central areolar 2 Benign/Likely benign (Jan 13, 2018)356746
6-42696762-T-C Cone-rod dystrophy • Choroidal dystrophy, central areolar 2 • Patterned macular dystrophy 1 • Adult-onset foveomacular vitelliform dystrophy • Retinitis pigmentosa • Pigmentary retinal dystrophy Uncertain significance (Apr 27, 2017)908376
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)356747
6-42696887-C-G Retinitis pigmentosa • Choroidal dystrophy, central areolar 2 • Pigmentary retinal dystrophy • Adult-onset foveomacular vitelliform dystrophy • Cone-rod dystrophy • Patterned macular dystrophy 1 Uncertain significance (Jan 13, 2018)356748
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)356749
6-42696923-G-T Retinitis pigmentosa • Pigmentary retinal dystrophy • Cone-rod dystrophy • Adult-onset foveomacular vitelliform dystrophy • Choroidal dystrophy, central areolar 2 • Patterned macular dystrophy 1 Benign/Likely benign (Jan 12, 2018)908443
6-42696925-T-A Benign (May 24, 2021)1279045
6-42696938-G-A Choroidal dystrophy, central areolar 2 • Pigmentary retinal dystrophy • Patterned macular dystrophy 1 • Cone-rod dystrophy • Retinitis pigmentosa • Adult-onset foveomacular vitelliform dystrophy Benign (May 14, 2021)356750
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)356751
6-42696996-G-A Patterned macular dystrophy 1 • Pigmentary retinal dystrophy • Cone-rod dystrophy • Retinitis pigmentosa • Choroidal dystrophy, central areolar 2 • Adult-onset foveomacular vitelliform dystrophy Uncertain significance (Jan 13, 2018)356752
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)356753
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)356754
6-42697216-C-T Cone-rod dystrophy • Pigmentary retinal dystrophy • Choroidal dystrophy, central areolar 2 • Adult-onset foveomacular vitelliform dystrophy • Retinitis pigmentosa • Patterned macular dystrophy 1 Conflicting classifications of pathogenicity (Jan 13, 2018)908512
6-42697288-G-T Adult-onset foveomacular vitelliform dystrophy • Choroidal dystrophy, central areolar 2 • Patterned macular dystrophy 1 • Pigmentary retinal dystrophy • Cone-rod dystrophy • Retinitis pigmentosa Uncertain significance (Jan 12, 2018)356755
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)356756
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)911537
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)356757
6-42697378-C-T Adult-onset foveomacular vitelliform dystrophy • Choroidal dystrophy, central areolar 2 • Cone-rod dystrophy • Retinitis pigmentosa • Patterned macular dystrophy 1 • Pigmentary retinal dystrophy Uncertain significance (Jan 13, 2018)356758
6-42697397-G-T Adult-onset foveomacular vitelliform dystrophy • Choroidal dystrophy, central areolar 2 • Patterned macular dystrophy 1 • Pigmentary retinal dystrophy • Cone-rod dystrophy • Retinitis pigmentosa Benign (May 14, 2021)356759
6-42697440-ATGTC-A not provided (-)98654
6-42697444-CTGAT-C Uncertain significance (May 27, 2021)1175233
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)356760

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PRPH2protein_codingprotein_codingENST00000230381 325973
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.1160.8791257330151257480.0000596
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.1021891930.9790.00001272273
Missense in Polyphen3949.8520.78232561
Synonymous-0.3929287.31.050.00000656681
Loss of Function2.44413.80.2917.39e-7145

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00006150.0000615
Ashkenazi Jewish0.00009920.0000992
East Asian0.00005440.0000544
Finnish0.0001390.000139
European (Non-Finnish)0.00007920.0000615
Middle Eastern0.00005440.0000544
South Asian0.00009800.0000653
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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
Molecular function