PRPH2
peripherin 2, the group of Tetraspanins
Basic information
Region (hg38): 6:42696598-42722597
Previous symbols: [ "RP7", "RDS" ]
Links
Phenotypes
GenCC
Source:
- 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
- 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
- hereditary macular dystrophy (Definitive), mode of inheritance: AD
- Leber congenital amaurosis (Definitive), mode of inheritance: AR
- PRPH2-related retinopathy (Definitive), mode of inheritance: AD
- inherited retinal dystrophy (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
| 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
- PRPH2-related_disorder (518 variants)
- not_provided (319 variants)
- Retinal_dystrophy (171 variants)
- Retinitis_pigmentosa (66 variants)
- Patterned_macular_dystrophy_1 (65 variants)
- Stargardt_disease (46 variants)
- Choroidal_dystrophy,_central_areolar_2 (46 variants)
- Pigmentary_retinal_dystrophy (42 variants)
- Retinitis_pigmentosa_7 (35 variants)
- Cone-rod_dystrophy (35 variants)
- Adult-onset_foveomacular_vitelliform_dystrophy (31 variants)
- Patterned_dystrophy_of_the_retinal_pigment_epithelium (30 variants)
- Vitelliform_macular_dystrophy_3 (26 variants)
- Inborn_genetic_diseases (19 variants)
- Vitelliform_macular_dystrophy_2 (12 variants)
- Macular_dystrophy (10 variants)
- not_specified (9 variants)
- maculopathy (3 variants)
- Isolated_macular_dystrophy (2 variants)
- Leber_congenital_amaurosis_18 (2 variants)
- Choroideremia (2 variants)
- Cone_dystrophy (2 variants)
- Multifocal_pattern_dystrophy_simulating_fundus_flavimaculatus (2 variants)
- Doyne_honeycomb_retinal_dystrophy (1 variants)
- Macular_degeneration (1 variants)
- Prostate_cancer (1 variants)
- Progressive_cone_dystrophy_(without_rod_involvement) (1 variants)
- Retinitis_punctata_albescens,_autosomal_dominant (1 variants)
- Choroidal_Dystrophy (1 variants)
- Central_areolar_choroidal_dystrophy (1 variants)
- Retinitis_pigmentosa_7,_digenic (1 variants)
- Optic_atrophy (1 variants)
- PRPH2-associated_retinal_disease (1 variants)
- Cone-Rod_Dystrophy,_Dominant (1 variants)
- Abnormality_of_retinal_pigmentation (1 variants)
- Blurred_vision (1 variants)
- Autosomal_recessive_bestrophinopathy (1 variants)
- Vitelliform_macular_dystrophy (1 variants)
- Pigmentary_retinopathy (1 variants)
- Retinitis_Pigmentosa,_Dominant (1 variants)
- Usher_syndrome (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. These statistics are base on transcript: NM_000000322.5. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 80 | 88 | ||||
| missense | 40 | 119 | 199 | 13 | 374 | |
| nonsense | 45 | 17 | 63 | |||
| start loss | 3 | 2 | 5 | |||
| frameshift | 103 | 23 | 131 | |||
| splice donor/acceptor (+/-2bp) | 14 | |||||
| Total | 200 | 165 | 214 | 93 | 3 |
Highest pathogenic variant AF is 0.0000861183
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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
- Molecular function