RP1
RP1 axonemal microtubule associated, the group of Doublecortin superfamily
Basic information
Region (hg38): 8:54509421-54871720
Links
Phenotypes
GenCC
Source:
- retinitis pigmentosa 1 (Definitive), mode of inheritance: AD
- retinitis pigmentosa (Supportive), mode of inheritance: AD
- retinitis pigmentosa 1 (Definitive), mode of inheritance: AD
- RP1-related dominant retinopathy (Definitive), mode of inheritance: Semidominant
- RP1-related recessive retinopathy (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Retinitis pigmentosa 1, autosomal dominant; Retinitis pigmentosa 1, autosomal recessive | AD/AR | General | 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 | 1783394; 10391211; 10391212; 18552984; 19933189; 20664799; 21746989; 22052604; 22317909; 22321012; 22917891; 23077400 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (1125 variants)
- Retinitis pigmentosa (156 variants)
- Retinitis pigmentosa 1 (86 variants)
- Inborn genetic diseases (64 variants)
- Retinal dystrophy (58 variants)
- not specified (23 variants)
- Autosomal recessive retinitis pigmentosa (11 variants)
- Retinitis Pigmentosa, Dominant (4 variants)
- RP1-related retinal dystrophy (2 variants)
- Retinal dystrophy;Visual impairment;Retinal pigment epithelial atrophy (1 variants)
- Leber congenital amaurosis 1 (1 variants)
- Leber optic atrophy (1 variants)
- Ductal breast carcinoma (1 variants)
- Hypertriglyceridemia, familial (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RP1 gene is commonly pathogenic or not.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | 214 | 11 | 233 | ||
| missense | 3 | 7 | 688 | 39 | 9 | 746 |
| nonsense | 60 | 25 | 5 | 90 | ||
| start loss | 0 | |||||
| frameshift | 108 | 34 | 6 | 148 | ||
| inframe indel | 9 | 9 | ||||
| splice variant | 3 | 3 | 6 | 4 | 1 | 17 |
| non coding | 9 | 10 | 2 | 21 | ||
| Total | 174 | 69 | 731 | 267 | 23 |
Highest pathogenic variant AF is 0.0000460
Variants in RP1
This is a list of pathogenic ClinVar variants found in the RP1 region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-54616061-T-C | Retinitis Pigmentosa, Dominant | Likely benign (Jun 14, 2016) | ||
| 8-54616109-G-A | Retinitis pigmentosa | Likely benign (Jan 13, 2018) | ||
| 8-54616114-G-A | Retinitis pigmentosa | Uncertain significance (Jan 13, 2018) | ||
| 8-54616164-A-G | Retinitis pigmentosa | Uncertain significance (Apr 27, 2017) | ||
| 8-54616178-T-C | Retinitis pigmentosa | Uncertain significance (Apr 27, 2017) | ||
| 8-54620943-T-C | Retinitis pigmentosa | Uncertain significance (Jan 13, 2018) | ||
| 8-54620970-AGT-A | Retinitis pigmentosa 1 | Pathogenic (Mar 14, 2022) | ||
| 8-54620981-T-C | Likely benign (Feb 09, 2022) | |||
| 8-54620987-T-C | Likely benign (Aug 16, 2022) | |||
| 8-54620987-T-G | Retinitis pigmentosa | Conflicting interpretations of pathogenicity (Oct 17, 2022) | ||
| 8-54620989-G-T | Inborn genetic diseases | Uncertain significance (Aug 02, 2021) | ||
| 8-54620998-T-A | Retinitis pigmentosa 1 | Uncertain significance (Jan 06, 2021) | ||
| 8-54621006-C-G | Uncertain significance (Sep 24, 2021) | |||
| 8-54621010-C-T | Uncertain significance (Oct 25, 2022) | |||
| 8-54621016-C-A | Uncertain significance (Aug 08, 2022) | |||
| 8-54621031-C-T | Uncertain significance (Oct 13, 2022) | |||
| 8-54621032-A-AC | Pathogenic (Jul 13, 2022) | |||
| 8-54621033-C-T | Uncertain significance (Aug 09, 2022) | |||
| 8-54621037-C-G | Uncertain significance (Sep 17, 2021) | |||
| 8-54621037-C-T | Uncertain significance (Aug 21, 2022) | |||
| 8-54621037-CT-C | Pathogenic (Sep 27, 2022) | |||
| 8-54621039-C-T | Uncertain significance (Aug 22, 2022) | |||
| 8-54621040-G-A | Retinitis pigmentosa | Uncertain significance (May 29, 2019) | ||
| 8-54621069-G-T | Inborn genetic diseases | Uncertain significance (Feb 15, 2023) | ||
| 8-54621070-C-T | Retinitis pigmentosa • Inborn genetic diseases | Uncertain significance (Jul 14, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RP1 | protein_coding | protein_coding | ENST00000220676 | 3 | 14768 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 4.41e-13 | 1.00 | 125529 | 0 | 219 | 125748 | 0.000871 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.894 | 1169 | 1.09e+3 | 1.08 | 0.0000553 | 14374 |
| Missense in Polyphen | 167 | 182.08 | 0.91716 | 2415 | ||
| Synonymous | 0.218 | 390 | 396 | 0.986 | 0.0000210 | 4037 |
| Loss of Function | 3.39 | 30 | 57.8 | 0.519 | 0.00000295 | 901 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00181 | 0.00180 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00305 | 0.00305 |
| Finnish | 0.000463 | 0.000462 |
| European (Non-Finnish) | 0.000724 | 0.000712 |
| Middle Eastern | 0.00305 | 0.00305 |
| South Asian | 0.000753 | 0.000752 |
| Other | 0.00115 | 0.00114 |
dbNSFP
Source:
- Function
- FUNCTION: Microtubule-associated protein regulating the stability and length of the microtubule-based axoneme of photoreceptors. Required for the differentiation of photoreceptor cells, it plays a role in the organization of the outer segment of rod and cone photoreceptors ensuring the correct orientation and higher-order stacking of outer segment disks along the photoreceptor axoneme (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Retinitis pigmentosa 1 (RP1) [MIM:180100]: 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. {ECO:0000269|PubMed:10391211, ECO:0000269|PubMed:10484783, ECO:0000269|PubMed:11095597, ECO:0000269|PubMed:15863674, ECO:0000269|PubMed:15933747, ECO:0000269|PubMed:19956407, ECO:0000269|PubMed:20664799, ECO:0000269|PubMed:22052604, ECO:0000269|PubMed:22334370}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- loftool
- 0.497
- rvis_EVS
- 0.85
- rvis_percentile_EVS
- 88.38
Haploinsufficiency Scores
- pHI
- 0.338
- hipred
- N
- hipred_score
- 0.203
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.0265
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Rp1
- 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); 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);
Gene ontology
- Biological process
- visual perception;phototransduction, visible light;axoneme assembly;intracellular signal transduction;photoreceptor cell outer segment organization;photoreceptor cell development;photoreceptor cell maintenance;retinal rod cell development;retinal cone cell development;retina development in camera-type eye;cellular response to light stimulus;positive regulation of non-motile cilium assembly
- Cellular component
- photoreceptor outer segment;photoreceptor inner segment;microtubule;microtubule associated complex;axoneme;photoreceptor connecting cilium;ciliary tip
- Molecular function
- protein binding;microtubule binding