RP1

RP1 axonemal microtubule associated, the group of Doublecortin superfamily

Basic information

Region (hg38): 8:54509422-54871720

Links

ENSG00000104237 ∙ NCBI:6101 ∙ OMIM:603937 ∙ HGNC:10263 ∙ Uniprot:P56715 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 1 (Definitive), mode of inheritance: AD
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 1 (Definitive), mode of inheritance: AD
• retinitis pigmentosa 1 (Strong), mode of inheritance: AD
• retinitis pigmentosa 1 (Strong), mode of inheritance: AR
• RP1-related dominant retinopathy (Definitive), mode of inheritance: Semidominant
• RP1-related recessive retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the RP1 gene.

• not provided (157 variants)
• Retinitis pigmentosa (23 variants)
• Retinitis pigmentosa 1 (16 variants)
• Retinal dystrophy (11 variants)
• Autosomal recessive retinitis pigmentosa (3 variants)
• RP1-related disorder (1 variants)
• Inborn genetic diseases (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.

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	13	224	10	248
missense	2	7	824	22	10	865
nonsense	58	27	5			90
start loss						0
frameshift	112	38	4			154
inframe indel			9			9
splice donor/acceptor (+/-2bp)	2	2	1			5
splice region			5	4	1	10
non coding			9	12	2	23
Total	174	75	865	258	22

Highest pathogenic variant AF is 0.0000460

Variants in RP1

This is a list of pathogenic ClinVar variants found in the RP1 region.

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

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 (Oct 02, 2023)
8-54620987-T-G		Retinitis pigmentosa	Conflicting classifications of pathogenicity (Dec 16, 2023)
8-54620989-G-T		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
8-54620998-T-A		Retinitis pigmentosa 1	Uncertain significance (Jan 06, 2021)
8-54621001-T-C			Uncertain significance (Dec 24, 2022)
8-54621006-C-G			Uncertain significance (Jul 05, 2023)
8-54621010-C-T			Uncertain significance (Oct 25, 2022)
8-54621011-G-A			Likely benign (Apr 15, 2023)
8-54621016-C-A			Uncertain significance (Aug 08, 2022)
8-54621021-G-A			Uncertain significance (Jan 06, 2024)
8-54621025-A-C		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
8-54621031-C-T			Uncertain significance (Oct 08, 2023)
8-54621032-A-AC			Pathogenic (Jul 13, 2022)
8-54621033-C-T			Uncertain significance (Aug 09, 2022)
8-54621035-C-T			Likely benign (Jun 24, 2023)
8-54621037-C-G			Uncertain significance (Aug 11, 2021)
8-54621037-C-T			Uncertain significance (Aug 21, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

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