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
• RP1-related recessive retinopathy (Definitive), mode of inheritance: AR
• RP1-related dominant retinopathy (Strong), mode of inheritance: AD
• RP1-related recessive retinopathy (Definitive), mode of inheritance: AR
• RP1-related dominant retinopathy (Definitive), mode of inheritance: Semidominant
• retinitis pigmentosa 1 (Definitive), mode of inheritance: AD
• retinitis pigmentosa 1 (Strong), mode of inheritance: AD
• retinitis pigmentosa 1 (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 1 (Strong), mode of inheritance: AD
• retinitis pigmentosa 1 (Strong), mode of inheritance: AR
• retinitis pigmentosa 1 (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 (1483 variants)
• Inborn_genetic_diseases (287 variants)
• Retinal_dystrophy (209 variants)
• Retinitis_pigmentosa (144 variants)
• Retinitis_pigmentosa_1 (127 variants)
• RP1-related_disorder (29 variants)
• not_specified (18 variants)
• Autosomal_recessive_retinitis_pigmentosa (10 variants)
• Retinal_disorder (4 variants)
• RP1-related_recessive_retinopathy (2 variants)
• RP1-related_retinal_dystrophy (2 variants)
• Leber_optic_atrophy (1 variants)
• Cone-rod_dystrophy (1 variants)
• Leber_congenital_amaurosis_1 (1 variants)
• Optic_atrophy (1 variants)
• Visual_impairment (1 variants)
• Retinal_pigment_epithelial_atrophy (1 variants)
• Breast_ductal_adenocarcinoma (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. These statistics are base on transcript: NM_000006269.2. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	12	291	10	314
missense	3	17	1031	58	6	1115
nonsense	77	41	4			122
start loss						0
frameshift	139	62	6			207
splice donor/acceptor (+/-2bp)	2	7				9
Total	221	128	1053	349	16

Highest pathogenic variant AF is 0.00014689002

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
		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

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

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