RPGRIP1

RPGR interacting protein 1, the group of C2 domain containing

Basic information

Region (hg38): 14:21280082-21351301

Previous symbols: [ "RPGRIP" ]

Links

ENSG00000092200 ∙ NCBI:57096 ∙ OMIM:605446 ∙ HGNC:13436 ∙ Uniprot:Q96KN7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber congenital amaurosis 6 (Definitive), mode of inheritance: AR
• cone-rod dystrophy 13 (Definitive), mode of inheritance: AR
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• Leber congenital amaurosis (Supportive), mode of inheritance: AD
• Leber congenital amaurosis 6 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leber congenital amaurosis 6; Cone-rod dystrophy 13	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	11283794; 11528500; 12920076; 20006823; 20301475

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RPGRIP1 gene.

• Cone-rod dystrophy 13;Leber congenital amaurosis 6 (421 variants)
• Leber congenital amaurosis 6;Cone-rod dystrophy 13 (322 variants)
• not provided (155 variants)
• Leber congenital amaurosis 6 (152 variants)
• Cone-rod dystrophy 13 (127 variants)
• Inborn genetic diseases (53 variants)
• not specified (47 variants)
• Leber congenital amaurosis (19 variants)
• Retinal dystrophy (16 variants)
• Leber congenital amaurosis 1 (9 variants)
• RPGRIP1L-Related Disorders (5 variants)
• Retinitis pigmentosa (4 variants)
• Cone-rod dystrophy (3 variants)
• Bardet-Biedl syndrome (2 variants)
• Anophthalmia-microphthalmia syndrome (2 variants)
• - (2 variants)
• Cone dystrophy (2 variants)
• RPGRIP1-related condition (2 variants)
• Microcephaly (1 variants)
• Abnormality of the eye (1 variants)
• Cone-Rod Dystrophy, Recessive (1 variants)
• Color vision defect;Retinal dystrophy;Visual impairment;Horizontal nystagmus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPGRIP1 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			12	154	7	173
missense	2	2	404	14	3	425
nonsense	27	6				33
start loss			1			1
frameshift	32	10	3			45
inframe indel			8			8
splice donor/acceptor (+/-2bp)	11	10				21
splice region	1	2	23	14	2	42
non coding	1	2	6	58	43	110
Total	73	30	434	226	53

Highest pathogenic variant AF is 0.0000398

Variants in RPGRIP1

This is a list of pathogenic ClinVar variants found in the RPGRIP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-21287984-A-G		Cone-rod dystrophy 13;Leber congenital amaurosis 6	Uncertain significance (Oct 30, 2020)
14-21287986-C-A		Cone-rod dystrophy 13;Leber congenital amaurosis 6	Uncertain significance (Sep 18, 2020)
14-21287988-G-A		Cone-rod dystrophy 13;Leber congenital amaurosis 6	Likely benign (Aug 19, 2022)
14-21287987-T-TGGTGGACCCTACATCA		Cone-rod dystrophy 13;Leber congenital amaurosis 6	Pathogenic (Jan 28, 2023)
14-21287999-C-CA		Leber congenital amaurosis 6;Cone-rod dystrophy 13	Pathogenic (Oct 27, 2022)
14-21288005-G-A		Cone-rod dystrophy 13;Leber congenital amaurosis 6 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 28, 2022)
14-21288015-A-G		Leber congenital amaurosis 6;Cone-rod dystrophy 13	Likely benign (Jun 20, 2023)
14-21288026-T-C		Leber congenital amaurosis 6 • Cone-rod dystrophy 13 • Cone-rod dystrophy 13;Leber congenital amaurosis 6	Conflicting classifications of pathogenicity (Aug 10, 2023)
14-21288030-T-C		Cone-rod dystrophy 13;Leber congenital amaurosis 6	Likely benign (May 08, 2023)
14-21288037-C-T		Leber congenital amaurosis 6;Cone-rod dystrophy 13	Uncertain significance (Mar 10, 2022)
14-21288050-C-T		Cone-rod dystrophy 13;Leber congenital amaurosis 6 • Leber congenital amaurosis 6 • Cone-rod dystrophy 13	Conflicting classifications of pathogenicity (Nov 07, 2023)
14-21288051-A-G		Leber congenital amaurosis 6;Cone-rod dystrophy 13	Likely benign (Jun 15, 2023)
14-21288053-C-T		Leber congenital amaurosis 6 • Cone-rod dystrophy 13 • Leber congenital amaurosis 6;Cone-rod dystrophy 13	Uncertain significance (Mar 20, 2022)
14-21288056-C-T		Cone-rod dystrophy 13;Leber congenital amaurosis 6	Uncertain significance (Dec 28, 2020)
14-21288061-G-A		Leber congenital amaurosis 6;Cone-rod dystrophy 13	Uncertain significance (Nov 01, 2022)
14-21288066-C-A			Uncertain significance (Jul 01, 2017)
14-21288072-C-T		Leber congenital amaurosis 6;Cone-rod dystrophy 13	Likely benign (Dec 30, 2021)
14-21288073-G-A		Cone-rod dystrophy 13;Leber congenital amaurosis 6	Likely benign (May 09, 2023)
14-21288073-G-T		Leber congenital amaurosis 6;Cone-rod dystrophy 13	Likely benign (Apr 18, 2022)
14-21288081-A-T		Leber congenital amaurosis 6;Cone-rod dystrophy 13	Likely benign (Oct 13, 2023)
14-21294412-T-C			Benign (Jun 20, 2021)
14-21294657-A-T		Leber congenital amaurosis 6;Cone-rod dystrophy 13	Benign (Jul 10, 2023)
14-21294676-G-A		Cone-rod dystrophy 13;Leber congenital amaurosis 6	Likely pathogenic (May 29, 2022)
14-21294685-A-G		Leber congenital amaurosis 6	Uncertain significance (May 06, 2021)
14-21294686-T-A		Cone-rod dystrophy 13;Leber congenital amaurosis 6 • Cone-rod dystrophy 13 • Leber congenital amaurosis 6 • not specified	Conflicting classifications of pathogenicity (Jan 31, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RPGRIP1	protein_coding	protein_coding	ENST00000400017	24	63363

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.26e-23	0.798	124511	0	146	124657	0.000586

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.248	636	654	0.973	0.0000325	8387
Missense in Polyphen		150	161.69	0.92771		2273
Synonymous	-0.219	256	252	1.02	0.0000129	2410
Loss of Function	2.40	47	68.4	0.687	0.00000389	794

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00153	0.00148
Ashkenazi Jewish	0.000714	0.000696
East Asian	0.00147	0.00145
Finnish	0.0000938	0.0000928
European (Non-Finnish)	0.000435	0.000416
Middle Eastern	0.00147	0.00145
South Asian	0.00118	0.000752
Other	0.000997	0.000826

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function as scaffolding protein. Required for normal location of RPGR at the connecting cilium of photoreceptor cells. Required for normal disk morphogenesis and disk organization in the outer segment of photoreceptor cells and for survival of photoreceptor cells. {ECO:0000250|UniProtKB:Q9EPQ2, ECO:0000305|PubMed:10958648}.
• Disease: DISEASE: Leber congenital amaurosis 6 (LCA6) [MIM:613826]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. {ECO:0000269|PubMed:11528500, ECO:0000269|PubMed:17306875, ECO:0000269|PubMed:17554762, ECO:0000269|PubMed:18682808, ECO:0000269|PubMed:24981858}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cone-rod dystrophy 13 (CORD13) [MIM:608194]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:10958648, ECO:0000269|PubMed:12920076}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Heterozygous non-synonymous variants of RPGRIP1 may cause or increase the susceptibility to various forms of glaucoma, a genetically heterogeneous disorder. It is the second cause of blindness worldwide owing to the progressive degeneration of retinal ganglion neurons (PubMed:21224891). {ECO:0000269|PubMed:21224891}.

Recessive Scores

• pRec: 0.182

Intolerance Scores

• loftool: 0.499
• rvis_EVS: 1.3
• rvis_percentile_EVS: 93.91

Haploinsufficiency Scores

• pHI: 0.0819
• hipred: N
• hipred_score: 0.153

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.549

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rpgrip1
• 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); vision/eye phenotype

Zebrafish Information Network

• Gene name: rpgrip1
• Affected structure: retinal rod cell
• Phenotype tag: abnormal
• Phenotype quality: absence due to degeneration

Gene ontology

• Biological process: visual perception;eye photoreceptor cell development;response to stimulus;retina development in camera-type eye;neural precursor cell proliferation
• Cellular component: axoneme;photoreceptor connecting cilium
• Molecular function: protein binding