RPGRIP1

RPGR interacting protein 1, the group of C2 domain containing

Basic information

Region (hg38): 14:21280083-21351301

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.

• Leber_congenital_amaurosis_6 (886 variants)
• Cone-rod_dystrophy_13 (857 variants)
• Inborn_genetic_diseases (134 variants)
• not_provided (129 variants)
• Retinal_dystrophy (51 variants)
• not_specified (40 variants)
• Leber_congenital_amaurosis (28 variants)
• RPGRIP1-related_disorder (17 variants)
• Leber_congenital_amaurosis_1 (8 variants)
• Retinitis_pigmentosa (8 variants)
• Cone-rod_dystrophy (3 variants)
• Anophthalmia-microphthalmia_syndrome (2 variants)
• Optic_atrophy (2 variants)
• Cone_dystrophy (2 variants)
• Bardet-Biedl_syndrome (2 variants)
• Joubert_syndrome_7 (1 variants)
• Visual_impairment (1 variants)
• Microcephaly (1 variants)
• Color_vision_defect (1 variants)
• Cone-Rod_Dystrophy,_Recessive (1 variants)
• Horizontal_nystagmus (1 variants)
• Abnormality_of_the_eye (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. These statistics are base on transcript: NM_000020366.4. 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			12	209	3	224
missense	3	12	455	33		503
nonsense	35	14	3			52
start loss						0
frameshift	52	22	6			80
splice donor/acceptor (+/-2bp)	16	20	2			38
Total	106	68	478	242	3

Highest pathogenic variant AF is 0.000357052

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