RPGRIP1L

RPGRIP1 like, the group of Protein phosphatase 1 regulatory subunits|C2 domain containing

Basic information

Region (hg38): 16:53598152-53703938

Links

ENSG00000103494 ∙ NCBI:23322 ∙ OMIM:610937 ∙ HGNC:29168 ∙ Uniprot:Q68CZ1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Meckel syndrome, type 5 (Definitive), mode of inheritance: AR
• Meckel syndrome (Supportive), mode of inheritance: AR
• COACH syndrome 1 (Supportive), mode of inheritance: AR
• Joubert syndrome with renal defect (Supportive), mode of inheritance: AR
• Joubert syndrome 7 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
COACH syndrome 3	AR	Gastrointestinal	In COACH syndrome, among other findings, individuals may have hepatic disease, and it has been suggested that identification of liver disease is critical as some patients may develop complications such as portal hypertension with fatal variceal bleeding	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	17558407; 17558409; 18565097; 19430481; 19574260; 20301500

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RPGRIP1L gene.

• Meckel-Gruber syndrome;Familial aplasia of the vermis (625 variants)
• Familial aplasia of the vermis;Meckel-Gruber syndrome (590 variants)
• not provided (229 variants)
• Familial aplasia of the vermis (220 variants)
• Joubert syndrome 7 (153 variants)
• Meckel syndrome, type 5 (141 variants)
• Nephronophthisis 8 (125 variants)
• Inborn genetic diseases (71 variants)
• not specified (64 variants)
• RPGRIP1L-related condition (61 variants)
• Joubert syndrome 7;Meckel syndrome, type 5;COACH syndrome 3 (48 variants)
• Meckel syndrome, type 5;Joubert syndrome 7;COACH syndrome 3 (33 variants)
• COACH syndrome 3;Joubert syndrome 7;Meckel syndrome, type 5 (27 variants)
• Meckel syndrome, type 5;COACH syndrome 3;Joubert syndrome 7 (25 variants)
• Joubert syndrome 7;COACH syndrome 3;Meckel syndrome, type 5 (14 variants)
• Joubert syndrome and related disorders (13 variants)
• Kidney disorder (9 variants)
• COACH syndrome 3;Meckel syndrome, type 5;Joubert syndrome 7 (7 variants)
• COACH syndrome 1 (6 variants)
• Nephronophthisis (4 variants)
• Retinal dystrophy (4 variants)
• Joubert syndrome 7;COACH syndrome 1;Meckel syndrome, type 5 (3 variants)
• RPGRIP1L-Related Disorders (3 variants)
• Meckel-Gruber syndrome (3 variants)
• COACH syndrome 3 (2 variants)
• Meckel syndrome, type 5;COACH syndrome 1;Joubert syndrome 7 (1 variants)
• Focal segmental glomerulosclerosis (1 variants)
• Bardet-Biedl syndrome (1 variants)
• Retinitis pigmentosa in ciliopathies, modifier of (1 variants)
• Microcephaly (1 variants)
• See cases (1 variants)
• Leber congenital amaurosis (1 variants)
• COACH syndrome 1;Joubert syndrome 7;Meckel syndrome, type 5 (1 variants)
• Meckel syndrome, type 5;Joubert syndrome 7;COACH syndrome 1 (1 variants)
• Abnormality of prenatal development or birth (1 variants)
• COACH syndrome 1;Joubert syndrome 7 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPGRIP1L 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			6	342	1	349
missense	3	2	475	11	4	495
nonsense	43	20				63
start loss						0
frameshift	69	15	2			86
inframe indel			6	1		7
splice donor/acceptor (+/-2bp)	5	33	1			39
splice region			31	63	4	98
non coding		1	44	142	34	221
Total	120	71	534	496	39

Highest pathogenic variant AF is 0.000158

Variants in RPGRIP1L

This is a list of pathogenic ClinVar variants found in the RPGRIP1L region.

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

Position	Type	Phenotype	Significance	ClinVar
16-53600193-G-C		Meckel syndrome, type 5 • Nephronophthisis 8 • Joubert syndrome 7	Uncertain significance (Jan 12, 2018)
16-53600207-T-C		Meckel syndrome, type 5 • Nephronophthisis 8 • Joubert syndrome 7	Uncertain significance (Jan 12, 2018)
16-53600383-C-T		Meckel syndrome, type 5 • Nephronophthisis 8 • Joubert syndrome 7	Benign (Jan 13, 2018)
16-53600431-T-A		Joubert syndrome 7 • Meckel syndrome, type 5 • Nephronophthisis 8	Uncertain significance (Jan 13, 2018)
16-53600449-C-T		Nephronophthisis 8 • Joubert syndrome 7 • Meckel syndrome, type 5	Conflicting classifications of pathogenicity (Jul 01, 2023)
16-53600479-C-T		Meckel syndrome, type 5 • Nephronophthisis 8 • Joubert syndrome 7	Uncertain significance (Jan 13, 2018)
16-53600492-C-A		Meckel syndrome, type 5 • Nephronophthisis 8 • Joubert syndrome 7	Conflicting classifications of pathogenicity (Nov 01, 2022)
16-53600566-C-T		Joubert syndrome 7 • Nephronophthisis 8 • Meckel syndrome, type 5	Uncertain significance (Jan 13, 2018)
16-53600594-C-T		Meckel syndrome, type 5 • Nephronophthisis 8 • Joubert syndrome 7	Uncertain significance (Jan 12, 2018)
16-53600615-T-A		Nephronophthisis 8 • Meckel syndrome, type 5 • Joubert syndrome 7	Uncertain significance (Jan 12, 2018)
16-53600691-T-C		Nephronophthisis 8 • Meckel syndrome, type 5 • Joubert syndrome 7	Uncertain significance (Jan 12, 2018)
16-53600767-G-T		Meckel syndrome, type 5 • Joubert syndrome 7 • Nephronophthisis 8	Uncertain significance (Jan 13, 2018)
16-53600800-C-T		Meckel syndrome, type 5 • Nephronophthisis 8 • Joubert syndrome 7	Uncertain significance (Jan 12, 2018)
16-53600869-C-T		Nephronophthisis 8 • Meckel syndrome, type 5 • Joubert syndrome 7	Uncertain significance (Jan 12, 2018)
16-53600870-G-A		Meckel syndrome, type 5 • Joubert syndrome 7 • Nephronophthisis 8	Uncertain significance (Jan 12, 2018)
16-53601041-A-G		Joubert syndrome 7 • Meckel syndrome, type 5 • Nephronophthisis 8	Uncertain significance (Jan 13, 2018)
16-53601043-C-T		Nephronophthisis 8 • Joubert syndrome 7 • Meckel syndrome, type 5	Conflicting classifications of pathogenicity (Jan 12, 2018)
16-53601096-A-G		Nephronophthisis 8 • Meckel syndrome, type 5 • Joubert syndrome 7	Uncertain significance (Jan 13, 2018)
16-53601175-T-C		Nephronophthisis • Meckel-Gruber syndrome • Familial aplasia of the vermis	Uncertain significance (Jun 14, 2016)
16-53601201-T-C		Nephronophthisis 8 • Joubert syndrome 7 • Meckel syndrome, type 5	Uncertain significance (Jan 13, 2018)
16-53601225-G-T		Meckel syndrome, type 5 • Joubert syndrome 7 • Nephronophthisis 8	Uncertain significance (Jan 12, 2018)
16-53601230-T-A		Joubert syndrome 7 • Meckel syndrome, type 5 • Nephronophthisis 8	Uncertain significance (Jan 12, 2018)
16-53601254-T-C		Nephronophthisis 8 • Joubert syndrome 7 • Meckel syndrome, type 5	Uncertain significance (Apr 27, 2017)
16-53601339-A-C		Nephronophthisis 8 • Joubert syndrome 7 • Meckel syndrome, type 5	Benign (Jan 13, 2018)
16-53601378-A-G		Meckel syndrome, type 5 • Nephronophthisis 8 • Joubert syndrome 7	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RPGRIP1L	protein_coding	protein_coding	ENST00000379925	26	106256

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.08e-31	0.0410	125530	0	218	125748	0.000867

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.108	696	688	1.01	0.0000373	8729
Missense in Polyphen		138	157.7	0.87507		2042
Synonymous	-0.00131	241	241	1.00	0.0000128	2362
Loss of Function	1.86	57	74.3	0.767	0.00000415	873

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00209	0.00209
Ashkenazi Jewish	0.00	0.00
East Asian	0.000935	0.000925
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000953	0.000932
Middle Eastern	0.000935	0.000925
South Asian	0.00138	0.00134
Other	0.000817	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negatively regulates signaling through the G-protein coupled thromboxane A2 receptor (TBXA2R) (PubMed:19464661). May be involved in mechanisms like programmed cell death, craniofacial development, patterning of the limbs, and formation of the left- right axis (By similarity). Involved in the organization of apical junctions; the function is proposed to implicate a NPHP1-4-8 module. Does not seem to be strictly required for ciliogenesis (PubMed:19464661). Involved in establishment of planar cell polarity such as in cochlear sensory epithelium and is proposed to implicate stabilization of disheveled proteins (By similarity). Involved in regulation of proteasomal activity at the primary cilium probably implicating association with PSDM2 (By similarity). {ECO:0000250|UniProtKB:Q8CG73, ECO:0000269|PubMed:19464661}.
• Disease: DISEASE: Joubert syndrome 7 (JBTS7) [MIM:611560]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. {ECO:0000269|PubMed:17558407, ECO:0000269|PubMed:17558409, ECO:0000269|PubMed:17960139, ECO:0000269|PubMed:22693042}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Meckel syndrome 5 (MKS5) [MIM:611561]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:17558409, ECO:0000269|PubMed:19430481}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: COACH syndrome (COACHS) [MIM:216360]: A disorder characterized by mental retardation, ataxia due to cerebellar hypoplasia, and hepatic fibrosis. Patients present the molar tooth sign, a midbrain-hindbrain malformation pathognomonic for Joubert syndrome and related disorders. Other features, such as coloboma and renal cysts, may be variable. {ECO:0000269|PubMed:19574260}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Olfactory bulb development and olfactory learning;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.229

Intolerance Scores

• loftool: 0.145
• rvis_EVS: 1.08
• rvis_percentile_EVS: 91.76

Haploinsufficiency Scores

• pHI: 0.293
• hipred: N
• hipred_score: 0.229
• ghis: 0.542

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.569

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rpgrip1l
• 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); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; growth/size/body region phenotype; hematopoietic system phenotype; 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); craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: rpgrip1l
• Affected structure: immature eye
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: in utero embryonic development;establishment of planar polarity;kidney development;liver development;establishment or maintenance of cell polarity;determination of left/right symmetry;regulation of smoothened signaling pathway;neural tube patterning;cerebellum development;lateral ventricle development;olfactory bulb development;corpus callosum development;embryonic forelimb morphogenesis;embryonic hindlimb morphogenesis;camera-type eye development;nose development;negative regulation of G protein-coupled receptor signaling pathway;pericardium development;cochlea development;ciliary basal body-plasma membrane docking;non-motile cilium assembly
• Cellular component: nucleoplasm;cytoplasm;centrosome;cytosol;axonemal microtubule;plasma membrane;cell-cell junction;bicellular tight junction;cilium;axoneme;photoreceptor connecting cilium;ciliary rootlet;ciliary transition zone;ciliary basal body
• Molecular function: protein binding;thromboxane A2 receptor binding