RP2

RP2 activator of ARL3 GTPase

Basic information

Region (hg38): X:46837042-46882358

Links

ENSG00000102218 ∙ NCBI:6102 ∙ OMIM:300757 ∙ HGNC:10274 ∙ Uniprot:O75695 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 2 (Strong), mode of inheritance: XL
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 2 (Definitive), mode of inheritance: XL
• RP2-related retinopathy (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 2	XL	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	9697692; 10053026; 10942419; 11462235; 12417528; 20021257; 20625056; 21738648

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RP2 gene.

• not provided (244 variants)
• Retinitis pigmentosa (50 variants)
• Retinitis pigmentosa 2 (30 variants)
• Retinal dystrophy (20 variants)
• Inborn genetic diseases (12 variants)
• Retinitis pigmentosa 3 (10 variants)
• not specified (5 variants)
• X-linked retinitis pigmentosa (2 variants)
• Macular dystrophy (1 variants)
• Leber congenital amaurosis (1 variants)
• Cone-rod dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RP2 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	14	7	22
missense	3	3	95	12	12	125
nonsense	23	3				26
start loss	6	1				7
frameshift	47	6				53
inframe indel		2	2			4
splice donor/acceptor (+/-2bp)	5	4	1			10
splice region	1	4	3			8
non coding		1	18	11	12	42
Total	84	20	117	37	31

Variants in RP2

This is a list of pathogenic ClinVar variants found in the RP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-46837057-G-C		Retinitis pigmentosa	Likely benign (Jan 13, 2018)
X-46837066-A-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
X-46837075-G-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
X-46837089-CGGGCTGGGACCAT-C			Pathogenic (Dec 09, 2020)
X-46837098-ACCATGGGCTGCTTCTTCTC-A			Pathogenic (May 26, 2023)
X-46837101-A-G			Pathogenic (Nov 15, 2022)
X-46837101-A-T			Pathogenic (Feb 14, 2022)
X-46837102-T-A			Pathogenic (Aug 28, 2021)
X-46837102-T-C		Retinitis pigmentosa • X-linked retinitis pigmentosa	Pathogenic/Likely pathogenic (Jul 12, 2022)
X-46837102-T-G			Pathogenic (May 29, 2022)
X-46837104-G-A			Uncertain significance (May 27, 2022)
X-46837104-G-T			Uncertain significance (Jan 15, 2023)
X-46837108-G-C		Retinitis pigmentosa 2	Conflicting classifications of pathogenicity (Jan 31, 2024)
X-46837108-GCTT-G		Macular dystrophy • Retinal dystrophy • Cone-rod dystrophy	Conflicting classifications of pathogenicity (Jul 24, 2023)
X-46837111-T-G		Retinitis pigmentosa	Conflicting classifications of pathogenicity (Jan 07, 2024)
X-46837111-TC-AA			Pathogenic (Sep 24, 2021)
X-46837114-TCTC-T		Retinitis pigmentosa 2 • Retinitis pigmentosa	Likely pathogenic (Oct 26, 2022)
X-46837118-CAA-C			Pathogenic (Jun 20, 2023)
X-46837119-A-C		Retinal dystrophy	Uncertain significance (Jul 28, 2021)
X-46837122-A-T			Pathogenic (Aug 23, 2021)
X-46837122-AGACG-A		Retinitis pigmentosa	Pathogenic (Jun 23, 2019)
X-46837125-CGGAAGGCTGACAA-C			Pathogenic (Dec 18, 2021)
X-46837128-A-G			Uncertain significance (Jun 30, 2021)
X-46837128-A-T		Retinal dystrophy	Likely pathogenic (Oct 01, 2023)
X-46837130-G-A		Retinitis pigmentosa	Conflicting classifications of pathogenicity (Jan 31, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RP2	protein_coding	protein_coding	ENST00000218340	5	45419

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.956	0.0439	123595	0	1	123596	0.00000405

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.633	112	133	0.845	0.00000987	2330
Missense in Polyphen		10	29.608	0.33774		502
Synonymous	0.932	40	48.2	0.829	0.00000361	650
Loss of Function	2.90	0	9.79	0.00	6.92e-7	179

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000542	0.0000341
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a GTPase-activating protein (GAP) involved in trafficking between the Golgi and the ciliary membrane. Involved in localization of proteins, such as NPHP3, to the cilium membrane by inducing hydrolysis of GTP ARL3, leading to the release of UNC119 (or UNC119B). Acts as a GTPase-activating protein (GAP) for tubulin in concert with tubulin-specific chaperone C, but does not enhance tubulin heterodimerization. Acts as guanine nucleotide dissociation inhibitor towards ADP-ribosylation factor-like proteins. {ECO:0000269|PubMed:11847227, ECO:0000269|PubMed:18376416, ECO:0000269|PubMed:20106869, ECO:0000269|PubMed:22085962}.
• Disease: DISEASE: Retinitis pigmentosa 2 (RP2) [MIM:312600]: 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:10090907, ECO:0000269|PubMed:10520237, ECO:0000269|PubMed:10634633, ECO:0000269|PubMed:10937588, ECO:0000269|PubMed:10942419, ECO:0000269|PubMed:11462235, ECO:0000269|PubMed:11847227, ECO:0000269|PubMed:11992260, ECO:0000269|PubMed:12657579, ECO:0000269|PubMed:14564670, ECO:0000269|PubMed:16472755, ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:9697692}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Trafficking of myristoylated proteins to the cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.288

Intolerance Scores

• loftool: 0.122
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.18

Haploinsufficiency Scores

• pHI: 0.156
• hipred: Y
• hipred_score: 0.547
• ghis: 0.522

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	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rp2
• 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: rp2
• Affected structure: retinal rod cell
• Phenotype tag: abnormal
• Phenotype quality: degeneration

Gene ontology

• Biological process: cell morphogenesis;protein folding;post-Golgi vesicle-mediated transport;post-chaperonin tubulin folding pathway;visual perception;protein transport;positive regulation of GTPase activity
• Cellular component: nucleoplasm;cytoplasm;Golgi apparatus;centriole;plasma membrane;cilium;nuclear body;cytoplasmic vesicle;ciliary basal body;extracellular exosome;periciliary membrane compartment
• Molecular function: magnesium ion binding;GTPase activator activity;protein binding;GTP binding;unfolded protein binding