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

Phenotypes

GenCC

Source: genCC

retinitis pigmentosa 2 (Strong), mode of inheritance: XL
retinitis pigmentosa (Supportive), mode of inheritance: AD
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 (227 variants)
Retinitis pigmentosa (56 variants)
Retinitis pigmentosa 2 (32 variants)
Retinal dystrophy (21 variants)
Retinitis pigmentosa 3 (10 variants)
not specified (5 variants)
Inborn genetic diseases (5 variants)
Leber congenital amaurosis (3 variants)
X-linked retinitis pigmentosa (2 variants)
Macular dystrophy (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 RP2 gene is commonly pathogenic or not.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		1	11	7	20
missense	3	6	92	12	12	125
nonsense	26	4				30
start loss						0
frameshift	54	9				63
inframe indel		3	3			6
splice variant	5	7	5			17
non coding		1	2	5	4	12
Total	89	30	103	28	23

Variants in RP2

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

Position	Phenotype	Significance	ClinVar
X-46837057-G-C	Retinitis pigmentosa	Likely benign (Jan 13, 2018)	link
X-46837066-A-G	Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)	link
X-46837075-G-T	Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)	link
X-46837089-CGGGCTGGGACCAT-C		Pathogenic (Dec 09, 2020)	link
X-46837101-A-G		Pathogenic (Aug 09, 2022)	link
X-46837101-A-T		Pathogenic (Feb 14, 2022)	link
X-46837102-T-A		Pathogenic (Aug 28, 2021)	link
X-46837102-T-C	Retinitis pigmentosa • X-linked retinitis pigmentosa	Pathogenic (Jul 12, 2022)	link
X-46837102-T-G		Pathogenic (May 29, 2022)	link
X-46837104-G-A		Uncertain significance (May 27, 2022)	link
X-46837104-G-T		Uncertain significance (May 06, 2022)	link
X-46837108-G-C	Retinitis pigmentosa 2	Conflicting interpretations of pathogenicity (Nov 01, 2022)	link
X-46837108-GCTT-G	Macular dystrophy • Retinal dystrophy • Cone-rod dystrophy	Conflicting interpretations of pathogenicity (Jul 24, 2023)	link
X-46837111-T-G	Retinitis pigmentosa	Conflicting interpretations of pathogenicity (Jul 19, 2022)	link
X-46837111-TC-AA		Pathogenic (Sep 24, 2021)	link
X-46837114-TCTC-T	Retinitis pigmentosa 2 • Retinitis pigmentosa	Likely pathogenic (Jun 13, 2022)	link
X-46837118-CAA-C		Pathogenic (Jul 19, 2022)	link
X-46837119-A-C	Retinal dystrophy	Uncertain significance (Jul 28, 2021)	link
X-46837122-A-T		Pathogenic (Aug 23, 2021)	link
X-46837122-AGACG-A	Retinitis pigmentosa	Pathogenic (Jun 23, 2019)	link
X-46837125-CGGAAGGCTGACAA-C		Pathogenic (Dec 18, 2021)	link
X-46837128-A-G		Uncertain significance (Jun 30, 2021)	link
X-46837130-G-A	Retinitis pigmentosa	Conflicting interpretations of pathogenicity (Nov 01, 2022)	link
X-46837137-A-T	Retinal dystrophy	Likely pathogenic (Dec 31, 2018)	link
X-46837138-A-T	Retinal dystrophy	Uncertain significance (Mar 27, 2019)	link

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