RGS9

regulator of G protein signaling 9, the group of Regulators of G-protein signaling

Basic information

Region (hg38): 17:65100812-65227703

Links

ENSG00000108370 ∙ NCBI:8787 ∙ OMIM:604067 ∙ HGNC:10004 ∙ Uniprot:O75916 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• bradyopsia (Strong), mode of inheritance: AR
• bradyopsia (Strong), mode of inheritance: AR
• bradyopsia (Supportive), mode of inheritance: AR
• bradyopsia (Moderate), mode of inheritance: AR
• bradyopsia (Definitive), mode of inheritance: AR
• bradyopsia (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Prolonged electroretinal response suppression 1	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	1790747; 14702087; 17826834

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RGS9 gene.

• not provided (19 variants)
• Bradyopsia (2 variants)
• Leber congenital amaurosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RGS9 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			4	114	4	122
missense	1	1	207	6	5	220
nonsense	12		1			13
start loss						0
frameshift	6					6
inframe indel			4			4
splice donor/acceptor (+/-2bp)		13	1			14
splice region			13	26		39
non coding			4	61	7	72
Total	19	14	221	181	16

Highest pathogenic variant AF is 0.000184

Variants in RGS9

This is a list of pathogenic ClinVar variants found in the RGS9 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-65137551-G-T			Uncertain significance (Jan 02, 2022)
17-65137555-C-T			Likely benign (Feb 09, 2023)
17-65137556-C-A		Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
17-65137559-G-C			Uncertain significance (May 20, 2020)
17-65137561-C-G			Likely benign (Mar 31, 2020)
17-65137563-A-G			Uncertain significance (Nov 20, 2019)
17-65137575-C-G			Uncertain significance (Dec 08, 2021)
17-65137577-A-G			Uncertain significance (Feb 04, 2022)
17-65137579-G-A			Likely benign (May 19, 2023)
17-65137586-T-C			Uncertain significance (Oct 15, 2019)
17-65137603-C-T			Uncertain significance (Jul 27, 2019)
17-65137607-G-A			Likely benign (Dec 13, 2021)
17-65137611-C-T			Likely benign (Jul 18, 2022)
17-65153410-T-C			Likely benign (Aug 19, 2020)
17-65153416-T-C			Likely benign (Aug 22, 2023)
17-65153421-G-T			Likely pathogenic (Feb 25, 2022)
17-65153429-C-T			Uncertain significance (Aug 23, 2022)
17-65153430-G-A		not specified	Likely benign (Jan 14, 2024)
17-65153433-C-T			Conflicting classifications of pathogenicity (Sep 08, 2023)
17-65153434-G-A			Uncertain significance (Aug 28, 2021)
17-65153442-C-T			Likely benign (Jun 03, 2021)
17-65153443-A-G			Uncertain significance (Dec 11, 2023)
17-65153446-C-T			Pathogenic (Feb 29, 2020)
17-65153450-A-T			Uncertain significance (Mar 20, 2021)
17-65153451-C-G			Uncertain significance (Jul 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RGS9	protein_coding	protein_coding	ENST00000262406	19	90273

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.13e-14	0.971	124723	0	87	124810	0.000349

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0381	377	379	0.994	0.0000231	4398
Missense in Polyphen		99	117.03	0.84591		1355
Synonymous	-1.40	168	146	1.15	0.00000956	1258
Loss of Function	2.41	30	48.0	0.625	0.00000318	473

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000668	0.000664
Ashkenazi Jewish	0.00	0.00
East Asian	0.000334	0.000334
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.000398	0.000397
Middle Eastern	0.000334	0.000334
South Asian	0.000493	0.000490
Other	0.000331	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to GNAT1. Involved in phototransduction; key element in the recovery phase of visual transduction (By similarity). {ECO:0000250}.
• Disease: DISEASE: Prolonged electroretinal response suppression (PERRS) [MIM:608415]: Characterized by difficulty adjusting to sudden changes in luminance levels mediated by cones. {ECO:0000269|PubMed:14702087}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Phototransduction - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);Myometrial Relaxation and Contraction Pathways;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding;Signal Transduction;Metabolism of proteins;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Chaperonin-mediated protein folding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;Visual signal transduction: Rods;Protein folding;G alpha (i) signalling events;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;GPCR signaling-G alpha i;GPCR downstream signalling;Visual signal transduction: Cones (Consensus)

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.948
• rvis_EVS: 0.27
• rvis_percentile_EVS: 70.64

Haploinsufficiency Scores

• pHI: 0.0953
• hipred: N
• hipred_score: 0.422
• ghis: 0.425

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.668

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rgs9
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton 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)

Gene ontology

• Biological process: response to amphetamine;protein folding;dopamine receptor signaling pathway;nervous system development;visual perception;regulation of G protein-coupled receptor signaling pathway;negative regulation of signal transduction;response to estradiol;intracellular signal transduction;positive regulation of GTPase activity;positive regulation of NMDA glutamate receptor activity;regulation of calcium ion export across plasma membrane
• Cellular component: nucleus;cytoplasm;photoreceptor disc membrane;postsynaptic density membrane;glutamatergic synapse
• Molecular function: GTPase activator activity