RGS9 (regulator of G protein signaling 9)

Gene

• Entrez ID: 8787
• Gene name: Regulator of G protein signaling 9
• Gene symbol: RGS9
• Synonyms (NCBI Gene): PERRS, PERRS1, RGS9L
• Chromosome: 17
• Chromosome location: 17q24.1
• Summary: This gene encodes a member of the RGS family of GTPase activating proteins that function in various signaling pathways by accelerating the deactivation of G proteins. This protein is anchored to photoreceptor membranes in retinal cells and deactivates G p

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121908449	T>C	Pathogenic	Coding sequence variant, missense variant
rs200798153	A>C,G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs201026246	T>C	Conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, coding sequence variant, missense variant
rs574696410	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, genic downstream transcript variant
rs786205509	C>T	Likely-pathogenic	Missense variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001975	Process	Response to amphetamine	IEA
GO:0003924	Function	GTPase activity	IEA
GO:0003924	Function	GTPase activity	TAS
GO:0005096	Function	GTPase activator activity	IBA
GO:0005096	Function	GTPase activator activity	IEA
GO:0005096	Function	GTPase activator activity	TAS	9765512
GO:0005515	Function	Protein binding	IPI	33961781
GO:0005737	Component	Cytoplasm	IBA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	TAS
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007212	Process	G protein-coupled dopamine receptor signaling pathway	IBA
GO:0007212	Process	G protein-coupled dopamine receptor signaling pathway	IEA
GO:0007399	Process	Nervous system development	IEA
GO:0007601	Process	Visual perception	IEA
GO:0008277	Process	Regulation of G protein-coupled receptor signaling pathway	IEA
GO:0008277	Process	Regulation of G protein-coupled receptor signaling pathway	TAS	9765512
GO:0009968	Process	Negative regulation of signal transduction	IEA
GO:0016020	Component	Membrane	IEA
GO:0032355	Process	Response to estradiol	IEA
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0036367	Process	Light adaption	IEA
GO:0042734	Component	Presynaptic membrane	IEA
GO:0043005	Component	Neuron projection	IBA
GO:0098839	Component	Postsynaptic density membrane	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:1905912	Process	Regulation of calcium ion export across plasma membrane	IEA
GO:1990603	Process	Dark adaptation	IEA

Other IDs

• MIM: 604067
• HGNC: 10004
• e!Ensembl: ENSG00000108370

Protein

• UniProt ID: O75916
• Protein name: Regulator of G-protein signaling 9 (RGS9)
• Protein 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 transd
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00610	DEP	33 → 103	Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)	Domain
  PF18148	RGS_DHEX	106 → 205	Regulator of G-protein signalling DHEX domain	Domain
  PF00631	G-gamma	219 → 283	GGL domain	Domain
  PF00615	RGS	302 → 416	Regulator of G protein signaling domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in the caudate and putamen, lower levels found in the hypothalamus and nucleus accumbens and very low levels in cerebellum. Not expressed in globus pallidus or cingulate cortex. Isoform 2 is expressed predominantly in
• Sequence:

  MTIRHQGQQYRPRMAFLQKIEALVKDMQNPETGVRMQNQRVLVTSVPHAMTGSDVLQWIV
  QRLWISSLEAQNLGNFIVRYGYIYPLQDPKNLILKPDGSLYRFQTPYFWPTQQWPAEDTD
  YAIYLAKRNIKKKGILEEYEKENYNFLNQKMNYKWDFVIMQAKEQYRAGKERNKADRYAL
  DCQEKAYWLVHRCPPGMDNVLDYGLDRVTNPNEVKVNQKQTVVAVKKEIMYYQQALMRST
  VKSSVSLGGIVKYSEQFSSNDAIMSGCLPSNPWITDDTQFWDLNAKLVEIPTKMRVERWA
  FNFSELIRDPKGRQSFQYFLKKEFSGENLGFWEACEDLKYGDQSKVKEKAEEIYKLFLAP
  GARRWINIDGKTMDITVKGLKHPHRYVLDAAQTHIYMLMKKDSYARYLKSPIYKDMLAKA
  IEPQETTKKSSTLPFMRRHLRSSPSPVILRQLEEEAKAREAANTVDITQPGQHMAPSPHL
  TVYTGTCMPPSPSSPFSSSCRSPRKPFASPSRFIRRPSTTICPSPIRVALESSSGLEQKG
  ECSGSMAPRGPSVTESSEASLDTSWPRSRPRAPPKARMALSFSRFLRRGCLASPVFARLS
  PKCPAVSHGRVQPLGDVGQQLPRLKSKRVANFFQIKMDVPTGSGTCLMDSEDAGTGESGD
  RATEKEVICPWESL

• Sequence length: 674

Pathways

KEGG:

Phototransduction
Cocaine addiction

Reactome:

Inactivation, recovery and regulation of the phototransduction cascade
G alpha (i) signalling events
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Bradyopsia	Pathogenic	rs760312819, rs121908449	RCV003229575 RCV000006220	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leber congenital amaurosis	Pathogenic	rs121908449	RCV000787876	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinal dystrophy	Likely pathogenic	rs199537336	RCV004813591	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Uterine corpus endometrial carcinoma	Likely pathogenic	rs776501006	RCV005908969	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANDROGENETIC ALOPECIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DYSKINESIA, DRUG-INDUCED	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LARGE ARTERY STROKE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OPTIC ATROPHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prolonged electroretinal response suppression 1	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSYCHOSES, SUBSTANCE-INDUCED	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINITIS PIGMENTOSA 1	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RGS9-related disorder	Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations