RGS13

Summary

RGS13 (regulator of G protein signaling 13, HGNC:9995) is a protein-coding gene on chromosome 1q31.2, encoding Regulator of G-protein signaling 13 (O14921). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.

The protein encoded by this gene is a member of the regulator of G protein signaling (RGS) family. RGS family members share similarity with S. cerevisiae SST2 and C. elegans egl-10 proteins, which contain a characteristic conserved RGS domain. RGS proteins accelerate GTPase activity of G protein alpha-subunits, thereby driving G protein into their inactive GDP-bound form, thus negatively regulating G protein signaling. RGS proteins have been implicated in the fine tuning of a variety of cellular events in response to G protein-coupled receptor activation. The biological function of this gene, however, is unknown. Two transcript variants encoding the same isoform exist.

Source: NCBI Gene 6003 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_002927

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9995
Approved symbol	RGS13
Name	regulator of G protein signaling 13
Location	1q31.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000127074
Ensembl biotype	protein_coding
OMIM	607190
Entrez	6003

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000391995, ENST00000462955, ENST00000482095, ENST00000543215, ENST00000910149

RefSeq mRNA: 2 — MANE Select: NM_002927 NM_002927, NM_144766

CCDS: CCDS1376

Canonical transcript exons

ENST00000391995 — 7 exons

Exon	Start	End
ENSE00000995899	192638164	192638203
ENSE00000995900	192637590	192637660
ENSE00003514507	192647926	192647987
ENSE00003545924	192659338	192660311
ENSE00003599649	192658201	192658367
ENSE00003606813	192644331	192644399
ENSE00003910110	192636147	192636317

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 83.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.0628 / max 1418.5422, expressed in 135 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7448	4.4447	119
7446	1.0646	57
7447	0.5096	43
7449	0.0440	26

Top tissues by expression

264 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
vermiform appendix	UBERON:0001154	83.83	gold quality
jejunal mucosa	UBERON:0000399	78.07	gold quality
lymph node	UBERON:0000029	77.98	gold quality
caecum	UBERON:0001153	76.65	gold quality
gall bladder	UBERON:0002110	73.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	73.88	gold quality
tonsil	UBERON:0002372	73.69	gold quality
epithelial cell of pancreas	CL:0000083	72.79	gold quality
mucosa of transverse colon	UBERON:0004991	72.30	gold quality
duodenum	UBERON:0002114	71.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.31	gold quality
rectum	UBERON:0001052	69.72	gold quality
skin of hip	UBERON:0001554	69.65	gold quality
small intestine	UBERON:0002108	69.06	gold quality
ileal mucosa	UBERON:0000331	68.38	gold quality
buccal mucosa cell	CL:0002336	68.16	silver quality
upper leg skin	UBERON:0004262	67.54	gold quality
colonic mucosa	UBERON:0000317	67.05	gold quality
right lung	UBERON:0002167	66.70	gold quality
lower lobe of lung	UBERON:0008949	64.78	gold quality
upper lobe of left lung	UBERON:0008952	64.72	gold quality
upper lobe of lung	UBERON:0008948	64.55	gold quality
lower esophagus muscularis layer	UBERON:0035833	64.22	gold quality
lower esophagus	UBERON:0013473	64.15	gold quality
lung	UBERON:0002048	63.80	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	63.55	gold quality
mucosa of stomach	UBERON:0001199	63.28	gold quality
smooth muscle tissue	UBERON:0001135	62.68	gold quality
intestine	UBERON:0000160	62.13	gold quality
transverse colon	UBERON:0001157	61.28	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	1135.91
E-CURD-46	yes	640.59
E-MTAB-3929	yes	221.04
E-HCAD-1	yes	42.78
E-CURD-88	yes	29.38
E-ANND-3	yes	19.55
E-MTAB-8410	yes	17.15
E-GEOD-130148	yes	16.00
E-MTAB-8142	yes	11.43
E-CURD-122	yes	10.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

64 targeting RGS13, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3140-3P	99.88	68.47	2069

Literature-anchored findings (GeneRIF, showing 7)

• Functional characterization of the G protein regulator RGS13 (PMID:11875076)
• Down-Regulation of regulator of G-protein signalling 13 is associated with mantle cell lymphoma (PMID:12970790)
• RGS1 and RGS13 act together to regulate chemokine receptor signaling in human germinal center B lymphocytes and contribute significantly to the rapid desensitization of the signaling pathway. (PMID:16565322)
• RGS13 overexpression inhibited CXCL12-evoked Ca(2+) mobilization, Akt phosphorylation and chemotaxis. (PMID:19017978)
• RGS13 turnover was significantly reduced in cells stimulated with cAMP, which was reversed by expression of the PKA-specific inhibitory peptide PKI. (PMID:20974683)
• p53 may modulate immune responses through suppression of RGS13 transcription in mast cells and B cells (PMID:21531726)
• Study demonstrates for the first time that miR-139 and miR-452 negatively regulate RGS13 expression which is known to be involved in germinal centers regulation. (PMID:30308012)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgs13a	ENSDARG00000017653
danio_rerio	rgs13b	ENSDARG00000100835
mus_musculus	Rgs13	ENSMUSG00000051079
rattus_norvegicus	Rgs13	ENSRNOG00000003888

Paralogs (23): RGS11 (ENSG00000076344), RGS1 (ENSG00000090104), RGS17 (ENSG00000091844), AXIN1 (ENSG00000103126), RGS9 (ENSG00000108370), RGS2 (ENSG00000116741), RGS4 (ENSG00000117152), RGSL1 (ENSG00000121446), RGS22 (ENSG00000132554), RGS8 (ENSG00000135824), RGS3 (ENSG00000138835), RGS5 (ENSG00000143248), RGS16 (ENSG00000143333), RGS20 (ENSG00000147509), RGS10 (ENSG00000148908), RGS18 (ENSG00000150681), RGS12 (ENSG00000159788), AXIN2 (ENSG00000168646), RGS14 (ENSG00000169220), RGS19 (ENSG00000171700), RGS6 (ENSG00000182732), RGS7 (ENSG00000182901), RGS21 (ENSG00000253148)

Protein

Protein identifiers

Regulator of G-protein signaling 13 — O14921 (reviewed: O14921)

All UniProt accessions (1): O14921

UniProt curated annotations — full annotation on UniProt →

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 both G(i)-alpha and G(q)-alpha.

RefSeq proteins (2): NP_002918, NP_658912 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016137	RGS	Domain
IPR024066	RGS_subdom1/3	Homologous_superfamily
IPR036305	RGS_sf	Homologous_superfamily
IPR044926	RGS_subdomain_2	Homologous_superfamily

Pfam: PF00615

UniProt features (3 total): chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14921-F1	93.39	0.84

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 119 (showing top): MODULE_169, MODULE_64, PUJANA_CHEK2_PCC_NETWORK, RHEIN_ALL_GLUCOCORTICOID_THERAPY_UP, WTGAAAT_UNKNOWN, MODULE_99, SASAKI_ADULT_T_CELL_LEUKEMIA, VECCHI_GASTRIC_CANCER_EARLY_DN, OCT1_B, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, CONCANNON_APOPTOSIS_BY_EPOXOMICIN_DN, RIZKI_TUMOR_INVASIVENESS_3D_UP, GOCC_CYTOPLASMIC_SIDE_OF_MEMBRANE, ZHENG_BOUND_BY_FOXP3, GOCC_SIDE_OF_MEMBRANE

GO Biological Process (3): G protein-coupled receptor signaling pathway (GO:0007186), negative regulation of G protein-coupled receptor signaling pathway (GO:0045744), negative regulation of signal transduction (GO:0009968)

GO Molecular Function (2): GTPase activity (GO:0003924), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
G protein-coupled receptor activity	1
G protein-coupled receptor signaling pathway	1
regulation of G protein-coupled receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
ribonucleoside triphosphate phosphatase activity	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS13	GNB5	O14775	878
RGS13	SUCLG2	Q96I99	852
RGS13	GNA13	Q14344	829
RGS13	GNAQ	P50148	793
RGS13	ARHGEF1	Q92888	786
RGS13	RGSL1	A5PLK6	777
RGS13	ARHGEF11	O15085	775
RGS13	GNA12	Q03113	767
RGS13	GRK2	P25098	766
RGS13	RGS7BP	Q6MZT1	720
RGS13	SUCLG1	P53597	708
RGS13	MCF2	P10911	694
RGS13	PLEK	P08567	686
RGS13	AKAP10	O43572	659
RGS13	PLEK2	Q9NYT0	650

IntAct

8 interactions, top by confidence:

A	B	Type	Score
RGS13	APOL6	psi-mi:“MI:0915”(physical association)	0.560
RGS13	CIAO1	psi-mi:“MI:0914”(association)	0.530
RGS13	rep	psi-mi:“MI:0915”(physical association)	0.370
RGS13	CFTR	psi-mi:“MI:0915”(physical association)	0.370
APOL6	RGS13	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): CCDC140 (Affinity Capture-MS), LIN9 (Affinity Capture-MS), SLAMF1 (Affinity Capture-MS), SRRT (Affinity Capture-MS), CIAO1 (Affinity Capture-MS), RGS13 (Protein-RNA), APOL6 (Two-hybrid), CCDC140 (Affinity Capture-MS), SLAMF1 (Affinity Capture-MS), LIN9 (Affinity Capture-MS), CIAO1 (Affinity Capture-MS), RGS13 (Affinity Capture-MS), RGS13 (Two-hybrid), RGS13 (PCA), RGS13 (Biochemical Activity)

ESM2 similar proteins: A1A643, O08849, O08850, O14921, O15539, O35119, O43665, O46470, O54829, P34295, P41220, P49758, P49800, P49802, P49803, P49806, P49808, P49809, P79100, P97844, Q08116, Q09777, Q0P5H5, Q10955, Q2KHW7, Q2M5E4, Q3S853, Q3T0T8, Q4L0E8, Q5M8L6, Q62240, Q6DGI0, Q6RG78, Q864Z2, Q8K443, Q8VYB9, Q99PG4, Q9CQE5, Q9FLY5, Q9JHX0

Diamond homologs: A1A643, F1S668, O08773, O08774, O08849, O08850, O08899, O14921, O14924, O15169, O15492, O15539, O35625, O42400, O43566, O43665, O46469, O46470, O46471, O54828, O54829, O70239, O70240, O70521, O75916, O76081, O88566, O94810, P34295, P41220, P49758, P49795, P49796, P49797, P49798, P49799, P49800, P49802, P49803, P49804

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates quantity by stabilization”	RGS13	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

22 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1070 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:192659461:T:C	F140L	0.989
1:192659462:T:C	F140S	0.989
1:192659463:T:A	F140L	0.989
1:192659463:T:G	F140L	0.989
1:192658260:T:C	F63L	0.987
1:192658262:C:A	F63L	0.987
1:192658262:C:G	F63L	0.987
1:192658261:T:C	F63S	0.985
1:192659452:T:G	Y137D	0.980
1:192647951:T:A	W31R	0.979
1:192647951:T:C	W31R	0.979
1:192658320:G:C	A83P	0.977
1:192659404:T:C	F121L	0.974
1:192659406:T:A	F121L	0.974
1:192659406:T:G	F121L	0.974
1:192659470:T:C	S143P	0.968
1:192658204:G:A	G44D	0.966
1:192658215:T:G	Y48D	0.964
1:192659414:C:A	A124D	0.964
1:192659426:T:A	V128D	0.963
1:192647953:G:C	W31C	0.962
1:192647953:G:T	W31C	0.962
1:192659405:T:C	F121S	0.962
1:192659418:G:C	Q125H	0.962
1:192659418:G:T	Q125H	0.962
1:192659462:T:G	F140C	0.960
1:192647973:T:C	L38S	0.959
1:192658274:T:G	C67W	0.958
1:192659405:T:G	F121C	0.958
1:192659339:T:G	I99S	0.957

dbSNP variants (sampled 300 via entrez): RS1000049431 (1:192658805 G>A,T), RS1000298691 (1:192648318 C>A), RS1000363763 (1:192646877 C>T), RS1000376043 (1:192653143 T>C), RS1000498194 (1:192647173 A>T), RS1000567986 (1:192642694 C>G,T), RS1000644511 (1:192641155 G>A), RS1000705119 (1:192648327 G>A), RS1000752654 (1:192648600 T>C), RS1000759434 (1:192641064 G>A), RS1000990994 (1:192658709 T>C), RS1001076839 (1:192652565 A>T), RS1001245895 (1:192635570 A>C,T), RS1001589563 (1:192654205 A>G), RS1001592398 (1:192635344 T>A)

Disease associations

OMIM: gene MIM:607190 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006295_5	Response to quetiapine in schizophrenia	2.000000e-06
GCST008163_81	Height	6.000000e-06
GCST009391_360	Metabolite levels	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010434	triacylglycerol 56:7 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — R4 family

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
methylmercuric chloride	decreases expression	2
Tretinoin	increases expression	2
perfluorooctanoic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Cytarabine	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	decreases expression	1
Fluorouracil	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Niclosamide	decreases expression	1
Tamoxifen	affects expression	1
Tetradecanoylphorbol Acetate	affects expression, affects cotreatment	1
Triclosan	increases expression	1
Zinc	affects cotreatment, affects expression	1
Raloxifene Hydrochloride	affects expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.