RGS22

Summary

RGS22 (regulator of G protein signaling 22, HGNC:24499) is a protein-coding gene on chromosome 8q22.2, encoding Regulator of G-protein signaling 22 (Q8NE09). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.

Enables G-protein alpha-subunit binding activity. Predicted to be involved in negative regulation of signal transduction. Located in actin cytoskeleton; cytosol; and fibrillar center.

Source: NCBI Gene 26166 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 173 total
• MANE Select transcript: NM_015668

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24499
Approved symbol	RGS22
Name	regulator of G protein signaling 22
Location	8q22.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434I092, PRTD-NY2, CT145
Ensembl gene	ENSG00000132554
Ensembl biotype	protein_coding
OMIM	615650
Entrez	26166

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 4 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000360863, ENST00000517769, ENST00000517828, ENST00000517843, ENST00000518474, ENST00000518719, ENST00000519092, ENST00000519408, ENST00000519421, ENST00000519725, ENST00000520117, ENST00000520923, ENST00000522064, ENST00000523287, ENST00000523437, ENST00000523600, ENST00000524182, ENST00000870307, ENST00000955932

RefSeq mRNA: 3 — MANE Select: NM_015668 NM_001286692, NM_001286693, NM_015668

CCDS: CCDS43758, CCDS69521, CCDS75775

Canonical transcript exons

ENST00000360863 — 28 exons

Exon	Start	End
ENSE00002135520	99960936	99961196
ENSE00003460768	99977917	99978075
ENSE00003471738	100080134	100080355
ENSE00003474256	99987458	99987619
ENSE00003479204	100041802	100041916
ENSE00003489114	100071369	100071537
ENSE00003495446	100052802	100052976
ENSE00003513327	99999262	99999420
ENSE00003517613	99965335	99965430
ENSE00003531740	99981937	99982116
ENSE00003534696	100047463	100047596
ENSE00003535570	100072145	100072230
ENSE00003535680	100093447	100093509
ENSE00003545460	99996462	99996530
ENSE00003549703	99962885	99962978
ENSE00003565603	100008375	100008569
ENSE00003575522	99962687	99962767
ENSE00003589954	100006017	100006109
ENSE00003595872	100038931	100039032
ENSE00003606273	100105374	100105402
ENSE00003619279	100063416	100064043
ENSE00003625956	100039962	100040087
ENSE00003635591	100003926	100004098
ENSE00003646337	100002202	100002364
ENSE00003665617	100066167	100066296
ENSE00003668565	99962394	99962443
ENSE00003688353	100062591	100062752
ENSE00003847541	100105897	100106049

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 99.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6479 / max 94.7278, expressed in 173 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94120	0.5109	143
94119	0.0738	41
94121	0.0514	20
94117	0.0060	3
94118	0.0058	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.46	gold quality
right testis	UBERON:0004534	96.13	gold quality
left testis	UBERON:0004533	96.08	gold quality
bronchial epithelial cell	CL:0002328	95.05	gold quality
testis	UBERON:0000473	93.74	gold quality
bronchus	UBERON:0002185	93.36	gold quality
right uterine tube	UBERON:0001302	88.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.40	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.24	gold quality
epithelium of nasopharynx	UBERON:0001951	86.40	gold quality
left ovary	UBERON:0002119	85.45	gold quality
oviduct epithelium	UBERON:0004804	85.41	gold quality
right ovary	UBERON:0002118	85.18	gold quality
decidua	UBERON:0002450	84.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.01	gold quality
caput epididymis	UBERON:0004358	83.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.92	gold quality
ovary	UBERON:0000992	82.33	gold quality
fallopian tube	UBERON:0003889	81.88	gold quality
kidney epithelium	UBERON:0004819	80.77	gold quality
adult organism	UBERON:0007023	80.01	gold quality
germinal epithelium of ovary	UBERON:0001304	78.96	gold quality
left uterine tube	UBERON:0001303	77.73	gold quality
cauda epididymis	UBERON:0004360	76.44	gold quality
epithelial cell of pancreas	CL:0000083	76.09	gold quality
body of uterus	UBERON:0009853	75.58	gold quality
cardiac muscle of right atrium	UBERON:0003379	74.85	gold quality
left ventricle myocardium	UBERON:0006566	74.65	gold quality
ventricular zone	UBERON:0003053	74.07	gold quality
tibialis anterior	UBERON:0001385	73.71	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.65
E-MTAB-7303	no	90.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting RGS22, 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-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-659-3P	99.85	70.69	1620
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-548AV-3P	99.43	68.50	1721

Literature-anchored findings (GeneRIF, showing 5)

• RGS22 may also play a role in GNA13 translocation from the cytoplasm to the nucleus during spermiogenesis (PMID:18703424)
• Over-expression of RGS22 in a highly metastatic esophageal cancer cell line causes decrease in cell migration and reduction in the invasive potential of the cells. (PMID:21533872)
• New basal cell carcinoma susceptibility loci were identified at TGM3 (rs214782) and RGS22(rs7006527). (PMID:24403052)
• RGS22 acts as a tumor suppressor, repressing human pancreatic adenocarcinoma cell migration by coupling to GNA12/13. (PMID:26323264)
• Regulator of G-protein signaling 22 (RGS22) was identified as a direct target of miR-1260b and was inhibited by miR-1260b. Knockdown of RGS22 increased proliferation of hepatocellular carcinoma cells. (PMID:29038925)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rgs22	ENSMUSG00000037627
rattus_norvegicus	Rgs22	ENSRNOG00000025551

Paralogs (23): RGS11 (ENSG00000076344), RGS1 (ENSG00000090104), RGS17 (ENSG00000091844), AXIN1 (ENSG00000103126), RGS9 (ENSG00000108370), RGS2 (ENSG00000116741), RGS4 (ENSG00000117152), RGSL1 (ENSG00000121446), RGS13 (ENSG00000127074), 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 22 — Q8NE09 (reviewed: Q8NE09)

All UniProt accessions (7): Q8NE09, E5RFV6, E5RGJ7, E5RHE4, E5RJ23, G3V112, H0YBV2

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.

Subunit / interactions. Interacts with GNA11, GNA12 and GNA13.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Testis-specific. Expressed in Leydig cells and spermatogenic cells from the spermatogonia to spermatid stages (at protein level).

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be due to competing donor splice site.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NE09-1	1	yes
Q8NE09-2	2
Q8NE09-3	3

RefSeq proteins (3): NP_001273621, NP_001273622, NP_056483* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016137	RGS	Domain
IPR036305	RGS_sf	Homologous_superfamily
IPR042651	Rgs22	Family
IPR044926	RGS_subdomain_2	Homologous_superfamily
IPR048073	RGS22_RGS_third	Domain
IPR048074	RGS22_RGS_fourth	Domain
IPR048075	RGS22_RGS_second	Domain

Pfam: PF00615

UniProt features (19 total): sequence conflict 9, domain 2, splice variant 2, sequence variant 2, chain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NE09-F1	65.90	0.10

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 47 (showing top): GOZGIT_ESR1_TARGETS_DN, WANG_LMO4_TARGETS_DN, HFH3_01, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, chr8q22, GOCC_NUCLEOLUS, GOMF_G_PROTEIN_ALPHA_SUBUNIT_BINDING, NIKOLSKY_MUTATED_AND_AMPLIFIED_IN_BREAST_CANCER, YOSHIMURA_MAPK8_TARGETS_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOCC_FIBRILLAR_CENTER, FOXN3_TARGET_GENES, ZNF664_TARGET_GENES, MIR548AR_3P, MIR4799_5P

GO Biological Process (2): negative regulation of signal transduction (GO:0009968), regulation of signal transduction (GO:0009966)

GO Molecular Function (1): G-protein alpha-subunit binding (GO:0001965)

GO Cellular Component (5): fibrillar center (GO:0001650), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), actin cytoskeleton (GO:0015629)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	2
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
protein binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cytoskeleton	1

Protein interactions and networks

STRING

1662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS22	GNA13	Q14344	510
RGS22	GNA12	Q03113	493
RGS22	GNA11	P29992	475
RGS22	SHISA3	A0PJX4	458
RGS22	B3GNT9	Q6UX72	426
RGS22	CDA	P32320	417
RGS22	SPATA31D4	Q6ZUB0	372
RGS22	GPR153	Q6NV75	371
RGS22	WSCD2	Q2TBF2	362
RGS22	MAP1S	Q66K74	353
RGS22	CT55	Q8WUE5	348
RGS22	GDPGP1	Q6ZNW5	339
RGS22	FANK1	Q8TC84	339
RGS22	LSMEM1	Q8N8F7	338
RGS22	RBM3	P98179	330

IntAct

3 interactions, top by confidence:

A	B	Type	Score
RGS22	PDIA6	psi-mi:“MI:0915”(physical association)	0.400
GSK3B	RGS22	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): RGS22 (Biochemical Activity), RGS22 (Affinity Capture-MS), RGS22 (Affinity Capture-MS), RGS22 (Proximity Label-MS), RGS22 (Cross-Linking-MS (XL-MS)), RGS22 (Cross-Linking-MS (XL-MS)), ZNF335 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2RRS8, A4D1B5, A5PLK6, D3Z6S9, E7FA21, G3UYX5, O75747, O75901, O88480, O88869, Q2T9P0, Q3UMB5, Q3UPC7, Q3URV1, Q402B2, Q4R9E9, Q5SUS0, Q5T0N1, Q5XI56, Q5XX13, Q642P2, Q6DHV5, Q6INI0, Q6P2C0, Q7L0X2, Q80X60, Q86VV8, Q86WZ0, Q8CDN1, Q8IV33, Q8IXR9, Q8K342, Q8N7B9, Q8N7X0, Q8ND61, Q8NE09, Q8NG48, Q8R4Y8, Q8TDY2, Q8TEV9

Diamond homologs: G3UYX5, Q8NE09

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	143
Likely benign	12
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

4124 predictions. Top by Δscore:

Variant	Effect	Δscore
8:100002294:T:A	donor_gain	1.0000
8:100002363:TG:T	acceptor_gain	1.0000
8:100002365:C:CC	acceptor_gain	1.0000
8:100006011:CCTTA:C	donor_loss	1.0000
8:100006012:CTTAC:C	donor_loss	1.0000
8:100006013:TTA:T	donor_loss	1.0000
8:100006014:TA:T	donor_loss	1.0000
8:100006015:A:AC	donor_gain	1.0000
8:100006016:C:CC	donor_gain	1.0000
8:100006016:CCT:C	donor_gain	1.0000
8:100006105:TCCAC:T	acceptor_gain	1.0000
8:100006106:CCAC:C	acceptor_gain	1.0000
8:100006106:CCACC:C	acceptor_gain	1.0000
8:100006107:CAC:C	acceptor_gain	1.0000
8:100006107:CACC:C	acceptor_gain	1.0000
8:100006108:AC:A	acceptor_gain	1.0000
8:100006108:ACCTA:A	acceptor_loss	1.0000
8:100006109:CC:C	acceptor_gain	1.0000
8:100006110:C:CC	acceptor_gain	1.0000
8:100006110:CTAAA:C	acceptor_loss	1.0000
8:100008565:AGATA:A	acceptor_gain	1.0000
8:100008566:GATA:G	acceptor_gain	1.0000
8:100008568:TA:T	acceptor_gain	1.0000
8:100008570:C:CC	acceptor_gain	1.0000
8:100071412:T:C	donor_gain	1.0000
8:100072139:TAGTA:T	donor_loss	1.0000
8:100072140:AGTAC:A	donor_loss	1.0000
8:100072141:GTA:G	donor_loss	1.0000
8:100072142:TACC:T	donor_loss	1.0000
8:100072143:A:AG	donor_loss	1.0000

AlphaMissense

8388 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:100038998:A:G	L700P	0.996
8:100062652:A:G	W485R	0.996
8:100062652:A:T	W485R	0.996
8:99987534:A:G	F1035S	0.996
8:100062592:A:G	W505R	0.995
8:100062592:A:T	W505R	0.995
8:100063468:A:G	W434R	0.995
8:100063468:A:T	W434R	0.995
8:100072165:A:C	S135R	0.995
8:100072165:A:T	S135R	0.995
8:100072167:T:G	S135R	0.995
8:99978034:G:C	F1134L	0.995
8:99978034:G:T	F1134L	0.995
8:99978036:A:G	F1134L	0.995
8:99982048:A:C	F1083L	0.995
8:99982048:A:T	F1083L	0.995
8:99982050:A:G	F1083L	0.995
8:99987483:A:G	F1052S	0.995
8:100072186:T:A	R128S	0.994
8:100072186:T:G	R128S	0.994
8:100093457:A:G	L36P	0.994
8:100093459:G:C	F35L	0.994
8:100093459:G:T	F35L	0.994
8:100093461:A:G	F35L	0.994
8:99978045:A:G	W1131R	0.994
8:99978045:A:T	W1131R	0.994
8:99999311:A:G	L967P	0.994
8:100072175:A:G	F132S	0.993
8:100002229:A:C	S921R	0.992
8:100002229:A:T	S921R	0.992

dbSNP variants (sampled 300 via entrez): RS1000033630 (8:99985617 TAAC>T), RS1000041795 (8:100047084 C>T), RS1000095899 (8:100000920 T>C), RS1000144869 (8:99993932 T>C), RS1000193355 (8:100019552 G>A,T), RS1000203459 (8:100100149 A>G), RS1000223719 (8:100106699 G>C,T), RS1000228669 (8:100081045 A>G,T), RS1000266831 (8:100012379 C>T), RS1000277578 (8:99975802 C>G,T), RS1000319296 (8:99998633 C>T), RS1000350232 (8:99998219 T>C), RS1000355477 (8:100073441 A>C,T), RS1000387718 (8:100048463 A>C), RS1000390107 (8:99975347 A>G)

Disease associations

OMIM: gene MIM:615650 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002331_10	Basal cell carcinoma	9.000000e-10
GCST002331_2	Basal cell carcinoma	9.000000e-13
GCST002842_9	Basal cell carcinoma	2.000000e-12
GCST003726_14	Basal cell carcinoma	2.000000e-15
GCST005896_63	Non-melanoma skin cancer	5.000000e-13
GCST90013410_42	Basal cell carcinoma	1.000000e-33

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009260	non-melanoma skin carcinoma

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
daidzein	affects cotreatment, increases expression	1
propionaldehyde	increases expression	1
daidzin	affects cotreatment, increases expression	1
butyraldehyde	increases expression	1
genistin	affects cotreatment, increases expression	1
pentanal	increases expression	1
glycitein	affects cotreatment, increases expression	1
glycitin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
Irinotecan	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Estradiol	increases expression	1
Nickel	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Genistein	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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