RGS6

Summary

RGS6 (regulator of G protein signaling 6, HGNC:10002) is a protein-coding gene on chromosome 14q24.2, encoding Regulator of G-protein signaling 6 (P49758). Regulates G protein-coupled receptor signaling cascades.

This gene encodes a member of the RGS (regulator of G protein signaling) family of proteins, which are defined by the presence of a RGS domain that confers the GTPase-activating activity of these proteins toward certain G alpha subunits. This protein also belongs to a subfamily of RGS proteins characterized by the presence of DEP and GGL domains, the latter a G beta 5-interacting domain. The RGS proteins negatively regulate G protein signaling, and may modulate neuronal, cardiovascular, lymphocytic activities, and cancer risk. Many alternatively spliced transcript variants encoding different isoforms with long or short N-terminal domains, complete or incomplete GGL domains, and distinct C-terminal domains, have been described for this gene, however, the full-length nature of some of these variants is not known.

Source: NCBI Gene 9628 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 82
• Clinical variants (ClinVar): 172 total
• MANE Select transcript: NM_001204424

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10002
Approved symbol	RGS6
Name	regulator of G protein signaling 6
Location	14q24.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182732
Ensembl biotype	protein_coding
OMIM	603894
Entrez	9628

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000343854, ENST00000355512, ENST00000402788, ENST00000404301, ENST00000406236, ENST00000407322, ENST00000434263, ENST00000553519, ENST00000553525, ENST00000553530, ENST00000553690, ENST00000554300, ENST00000554474, ENST00000554734, ENST00000554782, ENST00000555368, ENST00000555571, ENST00000556437, ENST00000622468, ENST00000644463

RefSeq mRNA: 34 — MANE Select: NM_001204424 NM_001204416, NM_001204417, NM_001204418, NM_001204419, NM_001204420, NM_001204421, NM_001204422, NM_001204423, NM_001204424, NM_001370270, NM_001370271, NM_001370272, NM_001370273, NM_001370274, NM_001370275, NM_001370276, NM_001370277, NM_001370278, NM_001370279, NM_001370280, NM_001370281, NM_001370282, NM_001370283, NM_001370284, NM_001370286, NM_001370287, NM_001370288, NM_001370289, NM_001370290, NM_001370291, NM_001370292, NM_001370293, NM_001370294, NM_004296

CCDS: CCDS55924, CCDS73655, CCDS91897, CCDS9808

Canonical transcript exons

ENST00000553525 — 18 exons

Exon	Start	End
ENSE00001294400	72495152	72495262
ENSE00001296991	72536186	72536275
ENSE00001299646	72518351	72518537
ENSE00001300134	72510154	72510279
ENSE00001306101	72352095	72352194
ENSE00001313498	72478268	72478329
ENSE00001555772	72540041	72540094
ENSE00002257105	71964772	71964875
ENSE00002444067	71932429	71932941
ENSE00002485462	72562417	72566530
ENSE00003517623	72458271	72458377
ENSE00003560158	72454528	72454578
ENSE00003584399	72459632	72459683
ENSE00003633363	72465758	72465822
ENSE00003639448	72472872	72472953
ENSE00003678813	72474625	72474699
ENSE00003680568	72476742	72476840
ENSE00003688574	72470007	72470083

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 89.50.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0991 / max 172.2434, expressed in 380 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140477	1.2766	358
140478	0.5012	130
140479	0.2565	95
140476	0.0648	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	89.50	gold quality
sural nerve	UBERON:0015488	87.76	gold quality
middle temporal gyrus	UBERON:0002771	87.67	gold quality
calcaneal tendon	UBERON:0003701	85.35	gold quality
prefrontal cortex	UBERON:0000451	85.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.06	gold quality
right frontal lobe	UBERON:0002810	83.00	gold quality
primary visual cortex	UBERON:0002436	82.71	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.43	gold quality
apex of heart	UBERON:0002098	82.35	gold quality
tibial nerve	UBERON:0001323	81.87	gold quality
frontal cortex	UBERON:0001870	81.72	gold quality
buccal mucosa cell	CL:0002336	81.50	silver quality
monocyte	CL:0000576	81.43	gold quality
right atrium auricular region	UBERON:0006631	81.19	gold quality
sperm	CL:0000019	81.14	silver quality
male germ cell	CL:0000015	80.96	silver quality
neocortex	UBERON:0001950	80.93	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.76	gold quality
mononuclear cell	CL:0000842	80.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.61	gold quality
left testis	UBERON:0004533	80.57	gold quality
cardiac atrium	UBERON:0002081	80.48	gold quality
right testis	UBERON:0004534	80.17	gold quality
leukocyte	CL:0000738	79.99	gold quality
heart left ventricle	UBERON:0002084	79.75	gold quality
cardiac ventricle	UBERON:0002082	79.35	gold quality
olfactory bulb	UBERON:0002264	78.91	gold quality
heart	UBERON:0000948	78.88	gold quality
diaphragm	UBERON:0001103	78.78	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	3130.10
E-HCAD-35	yes	107.13
E-HCAD-25	yes	76.69
E-CURD-119	yes	29.81
E-ANND-3	yes	7.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

212 targeting RGS6, 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-4283	100.00	66.42	2097
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4481	100.00	66.42	1669
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-4500	99.99	72.72	2367
HSA-MIR-1184	99.99	68.19	1458
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790

Literature-anchored findings (GeneRIF, showing 19)

• interacts with SCG10 and promotes neuronal differentiation; role of the G gamma subunit-like (GGL) domain of this protein (PMID:12140291)
• Role of the RGS domain in stress-induced trafficking of RGS6 protein (PMID:12761220)
• RGS6 gene structure, complex alternative splicing, and role of N terminus and G protein gamma-subunit-like (GGL) domain in subcellular localization of RGS6 splice variants (PMID:12761221)
• RGS6 is the first member of the RGS protein family shown to interact with proteins involved in transcriptional regulation. (PMID:14734556)
• Our results suggest that HA117 is a strong multidrug resistance gene. (PMID:20635168)
• RGS6-induced apoptosis in both breast cancer cells and mouse embryonic fibroblasts does not require its GAP activity toward G proteins (PMID:21041304)
• genetic association studies in Hispanic-American families in Texas and Colorado: SNP in RGS6 are associated with high dietary fat intake, food preferences, and adiposity/obesity phenotype (PMID:21233807)
• This suggests that HA117 might be an important resistance gene in pediatric solid tumors. (PMID:23619123)
• these date demonstrate that RGS6 decreases in tumor tissue and may serve as a novel biomarker for outcomes in pancreatic cancer patients and be a potential therapeutic target potential therapeutic target. (PMID:25120791)
• we found a novel mutation in RGS6, the splice-acceptor variant c.1369-1G>C that was not previously reported in congenital cataract phenotypes. (PMID:25525169)
• No significant association between SNPs of RGS6 and central adiposity has been found. (PMID:26340433)
• reduced RGS6 expression is associated with poor survival in colorectal cancer patients, suggesting that RGS6 expression may serve as an important prognostic marker (PMID:26653562)
• Data support the notion that the Galpha, but not Gbetagamma, arm of the Gi/o signalling is involved in TRPC4 activation and unveil new roles for RGS and RGS6 in fine-tuning TRPC4 activities. (PMID:26987813)
• genetic association studies on a population in Republic of Korea: Data suggest that an SNP in RGS6 (rs2239219) is closely linked to stress-induced abdominal obesity in the population studied. (PMID:28090039)
• study shows that HA117 potentially promotes the stem-like signature of the HL60/ATRA cell line by inhibiting by the ubiquitination and degradation of DNMT1 and by down-regulating the expression of the GGL domain of RGS6 (PMID:28665981)
• the results suggest that HA117 regulates the development of drug resistance in CT26 cells in vitro and in vivo. (PMID:28731026)
• Age-dependent nigral dopaminergic neurodegeneration and alpha-synuclein accumulation in RGS6-deficient mice. (PMID:31120439)
• RGS6 suppresses TGF-beta-induced epithelial-mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4. (PMID:35902557)
• RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21. (PMID:38409136)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgs6	ENSDARG00000015627
mus_musculus	Rgs6	ENSMUSG00000021219
rattus_norvegicus	Rgs6	ENSRNOG00000008082

Paralogs (23): RGS11 (ENSG00000076344), RGS1 (ENSG00000090104), RGS17 (ENSG00000091844), AXIN1 (ENSG00000103126), RGS9 (ENSG00000108370), RGS2 (ENSG00000116741), RGS4 (ENSG00000117152), RGSL1 (ENSG00000121446), RGS13 (ENSG00000127074), RGS22 (ENSG00000132554), RGS8 (ENSG00000135824), RGS3 (ENSG00000138835), RGS5 (ENSG00000143248), RGS16 (ENSG00000143333), RGS20 (ENSG00000147509), RGS10 (ENSG00000148908), RGS18 (ENSG00000150681), RGS12 (ENSG00000159788), AXIN2 (ENSG00000168646), RGS14 (ENSG00000169220), RGS19 (ENSG00000171700), RGS7 (ENSG00000182901), RGS21 (ENSG00000253148)

Protein

Protein identifiers

Regulator of G-protein signaling 6 — P49758 (reviewed: P49758)

Alternative names: S914

All UniProt accessions (7): P49758, A0A087WTW9, A0A0A0MRA9, A0A2R8Y8A2, B7Z2N1, B7Z7N5, Q2M3K2

UniProt curated annotations — full annotation on UniProt →

Function. Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. The RGS6/GNB5 dimer enhances GNAO1 GTPase activity.

Subunit / interactions. Interacts with GNB5. Interacts with RGS7BP, leading to regulate the subcellular location of the heterodimer formed with GNB5. Interacts with GNAI1.

Subcellular location. Cytoplasm. Cytosol. Membrane. Nucleus. Cell membrane.

Domain organisation. The RGS domain interacts avidly with Galpha and mediates the acceleration of Galpha-mediated GTP hydrolysis.

Isoforms (15)

UniProt ID	Names	Canonical?
P49758-4	1, RGS6Lalpha2	yes
P49758-2	2, RGS6Lgamma1, RGS6Lbeta1
P49758-3	3, RGS6Lalpha1
P49758-5	5, RGS6Lbeta
P49758-6	6, RGS6Lbeta-GGL
P49758-7	7, RGS6Lalpha2-GGL
P49758-8	8, RGS6Lgamma2, RGS6Lbeta2
P49758-9	9, RGS6Lalpha1-GGL
P49758-10	10, RGS6Lgamma1-GGL
P49758-11	11, RGS6Lgamma2-GGL
P49758-12	12, RGS6Sbeta1
P49758-13	13, RGS6Lepsilon
P49758-14	14, RGS6Ldelta
P49758-15	15, RGS6Lgamma
P49758-16	16, RGS6Leta

RefSeq proteins (34): NP_001191345, NP_001191346, NP_001191347, NP_001191348, NP_001191349, NP_001191350, NP_001191351, NP_001191352, NP_001191353, NP_001357199, NP_001357200, NP_001357201, NP_001357202, NP_001357203, NP_001357204, NP_001357205, NP_001357206, NP_001357207, NP_001357208, NP_001357209, NP_001357210, NP_001357211, NP_001357212, NP_001357213, NP_001357215, NP_001357216, NP_001357217, NP_001357218, NP_001357219, NP_001357220, NP_001357221, NP_001357222, NP_001357223, NP_004287 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000591	DEP_dom	Domain
IPR015898	G-protein_gamma-like_dom	Domain
IPR016137	RGS	Domain
IPR036284	GGL_sf	Homologous_superfamily
IPR036305	RGS_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR037956	RGS6_RGS	Domain
IPR040759	RGS_DHEX	Domain
IPR044926	RGS_subdomain_2	Homologous_superfamily
IPR047016	RGS6/7/9/11	Family
IPR047017	RGS6/7/9/11_DHEX_sf	Homologous_superfamily

Pfam: PF00610, PF00615, PF00631, PF18148

UniProt features (33 total): splice variant 10, helix 10, sequence conflict 5, domain 3, mutagenesis site 2, turn 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2ES0	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49758-F1	88.24	0.80

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (2):

Position	Phenotype
297	loss of interaction with gnb5.
309	diminishes interaction with gnb5.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-6814122	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding

MSigDB gene sets: 158 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, AHRARNT_01, LU_IL4_SIGNALING, RORA1_01, GOBP_REGULATION_OF_GTPASE_ACTIVITY, CAGCTG_AP4_Q5, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, chr14q24, BRN2_01, FOXJ2_01, ARGGGTTAA_UNKNOWN, TGACATY_UNKNOWN, CYTAGCAAY_UNKNOWN

GO Biological Process (5): G protein-coupled receptor signaling pathway (GO:0007186), regulation of G protein-coupled receptor signaling pathway (GO:0008277), negative regulation of signal transduction (GO:0009968), intracellular signal transduction (GO:0035556), positive regulation of GTPase activity (GO:0043547)

GO Molecular Function (3): GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), neuron projection (GO:0043005), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
Chaperonin-mediated protein folding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
signal transduction	3
regulation of signal transduction	2
intracellular anatomical structure	2
GTPase activity	2
nuclear lumen	2
G protein-coupled receptor activity	1
G protein-coupled receptor signaling pathway	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
ribonucleoside triphosphate phosphatase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
membrane	1
cell periphery	1
plasma membrane bounded cell projection	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS6	GNB5	O14775	998
RGS6	RGS7BP	Q6MZT1	942
RGS6	GGT5	P36269	916
RGS6	SUCLG2	Q96I99	891
RGS6	RGS9BP	Q6ZS82	883
RGS6	GNAQ	P50148	828
RGS6	ARHGEF1	Q92888	788
RGS6	GRK2	P25098	772
RGS6	PLEK	P08567	764
RGS6	ARHGEF11	O15085	762
RGS6	RGSL1	A5PLK6	761
RGS6	PLEK2	Q9NYT0	742
RGS6	GNAO1	P09471	733
RGS6	GNA13	Q14344	714
RGS6	SUCLG1	P53597	703

IntAct

9 interactions, top by confidence:

A	B	Type	Score
RGS6	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.520
HSP90AB1	RGS6	psi-mi:“MI:0915”(physical association)	0.520
RGS6	GNB5	psi-mi:“MI:0915”(physical association)	0.500
RGS6	H2BC12L	psi-mi:“MI:0915”(physical association)	0.400
RGS6	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
PSMD2	RGS6	psi-mi:“MI:0915”(physical association)	0.400
RGS6	AARSD1	psi-mi:“MI:0915”(physical association)	0.400
GNB5	CCT6A	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): GNB5 (Affinity Capture-MS), CCDC85B (Affinity Capture-MS), DMAP1 (Affinity Capture-Western), DMAP1 (Reconstituted Complex), DNMT1 (Reconstituted Complex), DMAP1 (Two-hybrid), STMN2 (Two-hybrid), RGS6 (Affinity Capture-Western), RGS6 (Proximity Label-MS), LOC102724334 (Proximity Label-MS), HIST2H2BE (Proximity Label-MS), GNB5 (Affinity Capture-MS), GNB5 (Reconstituted Complex), RGS6 (Affinity Capture-MS), RGS6 (Affinity Capture-MS)

ESM2 similar proteins: A0A571BF63, A0A5F8MPE6, A1A535, A8QHQ0, B0W730, O23463, O46470, O54829, O64851, O82645, P49758, P49802, P49803, P49809, Q058N0, Q0VA04, Q14D04, Q28IH8, Q4R6I5, Q4R7Z7, Q502W7, Q569B9, Q5PQS3, Q5SPP5, Q5XG48, Q5XIR8, Q641A2, Q6ZQ18, Q7T0S7, Q86VD1, Q8BG67, Q8BMD7, Q8CDN8, Q8H1E8, Q8IGJ0, Q8N957, Q8NCR3, Q8NHS4, Q96L03, Q96LI9

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
RGS6	down-regulates	ITGB3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	42
Benign	57

Top pathogenic / likely-pathogenic (0)

SpliceAI

6665 predictions. Top by Δscore:

Variant	Effect	Δscore
14:71964770:A:AG	acceptor_gain	1.0000
14:71964770:AGTGT:A	acceptor_gain	1.0000
14:71964771:G:GA	acceptor_gain	1.0000
14:71964771:GT:G	acceptor_gain	1.0000
14:71964771:GTGT:G	acceptor_gain	1.0000
14:71964771:GTGTG:G	acceptor_gain	1.0000
14:71964844:A:T	donor_gain	1.0000
14:71964871:GCAAA:G	donor_gain	1.0000
14:71964876:G:GG	donor_gain	1.0000
14:71964889:TC:T	donor_gain	1.0000
14:72242664:GA:G	donor_gain	1.0000
14:72242681:A:G	donor_gain	1.0000
14:72352091:TCA:T	acceptor_loss	1.0000
14:72352092:CAG:C	acceptor_loss	1.0000
14:72352093:A:AG	acceptor_gain	1.0000
14:72352093:AGAT:A	acceptor_loss	1.0000
14:72352093:AGATT:A	acceptor_gain	1.0000
14:72352094:G:GG	acceptor_gain	1.0000
14:72352094:GA:G	acceptor_gain	1.0000
14:72352094:GAT:G	acceptor_gain	1.0000
14:72352094:GATT:G	acceptor_gain	1.0000
14:72352094:GATTG:G	acceptor_gain	1.0000
14:72352193:AG:A	donor_loss	1.0000
14:72352194:GGTAA:G	donor_loss	1.0000
14:72352195:G:C	donor_loss	1.0000
14:72458254:A:AG	acceptor_gain	1.0000
14:72458254:AT:A	acceptor_gain	1.0000
14:72458255:T:G	acceptor_gain	1.0000
14:72458258:A:AG	acceptor_gain	1.0000
14:72458258:ACT:A	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002332 (14:72604911 A>G), RS1000005487 (14:72230575 C>T), RS1000014136 (14:71958447 A>C), RS1000017254 (14:71976402 C>A,G), RS1000017973 (14:72077811 T>C), RS1000022501 (14:72521227 A>G,T), RS1000028006 (14:72200093 C>T), RS1000028471 (14:72083756 G>A), RS1000028921 (14:72569321 C>T), RS1000030540 (14:71936149 G>A), RS1000034592 (14:72565423 T>C), RS1000037796 (14:71929663 C>G,T), RS1000040363 (14:72340638 T>A), RS1000043121 (14:71922738 A>T), RS1000047590 (14:72056683 TGCCA>T)

Disease associations

OMIM: gene MIM:603894 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

82 associations (top):

Study	Trait	p-value
GCST000778_1	Smoking cessation	4.000000e-06
GCST000965_6	C-reactive protein levels	5.000000e-06
GCST001240_3	Obesity (extreme)	5.000000e-06
GCST001512_16	Economic and political preferences (environmentalism)	1.000000e-06
GCST002337_37	Amyotrophic lateral sclerosis (sporadic)	5.000000e-06
GCST002539_21	Schizophrenia	5.000000e-09
GCST002728_1	Yang-deficiency constitution	4.000000e-07
GCST003269_4	Cutaneous psoriasis	4.000000e-07
GCST003341_2	antipsychotic drug dosage in schizophrenia or schizoaffective disorder	9.000000e-07
GCST003542_156	Night sleep phenotypes	1.000000e-06
GCST003818_31	Resting heart rate	9.000000e-19
GCST004521_140	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_156	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004715_2	Heart rate	7.000000e-07
GCST004733_17	Heart rate variability traits (RMSSD)	4.000000e-10
GCST004733_4	Heart rate variability traits (RMSSD)	2.000000e-09
GCST004733_8	Heart rate variability traits (RMSSD)	5.000000e-11
GCST004733_9	Heart rate variability traits (RMSSD)	1.000000e-11
GCST004734_10	Heart rate variability traits (SDNN)	6.000000e-13
GCST004734_15	Heart rate variability traits (SDNN)	2.000000e-12
GCST004734_18	Heart rate variability traits (SDNN)	6.000000e-13
GCST004734_21	Heart rate variability traits (SDNN)	3.000000e-13
GCST004734_7	Heart rate variability traits (SDNN)	2.000000e-12
GCST004734_8	Heart rate variability traits (SDNN)	2.000000e-14
GCST004746_42	Small cell lung carcinoma	2.000000e-06
GCST004946_21	Schizophrenia	5.000000e-11
GCST005232_147	Neuroticism	1.000000e-06
GCST005576_9	Intracranial aneurysm	3.000000e-06
GCST005787_32	Heart rate response to exercise	3.000000e-06
GCST005788_2	Heart rate response to recovery post exercise	1.000000e-06

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004319	smoking cessation
EFO:0004458	C-reactive protein measurement
EFO:0004827	economic and social preference
EFO:0006817	yang deficiency
EFO:0007773	cutaneous psoriasis measurement
EFO:0007792	antipsychotic drug use measurement
EFO:0008003	heart rate variability measurement
EFO:0007660	neuroticism measurement
EFO:0009184	heart rate response to exercise
EFO:0009185	heart rate response to recovery post exercise
EFO:0007702	hip bone mineral density
EFO:0006335	systolic blood pressure
EFO:0008579	risk-taking behaviour
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0004327	electrocardiography
EFO:0004531	urate measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17179470	RGS6		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — R7 family

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Doxorubicin	decreases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects methylation, affects cotreatment, increases methylation	1
sodium arsenite	affects methylation	1
manganese chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
abrine	increases expression	1
MRK 003	decreases expression	1
(+)-JQ1 compound	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants, Occupational	increases expression	1
Amiodarone	increases expression	1
Copper	affects cotreatment, decreases expression	1
Lead	affects expression	1
Manganese	increases expression	1
Methapyrilene	increases methylation	1
Nickel	increases expression	1
Smoke	decreases expression	1
Triclosan	decreases expression	1
Zidovudine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice