GPSM1

Summary

GPSM1 (G protein signaling modulator 1, HGNC:17858) is a protein-coding gene on chromosome 9q34.3, encoding G-protein-signaling modulator 1 (Q86YR5). Guanine nucleotide dissociation inhibitor (GDI) which functions as a receptor-independent activator of heterotrimeric G-protein signaling.

G-protein signaling modulators (GPSMs) play diverse functional roles through their interaction with G-protein subunits. This gene encodes a receptor-independent activator of G protein signaling, which is one of several factors that influence the basal activity of G-protein signaling systems. The protein contains seven tetratricopeptide repeats in its N-terminal half and four G-protein regulatory (GPR) motifs in its C-terminal half. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 26086 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 171 total
• MANE Select transcript: NM_001145638

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17858
Approved symbol	GPSM1
Name	G protein signaling modulator 1
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	AGS3, DKFZP727I051
Ensembl gene	ENSG00000160360
Ensembl biotype	protein_coding
OMIM	609491
Entrez	26086

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000291775, ENST00000354753, ENST00000392944, ENST00000429455, ENST00000440944, ENST00000616132

RefSeq mRNA: 5 — MANE Select: NM_001145638 NM_001145638, NM_001145639, NM_001200003, NM_001412257, NM_015597

CCDS: CCDS48055, CCDS48056, CCDS6996

Canonical transcript exons

ENST00000440944 — 14 exons

Exon	Start	End
ENSE00001051811	136356342	136356550
ENSE00001095407	136358014	136359601
ENSE00001399393	136335966	136336101
ENSE00001403079	136337441	136337564
ENSE00001409448	136339707	136339815
ENSE00001416773	136349587	136349763
ENSE00001421238	136338555	136338710
ENSE00001425653	136337846	136337961
ENSE00001428147	136340870	136340993
ENSE00001431473	136348697	136348767
ENSE00001433428	136336921	136337072
ENSE00001797036	136334447	136334668
ENSE00003564669	136355690	136355846
ENSE00003845381	136327539	136327763

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 99.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.6206 / max 265.8441, expressed in 1661 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99493	7.7131	1563
99492	5.3387	1488
99491	0.4265	208
99496	0.0779	26
99495	0.0544	21
99494	0.0100	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.01	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.51	silver quality
right hemisphere of cerebellum	UBERON:0014890	97.09	gold quality
pigmented layer of retina	UBERON:0001782	97.06	gold quality
cerebellar hemisphere	UBERON:0002245	96.80	gold quality
cerebellar cortex	UBERON:0002129	96.78	gold quality
apex of heart	UBERON:0002098	96.73	gold quality
cerebellum	UBERON:0002037	96.58	gold quality
left ventricle myocardium	UBERON:0006566	96.46	silver quality
embryo	UBERON:0000922	94.87	gold quality
ganglionic eminence	UBERON:0004023	94.87	gold quality
cerebellar vermis	UBERON:0004720	94.80	gold quality
sural nerve	UBERON:0015488	94.74	gold quality
cardiac atrium	UBERON:0002081	94.69	gold quality
right atrium auricular region	UBERON:0006631	94.62	gold quality
cortical plate	UBERON:0005343	94.34	gold quality
ventricular zone	UBERON:0003053	93.77	gold quality
decidua	UBERON:0002450	93.63	gold quality
heart left ventricle	UBERON:0002084	93.52	gold quality
middle temporal gyrus	UBERON:0002771	93.43	gold quality
myocardium	UBERON:0002349	93.41	silver quality
cardiac ventricle	UBERON:0002082	93.38	gold quality
nerve	UBERON:0001021	93.09	gold quality
tibial nerve	UBERON:0001323	93.09	gold quality
amniotic fluid	UBERON:0000173	92.95	gold quality
stromal cell of endometrium	CL:0002255	92.71	gold quality
right frontal lobe	UBERON:0002810	92.54	gold quality
endothelial cell	CL:0000115	92.17	silver quality
corpus epididymis	UBERON:0004359	92.07	gold quality
primary visual cortex	UBERON:0002436	91.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	5.89
E-ANND-3	no	2.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting GPSM1, 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-126-5P	100.00	72.71	3180
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-4690-3P	97.02	64.72	981

Literature-anchored findings (GeneRIF, showing 24)

• The GPR motif in this protein and other proteins is actually associated with activity as a GDI - guanine nucleotide dissociation inhibitor and not GTPase activator as initially suggested. (PMID:10969064)
• AGS3 is involved in an early event during the autophagic pathway probably prior to the formation of the autophagosome. (PMID:12642577)
• cortical localization in mitotic cell culture systems and requirement for normal cell cycle progression (PMID:12925752)
• data support a model wherein AGS3 modulates the protein trafficking along the TGN/plasma membrane/endosome loop (PMID:17991770)
• The PDZ and band 4.1 containing protein Frmpd1 regulates the subcellular location of activator of G-protein signaling 3 and its interaction with G-proteins. (PMID:18566450)
• These data present AGS3, G-proteins, and mInsc as candidate proteins involved in regulating cellular stress associated with protein-processing pathologies. (PMID:20065032)
• unlike wild-type AGS3, over-expression of an AGS3 mutant lacking this modification fails to enhance macroautophagic activity. These observations imply that AGS3 phosphorylation may participate in the modulation of macroautophagy (PMID:20126274)
• AGS3 receptor coupling to both Galphabetagamma and GPR-Galpha(i) offer additional flexibility for systems to respond and adapt to challenges and orchestrate complex behaviors (PMID:20716524)
• These results provide mechanistic insights into how reversible modulation of Galpha(i3) activity by AGS3 and GIV maintains the delicate equilibrium between promotion and inhibition of autophagy. (PMID:21209316)
• Data identified three new loci for type 2 diabetes with genome-wide significance: MIR129-LEP, GPSM1 and SLC16A13. (PMID:23945395)
• Our data indicate that decreased expression of AGS3 is correlated with reduced levels of p-CREB in the apoptotic model. The negative role of AGS3 in cell apoptosis was further confirmed by knocking down AGS3. (PMID:24307516)
• these results indicate that GRK6 complexes with AGS3-Galphai2 to regulate CXCR2-mediated leukocyte functions at different levels, including downstream effector activation, receptor trafficking, and expression at the cell membrane. (PMID:24510965)
• Results confirmed that Ric-8A can directly bind to AGS3S but failed to facilitate Galpha(i)-induced suppression of adenylyl cyclase, suggesting that it may not serve as a guanine exchange factor for AGS3/Galpha(i/o)-GDP complex in a cellular environment. (PMID:25480567)
• High GPSM1 gene methylation is associated with gastric tumor aggressiveness. (PMID:25740824)
• Activator of G-protein Signaling 3 is an important regulator of esophageal squamous cell carcinoma proliferation (PMID:25812748)
• 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 AGS3 in fine-tuning TRPC4 activities. (PMID:26987813)
• The G-protein Regulatory motif of AGS3 is critical for regulating MUC1/Muc1 expression and cytokine production in the inflammatory microenvironment. (PMID:27270970)
• the data indicate that the effect of AGS3 in prostate cancer development and progression is probably mediated via a MAPK/AR-dependent pathway. (PMID:31215992)
• Genome-wide meta-analysis associates GPSM1 with type 2 diabetes, a plausible gene involved in skeletal muscle function. (PMID:31959871)
• AGS3 and Galphai3 Are Concomitantly Upregulated as Part of the Spindle Orientation Complex during Differentiation of Human Neural Progenitor Cells. (PMID:33172018)
• Depletion of GPSM1 enhances ovarian granulosa cell apoptosis via cAMP-PKA-CREB pathway in vitro. (PMID:33220708)
• Knockdown of GPSM1 Inhibits the Proliferation and Promotes the Apoptosis of B-Cell Acute Lymphoblastic Leukemia Cells by Suppressing the ADCY6-RAPGEF3-JNK Signaling Pathway. (PMID:34257610)
• G-protein signaling modulator 1 promotes colorectal cancer metastasis by PI3K/AKT/mTOR signaling and autophagy. (PMID:36758790)
• Properties of biomolecular condensates defined by Activator of G-protein Signaling 3. (PMID:38264908)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpsm1b	ENSDARG00000054874
danio_rerio	gpsm1a	ENSDARG00000092517
mus_musculus	Gpsm1	ENSMUSG00000026930
rattus_norvegicus	Gpsm1	ENSRNOG00000018666
drosophila_melanogaster	pins	FBGN0040080

Paralogs (6): TTC28 (ENSG00000100154), GPSM2 (ENSG00000121957), TTC29 (ENSG00000137473), RAPSN (ENSG00000165917), TTC24 (ENSG00000187862), GPSM3 (ENSG00000213654)

Protein

Protein identifiers

G-protein-signaling modulator 1 — Q86YR5 (reviewed: Q86YR5)

Alternative names: Activator of G-protein signaling 3

All UniProt accessions (4): Q86YR5, A0A087WVF5, A0A0A0MRC4, A0A0A0MSK4

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide dissociation inhibitor (GDI) which functions as a receptor-independent activator of heterotrimeric G-protein signaling. Keeps G(i/o) alpha subunit in its GDP-bound form thus uncoupling heterotrimeric G-proteins signaling from G protein-coupled receptors. Controls spindle orientation and asymmetric cell fate of cerebral cortical progenitors. May also be involved in macroautophagy in intestinal cells. May play a role in drug addiction.

Subunit / interactions. Interacts with GNAI1, GNAI2 and GNAI3 preferentially in their GDP-bound state. May also interact with GNAO1. Interacts with STK11/LKB1 and MACF1. Interacts with INSC/inscuteable and FRMPD1.

Subcellular location. Cytoplasm. Cytosol. Endoplasmic reticulum membrane. Golgi apparatus membrane. Cell membrane.

Tissue specificity. Expressed in intestinal cells.

Post-translational modifications. Phosphorylation regulates interaction with G(i/o) alpha.

Domain organisation. The GoLoco domains mediate interaction with G(i/o) alpha. The GoLoco domains are essential for the GDI activity toward G(i/o) alpha.

Miscellaneous. Minor isoform. Major isoform.

Similarity. Belongs to the GPSM family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q86YR5-1	1	yes
Q86YR5-2	2, Short
Q86YR5-3	3
Q86YR5-4	4, FL

RefSeq proteins (5): NP_001139110, NP_001139111, NP_001186932, NP_001399186, NP_056412 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003109	GoLoco_motif	Conserved_site
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR052386	GPSM	Family

Pfam: PF02188, PF13176, PF13424

UniProt features (35 total): repeat 9, modified residue 9, region of interest 6, domain 4, splice variant 4, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YR5-F1	68.24	0.43

Functional residue map

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

Post-translational modifications (9): 413, 421, 445, 469, 471, 492, 493, 545, 569

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 127 (showing top): GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_SPINDLE_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_REGULATION_OF_GTPASE_ACTIVITY, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_MACROAUTOPHAGY, GOBP_POSITIVE_REGULATION_OF_BINDING, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, MARTINEZ_RB1_TARGETS_UP, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY

GO Biological Process (6): establishment of mitotic spindle orientation (GO:0000132), nervous system development (GO:0007399), positive regulation of macroautophagy (GO:0016239), cell differentiation (GO:0030154), negative regulation of GTPase activity (GO:0034260), negative regulation of guanyl-nucleotide exchange factor activity (GO:1905098)

GO Molecular Function (4): G-protein alpha-subunit binding (GO:0001965), GDP-dissociation inhibitor activity (GO:0005092), protein binding (GO:0005515), GTPase regulator activity (GO:0030695)

GO Cellular Component (11): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cell cortex (GO:0005938), membrane (GO:0016020)

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
cytoplasm	4
cellular anatomical structure	4
GTPase activity	2
regulation of GTPase activity	2
cell periphery	2
endomembrane system	2
intracellular membrane-bounded organelle	2
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
system development	1
positive regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
cellular developmental process	1
negative regulation of biological process	1
negative regulation of hydrolase activity	1
guanyl-nucleotide exchange factor activity	1
negative regulation of molecular function	1
positive regulation of binding	1
protein binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
nucleoside-triphosphatase regulator activity	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cellular_component	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPSM1	PARD3B	Q8TEW8	777
GPSM1	FRMPD1	Q5SYB0	700
GPSM1	RASD1	Q9Y272	697
GPSM1	GNAO1	P09471	614
GPSM1	GNAI2	P04899	612
GPSM1	GPSM3	Q9Y4H4	599
GPSM1	GNAI3	P08754	591
GPSM1	INSC	Q1MX18	583
GPSM1	PLCB2	Q00722	570
GPSM1	ENTR1	Q96C92	565
GPSM1	PLCB3	Q01970	562
GPSM1	RIC8A	Q9NPQ8	543
GPSM1	ALDH18A1	P54886	538
GPSM1	SLC16A13	Q7RTY0	505
GPSM1	RAP1GAP	P47736	502

IntAct

30 interactions, top by confidence:

A	B	Type	Score
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
GPSM1	CCDC158	psi-mi:“MI:0915”(physical association)	0.550
GNAI1	GNAT3	psi-mi:“MI:0914”(association)	0.530
WDR83	SH2B2	psi-mi:“MI:0914”(association)	0.530
Btf3	GPSM1	psi-mi:“MI:0915”(physical association)	0.400
GPSM1	CTDSP1	psi-mi:“MI:0915”(physical association)	0.370
GPSM1	FXR2	psi-mi:“MI:0915”(physical association)	0.370
TRIP13	GPSM1	psi-mi:“MI:0915”(physical association)	0.370
GPSM1	USHBP1	psi-mi:“MI:0915”(physical association)	0.370
GPSM1	ZBED1	psi-mi:“MI:0915”(physical association)	0.370
DAZAP2	GPSM1	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
TANK	CNOT1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
INSC	A2ML1	psi-mi:“MI:0914”(association)	0.350
GPSM1	BRD4	psi-mi:“MI:0914”(association)	0.350
NPAS1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
WDR83	ISY1-RAB43	psi-mi:“MI:0914”(association)	0.350
SLC37A2	WWP2	psi-mi:“MI:0914”(association)	0.350
FGFR4	SH3PXD2B	psi-mi:“MI:2364”(proximity)	0.270
MAPT	PITPNM1	psi-mi:“MI:2364”(proximity)	0.270
MAPT	DCTN6	psi-mi:“MI:2364”(proximity)	0.270
MAPT		psi-mi:“MI:2364”(proximity)	0.270

BioGRID (110): GPSM1 (Two-hybrid), GPSM1 (Two-hybrid), GNAI3 (Reconstituted Complex), GPSM1 (Affinity Capture-Western), MAP1LC3A (Affinity Capture-Western), GPSM1 (Affinity Capture-Western), GPSM1 (Reconstituted Complex), GPSM1 (Affinity Capture-MS), GPSM1 (Affinity Capture-MS), GPSM1 (Affinity Capture-MS), NUMA1 (Affinity Capture-MS), UGP2 (Affinity Capture-MS), BRD4 (Affinity Capture-MS), PPP6R3 (Affinity Capture-MS), SAPCD2 (Affinity Capture-MS)

ESM2 similar proteins: A2AWP8, B3F209, O08838, O35185, O43312, O70373, O77638, O94827, O95644, P12660, P22681, P22682, P42226, P49797, P55199, P98201, Q13469, Q14CM0, Q29RM4, Q3U1Z5, Q3UR85, Q4FZH1, Q5EA15, Q5JSP0, Q5R5M3, Q5R5T1, Q60591, Q66T02, Q68FF6, Q6IR34, Q6MG88, Q6NZ67, Q6P582, Q6RFZ7, Q702N8, Q70EL4, Q86YR5, Q8CEG5, Q8IVA1, Q8R1S4

Diamond homologs: P81274, Q6IR34, Q80XJ3, Q86YR5, Q8VDU0, Q96AY4, Q9R080, D3ZSP7, F8RP11, O13797, O16259, O35814, O54981, O88196, P0CT30, P15705, P25407, P31948, P33313, P50503, P53041, P53042, P53804, Q12118, Q2U919, Q32PZ3, Q3ZBZ8, Q43468, Q496Y0, Q49AM3, Q4R8N7, Q4WTC0, Q54DA8, Q5RAP0, Q5XEP2, Q5ZLF0, Q60676, Q60864, Q7ZWU1, Q80ZK9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	147
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3545 predictions. Top by Δscore:

Variant	Effect	Δscore
9:136334444:CAGGA:C	acceptor_loss	1.0000
9:136334445:A:AG	acceptor_gain	1.0000
9:136334445:AG:A	acceptor_gain	1.0000
9:136334445:AGGAT:A	acceptor_gain	1.0000
9:136334446:G:GG	acceptor_gain	1.0000
9:136334446:GG:G	acceptor_gain	1.0000
9:136334446:GGAT:G	acceptor_gain	1.0000
9:136334446:GGATG:G	acceptor_gain	1.0000
9:136335956:T:A	acceptor_gain	1.0000
9:136335960:A:AG	acceptor_gain	1.0000
9:136335961:T:G	acceptor_gain	1.0000
9:136335961:TCCA:T	acceptor_loss	1.0000
9:136335962:CCA:C	acceptor_loss	1.0000
9:136335963:CA:C	acceptor_loss	1.0000
9:136335964:A:AG	acceptor_gain	1.0000
9:136335964:A:C	acceptor_loss	1.0000
9:136335964:AG:A	acceptor_gain	1.0000
9:136335965:G:GA	acceptor_gain	1.0000
9:136335965:GG:G	acceptor_gain	1.0000
9:136335965:GGA:G	acceptor_gain	1.0000
9:136335965:GGACC:G	acceptor_gain	1.0000
9:136336093:G:GT	donor_gain	1.0000
9:136336094:G:T	donor_gain	1.0000
9:136336097:ACAAG:A	donor_loss	1.0000
9:136336099:AAG:A	donor_loss	1.0000
9:136336100:AGGTG:A	donor_loss	1.0000
9:136336102:GT:G	donor_loss	1.0000
9:136336103:T:G	donor_loss	1.0000
9:136336915:CCACA:C	acceptor_loss	1.0000
9:136336916:CACA:C	acceptor_loss	1.0000

AlphaMissense

4403 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:136334596:G:A	G73D	1.000
9:136336951:G:T	G153W	1.000
9:136336952:G:A	G153E	1.000
9:136337509:G:A	G216D	1.000
9:136337909:G:T	G256W	1.000
9:136337910:G:A	G256E	1.000
9:136334481:G:C	G35R	0.999
9:136334482:G:A	G35D	0.999
9:136334539:C:A	A54D	0.999
9:136334572:T:C	L65P	0.999
9:136334583:T:G	Y69D	0.999
9:136334593:T:C	L72P	0.999
9:136334595:G:C	G73R	0.999
9:136334596:G:T	G73V	0.999
9:136334656:T:C	L93P	0.999
9:136336008:C:A	N111K	0.999
9:136336008:C:G	N111K	0.999
9:136336010:T:C	L112P	0.999
9:136336013:G:A	G113E	0.999
9:136336951:G:A	G153R	0.999
9:136336951:G:C	G153R	0.999
9:136336952:G:T	G153V	0.999
9:136337500:G:A	G213D	0.999
9:136337504:C:A	N214K	0.999
9:136337504:C:G	N214K	0.999
9:136337506:T:C	L215P	0.999
9:136337508:G:C	G216R	0.999
9:136337509:G:T	G216V	0.999
9:136337859:C:A	A239D	0.999
9:136337907:T:C	L255P	0.999

dbSNP variants (sampled 300 via entrez): RS1000019412 (9:136351728 C>T), RS1000069413 (9:136329239 A>G), RS1000117599 (9:136343775 G>A,T), RS1000135106 (9:136357803 G>A), RS1000225230 (9:136349383 G>A), RS1000332174 (9:136345704 G>A), RS1000652704 (9:136341127 G>C), RS1000665795 (9:136332306 T>C), RS1000747664 (9:136359534 G>A), RS1000792907 (9:136328095 G>A), RS1000806531 (9:136337007 G>A,C,T), RS1000811409 (9:136359727 C>T), RS1000832482 (9:136356640 C>A,T), RS1000961196 (9:136341386 T>C), RS1001121201 (9:136353830 C>T)

Disease associations

OMIM: gene MIM:609491 | disease phenotypes: MIM:614959, MIM:615005

GenCC curated gene-disease

Mondo (2): developmental and epileptic encephalopathy, 14 (MONDO:0013989), autosomal dominant nocturnal frontal lobe epilepsy 5 (MONDO:0014002)

Orphanet (2): Epilepsy of infancy with migrating focal seizures (Orphanet:293181), Sleep-related hypermotor epilepsy (Orphanet:98784)

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST002128_15	Type 2 diabetes	2.000000e-10
GCST003400_47	Type 2 diabetes	1.000000e-08
GCST004131_21	Inflammatory bowel disease	5.000000e-36
GCST004132_11	Crohn’s disease	6.000000e-30
GCST004133_17	Ulcerative colitis	2.000000e-16
GCST004894_150	Type 2 diabetes	2.000000e-12
GCST005973_38	White blood cell count	3.000000e-08
GCST006677_1	Acute insulin response (insulin secretion adjusted)	4.000000e-08
GCST007515_33	Type 2 diabetes	3.000000e-16
GCST007516_25	Type 2 diabetes (adjusted for BMI)	7.000000e-16
GCST007517_15	Type 2 diabetes	5.000000e-15
GCST007518_19	Type 2 diabetes (adjusted for BMI)	2.000000e-15
GCST007847_18	Type 2 diabetes	6.000000e-21
GCST008110_4	Insulinogenic index	1.000000e-08
GCST008362_191	Birth weight	2.000000e-15
GCST008363_71	Offspring birth weight	4.000000e-06
GCST008643_2	Joint damage in rheumatoid arthritis	1.000000e-06
GCST008833_5	Type 2 diabetes	2.000000e-08
GCST009379_93	Type 2 diabetes	1.000000e-06
GCST009379_94	Type 2 diabetes	7.000000e-26
GCST009379_95	Type 2 diabetes	2.000000e-07
GCST009379_96	Type 2 diabetes	8.000000e-06
GCST010118_178	Type 2 diabetes	5.000000e-26
GCST011364_14	Myocardial infarction	2.000000e-08
GCST011365_1	Myocardial infarction	2.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006831	acute insulin response measurement
EFO:0009961	Insulinogenic index measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0005413	joint damage measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression, affects expression	5
Benzo(a)pyrene	increases expression, increases methylation	3
bisphenol A	increases expression	2
Estradiol	increases expression	2
Aflatoxin B1	increases expression	2
methyleugenol	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
2-amino-9H-pyrido(2,3-b)indole	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Copper	affects binding, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diazinon	decreases methylation	1
Disulfiram	affects binding, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07600736	PHASE2	RECRUITING	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Clinical Activity of ABS-1230 in Pediatric Participants With KCNT1-related Epilepsy
NCT07156201	PHASE1	RECRUITING	A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of ABS-1230 Given Orally Compared With Placebo in Healthy Participants Aged 18 to 55 Years
NCT04924153	Not specified	COMPLETED	A Natural History Study of Participants With Potassium Sodium-Activated Channel Subfamily T Member 1 (KCNT1)-Related Epilepsy