KCNJ12

Summary

KCNJ12 (potassium inwardly rectifying channel subfamily J member 12, HGNC:6258) is a protein-coding gene on chromosome 17p11.2, encoding ATP-sensitive inward rectifier potassium channel 12 (Q14500). Inward rectifying potassium channel that probably participates in controlling the resting membrane potential in electrically excitable cells.

This gene encodes an inwardly rectifying K+ channel which may be blocked by divalent cations. This protein is thought to be one of multiple inwardly rectifying channels which contribute to the cardiac inward rectifier current (IK1). The gene is located within the Smith-Magenis syndrome region on chromosome 17.

Source: NCBI Gene 3768 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 124 total
• Druggable target: yes
• MANE Select transcript: NM_021012

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6258
Approved symbol	KCNJ12
Name	potassium inwardly rectifying channel subfamily J member 12
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	Kir2.2, Kir2.2v, IRK2, hIRK1
Ensembl gene	ENSG00000184185
Ensembl biotype	protein_coding
OMIM	602323
Entrez	3768

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000331718, ENST00000583088, ENST00000904708, ENST00000904709, ENST00000904710, ENST00000904711, ENST00000904712, ENST00000904713, ENST00000918243, ENST00000948712, ENST00000948713, ENST00000948714

RefSeq mRNA: 1 — MANE Select: NM_021012 NM_021012

CCDS: CCDS11219

Canonical transcript exons

ENST00000583088 — 3 exons

Exon	Start	End
ENSE00002455083	21376357	21376913
ENSE00002468293	21408519	21408640
ENSE00002732101	21415287	21419870

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 94.98.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2871 / max 128.3198, expressed in 429 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159917	1.0821	387
159919	0.0923	25
159916	0.0832	28
159918	0.0294	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.98	gold quality
cerebellar vermis	UBERON:0004720	91.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.21	gold quality
cerebellar cortex	UBERON:0002129	90.63	gold quality
cerebellar hemisphere	UBERON:0002245	90.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.42	gold quality
cerebellum	UBERON:0002037	90.39	gold quality
gastrocnemius	UBERON:0001388	89.38	gold quality
muscle of leg	UBERON:0001383	89.13	gold quality
quadriceps femoris	UBERON:0001377	88.12	silver quality
vastus lateralis	UBERON:0001379	88.05	gold quality
skeletal muscle tissue	UBERON:0001134	87.60	gold quality
tibialis anterior	UBERON:0001385	85.57	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.80	gold quality
biceps brachii	UBERON:0001507	83.82	gold quality
muscle tissue	UBERON:0002385	83.17	gold quality
deltoid	UBERON:0001476	82.61	silver quality
dorsal root ganglion	UBERON:0000044	81.32	gold quality
apex of heart	UBERON:0002098	81.15	gold quality
body of tongue	UBERON:0011876	80.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.85	gold quality
heart left ventricle	UBERON:0002084	76.10	gold quality
tongue	UBERON:0001723	75.70	silver quality
cardiac ventricle	UBERON:0002082	75.68	gold quality
lateral nuclear group of thalamus	UBERON:0002736	74.47	gold quality
right atrium auricular region	UBERON:0006631	74.45	gold quality
prefrontal cortex	UBERON:0000451	74.12	gold quality
cardiac atrium	UBERON:0002081	74.06	gold quality
trigeminal ganglion	UBERON:0001675	72.76	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

97 targeting KCNJ12, 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-8485	100.00	77.57	4731
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-5692A	100.00	74.40	6850
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-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-574-5P	100.00	66.01	989
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6764-5P	99.75	67.89	2304

Literature-anchored findings (GeneRIF, showing 19)

• heteromerization contributes to the phenotype of Andersen syndrome (PMID:12032359)
• Molecular cloning of functional KCNJ12 with an arginine residue at position 285. (PMID:12417321)
• transcripts for Kir2.2 potassium channels are identified in proliferative smooth muscle cells (PMID:12598232)
• Kir2.2 and Kir2.1 are primary determinants of endogenous K(+) conductance in HAECs under resting conditions and that Kir2.2 provides the dominant conductance in these cells. (PMID:15958527)
• Results describe the regulation of inwardly rectifying potassium current and its main molecular correlates, Kir2.1, Kir2.2 and Kir2.3 channels, by endothelin-1 in human atrial cardiomyocytes. (PMID:16258766)
• In conclusion, the data are consistent with the universal mechanism of rectification in Kir2 channels, but also point to significant, and physiologically important, quantitative differences between Kir2 isoforms. (PMID:16373386)
• Data show that the recovery of K(ir)2.2 from inhibition by FCCP requires intracellular components, but direct depletion of ATP does not reproduce the differential inhibitory effect of FCCP. (PMID:19016473)
• Kir2.1 and Kir2.2 subunits exert neither a dominant nor an anomalous effect on any of the properties of heteromeric channels. (PMID:20676672)
• Kir2.2 knockdown induces senescence of cancer cells by a mechanism involving reactive oxygen species accumulation. (PMID:20841375)
• KIr2.1 and Kir2.2 are directly activated by membrane phosphatidylinositol 4,5-bisphosphate. (PMID:20921230)
• Kir2.1 and Kir2.2 have two distinct lipid requirements for activity. (PMID:21281576)
• Unconventional role of the inwardly rectifying potassium channel Kir2.2 as a constitutive activator of RelA in cancer. (PMID:23269273)
• The augmentation of Ca(2+) influx and cytokine release suggests a physiological role for Kir2.2 in TLR4-stimulated monocytes. (PMID:26324774)
• Cellular electrophysiology assays of mouse Kir2.1 and human Kir2.2 indicated that, consistent with simulations, the Leu residue increased the channel responses to phosphatidylinositol diphosphate (PIP2) through increased binding affinity and faster activation kinetics, and the deactivation kinetics decreased upon PIP2 inhibition. (PMID:26520451)
• Nav1.5 N-terminal domain binding to alpha1-syntrophin increases membrane density of human Kir2.1, Kir2.2 and Nav1.5 channels (PMID:26786162)
• This report is the first to describe the KCNJ12 gene as a cause of familial dilated cardiomyopathy in patients (PMID:28816949)
• Four of these 16 variants were rare damaging mutations including novel mutations in KCNJ12/KCNJ18, and GPRIN2 genes. This WES study in Iranian patients with ESCC, provides insight into the identification of novel germline mutations in familial ESCC. Our data suggest an association between specific mutations and increased risk of ESCC (PMID:29405996)
• Therefore, we conclude that Kir2.2 p.Thr140Met may be most safely interpreted as a SPP susceptibility variant and it should be included in the genetic testing scheme for diagnosing SPP. (PMID:30838349)
• CircRNA hsa_circ_0014130 function as a miR-132-3p sponge for playing oncogenic roles in bladder cancer via upregulating KCNJ12 expression. (PMID:34755307)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnj12b	ENSDARG00000062618
danio_rerio	kcnj12a	ENSDARG00000104965
mus_musculus	Kcnj12	ENSMUSG00000042529
rattus_norvegicus	Kcnj12	ENSRNOG00000002303

Paralogs (15): KCNJ13 (ENSG00000115474), KCNJ5 (ENSG00000120457), KCNJ8 (ENSG00000121361), KCNJ2 (ENSG00000123700), KCNJ1 (ENSG00000151704), KCNJ16 (ENSG00000153822), KCNJ6 (ENSG00000157542), KCNJ15 (ENSG00000157551), KCNJ9 (ENSG00000162728), KCNJ3 (ENSG00000162989), KCNJ4 (ENSG00000168135), KCNJ10 (ENSG00000177807), KCNJ14 (ENSG00000182324), KCNJ11 (ENSG00000187486), KCNJ18 (ENSG00000260458)

Protein

Protein identifiers

ATP-sensitive inward rectifier potassium channel 12 — Q14500 (reviewed: Q14500)

Alternative names: Inward rectifier K(+) channel Kir2.2, Inward rectifier K(+) channel Kir2.2v, Potassium channel, inwardly rectifying subfamily J member 12

All UniProt accessions (1): Q14500

UniProt curated annotations — full annotation on UniProt →

Function. Inward rectifying potassium channel that probably participates in controlling the resting membrane potential in electrically excitable cells. Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium.

Subunit / interactions. Homotetramer. Forms heteromer with KCNJ4. Can form heteromeric channels with Kir2.6/KCNJ18. Association, via its PDZ-recognition domain, with LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1 plays a key role in its localization and trafficking.

Subcellular location. Membrane. Cell membrane. Sarcolemma. T-tubule.

Activity regulation. Activated by phosphatidylinositol 4,5-biphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 binding to the cytoplasmic side of the channel triggers a conformation change leading to channel opening. Inhibited by Ba(2+).

Similarity. Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ12 subfamily.

RefSeq proteins (1): NP_066292* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003272	K_chnl_inward-rec_Kir2.2	Family
IPR013518	K_chnl_inward-rec_Kir_cyto	Homologous_superfamily
IPR013673	K_chnl_inward-rec_Kir_N	Domain
IPR014756	Ig_E-set	Homologous_superfamily
IPR016449	K_chnl_inward-rec_Kir	Family
IPR040445	Kir_TM	Domain
IPR041647	IRK_C	Domain

Pfam: PF01007, PF08466, PF17655

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (56 total): sequence conflict 22, binding site 11, sequence variant 8, topological domain 4, short sequence motif 2, transmembrane region 2, chain 1, compositionally biased region 1, site 1, modified residue 1, disulfide bond 1, intramembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14500-F1	81.18	0.65

Functional residue map

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

Catalytic / active sites (1): 173 (role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium)

Ligand- & substrate-binding residues (11): 79; 81; 143; 143; 144; 144; 145; 145; 146; 183; 188

Post-translational modifications (1): 75

Disulfide bonds (1): 123–155

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-1296041	Activation of G protein gated Potassium channels
R-HSA-1296053	Classical Kir channels
R-HSA-5576886	Phase 4 - resting membrane potential
R-HSA-997272	Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1296059	G protein gated Potassium channels
R-HSA-1296065	Inwardly rectifying K+ channels
R-HSA-1296071	Potassium Channels
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction
R-HSA-977443	GABA receptor activation
R-HSA-977444	GABA B receptor activation
R-HSA-991365	Activation of GABAB receptors

MSigDB gene sets: 118 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_PROTEIN_HOMOTETRAMERIZATION, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, PEREZ_TP63_TARGETS, AMIT_EGF_RESPONSE_60_HELA, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_SYSTEM_PROCESS, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, PEREZ_TP53_AND_TP63_TARGETS, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_HEART_PROCESS

GO Biological Process (8): potassium ion transport (GO:0006813), muscle contraction (GO:0006936), regulation of heart contraction (GO:0008016), regulation of monoatomic ion transmembrane transport (GO:0034765), protein homotetramerization (GO:0051289), potassium ion import across plasma membrane (GO:1990573), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (3): inward rectifier potassium channel activity (GO:0005242), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), membrane (GO:0016020), T-tubule (GO:0030315), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Inwardly rectifying K+ channels	2
Neuronal System	2
G protein gated Potassium channels	1
Cardiac conduction	1
Activation of GABAB receptors	1
Transmission across Chemical Synapses	1
Potassium Channels	1
Muscle contraction	1
Neurotransmitter receptors and postsynaptic signal transmission	1
GABA receptor activation	1
GABA B receptor activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
metal ion transport	1
muscle system process	1
heart contraction	1
regulation of blood circulation	1
monoatomic ion transmembrane transport	1
regulation of transmembrane transport	1
regulation of monoatomic ion transport	1
protein homooligomerization	1
protein tetramerization	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
voltage-gated potassium channel activity	1
ligand-gated monoatomic cation channel activity	1
cation binding	1
binding	1
membrane	1
cell periphery	1
sarcolemma	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

1036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNJ12	KCNJ4	P48050	762
KCNJ12	KCNJ2	P48049	741
KCNJ12	KCNA3	P22001	624
KCNJ12	KCND3	Q9UK17	619
KCNJ12	DLG1	Q12959	608
KCNJ12	KRT76	Q01546	604
KCNJ12	KCNH2	Q12809	592
KCNJ12	KCNA5	P22460	588
KCNJ12	SCN5A	Q14524	587
KCNJ12	KCND2	Q9NZV8	587
KCNJ12	KCNQ1	P51787	547
KCNJ12	KCNA4	P22459	544
KCNJ12	HCN4	Q9Y3Q4	543
KCNJ12	KCNA2	P16389	538
KCNJ12	PALS2	Q9NZW5	523

IntAct

133 interactions, top by confidence:

A	B	Type	Score
SCRIB	KCNJ12	psi-mi:“MI:0915”(physical association)	0.720
SCRIB	KCNJ12	psi-mi:“MI:0407”(direct interaction)	0.720
DLG1	KCNJ12	psi-mi:“MI:0915”(physical association)	0.610
KCNJ12	DLG1	psi-mi:“MI:0407”(direct interaction)	0.610
EMD	KCNJ12	psi-mi:“MI:0915”(physical association)	0.560
KCNJ12	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
DLG3	KCNJ12	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ12	AHNAK	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (49): DLG1 (Affinity Capture-MS), DLG4 (Affinity Capture-MS), DLG4 (Affinity Capture-Western), DLG1 (Affinity Capture-Western), MPP6 (Affinity Capture-MS), APBA1 (Affinity Capture-MS), CASK (Affinity Capture-MS), DLG3 (Affinity Capture-MS), DLG2 (Affinity Capture-MS), LIN7A (Affinity Capture-MS), LIN7C (Affinity Capture-MS), DLG2 (Affinity Capture-Western), DLG3 (Affinity Capture-Western), LIN7A (Affinity Capture-Western), LIN7C (Affinity Capture-Western)

ESM2 similar proteins: B7U540, E1BNE9, F1MYR9, F1NHE9, O02670, O02822, O18839, O19182, O70617, P35561, P48050, P48051, P48542, P48543, P48544, P48545, P48548, P48549, P48550, P49656, P49658, P52185, P52186, P52187, P52188, P52189, P52190, P52191, P52192, P63250, P63251, P63252, P63253, P70673, P97794, Q14500, Q14654, Q15842, Q4TZY1, Q5NVJ6

Diamond homologs: B7U540, E1BN00, E1BNE9, F1MYR9, F1NHE9, O02670, O02822, O18839, O19182, O60928, O70339, O70596, O70617, O88335, O88932, P35560, P35561, P48048, P48050, P48051, P48542, P48543, P48544, P48545, P48548, P48549, P48550, P49655, P49656, P49658, P52185, P52186, P52187, P52188, P52189, P52190, P52191, P52192, P63250, P63251

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKACA	“down-regulates activity”	KCNJ12	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	54.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	52.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	52.3×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	48.8×	5e-13
Dopamine Neurotransmitter Release Cycle	5	47.7×	2e-06
Long-term potentiation	5	45.8×	2e-06
Neurexins and neuroligins	11	41.6×	2e-13
Protein-protein interactions at synapses	7	35.8×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	83.0×	1e-16
protein localization to synapse	6	59.7×	6e-08
receptor clustering	7	56.7×	6e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	45.1×	3e-08
protein-containing complex assembly	9	13.3×	2e-06
cell-cell adhesion	10	13.2×	3e-07
protein localization to plasma membrane	5	7.1×	1e-02
chemical synaptic transmission	7	7.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	14
Benign	37

Top pathogenic / likely-pathogenic (0)

SpliceAI

930 predictions. Top by Δscore:

Variant	Effect	Δscore
17:21376911:GAG:G	donor_gain	1.0000
17:21376912:AGGT:A	donor_loss	1.0000
17:21376913:GGTA:G	donor_loss	1.0000
17:21376914:G:C	donor_loss	1.0000
17:21376915:T:G	donor_loss	1.0000
17:21408638:GAG:G	donor_gain	1.0000
17:21376914:G:GG	donor_gain	0.9900
17:21408517:A:AG	acceptor_gain	0.9900
17:21408518:G:GG	acceptor_gain	0.9900
17:21408518:GGAT:G	acceptor_gain	0.9900
17:21408636:AAGAG:A	donor_loss	0.9900
17:21408638:GAGG:G	donor_loss	0.9900
17:21408641:GT:G	donor_loss	0.9900
17:21408642:T:A	donor_loss	0.9900
17:21412545:GCGTC:G	donor_gain	0.9900
17:21376909:CCGAG:C	donor_gain	0.9800
17:21376910:CGAG:C	donor_gain	0.9800
17:21376911:GAGG:G	donor_gain	0.9800
17:21376912:AG:A	donor_gain	0.9800
17:21376913:GG:G	donor_gain	0.9800
17:21408516:TAGGA:T	acceptor_gain	0.9800
17:21408517:AG:A	acceptor_gain	0.9800
17:21408518:GG:G	acceptor_gain	0.9800
17:21412591:G:GT	donor_gain	0.9800
17:21415281:TTGCA:T	acceptor_loss	0.9800
17:21415282:TGCAG:T	acceptor_loss	0.9800
17:21415283:GCAGG:G	acceptor_loss	0.9800
17:21415285:A:AC	acceptor_loss	0.9800
17:21415285:A:AG	acceptor_gain	0.9800
17:21415286:G:GG	acceptor_gain	0.9800

AlphaMissense

2870 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:21415482:T:A	V47D	1.000
17:21415494:G:A	G51D	1.000
17:21415494:G:T	G51V	1.000
17:21415580:T:A	W80R	1.000
17:21415580:T:C	W80R	1.000
17:21415625:T:A	W95R	1.000
17:21415625:T:C	W95R	1.000
17:21415770:C:T	T143I	1.000
17:21415776:G:A	G145D	1.000
17:21415782:G:A	G147E	1.000
17:21415805:T:C	C155R	1.000
17:21415874:G:C	G178R	1.000
17:21415875:G:A	G178D	1.000
17:21415891:G:C	K183N	1.000
17:21415891:G:T	K183N	1.000
17:21415928:T:C	F196L	1.000
17:21415929:T:C	F196S	1.000
17:21415930:C:A	F196L	1.000
17:21415930:C:G	F196L	1.000
17:21415931:A:C	S197R	1.000
17:21415932:G:T	S197I	1.000
17:21415933:C:A	S197R	1.000
17:21415933:C:G	S197R	1.000
17:21415974:T:C	L211P	1.000
17:21415979:T:A	W213R	1.000
17:21415979:T:C	W213R	1.000
17:21415983:G:C	R214P	1.000
17:21415989:G:A	G216D	1.000
17:21415993:C:A	N217K	1.000
17:21415993:C:G	N217K	1.000

dbSNP variants (sampled 300 via entrez): RS1000591177 (17:21399319 G>A,C), RS1000644983 (17:21399129 C>A,T), RS1000944798 (17:21393398 C>T), RS1001062036 (17:21379247 C>T), RS1001113988 (17:21378932 C>G,T), RS1001130820 (17:21379688 G>C), RS1001337431 (17:21383921 T>C), RS1001604649 (17:21395851 A>T), RS1001875792 (17:21387956 T>G), RS1001896827 (17:21389471 C>A,G,T), RS1001987512 (17:21393892 A>G), RS1002090897 (17:21399496 A>C,G), RS1002339893 (17:21394133 A>G), RS1002594123 (17:21397296 A>C,T), RS1002646366 (17:21397054 C>G)

Disease associations

OMIM: gene MIM:602323 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000817_144	Height	2.000000e-08
GCST002783_140	Body mass index	1.000000e-07
GCST002783_327	Body mass index	2.000000e-07
GCST004064_60	Waist-hip ratio	1.000000e-06
GCST004064_67	Waist-hip ratio	3.000000e-08
GCST004904_123	Body mass index	2.000000e-10
GCST008839_363	Height	2.000000e-12
GCST010988_57	Adult body size	3.000000e-19
GCST012227_399	Hip circumference adjusted for BMI	4.000000e-09
GCST012227_400	Hip circumference adjusted for BMI	2.000000e-11
GCST90000025_125	Appendicular lean mass	1.000000e-38
GCST90002385_407	High light scatter reticulocyte count	1.000000e-09
GCST90002386_179	High light scatter reticulocyte percentage of red cells	9.000000e-17
GCST90002387_24	Immature fraction of reticulocytes	1.000000e-11
GCST90002390_107	Mean corpuscular hemoglobin	6.000000e-18
GCST90002392_11	Mean corpuscular volume	2.000000e-21
GCST90002403_354	Red blood cell count	2.000000e-13
GCST90002406_452	Reticulocyte fraction of red cells	1.000000e-10
GCST90020028_1409	Hip circumference adjusted for BMI	3.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004343	waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196089 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Inwardly rectifying potassium channels (K_IR)

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
Mg2+	Inhibitor	4.96	pIC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases methylation	2
testosterone enanthate	affects expression	1
propionaldehyde	increases expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Barium	increases transport, decreases reaction	1
Camptothecin	increases expression	1
Carbamazepine	affects expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Nickel	decreases expression	1
Phthalic Acids	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6141319	Binding	Inhibition of Kir2.2 (unknown origin) channel at 10 uM relative to control	Discovery of ONO-TR-772 (VU6018042): A Highly Selective and CNS Penetrant TREK Inhibitor in Vivo Tool Compound. — ACS Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0UF	Ubigene Hep G2 KCNJ12 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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