KCNJ14

Summary

KCNJ14 (potassium inwardly rectifying channel subfamily J member 14, HGNC:6260) is a protein-coding gene on chromosome 19q13.33, encoding ATP-sensitive inward rectifier potassium channel 14 (Q9UNX9). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.

Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel, and probably has a role in controlling the excitability of motor neurons.

Source: NCBI Gene 3770 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_013348

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6260
Approved symbol	KCNJ14
Name	potassium inwardly rectifying channel subfamily J member 14
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	Kir2.4, IRK4
Ensembl gene	ENSG00000182324
Ensembl biotype	protein_coding
OMIM	603953
Entrez	3770

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000342291, ENST00000391884

RefSeq mRNA: 1 — MANE Select: NM_013348 NM_013348

CCDS: CCDS12721

Canonical transcript exons

ENST00000342291 — 3 exons

Exon	Start	End
ENSE00001249475	48464181	48466980
ENSE00001375684	48461670	48462438
ENSE00001386307	48455574	48455858

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 69.53.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0189 / max 7.0574, expressed in 7 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176790	0.0189	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	69.53	gold quality
putamen	UBERON:0001874	68.72	gold quality
stromal cell of endometrium	CL:0002255	65.82	gold quality
gastrocnemius	UBERON:0001388	65.60	gold quality
skin of leg	UBERON:0001511	64.70	gold quality
primary visual cortex	UBERON:0002436	64.50	gold quality
muscle of leg	UBERON:0001383	64.42	gold quality
zone of skin	UBERON:0000014	64.24	gold quality
ventricular zone	UBERON:0003053	64.11	gold quality
skin of abdomen	UBERON:0001416	63.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	63.78	gold quality
caudate nucleus	UBERON:0001873	63.72	gold quality
skeletal muscle tissue	UBERON:0001134	62.41	gold quality
prefrontal cortex	UBERON:0000451	62.06	gold quality
frontal cortex	UBERON:0001870	61.61	gold quality
cortical plate	UBERON:0005343	61.46	gold quality
bone marrow	UBERON:0002371	61.32	gold quality
right frontal lobe	UBERON:0002810	61.16	gold quality
ganglionic eminence	UBERON:0004023	61.00	gold quality
muscle tissue	UBERON:0002385	60.64	gold quality
cerebellum	UBERON:0002037	60.34	gold quality
esophagus mucosa	UBERON:0002469	60.26	gold quality
bone marrow cell	CL:0002092	60.23	gold quality
cerebellar cortex	UBERON:0002129	60.23	gold quality
cerebellar hemisphere	UBERON:0002245	60.16	gold quality
right hemisphere of cerebellum	UBERON:0014890	60.01	gold quality
cerebral cortex	UBERON:0000956	59.97	gold quality
superior frontal gyrus	UBERON:0002661	59.83	gold quality
brain	UBERON:0000955	59.54	gold quality
anterior cingulate cortex	UBERON:0009835	59.09	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	34.64
E-GEOD-137537	yes	16.68
E-ANND-3	yes	3.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting KCNJ14, 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-9-5P	100.00	72.28	2361
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440

Literature-anchored findings (GeneRIF, showing 4)

• 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)
• Using patch-clamp techniques, we characterized K(IR) channels in cultured pulmonary artery smooth muscle cells and compared them to cloned Kir2.1 and Kir2.4 channels (PMID:17347781)
• KCNJ14 knockdown significantly inhibited the proliferation and migration of colorectal cells. (PMID:36100894)
• Comprehensive Analysis of KCNJ14 Potassium Channel as a Biomarker for Cancer Progression and Development. (PMID:36768373)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnj14	ENSDARG00000075914
mus_musculus	Kcnj14	ENSMUSG00000058743
rattus_norvegicus	Kcnj14	ENSRNOG00000021056
rattus_norvegicus	Kcnj14	ENSRNOG00000083583

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), KCNJ12 (ENSG00000184185), KCNJ11 (ENSG00000187486), KCNJ18 (ENSG00000260458)

Protein

Protein identifiers

ATP-sensitive inward rectifier potassium channel 14 — Q9UNX9 (reviewed: Q9UNX9)

Alternative names: Inward rectifier K(+) channel Kir2.4, Potassium channel, inwardly rectifying subfamily J member 14

All UniProt accessions (1): Q9UNX9

UniProt curated annotations — full annotation on UniProt →

Function. 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.

Subcellular location. Membrane.

Tissue specificity. Expressed preferentially in retina.

Activity regulation. Channel activity is regulated by variations of cytosolic pH; channels are activated by alkaline and inhibited by acidic pH values. Inhibited by Ba(2+) and Cs(+) in a voltage-dependent manner; sensitivity to those inhibitors is lower than in other Kir channels.

Similarity. Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ14 subfamily.

RefSeq proteins (1): NP_037480* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013518	K_chnl_inward-rec_Kir_cyto	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR016449	K_chnl_inward-rec_Kir	Family
IPR040445	Kir_TM	Domain
IPR041647	IRK_C	Domain

Pfam: PF01007, PF17655

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (15 total): topological domain 4, compositionally biased region 2, transmembrane region 2, region of interest 2, chain 1, short sequence motif 1, modified residue 1, sequence variant 1, intramembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNX9-F1	80.89	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.

Post-translational modifications (1): 81

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1296053	Classical Kir channels
R-HSA-5576886	Phase 4 - resting membrane potential
R-HSA-112316	Neuronal System
R-HSA-1296065	Inwardly rectifying K+ channels
R-HSA-1296071	Potassium Channels
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction

MSigDB gene sets: 104 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, RNGTGGGC_UNKNOWN, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GGGTGGRR_PAX4_03, GOBP_MONOATOMIC_CATION_TRANSPORT, BLALOCK_ALZHEIMERS_DISEASE_UP, ZIC1_01, GOBP_IMPORT_INTO_CELL, GOBP_TRANSMEMBRANE_TRANSPORT, TGGAAA_NFAT_Q4_01, LEIN_PONS_MARKERS, LEIN_MEDULLA_MARKERS, GOCC_POTASSIUM_CHANNEL_COMPLEX

GO Biological Process (5): regulation of monoatomic ion transmembrane transport (GO:0034765), potassium ion import across plasma membrane (GO:1990573), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (1): inward rectifier potassium channel activity (GO:0005242)

GO Cellular Component (4): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Inwardly rectifying K+ channels	1
Cardiac conduction	1
Potassium Channels	1
Neuronal System	1
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic ion transmembrane transport	1
regulation of transmembrane transport	1
regulation of monoatomic ion transport	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
voltage-gated potassium channel activity	1
ligand-gated monoatomic cation channel activity	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
cellular anatomical structure	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNJ14	LRIT2	A6NDA9	518
KCNJ14	KCNK6	Q9Y257	485
KCNJ14	TMEM68	Q96MH6	472
KCNJ14	CCDC126	Q96EE4	466
KCNJ14	NTN5	Q8WTR8	461
KCNJ14	WDR17	Q8IZU2	459
KCNJ14	KCNB2	Q92953	442
KCNJ14	KCNB1	Q14721	422
KCNJ14	SCN4A	P35499	416
KCNJ14	HAO1	Q9UJM8	411
KCNJ14	CACNA1S	Q13698	410
KCNJ14	KCNN2	Q9H2S1	391
KCNJ14	KCNA7	Q96RP8	388
KCNJ14	KCND1	Q9NSA2	382
KCNJ14	KCNC4	Q03721	344

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: B7U540, E1BN00, E1BNE9, F1NHE9, O02822, O18839, O19182, O60928, O70617, P35561, P48050, P48051, P48542, P48543, P48549, P48550, P49656, P49658, P52185, P52186, P52187, P52188, P52189, P52190, P52191, P52192, P63250, P63251, P63252, P63253, P70673, P86046, P97794, Q14500, Q14654, Q15842, Q4TZY1, Q5NVJ6, Q61743, Q63511

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

490 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48455649:G:GT	donor_gain	0.9900
19:48455649:G:T	donor_gain	0.9900
19:48464152:T:A	acceptor_gain	0.9900
19:48464158:T:A	acceptor_gain	0.9900
19:48464159:G:A	acceptor_gain	0.9900
19:48465942:G:GT	donor_gain	0.9900
19:48465943:A:T	donor_gain	0.9900
19:48465953:TGAAG:T	donor_loss	0.9900
19:48465956:AG:A	donor_loss	0.9900
19:48465957:GG:G	donor_loss	0.9900
19:48465958:GTG:G	donor_loss	0.9900
19:48464140:T:TA	acceptor_gain	0.9800
19:48464149:T:A	acceptor_gain	0.9800
19:48464180:GCCCC:G	acceptor_gain	0.9800
19:48464080:T:TA	acceptor_gain	0.9700
19:48464134:C:A	acceptor_gain	0.9700
19:48464142:T:TA	acceptor_gain	0.9700
19:48464173:T:A	acceptor_gain	0.9700
19:48455629:AAG:A	donor_gain	0.9600
19:48464103:A:AG	acceptor_gain	0.9600
19:48464104:T:G	acceptor_gain	0.9600
19:48464166:C:CA	acceptor_gain	0.9600
19:48464176:T:A	acceptor_gain	0.9600
19:48464176:TGCA:T	acceptor_loss	0.9600
19:48464179:A:AC	acceptor_loss	0.9600
19:48464180:G:GC	acceptor_loss	0.9600
19:48464180:GC:G	acceptor_gain	0.9600
19:48456592:A:G	acceptor_gain	0.9500
19:48460820:A:G	acceptor_gain	0.9500
19:48464121:C:G	acceptor_gain	0.9500

AlphaMissense

2820 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48462322:T:C	F200L	1.000
19:48462323:T:C	F200S	1.000
19:48462324:C:A	F200L	1.000
19:48462324:C:G	F200L	1.000
19:48462325:A:C	S201R	1.000
19:48462326:G:T	S201I	1.000
19:48462327:C:A	S201R	1.000
19:48462327:C:G	S201R	1.000
19:48462373:T:A	W217R	1.000
19:48462373:T:C	W217R	1.000
19:48462425:C:A	A234D	1.000
19:48464278:C:A	P271H	1.000
19:48464374:T:C	L303P	1.000
19:48464424:T:G	Y320D	1.000
19:48464445:T:A	W327R	1.000
19:48464445:T:C	W327R	1.000
19:48464447:G:C	W327C	1.000
19:48464447:G:T	W327C	1.000
19:48461893:G:T	G57W	0.999
19:48461894:G:A	G57E	0.999
19:48461894:G:T	G57V	0.999
19:48462317:T:C	L198P	0.999
19:48462322:T:A	F200I	0.999
19:48462323:T:G	F200C	0.999
19:48462326:G:A	S201N	0.999
19:48462335:C:A	A204D	0.999
19:48462338:T:A	V205D	0.999
19:48462343:G:C	A207P	0.999
19:48462368:T:C	L215P	0.999
19:48462376:C:A	R218S	0.999

dbSNP variants (sampled 300 via entrez): RS1000055611 (19:48456853 A>G,T), RS1000126016 (19:48454942 ATTTCT>A), RS1000128892 (19:48458300 C>A,T), RS1000178712 (19:48455144 A>G,T), RS1000430115 (19:48457139 G>C), RS1000511465 (19:48454071 C>A,T), RS1001357501 (19:48464019 C>T), RS1001416266 (19:48462481 G>A,T), RS1002235592 (19:48456491 G>A), RS1002633823 (19:48461396 G>A), RS1002739895 (19:48456628 G>A), RS1002789952 (19:48466828 G>A), RS1003034342 (19:48462658 C>T), RS1003086708 (19:48462451 G>A,C), RS1003093799 (19:48467148 A>C)

Disease associations

OMIM: gene MIM:603953 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
H+	Antagonist	7.14	pKi
Cs+	Antagonist	4.08	pKd
Ba2+	Antagonist	3.32	pKd

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Potassium	decreases reaction, increases transport	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
sulforaphane	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases methylation	1
Barium	decreases reaction, increases transport	1
Cisplatin	affects cotreatment, decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Hydrogen Peroxide	affects expression	1
Naphthoquinones	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	affects methylation	1
Copper Sulfate	increases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_YA64	IDG-HEK293T-KCNJ14-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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