KCNJ16

Summary

KCNJ16 (potassium inwardly rectifying channel subfamily J member 16, HGNC:6262) is a protein-coding gene on chromosome 17q24.3, encoding Inward rectifier potassium channel 16 (Q9NPI9). 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. The encoded protein, which tends to allow potassium to flow into rather than out of a cell, can form heterodimers with two other inward-rectifier type potassium channels. It may function in fluid and pH balance regulation. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 3773 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypokalemic alkalosis, familial, with specific renal tubulopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 48 total — 8 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 8
• MANE Select transcript: NM_170741

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6262
Approved symbol	KCNJ16
Name	potassium inwardly rectifying channel subfamily J member 16
Location	17q24.3
Locus type	gene with protein product
Status	Approved
Aliases	Kir5.1, BIR9
Ensembl gene	ENSG00000153822
Ensembl biotype	protein_coding
OMIM	605722
Entrez	3773

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 25 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000283936, ENST00000392670, ENST00000392671, ENST00000586462, ENST00000587698, ENST00000587892, ENST00000588112, ENST00000589377, ENST00000591891, ENST00000615244, ENST00000858860, ENST00000858861, ENST00000858862, ENST00000858863, ENST00000858864, ENST00000858865, ENST00000858866, ENST00000858867, ENST00000858868, ENST00000858869, ENST00000858870, ENST00000858871, ENST00000858872, ENST00000858873, ENST00000858874, ENST00000858875, ENST00000858876

RefSeq mRNA: 8 — MANE Select: NM_170741 NM_001270422, NM_001291622, NM_001291623, NM_001291624, NM_001291625, NM_018658, NM_170741, NM_170742

CCDS: CCDS11687

Canonical transcript exons

ENST00000392671 — 4 exons

Exon	Start	End
ENSE00001342170	70100658	70100766
ENSE00001342177	70075225	70075390
ENSE00003528835	70130879	70130975
ENSE00003635897	70131995	70135608

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 99.45.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2190 / max 497.8334, expressed in 239 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162494	1.2188	91
162489	0.8733	105
162487	0.5285	41
162491	0.2200	80
162492	0.2117	79
162493	0.0704	43
162488	0.0543	17
162495	0.0421	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	99.45	gold quality
nephron tubule	UBERON:0001231	98.17	gold quality
caput epididymis	UBERON:0004358	97.59	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.07	gold quality
renal glomerulus	UBERON:0000074	96.72	gold quality
thyroid gland	UBERON:0002046	96.70	gold quality
kidney epithelium	UBERON:0004819	96.70	gold quality
adult mammalian kidney	UBERON:0000082	96.60	gold quality
metanephric glomerulus	UBERON:0004736	96.52	gold quality
left lobe of thyroid gland	UBERON:0001120	96.41	gold quality
right lobe of thyroid gland	UBERON:0001119	96.08	gold quality
pons	UBERON:0000988	95.90	gold quality
corpus epididymis	UBERON:0004359	95.37	gold quality
seminal vesicle	UBERON:0000998	95.27	gold quality
kidney	UBERON:0002113	95.17	gold quality
metanephros cortex	UBERON:0010533	95.08	gold quality
superior vestibular nucleus	UBERON:0007227	93.56	gold quality
medial globus pallidus	UBERON:0002477	93.32	gold quality
buccal mucosa cell	CL:0002336	92.82	gold quality
body of pancreas	UBERON:0001150	92.67	gold quality
cortex of kidney	UBERON:0001225	92.36	gold quality
globus pallidus	UBERON:0001875	91.98	gold quality
medulla oblongata	UBERON:0001896	91.75	gold quality
cerebellar vermis	UBERON:0004720	91.09	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.45	gold quality
bronchial epithelial cell	CL:0002328	90.44	gold quality
metanephros	UBERON:0000081	90.42	gold quality
adult organism	UBERON:0007023	89.79	gold quality
inferior olivary complex	UBERON:0002127	88.73	gold quality
ventral tegmental area	UBERON:0002691	88.66	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	55.52
E-HCAD-10	yes	14.07
E-ANND-3	yes	11.87
E-CURD-135	no	1256.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

106 targeting KCNJ16, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7-1-3P	99.91	71.53	4384

Literature-anchored findings (GeneRIF, showing 8)

• study provides an explanation for the pathophysiology of the p.A167V KCNJ10 mutation, which had not been considered pathogenic on its own; findings provide evidence for functional cooperation of KCNJ10 and KCNJ16; in vitro ascertainment of KCNJ10 function may necessitate co-expression with KCNJ16 (PMID:24193250)
• Five de novo mutations were identified in four genes (SCNN1A, KCNJ16, KCNB2, and KCNT1) in three Brugada syndrome patients (PMID:25339316)
• Variability has been found in a three-generation family with Pierre Robin sequence, acampomelic campomelic dysplasia, and intellectual disability due to a novel approximately 1 Mb deletion upstream of SOX9, and including KCNJ2 and KCNJ16. (PMID:26663529)
• Gene expression levels of three randomly selected DEGs, VCAN, COL5A1 and KCNJ16, were examined using RT-PCR in 10 ATC samples.. angiogenesis was activated by the high expression of CTHRC1, VCAN and POSTN, providing necessary nutrition for tumor cells (PMID:27599582)
• HNF1beta is a transcriptional activator of Kcnj16. Hence, patients with HNF1beta mutations may have reduced Kir5.1 activity in the kidney, resulting in hypokalemia and hypomagnesemia. (PMID:28577853)
• Defects in KCNJ16 Cause a Novel Tubulopathy with Hypokalemia, Salt Wasting, Disturbed Acid-Base Homeostasis, and Sensorineural Deafness. (PMID:33811157)
• lncRNA XIST is associated with preeclampsia and mediates trophoblast cell invasion via miR-340-5p/KCNJ16 signaling pathway. (PMID:35809813)
• Kir5.1 channels: potential role in epilepsy and seizure disorders. (PMID:35848616)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnj16a	ENSDARG00000045039
mus_musculus	Kcnj16	ENSMUSG00000051497
rattus_norvegicus	Kcnj16	ENSRNOG00000004713

Paralogs (15): KCNJ13 (ENSG00000115474), KCNJ5 (ENSG00000120457), KCNJ8 (ENSG00000121361), KCNJ2 (ENSG00000123700), KCNJ1 (ENSG00000151704), KCNJ6 (ENSG00000157542), KCNJ15 (ENSG00000157551), KCNJ9 (ENSG00000162728), KCNJ3 (ENSG00000162989), KCNJ4 (ENSG00000168135), KCNJ10 (ENSG00000177807), KCNJ14 (ENSG00000182324), KCNJ12 (ENSG00000184185), KCNJ11 (ENSG00000187486), KCNJ18 (ENSG00000260458)

Protein

Protein identifiers

Inward rectifier potassium channel 16 — Q9NPI9 (reviewed: Q9NPI9)

Alternative names: Inward rectifier K(+) channel Kir5.1, Potassium channel, inwardly rectifying subfamily J member 16

All UniProt accessions (3): Q9NPI9, K7EKJ4, K7ELL5

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. The inward rectification is mainly due to the blockage of outward current by internal magnesium. KCNJ16 may be involved in the regulation of fluid and pH balance. In the kidney, together with KCNJ10, mediates basolateral K(+) recycling in distal tubules; this process is critical for Na(+) reabsorption at the tubules.

Subunit / interactions. It forms heteromeric channels with Kir4.1/KCNJ10; this interaction is required for KCNJ16 localization to the basolateral membrane in kidney cells. As a heteromer with KCNJ10, may interact with MAGI1; this interaction may facilitate KCNJ10/KCNJ16 potassium channel expression at the basolateral membrane in kidney cells. May form heteromers with Kir2.1/KCNJ2. Can form heteromeric channels with Kir4.2/KCNJ15.

Subcellular location. Membrane. Basolateral cell membrane.

Tissue specificity. Widely expressed, with highest levels in adult and fetal kidney (at protein level). In the kidney, expressed in the proximal and distal convoluted tubules, but not in glomeruli nor collecting ducts.

Disease relevance. Hypokalemic tubulopathy and deafness (HKTD) [MIM:619406] An autosomal recessive disease characterized by renal tubulopathy with hypokalemia, salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Channel activity is strongly regulated by variations of cytosolic pH; channels are activated by alkaline and inhibited by acidic pH values. Activated by phosphatidylinositol 4,5 biphosphate (PtdIns(4,5)P2).

Similarity. Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ16 subfamily.

RefSeq proteins (8): NP_001257351, NP_001278551, NP_001278552, NP_001278553, NP_001278554, NP_061128, NP_733937, NP_733938 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008061	K_chnl_inward-rec_Kir5	Family
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 (19 total): sequence variant 7, topological domain 4, modified residue 2, transmembrane region 2, chain 1, intramembrane region 1, short sequence motif 1, site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9MAE	ELECTRON MICROSCOPY	3.13
9MA5	ELECTRON MICROSCOPY	3.18
9MAI	ELECTRON MICROSCOPY	3.35
9MAG	ELECTRON MICROSCOPY	3.37

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPI9-F1	78.29	0.50

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): 161 (role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium)

Post-translational modifications (2): 373, 375

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1296041	Activation of G protein gated Potassium channels
R-HSA-1296067	Potassium transport channels
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-977443	GABA receptor activation
R-HSA-977444	GABA B receptor activation
R-HSA-991365	Activation of GABAB receptors

MSigDB gene sets: 140 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, YAATNRNNNYNATT_UNKNOWN, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, NKX61_01, WCTCNATGGY_UNKNOWN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, MAF_Q6, RFX1_02, VECCHI_GASTRIC_CANCER_EARLY_DN, REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES, GOBP_IMPORT_INTO_CELL, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON

GO Biological Process (7): potassium ion transport (GO:0006813), regulation of monoatomic ion transmembrane transport (GO:0034765), potassium ion transmembrane transport (GO:0071805), potassium ion import across plasma membrane (GO:1990573), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), monoatomic cation transmembrane transport (GO:0098655)

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

GO Cellular Component (5): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), basolateral plasma membrane (GO:0016323), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Inwardly rectifying K+ channels	2
Neuronal System	2
G protein gated Potassium channels	1
Activation of GABAB receptors	1
Transmission across Chemical Synapses	1
Potassium Channels	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
monoatomic ion transmembrane transport	2
metal ion transport	1
regulation of transmembrane transport	1
regulation of monoatomic ion transport	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic cation 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
basal plasma membrane	1
plasma membrane region	1
cellular anatomical structure	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNJ16	KCNJ10	P78508	983
KCNJ16	DLG4	P78352	738
KCNJ16	MAP2K6	P52564	576
KCNJ16	NEDD4L	Q96PU5	566
KCNJ16	DLG2	Q15700	560
KCNJ16	KCNK1	O00180	552
KCNJ16	SLC12A3	P55017	551
KCNJ16	LIN7C	Q9NUP9	519
KCNJ16	KCNK2	O95069	507
KCNJ16	CACNG2	Q9Y698	506
KCNJ16	KCNK5	O95279	497
KCNJ16	GNG13	Q9P2W3	494
KCNJ16	BSND	Q8WZ55	489
KCNJ16	GRIA1	P42261	481
KCNJ16	SLC12A1	Q13621	472

IntAct

4 interactions, top by confidence:

A	B	Type	Score
KCNJ16	KCNJ10	psi-mi:“MI:0403”(colocalization)	0.460
KCNJ10	KCNJ16	psi-mi:“MI:0915”(physical association)	0.460
KCNJ16		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): KCNJ16 (Affinity Capture-Western), NEDD4 (Affinity Capture-Western), NEDD4 (Reconstituted Complex), KCNJ16 (Affinity Capture-RNA)

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
KCNJ16	“up-regulates quantity”	potassium(1+)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	6
Uncertain significance	12
Likely benign	4
Benign	15

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1174516	NM_170741.4(KCNJ16):c.409C>T (p.Arg137Cys)	Pathogenic
1174517	NM_170741.4(KCNJ16):c.526C>T (p.Arg176Ter)	Pathogenic
1174518	NM_170741.4(KCNJ16):c.395T>G (p.Ile132Arg)	Pathogenic
1174519	NM_170741.4(KCNJ16):c.749C>T (p.Pro250Leu)	Pathogenic
1174520	NM_170741.4(KCNJ16):c.404G>C (p.Gly135Ala)	Pathogenic
1174521	NM_170741.4(KCNJ16):c.191C>T (p.Thr64Ile)	Pathogenic
2633613	NM_170741.4(KCNJ16):c.397_399dup (p.Gly133_Tyr134insGly)	Pathogenic
3233748	NM_170741.4(KCNJ16):c.255G>A (p.Trp85Ter)	Pathogenic
2571001	NM_170741.4(KCNJ16):c.409C>G (p.Arg137Gly)	Likely pathogenic
2636067	NM_170741.4(KCNJ16):c.467T>G (p.Leu156Ter)	Likely pathogenic
3068382	NM_170741.4(KCNJ16):c.12C>G (p.Tyr4Ter)	Likely pathogenic
3068383	NM_170741.4(KCNJ16):c.397G>T (p.Gly133Ter)	Likely pathogenic
3393077	NM_170741.4(KCNJ16):c.904C>T (p.Arg302Ter)	Likely pathogenic
815949	GRCh37/hg19 17q24.3(chr17:68056381-68268736)x1	Likely pathogenic

SpliceAI

940 predictions. Top by Δscore:

Variant	Effect	Δscore
17:70130878:GGA:G	acceptor_gain	0.9900
17:70131989:TTTTA:T	acceptor_loss	0.9900
17:70131991:TTAG:T	acceptor_loss	0.9900
17:70131992:TAGG:T	acceptor_loss	0.9900
17:70131993:A:AG	acceptor_gain	0.9900
17:70131994:G:C	acceptor_loss	0.9900
17:70131994:G:GG	acceptor_gain	0.9900
17:70130875:A:AG	acceptor_gain	0.9800
17:70130875:ACAG:A	acceptor_gain	0.9800
17:70130876:C:G	acceptor_gain	0.9800
17:70130973:ATGG:A	donor_loss	0.9800
17:70130974:TGGT:T	donor_loss	0.9800
17:70130975:GGT:G	donor_loss	0.9800
17:70130976:GTAA:G	donor_loss	0.9800
17:70130977:T:TC	donor_loss	0.9800
17:70131994:GGTT:G	acceptor_gain	0.9800
17:70075387:AAAGG:A	donor_loss	0.9700
17:70075388:AAGG:A	donor_loss	0.9700
17:70075389:AGG:A	donor_loss	0.9700
17:70075390:GGTA:G	donor_loss	0.9700
17:70075392:T:A	donor_loss	0.9700
17:70106696:TTCAG:T	acceptor_gain	0.9700
17:70106697:TCAGC:T	acceptor_gain	0.9700
17:70131350:A:AG	acceptor_gain	0.9700
17:70131351:A:G	acceptor_gain	0.9700
17:70131993:AG:A	acceptor_gain	0.9700
17:70131994:GG:G	acceptor_gain	0.9700
17:70130873:GCACA:G	acceptor_loss	0.9600
17:70130874:CACAG:C	acceptor_loss	0.9600
17:70130876:CAGGA:C	acceptor_loss	0.9600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000053494 (17:70093716 A>G), RS1000091102 (17:70099772 C>G,T), RS1000216574 (17:70106080 A>C,T), RS1000249230 (17:70105872 T>A), RS1000296966 (17:70075640 G>T), RS1000356069 (17:70109225 A>G), RS1000473769 (17:70111138 T>C), RS1000499049 (17:70087960 G>A), RS1000504524 (17:70104438 C>A,T), RS1000524938 (17:70099583 T>C), RS1000583909 (17:70075896 C>G), RS1000590089 (17:70104632 A>G), RS1000619100 (17:70103997 G>A), RS1000633059 (17:70120165 G>A), RS1000665209 (17:70092339 C>A)

Disease associations

OMIM: gene MIM:605722 | disease phenotypes: MIM:619406, MIM:601144

GenCC curated gene-disease

Disease	Classification	Inheritance
hypokalemic tubulopathy and deafness	Strong	Autosomal recessive
inherited renal tubular disease	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hypokalemic alkalosis, familial, with specific renal tubulopathy	Definitive	AR

Mondo (4): hypokalemic tubulopathy and deafness (MONDO:0859167), Brugada syndrome 1 (MONDO:0011001), first-degree atrioventricular block (MONDO:0000466), inherited renal tubular disease (MONDO:0015962)

Orphanet (1): Brugada syndrome (Orphanet:130)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000127	Renal salt wasting
HP:0000407	Sensorineural hearing impairment
HP:0000848	Increased circulating renin concentration
HP:0000859	Increased circulating aldosterone concentration
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001941	Acidosis

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001627_1	Thyrotoxic hypokalemic periodic paralysis	8.000000e-14
GCST001841_6	Palmitoleic acid (16:1n-7) levels	3.000000e-07
GCST002030_12	Primary tooth development (time to first tooth eruption)	8.000000e-34
GCST002031_10	Primary tooth development (number of teeth)	2.000000e-19
GCST002129_11	Periodontitis (DPAL)	5.000000e-06
GCST003074_19	Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging)	6.000000e-07
GCST005951_19	Body mass index	3.000000e-08
GCST005956_52	Waist-to-hip ratio adjusted for BMI	9.000000e-07
GCST005962_38	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	4.000000e-07
GCST008362_22	Birth weight	1.000000e-10
GCST009391_234	Metabolite levels	5.000000e-06
GCST009391_317	Metabolite levels	1.000000e-06
GCST009893_6	Serum metabolite levels	2.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007707	cerebral amyloid deposition measurement
EFO:0004340	body mass index
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004344	birth weight
EFO:0010493	glycodeoxycholate measurement
EFO:0010431	triacylglycerol 56:4 measurement

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)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Estradiol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
bisphenol A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
dinophysistoxin 1	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
ormosil	affects binding, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Decitabine	decreases expression, decreases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	decreases expression	1
Atrazine	increases expression	1
Chenodeoxycholic Acid	affects cotreatment, decreases expression	1
Deoxycholic Acid	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	1
Glycocholic Acid	affects cotreatment, decreases expression	1
Glycodeoxycholic Acid	affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects expression	1
Phenobarbital	affects expression	1
Polyethylene Glycols	affects binding, decreases expression	1
Progesterone	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03572881	Not specified	UNKNOWN	Rhythmic Risk of Type 1 Brugada Syndrome and Pulmonary Infundibulum Mapping
NCT04641585	Not specified	UNKNOWN	Brugada Syndrome and Artificial Intelligence Applications to Diagnosis
NCT01275833	Not specified	TERMINATED	Restoration of Atrioventricular Synchrony Trial
NCT01985802	Not specified	COMPLETED	Pacing in First-degree AV-block
NCT02150538	Not specified	UNKNOWN	BiventRicular Pacing in prolongEd Atrio-Ventricular intervaL: the REAL-CRT Study