CLCNKB

Summary

CLCNKB (chloride voltage-gated channel Kb, HGNC:2027) is a protein-coding gene on chromosome 1p36.13, encoding Chloride channel protein ClC-Kb (P51801). Anion-selective channel permeable to small monovalent anions with ion selectivity for chloride > bromide > nitrate > iodide.

The protein encoded by this gene is a member of the family of voltage-gated chloride channels. Chloride channels have several functions, including the regulation of cell volume, membrane potential stabilization, signal transduction and transepithelial transport. This gene is expressed predominantly in the kidney and may be important for renal salt reabsorption. Mutations in this gene are associated with autosomal recessive Bartter syndrome type 3 (BS3). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1188 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Bartter disease type 4B (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 638 total — 34 pathogenic, 30 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 29 tissues, sQTL in 6 (q < 0.05)
• Phenotypes (HPO): 125
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.07 (unconstrained)
• MANE Select transcript: NM_000085

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2027
Approved symbol	CLCNKB
Name	chloride voltage-gated channel Kb
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	hClC-Kb, CLCKB, ClC-K2, ClC-Kb
Ensembl gene	ENSG00000184908
Ensembl biotype	protein_coding
OMIM	602023
Entrez	1188

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 27 protein_coding, 7 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000375679

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 5: 1

ENST00000375679, ENST00000375667, ENST00000431772, ENST00000682338, ENST00000682793, ENST00000682838, ENST00000683578, ENST00000683606, ENST00000683661, ENST00000684324, ENST00000684545, ENST00000684624, ENST00000684650, ENST00000684714, ENST00000684731, ENST00000906258, ENST00000906259, ENST00000906260, ENST00000906261, ENST00000906262, ENST00000906263, ENST00000906264, ENST00000906265, ENST00000906266, ENST00000906267, ENST00000906268, ENST00000906269, ENST00000906270, ENST00000906271, ENST00000906272, ENST00000906273, ENST00000906274, ENST00000906275, ENST00000996854, ENST00000996855, ENST00000996856, ENST00000996857, ENST00000996859, ENST00001144558

RefSeq mRNA: 2 — MANE Select: NM_000085 NM_000085, NM_001165945

CCDS: CCDS168, CCDS57974

Canonical transcript exons

ENST00000375679 — 20 exons

Exon	Start	End
ENSE00001295583	16053639	16053772
ENSE00001623837	16049618	16049702
ENSE00001629577	16050875	16051048
ENSE00001629974	16056422	16056508
ENSE00001638743	16046535	16046663
ENSE00001638879	16052198	16052411
ENSE00001644923	16055435	16055523
ENSE00001681519	16047905	16048044
ENSE00001682331	16055675	16055758
ENSE00001682955	16051710	16051820
ENSE00001688733	16048504	16048582
ENSE00001691281	16050516	16050600
ENSE00001705434	16048343	16048420
ENSE00001713263	16049120	16049245
ENSE00001734426	16049815	16049916
ENSE00001788569	16051478	16051547
ENSE00001789972	16045558	16045686
ENSE00001877330	16043782	16043880
ENSE00002725418	16044486	16044592
ENSE00003900225	16056869	16057308

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 98.96.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5702 / max 100.7985, expressed in 221 samples.

Highest expression (Bgee): renal medulla, adult mammalian kidney, metanephros cortex, kidney, adult organism.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CLCNKB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 35 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	2.9e-86	+0.64	1:16043720:A:G
Thyroid	sqtl	1.2e-26	-0.61	1:16043720:A:G
Brain Cerebellum	eqtl	3.5e-24	+0.81	1:16040432:A:C
Brain Cerebellar Hemisphere	eqtl	2.7e-22	+0.73	1:16040432:A:C
Lung	eqtl	1.8e-18	+0.64	1:16042892:G:A
Colon Transverse	eqtl	4.2e-17	+0.50	1:16041357:G:A
Nerve Tibial	eqtl	7.3e-17	+0.35	1:16042892:G:A
Pancreas	eqtl	6.3e-16	+0.56	1:16043381:C:T
Brain Cerebellum	sqtl	4.0e-15	-1.05	1:16045015:G:A
Artery Tibial	eqtl	2.6e-14	+0.43	1:16046056:C:A
Minor Salivary Gland	eqtl	2.0e-12	+0.43	1:16041201:C:T
Stomach	eqtl	4.4e-12	+0.44	1:16043381:C:T
Heart Atrial Appendage	eqtl	5.0e-11	+0.34	1:16050613:G:C
Heart Left Ventricle	eqtl	3.5e-09	-0.63	1:16049015:G:A
Adrenal Gland	eqtl	1.5e-08	+0.50	1:16044246:C:T
Ovary	eqtl	1.8e-08	+0.54	1:16041986:C:CCT
Brain Cerebellar Hemisphere	sqtl	3.1e-07	-1.01	1:16045015:G:A
Artery Aorta	eqtl	8.6e-06	-0.31	1:16048715:G:A
Testis	eqtl	1.9e-05	+0.81	1:15874769:G:A
Esophagus Muscularis	eqtl	2.6e-05	+0.30	1:16046056:C:A

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
960	0.2523	161
956	0.1196	14
959	0.0636	28
201375	0.0555	23
958	0.0410	10
957	0.0324	8
955	0.0060	4

Top tissues by expression

showing 100 of 262 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	98.96	gold quality
adult mammalian kidney	UBERON:0000082	97.10	gold quality
metanephros cortex	UBERON:0010533	95.22	gold quality
kidney	UBERON:0002113	90.11	gold quality
adult organism	UBERON:0007023	89.57	gold quality
parotid gland	UBERON:0001831	88.19	gold quality
sperm	CL:0000019	86.52	gold quality
male germ cell	CL:0000015	83.42	gold quality
right lobe of thyroid gland	UBERON:0001119	83.14	gold quality
left lobe of thyroid gland	UBERON:0001120	82.98	gold quality
thyroid gland	UBERON:0002046	82.75	gold quality
cortex of kidney	UBERON:0001225	80.51	gold quality
apex of heart	UBERON:0002098	79.57	gold quality
metanephros	UBERON:0000081	78.70	gold quality
saliva-secreting gland	UBERON:0001044	77.67	gold quality
oocyte	CL:0000023	76.48	silver quality
cerebellar hemisphere	UBERON:0002245	76.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.40	gold quality
cerebellar cortex	UBERON:0002129	76.20	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	75.81	gold quality
cerebellum	UBERON:0002037	75.48	gold quality
nephron tubule	UBERON:0001231	75.18	silver quality
minor salivary gland	UBERON:0001830	74.32	gold quality
kidney epithelium	UBERON:0004819	74.25	silver quality
triceps brachii	UBERON:0001509	73.89	gold quality
mouth mucosa	UBERON:0003729	73.34	gold quality
gluteal muscle	UBERON:0002000	71.49	gold quality
right atrium auricular region	UBERON:0006631	71.48	gold quality
gingival epithelium	UBERON:0001949	71.26	gold quality
cerebellar vermis	UBERON:0004720	70.84	gold quality
endothelial cell	CL:0000115	70.32	gold quality
cardiac atrium	UBERON:0002081	70.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	70.03	silver quality
secondary oocyte	CL:0000655	68.34	gold quality
metanephric glomerulus	UBERON:0004736	67.96	silver quality
right adrenal gland cortex	UBERON:0035827	67.92	gold quality
renal glomerulus	UBERON:0000074	67.81	silver quality
heart left ventricle	UBERON:0002084	66.49	gold quality
right adrenal gland	UBERON:0001233	66.47	gold quality
cardiac ventricle	UBERON:0002082	66.38	gold quality
left adrenal gland cortex	UBERON:0035825	65.79	gold quality
adrenal cortex	UBERON:0001235	65.74	gold quality
heart	UBERON:0000948	65.46	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	65.30	gold quality
pituitary gland	UBERON:0000007	64.97	gold quality
left adrenal gland	UBERON:0001234	64.85	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	64.74	silver quality
medial globus pallidus	UBERON:0002477	64.71	silver quality
germinal epithelium of ovary	UBERON:0001304	64.17	silver quality
vena cava	UBERON:0004087	64.08	gold quality
skin of hip	UBERON:0001554	63.34	silver quality
bronchial epithelial cell	CL:0002328	63.19	silver quality
globus pallidus	UBERON:0001875	63.15	silver quality
adenohypophysis	UBERON:0002196	62.69	gold quality
pons	UBERON:0000988	62.23	silver quality
adrenal gland	UBERON:0002369	62.23	gold quality
nasal cavity mucosa	UBERON:0001826	62.13	gold quality
urethra	UBERON:0000057	61.63	gold quality
decidua	UBERON:0002450	61.52	gold quality
cardia of stomach	UBERON:0001162	61.34	silver quality
pigmented layer of retina	UBERON:0001782	61.30	silver quality
mucosa of stomach	UBERON:0001199	61.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	61.13	silver quality
epithelium of bronchus	UBERON:0002031	61.01	silver quality
bronchus	UBERON:0002185	61.01	silver quality
palpebral conjunctiva	UBERON:0001812	60.66	silver quality
body of tongue	UBERON:0011876	60.61	gold quality
cartilage tissue	UBERON:0002418	60.49	gold quality
seminal vesicle	UBERON:0000998	60.23	silver quality
tonsil	UBERON:0002372	60.09	gold quality
nasal cavity epithelium	UBERON:0005384	59.96	gold quality
squamous epithelium	UBERON:0006914	59.89	gold quality
synovial joint	UBERON:0002217	59.65	gold quality
pericardium	UBERON:0002407	59.61	gold quality
mammalian vulva	UBERON:0000997	59.35	gold quality
upper leg skin	UBERON:0004262	59.32	silver quality
inferior vagus X ganglion	UBERON:0005363	59.23	gold quality
ovary	UBERON:0000992	58.96	gold quality
medulla oblongata	UBERON:0001896	58.91	gold quality
penis	UBERON:0000989	58.71	silver quality
substantia nigra pars compacta	UBERON:0001965	58.50	gold quality
left ovary	UBERON:0002119	58.45	gold quality
substantia nigra pars reticulata	UBERON:0001966	58.08	gold quality
esophagus squamous epithelium	UBERON:0006920	58.03	gold quality
superior vestibular nucleus	UBERON:0007227	57.82	gold quality
ventral tegmental area	UBERON:0002691	57.76	gold quality
myometrium	UBERON:0001296	57.64	gold quality
lateral nuclear group of thalamus	UBERON:0002736	57.51	gold quality
superficial temporal artery	UBERON:0001614	57.42	gold quality
right testis	UBERON:0004534	57.39	gold quality
epithelium of esophagus	UBERON:0001976	57.34	gold quality
deltoid	UBERON:0001476	57.33	gold quality
fundus of stomach	UBERON:0001160	57.32	gold quality
testis	UBERON:0000473	57.08	gold quality
placenta	UBERON:0001987	57.07	gold quality
trabecular bone tissue	UBERON:0002483	56.90	gold quality
corpus epididymis	UBERON:0004359	56.81	silver quality
buccal mucosa cell	CL:0002336	56.71	gold quality
left testis	UBERON:0004533	56.71	gold quality
body of pancreas	UBERON:0001150	56.58	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	1075.15
E-CURD-119	yes	43.36
E-HCAD-10	yes	14.81
E-CURD-114	yes	11.40
E-ANND-3	no	2.27

HPA expression

RNA tissue specificity: Group enriched

46 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Kidney	tissue	82.5	low
Salivary gland	tissue	40.2	low
Cerebellum	tissue	7.4	not detected
Thyroid gland	tissue	5.8	low
Parathyroid gland	tissue	2.3	not detected
Choroid plexus	tissue	1.6
Heart muscle	tissue	1.3	not detected
Seminal vesicle	tissue	1.3	not detected
Pons	tissue	1.2
Pituitary gland	tissue	0.9
Adrenal gland	tissue	0.9	not detected
Pancreas	tissue	0.6	not detected
Midbrain	tissue	0.6
Hypothalamus	tissue	0.6
Testis	tissue	0.5	medium
Retina	tissue	0.5
Ovary	tissue	0.5	not detected
Cervix	tissue	0.4	not detected
Stomach 1	tissue	0.4	not detected
Cerebral cortex	tissue	0.4	not detected
Medulla oblongata	tissue	0.4
Thalamus	tissue	0.4
Retrosplenial cortex	tissue	0.4
Epididymis	tissue	0.3	not detected
Spinal cord	tissue	0.3
Prostate	tissue	0.3	not detected
Colon	tissue	0.2	not detected
Basal ganglia	tissue	0.2	not detected
Amygdala	tissue	0.2
Substantia nigra	tissue	0.2
Locus coeruleus	tissue	0.2
Hippocampal formation	tissue	0.2
Vagina	tissue	0.1	not detected
Adipose tissue	tissue	0.1	not detected
Rectum	tissue	0.1	not detected
Smooth muscle	tissue	0.1	not detected
Endometrium 1	tissue	0.1	not detected
Putamen	tissue	0.1
Nucleus accumbens	tissue	0.1
Placenta	tissue	0.1	not detected
Lung	tissue	0.1	not detected
Hippocampus	tissue	0.1	not detected
Thymus	tissue	0.1
Postcentral gyrus	tissue	0.1
Fallopian tube	tissue	0.1	not detected
Occipital cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 180; highest nTPM — Flocculonodular lobe (7.4), Vermis (7.1), Cerebellar cortex (6.0), Anterior cochlear nucleus, ventral (1.2), Lateral vestibular nucleus (0.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CLCNKB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 31 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-6514-3P	97.52	66.50	808
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-1292-5P	96.74	62.14	238
HSA-MIR-6894-3P	96.73	65.64	798

Functional genomics

gnomAD constraint: pLI 1.47e-22, LOEUF 1.07, missense Z 1.29 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000375679 — one region, missense o/e 0.89. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• DNA mutational analysis of CLCNKB in Bartter syndrome type 3. (PMID:11865110)
• presence of Gitelman and Bartter syndrome and CBS phenotypes, in a kindred with the CLCNKB R438H mutation. (PMID:12472765)
• CLCKB expression is demonstrated in stria vascularis, spiral ligament and limbal fibrocytes, interdental cells and satellite cells of spiral ganglion neurons of mice harboring enhanced green fluorescence protein gene driven by the human CLCKB promoter. (PMID:14502078)
• Genetic heterogeneity of ClC-Kb chloride channels correlates with functional heterogeneity, which assigns ClC-Kb to a set of genes potentially relevant for polygenic salt-sensitivity of blood pressure regulation. (PMID:14675050)
• Combined impairment of ClC-Ka and ClC-Kb results in phenotype that mimics neonatal Barrter’s syndrome with deafness (PMID:15044642)
• The mutation ClC-Kb(T481S) of the renal epithelial Cl- channel ClC-Kb strongly activates ClC-Kb chloride channel function in vitro and may predispose to the development of essential hypertension in vivo. (PMID:15148291)
• There is no association with hypertension of CLCNKB polymorphism at a hypertension locus on chromosome 1p36. (PMID:16003175)
• confirms a weak genotype-phenotype correlation in patients with CLCNKB mutations and supports the founder effect of the A204T mutation in Spain (PMID:16391491)
• Barttin modulates trafficking and function of ClC-K1 and ClC-Kb channels (PMID:16849430)
• Identification of a novel mutation of the CLCNKB gene, DeltaL130 associated with Bartter syndrome. (PMID:16902263)
• Results identify large heterozygous deletion mutations in the CLCNKB gene in patients with type III Bartter syndrome. (PMID:17622951)
• roles of Thr418Ser polymorphism of the CLCNKB gene and Arg904Gln polymorphism in the TSC gene on essential hypertension need to be explored in other ethnic groups (PMID:17997379)
• Disruption of the gene encoding Barttin, BSND, results in a ‘double knockout’ of the functions of both ClCKA and ClCKB, manifesting as Bartter syndrome type IV with sensorineural deafness and an especially severe salt-losing phenotype. (PMID:18094726)
• ClC-Ka and ClC-Kb differ in how conformational changes are translated to the extracellular domain, despite the fact that the cytoplasmic domains share the same quaternary structure (PMID:18648499)
• In a large cohort of ante/neonatal Bartter syndrome, deafness, transient hyperkalaemia and severe hypokalaemic hypochloraemic alkalosis orientate molecular investigations to BSND, KCNJ1 and CLCNKB genes, respectively. (PMID:19096086)
• Threonine change to serine at position 481 in CLCNKB is associated with essential hypertension in males within the Ghanaian population. (PMID:19226700)
• Three novel CLCNKB mutations are identified associated with classic Bartter syndrome with a role in altering the functional properties of ClC-Kb channels. (PMID:19807735)
• Identify a protein region that is involved in calcium binding and that is likely undergoing conformational changes underlying the complex gating of CLC-K channels. (PMID:20805576)
• novel missense variant of the CLCNKB gene in two patients with type III Bartter syndrome (PMID:21479528)
• four mutations in the CLCNKB gene, among patients suffering from bartter and Gitelman syndromes (PMID:21631963)
• there was no significant association between the SLC12A3 R904Q variant and the ClC-Kb-T481S variant and essential hypertension in Mongolian and Han populations in Inner Mongolia (PMID:21644212)
• CLCNKB mutations are associated with Bartter syndrome. (PMID:21865213)
• expands the association between CLCNKB and essential hypertension to a non-European ancestry population (PMID:22578033)
• This article presents the case of a patient with hypokalaemia caused by CLCNKB gene mutation hard to categorise as GS or BS type 3. (PMID:23345488)
• study investigated the functional consequences of seven mutations; four mutants carried no current whereas others displayed a 30-60 percent reduction in conductance as compared with wild-type ClC-Kb (PMID:23703872)
• we report here for the first time that ClC-Kb disease-causing mutations located around the selectivity filter can result in both reduced surface expression and hyperactivity in heterologous expression systems (PMID:24271511)
• HEK293 cells the potentiating effect of niflumic acid (NFA) on CLC-Ka/barttin and CLC-Kb/barttin channels seems to be absent while the blocking efficacy of niflumic acid and benzofuran derivatives observed in oocytes is preserved (PMID:24863058)
• Single loci of tag Single Nucleotide Polymorphisms of CLCNKA_B are not enough to increase the Essential Hypertension susceptibility, the combination of CLCNKA SNP, salt, marine products, meat, edible oil consumption is associated with elevated risk (PMID:25919862)
• Case Report: 2 mutations in the CLCNKB gene, leading to a molecular diagnosis of Bartter syndrome type III in case of sudden infant death. (PMID:25923035)
• R8W and G47R, two naturally occurring barttin mutations identified in patients with Bartter syndrome type IV, reduce barttin palmitoylation and CLC-K/barttin channel activity. (PMID:26013830)
• These results demonstrate that mutations in a cluster of hydrophobic residues within transmembrane domain 1 affect barttin-CLC-K interaction and impair gating modification by the accessory subunit (PMID:26063802)
• results demonstrate that the carboxyl terminus of hClC-Kb is not part of the binding site for barttin, but functionally modifies the interplay with barttin. (PMID:26453302)
• Five patients had 1 or more mutations in CLCNKB, of whom 3 had homozygous mutations and 2 had single heterozygous mutations and only in CLCNKB had hypocalciuria. (PMID:26770037)
• Taking advantage of the largest number of functional results of CLCNKB mutations, we reveal the functionally important domains and severe mutational spots of the hClC-Kb channel and establish the genotype-phenotype association in classic Bartter’s Syndrome. (PMID:28555925)
• results suggested that the compound defective mutations of the CLCNKB gene are the molecular mechanism of the two classic Bartter syndrome siblings (PMID:29442545)
• Nine variants in the chloride voltagegated channel Kb (CLCNKB) gene were detected, including eight sequence variants and one whole CLCNKB gene deletion. One sequence variant (c.1967T>C) was novel, whereas the remaining variants (c.595G>T, c.908A>C, c.1004T>C, c.1312C>T, c.1334_1335delCT and c.1718C>A) and the whole gene deletion had been previously reported. (PMID:31115572)
• Bartter syndrome (BS) is a rare autosomal recessive disorder of salt reabsorption at the thick ascending limb of the Henle loop, characterized by hypokalemia, salt loss, metabolic alkalosis, hyperreninemic hyperaldosteronism with normal blood pressure. BS type III, often known as classic BS (CBS), is caused by loss-of-function mutations in CLCNKB (chloride voltage-gated channel Kb) encoding basolateral ClC-Kb. (PMID:31409296)
• Analysis of CLCNKB mutations at dimer-interface, calcium-binding site, and pore reveals a variety of functional alterations in ClC-Kb channel leading to Bartter syndrome. (PMID:31803959)
• Thirteen novel CLCNKB variants and genotype/phenotype association study in 42 Chinese patients with Bartter syndrome type 3. (PMID:31834604)
• Simultaneous Homozygous Mutations in SLC12A3 and CLCNKB in an Inbred Chinese Pedigree. (PMID:33807568)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Clcnkb	ENSMUSG00000006216
mus_musculus	Clcnka	ENSMUSG00000033770
rattus_norvegicus	Clcnkb	ENSRNOG00000009897
rattus_norvegicus	Clcnka	ENSRNOG00000052368
drosophila_melanogaster	ClC-c	FBGN0036566
drosophila_melanogaster	ClC-a	FBGN0051116
caenorhabditis_elegans		WBGENE00000530
caenorhabditis_elegans		WBGENE00000532

Paralogs (8): CLCN6 (ENSG00000011021), CLCN4 (ENSG00000073464), CLCN7 (ENSG00000103249), CLCN3 (ENSG00000109572), CLCN2 (ENSG00000114859), CLCN5 (ENSG00000171365), CLCNKA (ENSG00000186510), CLCN1 (ENSG00000188037)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1930643) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 75 distinct phenotype terms.

Mouse phenotype (MP)	Records
polyuria	3
decreased urine osmolality	3
postnatal growth retardation	2
increased circulating alkaline phosphatase level	2
small kidney	2
decreased physiological sensitivity to xenobiotic	2
decreased total body fat amount	2
increased urine prostaglandin level	2
increased circulating calcium level	1
increased neutrophil cell number	1
abnormal heart morphology	1
enlarged heart	1
abnormal heart shape	1
abnormal stomach morphology	1
hydronephrosis	1
abnormal kidney vasculature morphology	1
abnormal urinary bladder morphology	1
abnormal liver morphology	1
enlarged liver	1
abnormal spleen morphology	1
enlarged spleen	1
enlarged lymph nodes	1
abnormal ovary morphology	1
small testis	1
abnormal retina morphology	1

+50 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryctolagus cuniculus	P51803	99.7%	Diamond
Torpedo marmorata	P21564	97.0%	Diamond
Tetronarce californica	P35522	97.0%	Diamond
Cavia porcellus	Q9WU45	94.0%	Diamond
Canis lupus familiaris	Q9MZT1	88.4%	Diamond
Cronobacter sakazakii ATCC BAA-894	A7MGR4	80.6%	Diamond
Xenopus laevis	Q9W701	62.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ARHGEF19	protein-coding	128272
EPHA2	protein-coding	1969
FAM131C	protein-coding	348487
CLCNKA	protein-coding	1187
SRARP	protein-coding	149563
HSPB7	protein-coding	27129
EPHA2-AS1	ncRNA	101927479

Protein

Protein identifiers

Chloride channel protein ClC-Kb — P51801 (reviewed: P51801)

Alternative names: ClC-K2

All UniProt accessions (5): A0A804HI21, A0A804HJB2, A0A804HJU7, P51801, Q5T5Q6

UniProt curated annotations — full annotation on UniProt →

Function. Anion-selective channel permeable to small monovalent anions with ion selectivity for chloride > bromide > nitrate > iodide. Forms a homodimeric channel where each subunit has its own ion conduction pathway. May conduct double-barreled currents controlled by two types of gates, two fast gates that control each subunit independently and a slow common gate that opens and shuts off both subunits simultaneously. Assembles with the regulatory subunit BSND/Barttin for sorting at the basolateral plasma membrane domain and functional switch to the ion conducting state. CLCNKB:BSND channels display mostly a linear current-voltage relationship controlled by common gate. Mediates chloride conductance along nephron segments, namely the thick ascending limb of Henle’s loop, convoluted tubule and the collecting duct, contributing to the maintenance of systemic acid-base and electrolyte homeostasis. Conducts chloride currents in the stria vascularis of the inner ear to establish the endocochlear potential necessary for normal hearing.

Subunit / interactions. Homodimer. Interacts with BSND.

Subcellular location. Basolateral cell membrane.

Post-translational modifications. N-glycosylated.

Disease relevance. Bartter syndrome 3 (BARTS3) [MIM:607364] A form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. The disease is caused by variants affecting the gene represented in this entry. Bartter syndrome 4B, neonatal, with sensorineural deafness (BARTS4B) [MIM:613090] A digenic form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BARTS4B is associated with sensorineural deafness. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Loss-of-function of both CLCNKA and CLCNKB results in the disease phenotype.

Activity regulation. Activated by extracellular Ca(2+) and inhibited by extracellular acidic pH.

Miscellaneous. Compared with CLCNKA/BSND, CLCNKB/BSND is more sensitive to pH and less responsive to Ca(2+).

Similarity. Belongs to the chloride channel (TC 2.A.49) family. CLCNKB subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P51801-1	1	yes
P51801-2	2

RefSeq proteins (2): NP_000076, NP_001159417 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000644	CBS_dom	Domain
IPR001807	ClC	Family
IPR002250	Cl_channel-K	Family
IPR014743	Cl-channel_core	Homologous_superfamily
IPR046342	CBS_dom_sf	Homologous_superfamily
IPR050970	Cl_channel_volt-gated	Family

Pfam: PF00571, PF00654

Catalyzed reactions (Rhea)

• chloride(in) = chloride(out) (RHEA:29823)
• nitrate(in) = nitrate(out) (RHEA:34923)
• iodide(out) = iodide(in) (RHEA:66324)
• bromide(in) = bromide(out) (RHEA:75383)

UniProt features (58 total): sequence variant 28, transmembrane region 10, binding site 6, intramembrane region 4, splice variant 3, topological domain 2, domain 2, chain 1, glycosylation site 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51801-F1	87.16	0.60

Human Protein Atlas

Protein class: Transporters, Electrochemical Potential-driven transporters, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

Functional residue map

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

Ligand- & substrate-binding residues (6)

Position	Role
121	chloride
259	Ca(2+)
261	Ca(2+)
278	Ca(2+)
281	Ca(2+)
426	chloride

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	193

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-2672351	Stimuli-sensing channels	curated
R-HSA-983712	Ion channel transport	—
R-HSA-382551	Transport of small molecules	—

MSigDB gene sets: 327 (showing top): MODULE_416, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CHLORIDE_TRANSPORT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, DELYS_THYROID_CANCER_DN, GOBP_TRANSEPITHELIAL_TRANSPORT, MODULE_99, GOBP_RENAL_ABSORPTION, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, GOBP_RENAL_SYSTEM_PROCESS, GOCC_CHLORIDE_CHANNEL_COMPLEX, GOCC_TRANSPORTER_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX

GO Biological Process (8): chloride transport (GO:0006821), transepithelial chloride transport (GO:0030321), renal absorption (GO:0070293), renal sodium ion absorption (GO:0070294), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085), chloride transmembrane transport (GO:1902476)

GO Molecular Function (5): voltage-gated chloride channel activity (GO:0005247), chloride channel activity (GO:0005254), metal ion binding (GO:0046872), protein binding (GO:0005515), chloride transmembrane transporter activity (GO:0015108)

GO Cellular Component (4): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), chloride channel complex (GO:0034707), membrane (GO:0016020)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Ion channel transport	1
Transport of small molecules	1

GO top-level categories

26 GO namespaces:

Category	Terms
chloride transport	2
transport	2
monoatomic anion transport	1
inorganic anion transport	1
transepithelial transport	1
renal system process	1
renal sodium ion transport	1
renal absorption	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
monoatomic anion transmembrane transport	1
chloride channel activity	1
voltage-gated monoatomic anion channel activity	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
cation binding	1
binding	1
monoatomic anion transmembrane transporter activity	1
chloride transmembrane transport	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
monoatomic ion channel complex	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
renal sodium ion absorption	BP	mutant phenotype
basolateral plasma membrane	CC	direct assay
chloride channel activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 639 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLCNKB	BSND	Q8WZ55	992
CLCNKB	SLC12A3	P55017	949
CLCNKB	SLC12A1	Q13621	949
CLCNKB	KCNJ1	P48048	936
CLCNKB	KLF15	Q9UIH9	754
CLCNKB	REN	P00797	668
CLCNKB	MAGED2	Q9UNF1	652
CLCNKB	CASR	P41180	652
CLCNKB	TRPM6	Q9BX84	645
CLCNKB	CLDN16	Q9Y5I7	620
CLCNKB	KCNJ10	P78508	606
CLCNKB	MAZ	P56270	582
CLCNKB	WNK4	Q96J92	574
CLCNKB	SLC9A1	P19634	574
CLCNKB	CLDN19	Q8N6F1	568

IntAct

Human interaction partners of CLCNKB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
CFTR	physical association	0.370	1

BioGRID (1 interactions; top human partners by supporting records): CFTR (PCA)

Disease & clinical

Genetic variants

Variant evidence for CLCNKB: 638 ClinVar records (64 pathogenic / likely pathogenic); 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	30
Uncertain significance	195
Likely benign	183
Benign	135

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 64 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
7599	NM_000085.5(CLCNKB):c.1830G>A (p.Trp610Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
447098	NM_000085.5(CLCNKB):c.1783C>T (p.Arg595Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
585704	NM_000085.5(CLCNKB):c.18dup (p.Leu7fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
975076	NM_000085.5(CLCNKB):c.226C>T (p.Arg76Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
2055600	NM_000085.5(CLCNKB):c.1313G>A (p.Arg438His)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
7591	NM_000085.5(CLCNKB):c.371C>T (p.Pro124Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
801447	NM_000085.5(CLCNKB):c.708C>A (p.Tyr236Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
447106	NM_000085.5(CLCNKB):c.73del (p.Cys25fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
801446	NM_000085.5(CLCNKB):c.673G>T (p.Glu225Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1805279	NM_000085.5(CLCNKB):c.619del (p.Val207fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2202706	NM_000085.5(CLCNKB):c.1172G>A (p.Trp391Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
974420	NM_000085.5(CLCNKB):c.1270G>A (p.Gly424Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
497329	NM_000085.5(CLCNKB):c.1166G>A (p.Trp389Ter)	Pathogenic	criteria provided, single submitter	1
974551	NM_000085.5:c.(?-1)(*1_?)del	Pathogenic	criteria provided, single submitter	1
1917648	NM_000085.5(CLCNKB):c.1183_1184dup (p.Phe396fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CLCNKB’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 1,616):

Position(s)	Effect	Δscore	Sites
1:16043881	donor_loss	1.0000	2
1:16044484–16044485	acceptor_loss	1.0000	2
1:16044593–16044594	donor_loss	1.0000	5
1:16048039	donor_gain	1.0000
1:16048421–16048422	donor_loss	1.0000	3
1:16049164–16049165	acceptor_gain	1.0000	2
1:16049616–16049617	acceptor_loss	1.0000	4
1:16050872	acceptor_gain	1.0000
1:16051476	acceptor_loss	1.0000	2
1:16051548–16051549	donor_loss	1.0000	4

AlphaMissense

1,034 missense substitutions predicted likely pathogenic (of 4,460 scored), across 346 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H171	8	0.816	0.935
F430	8	0.787	0.930
W391	7	0.943	0.988
W96	7	0.939	0.985
F277	7	0.935	0.988
E225	7	0.931	0.970
W367	7	0.906	0.975
E490	7	0.905	0.943
E442	7	0.903	0.926
F285	7	0.898	0.972
F162	7	0.876	0.947
F222	7	0.876	0.938
F213	7	0.872	0.956
E281	7	0.871	0.944
F405	7	0.848	0.949
F474	7	0.846	0.942
F271	7	0.814	0.902
G437	6	0.962	0.989
G424	6	0.933	0.980
K147	6	0.927	0.976

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Kidney Chromophobe)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	1.7e-06

Disease associations

OMIM: gene MIM:602023 | disease phenotypes: MIM:613090, MIM:607364, MIM:601678, MIM:607634, MIM:604364

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
Bartter disease type 3	Definitive	Autosomal recessive	3
Bartter disease type 4B	Definitive	Digenic inheritance	2
Gitelman syndrome	Supportive	Autosomal recessive
Bartter syndrome type 4	Supportive	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	green
Nephrocalcinosis or nephrolithiasis	green
Paediatric disorders	green
Renal tubulopathies	green
Unexplained young onset end-stage renal disease	green

Mondo (8): Bartter disease type 4B (MONDO:0000909), Bartter disease type 3 (MONDO:0011822), Bartter syndrome (MONDO:0015231), proteinuria (MONDO:0003634), autosomal dominant osteopetrosis 1 (MONDO:0011877), epilepsy, familial focal, with variable foci 1 (MONDO:0024556), Gitelman syndrome (MONDO:0009904), Bartter syndrome type 4 (MONDO:0019524)

Orphanet (3): Bartter syndrome (Orphanet:112), Bartter syndrome type 3 (Orphanet:93605), Autosomal dominant osteopetrosis type 1 (Orphanet:2783)

HPO phenotypes

showing 60 of 125 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000017	Nocturia
HP:0000020	Urinary incontinence
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000103	Polyuria
HP:0000121	Nephrocalcinosis
HP:0000127	Renal salt wasting
HP:0000128	Renal potassium wasting
HP:0000325	Triangular face
HP:0000360	Tinnitus
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000591	Abnormal sclera morphology
HP:0000610	Abnormal choroid morphology
HP:0000622	Blurred vision
HP:0000712	Emotional lability
HP:0000805	Enuresis
HP:0000822	Hypertension
HP:0000823	Delayed puberty
HP:0000841	Hyperactive renin-angiotensin system
HP:0000848	Increased circulating renin concentration
HP:0000855	Insulin resistance
HP:0000859	Increased circulating aldosterone concentration
HP:0000872	Hashimoto thyroiditis
HP:0000934	Chondrocalcinosis
HP:0000969	Edema
HP:0000975	Hyperhidrosis
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001262	Excessive daytime somnolence
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001279	Syncope
HP:0001290	Generalized hypotonia
HP:0001324	Muscle weakness
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age
HP:0001525	Severe failure to thrive
HP:0001561	Polyhydramnios
HP:0001563	Fetal polyuria
HP:0001622	Premature birth
HP:0001657	Prolonged QT interval
HP:0001663	Ventricular fibrillation
HP:0001698	Pericardial effusion
HP:0001891	Iron deficiency anemia
HP:0001919	Acute kidney injury
HP:0001944	Dehydration
HP:0001947	Renal tubular acidosis
HP:0001952	Glucose intolerance
HP:0001953	Diabetic ketoacidosis
HP:0001959	Polydipsia
HP:0001960	Hypokalemic metabolic alkalosis
HP:0001962	Palpitations
HP:0001970	Tubulointerstitial nephritis
HP:0001994	Renal Fanconi syndrome
HP:0001997	Gout
HP:0002013	Vomiting
HP:0002014	Diarrhea

GWAS associations

5 associations:

Study	Trait	p-value
GCST90002383_458	Hematocrit	4e-23
GCST90002384_203	Hemoglobin	5e-22
GCST90002403_258	Red blood cell count	5e-20
GCST004601_46	Red blood cell count	1e-9
GCST010083_229	Hemoglobin levels	2e-8

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit

MeSH disease descriptors

4 disease descriptors:

Descriptor	Name	Tree numbers
D001477	Bartter Syndrome	C12.050.351.968.419.815.279; C12.200.777.419.815.279; C12.950.419.815.279; C19.053.800.604.249
D053579	Gitelman Syndrome	C12.050.351.968.419.815.491; C12.200.777.419.815.491; C12.950.419.815.491; C16.320.831.491
D011507	Proteinuria	C12.050.351.968.934.734; C12.200.777.934.734; C12.950.934.734; C23.888.942.750
C536056	Osteopetrosis autosomal dominant type 1 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: other ic — ClC family

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

Ligand	Action	Affinity	Parameter
niflumic acid	Activator	5.0	pEC50

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
entinostat	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
perfluorobutanesulfonic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Catechin	affects cotreatment, increases expression	1
Methapyrilene	decreases methylation	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1
Zinc Sulfate	decreases expression	1
Magnetite Nanoparticles	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_F0RG	HHUUKDi014-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 144 trials:

NCT	Phase	Status	Title
NCT02297048	Phase 4	COMPLETED	Monocentric STUDY, Randomised Double Blinded (Healthy Subjects, or Transversal (Patients With Gitelman Syndrome)
NCT00067990	Phase 4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00234871	Phase 4	COMPLETED	Tarka® vs. Lotrel® in Hypertensive, Diabetic Subjects With Renal Disease (TANDEM)
NCT00241085	Phase 4	COMPLETED	Effect of Valsartan on Proteinuria in Patients With Hypertension and Diabetes Mellitus
NCT00369538	Phase 4	SUSPENDED	Specific Blockage of Angiotensine 2 and Podocyturia in Glomerular Nephropathies With Hypertension and Proteinuria
NCT00508898	Phase 4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00550095	Phase 4	COMPLETED	To Assess the Effects of Valsartan on Albuminuria/Proteinuria in Hypertensive Patients With Type 2 Diabetes Mellitus
NCT00674596	Phase 4	COMPLETED	The Effect of Renin Angiotensin System Blockage (RAS) Blockade On PTX3 Levels In Diabetic Patients With Proteinuria
NCT00858299	Phase 4	UNKNOWN	The Change of Urinary Angiotensinogen Excretion After Valsartan Treatment in Patients With Persistent Proteinuria
NCT00893425	Phase 4	COMPLETED	Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria
NCT00921570	Phase 4	COMPLETED	The Effects of Renin Angiotensin System Blockage (RAS), Calcium Channel Blocker and Combined Drugs on TWEAK, PTX3 and FMD Levels in Diabetic Proteinuric Patients With Hypertension
NCT00961207	Phase 4	TERMINATED	Triple Blockade of the Renin Angiotensin Aldosterone System in Diabetic (Type 1&2) Proteinuric Patients
NCT01169857	Phase 4	WITHDRAWN	Velcade for Proliferative Lupus Nephritis
NCT01219413	Phase 4	COMPLETED	Influence of Aliskiren on Proteinuria
NCT01386554	Phase 4	COMPLETED	Acthar for Treatment of Proteinuria in Membranous Nephropathy Patients
NCT01512862	Phase 4	UNKNOWN	Anti-proteinuric Effect of Calcitriol in Non-diabetic Kidney Disease Patients
NCT01541267	Phase 4	COMPLETED	The Effect of Various Types of the Renin-angiotensin-aldosterone System Blockade on Proteinuria
NCT01637259	Phase 4	COMPLETED	MARCH Renal Substudy
NCT01703234	Phase 4	COMPLETED	FGF-23 and Endothelial Dysfunction in Diabetic Proteinuric Patients
NCT01820832	Phase 4	UNKNOWN	Oral Calcitriol for Reduction of Mild Proteinuria in Patients With CKD
NCT01827202	Phase 4	COMPLETED	RAS Quantification in Patients With Aliskiren or Candesartan
NCT02057523	Phase 4	TERMINATED	Acthar as Rescue Therapy for Transplant Glomerulopathy in Kidney Transplant Recipients
NCT02063100	Phase 4	UNKNOWN	Efficacy and Safety of Shenyankangfu Tablets for Primary Glomerulonephritis
NCT02382523	Phase 4	WITHDRAWN	Acthar on Proteinuria in IgA Nephropathy Patients
NCT02522650	Phase 4	UNKNOWN	A Crossover Pilot Study of the Effect of Amiloride on Proteinuria
NCT03195023	Phase 4	UNKNOWN	Effect of RAS Blockers on CKD Progression in Elderly Patients With Non Proteinuric Nephropathies (PROERCAN01)
NCT03550859	Phase 4	UNKNOWN	HMG-CoA Reductase add-on in Chronic Kidney Disease Patients With Proteinuria
NCT03983551	Phase 4	COMPLETED	Comparing the Renal Effect of Dipeptidyl-peptidase 4 Inhibitors and Sulfonylureas
NCT04531397	Phase 4	WITHDRAWN	Efficacy and Safety of Dapagliflozin in Children With Proteinuric Chronic Kidney Disease
NCT04534270	Phase 4	COMPLETED	Efficacy and Safety of Dapagliflozin in Children With Proteinuria
NCT06374043	Phase 4	COMPLETED	Decentralized N=1 Study: A Feasible Approach to Evaluate Individual Therapy Response to Dapagliflozin.
NCT07030894	Phase 4	RECRUITING	Nefecon and Ambrisentan in IgA Nephropathy
NCT07219121	Phase 4	ACTIVE_NOT_RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT07358520	Phase 4	NOT_YET_RECRUITING	Clinical Study on the Use of Huaier Granules for the Treatment of Proteinuria Related to Bevacizumab and Anlotinib in Lung Cancer Patients
NCT00141453	Phase 3	COMPLETED	ORIENT: Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial
NCT00199927	Phase 3	COMPLETED	Statins in Proteinuric Nephropathies
NCT00242346	Phase 3	COMPLETED	High Doses of Candesartan Cilexetil on the Reduction of Proteinuria
NCT00362960	Phase 3	COMPLETED	Olmesartan Medoxomil and Diabetic Nephropathy
NCT00507494	Phase 3	COMPLETED	Influence of Pioglitazone for Renal Transplant Function in Diabetics
NCT00568178	Phase 3	COMPLETED	An Extension Study Designed to Assess Effects of Losartan on Proteinuria in Pediatric Populations (MK-0954-326 AM1,EXT1(AM2))
NCT01029002	Phase 3	COMPLETED	The Effects of Vitamin D Repletion in Vitamin D Deficient Patients With Stage 3 and 4 Chronic Kidney Disease
NCT01091324	Phase 3	UNKNOWN	Dextromethorphan and Silymarin in Chronic Kidney Disease (CKD) Patients
NCT01164098	Phase 3	TERMINATED	Rituximab to Prevent Recurrence of Proteinuria
NCT01436747	Phase 3	COMPLETED	Efficacy and Safety of Paricalcitol for Reduction of Proteinuria in Kidney Transplant Recipients
NCT01694160	Phase 3	COMPLETED	Oral Paricalcitol in Renal Transplant Recipients for Reducing Albuminuria
NCT01831193	Phase 3	COMPLETED	Effect of Oral Supplementation With Curcumin (Turmeric) in Patients With Proteinuric Chronic Kidney Disease
NCT02232763	Phase 3	COMPLETED	Efficacy and Safety of Losartan in Pediatric Chronic Kidney Disease With Tubular Proteinuria
NCT02282930	Phase 3	COMPLETED	Pilot Study of ACTH in the Treatment of Immunoglobulin A (IgA) Nephropathy at High Risk of Progression
NCT05196035	Phase 3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well the Study Treatment Finerenone Works, How Safe it is, How it Moves Into, Through, and Out of the Body, and the Effects it Has on the Body When Taken With an ACE Inhibitor or Angiotensin Receptor Blocker in Children With Chronic Kidney Disease and Proteinuria
NCT05283057	Phase 3	COMPLETED	Empagliflozin in Patients With Glomerulonephritis
NCT05457283	Phase 3	RECRUITING	A Study to Learn More About How Safe the Study Treatment Finerenone is in Long-term Use When Taken With an ACE Inhibitor or Angiotensin Receptor Blocker Over 18 Months of Use in Children and Young Adults From 1 to 18 Years of Age With Chronic Kidney Disease and Proteinuria
NCT00001959	Phase 2	COMPLETED	Pirfenidone to Treat Kidney Disease (Focal Segmental Glomerulosclerosis)
NCT00817037	Phase 2	COMPLETED	Sitaxsentan in Proteinuric Chronic Kidney Disease
NCT00915200	Phase 2	COMPLETED	N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy
NCT00977977	Phase 2	RECRUITING	Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
NCT01265563	Phase 2	COMPLETED	N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy
NCT01642979	Phase 2	UNKNOWN	Safety and Efficacy of Levamisole Combined With Cyclosporine A in Patients With Classic Paroxysmal Nocturnal Hemoglobinuria
NCT01760096	Phase 2	UNKNOWN	Safety and Efficacy of Levamisole Combined With Cyclosporine A in Patients With Subclinical Paroxysmal Nocturnal Hemoglobinuria and PNH in the Setting of Another Bone Marrow Failure Syndromes(PNH-2013)
NCT02173106	Phase 2	UNKNOWN	A Controlled Study of Steroids Plus Cyclosporin Therapy for Patients of Idiopathic Membranous Nephropathy
NCT02327403	Phase 2	COMPLETED	Belatacept Conversion in Proteinuric Kidney Transplant Recipients