KCNJ1

potassium inwardly rectifying channel subfamily J member 1, the group of Potassium inwardly rectifying channel subfamily J

Basic information

Region (hg38): 11:128836314-128867373

Links

ENSG00000151704 ∙ NCBI:3758 ∙ OMIM:600359 ∙ HGNC:6255 ∙ Uniprot:P48048 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bartter disease type 2 (Strong), mode of inheritance: AR
• antenatal Bartter syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bartter syndrome, antenatal, type 2	AR	Renal	Prenatal therapy has been reported as being beneficial; In infants, specific medications (eg, COX2 inhibitors) have been reported as beneficial; Correction of hypokalemic alkalosis can be beneficial	Renal	841184; 9002665; 10049979; 10979805

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNJ1 gene.

• not provided (103 variants)
• Bartter disease type 2 (76 variants)
• Inborn genetic diseases (16 variants)
• Antenatal Bartter syndrome (10 variants)
• not specified (8 variants)
• Bartter syndrome (6 variants)
• Intellectual disability;Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNJ1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	21		26
missense	5	14	60	3		82
nonsense	4	3				7
start loss						0
frameshift	3	2				5
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			13	9	9	31
Total	12	19	78	33	9

Highest pathogenic variant AF is 0.0000985

Variants in KCNJ1

This is a list of pathogenic ClinVar variants found in the KCNJ1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-128838080-G-C		Antenatal Bartter syndrome	Benign (Jun 14, 2016)
11-128838114-G-A		Antenatal Bartter syndrome	Benign (Jun 14, 2016)
11-128838157-A-T		Bartter disease type 2	Uncertain significance (Jan 13, 2018)
11-128838161-T-C		Bartter disease type 2	Uncertain significance (Jan 13, 2018)
11-128838261-C-A		Bartter disease type 2	Uncertain significance (Jan 12, 2018)
11-128838324-G-A		Bartter disease type 2	Likely benign (Jan 13, 2018)
11-128838388-A-G		Bartter disease type 2	Uncertain significance (Jan 12, 2018)
11-128838449-T-C		Antenatal Bartter syndrome	Benign (Jun 14, 2016)
11-128838456-T-C		Antenatal Bartter syndrome	Likely benign (Jun 14, 2016)
11-128838528-G-A		Antenatal Bartter syndrome	Uncertain significance (Jun 14, 2016)
11-128838572-G-A		Bartter disease type 2	Uncertain significance (Jan 12, 2018)
11-128838618-G-A		Bartter disease type 2	Likely benign (Jan 13, 2018)
11-128838623-C-CTTG		Antenatal Bartter syndrome	Benign (Jun 14, 2016)
11-128838673-C-T		Bartter disease type 2	Uncertain significance (Jan 12, 2018)
11-128838743-C-T		Bartter disease type 2	Uncertain significance (Jan 13, 2018)
11-128838777-G-A		Bartter disease type 2	Benign (Jan 12, 2018)
11-128838984-C-T		Antenatal Bartter syndrome	Uncertain significance (Jun 14, 2016)
11-128839028-TC-T			Likely benign (Nov 02, 2020)
11-128839037-C-T		Bartter disease type 2	Likely benign (Jan 12, 2018)
11-128839042-C-T		Bartter disease type 2	Uncertain significance (Jan 13, 2018)
11-128839052-T-A		Antenatal Bartter syndrome	Benign (Nov 12, 2018)
11-128839109-C-T		Bartter disease type 2	Likely benign (Feb 03, 2021)
11-128839120-C-T			Uncertain significance (-)
11-128839124-G-C		Bartter disease type 2	Uncertain significance (May 17, 2022)
11-128839128-C-T		Bartter disease type 2	Uncertain significance (May 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNJ1	protein_coding	protein_coding	ENST00000392664	2	31059

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000463	0.666	125623	0	121	125744	0.000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.277	229	218	1.05	0.0000118	2606
Missense in Polyphen		114	112.5	1.0133		1404
Synonymous	0.232	74	76.6	0.966	0.00000390	760
Loss of Function	0.892	8	11.2	0.713	6.51e-7	136

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00137	0.00131
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.000370	0.000370
European (Non-Finnish)	0.000407	0.000404
Middle Eastern	0.000381	0.000381
South Asian	0.0000327	0.0000327
Other	0.00261	0.00261

dbNSFP

Source: dbNSFP

• Function: FUNCTION: In the kidney, probably plays a major role in potassium homeostasis. 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. This channel is activated by internal ATP and can be blocked by external barium.
• Disease: DISEASE: Bartter syndrome 2, antenatal (BARTS2) [MIM:241200]: 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. BARTS2 is a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia. {ECO:0000269|PubMed:8841184, ECO:0000269|PubMed:9002665, ECO:0000269|PubMed:9727001}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gastric acid secretion - Homo sapiens (human);Aldosterone-regulated sodium reabsorption - Homo sapiens (human);Diuretics Pathway, Pharmacodynamics;Neuronal System;Potassium transport channels;Inwardly rectifying K+ channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.241

Intolerance Scores

• loftool: 0.0329
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.43

Haploinsufficiency Scores

• pHI: 0.107
• hipred: Y
• hipred_score: 0.517
• ghis: 0.428

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.360

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Kcnj1
• Phenotype: renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: kcnj1a.1
• Affected structure: heart contraction
• Phenotype tag: abnormal
• Phenotype quality: increased rate

Gene ontology

• Biological process: potassium ion transport;excretion;regulation of ion transmembrane transport;potassium ion import across plasma membrane
• Cellular component: plasma membrane;voltage-gated potassium channel complex
• Molecular function: inward rectifier potassium channel activity;ATP binding;phosphatidylinositol-4,5-bisphosphate binding;ATP-activated inward rectifier potassium channel activity