KCNJ16

potassium inwardly rectifying channel subfamily J member 16, the group of Potassium inwardly rectifying channel subfamily J

Basic information

Region (hg38): 17:70053429-70135608

Links

ENSG00000153822 ∙ NCBI:3773 ∙ OMIM:605722 ∙ HGNC:6262 ∙ Uniprot:Q9NPI9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypokalemic tubulopathy and deafness (Moderate), mode of inheritance: AR
• hypokalemic tubulopathy and deafness (Strong), mode of inheritance: AR
• hypokalemic alkalosis, familial, with specific renal tubulopathy (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypokalemic tubulopathy and deafness	AR	Audiologic/Otolaryngologic; Renal	Early recognition of hearing impairment may improve outcomes, including related to speech and language development; The condition can involve sequelae of renal disease (eg, including renal salt wasting), and awareness may allow medical interventions related to kidney function	Audiologic/Otolaryngologic; Renal	33811157

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNJ16 gene.

• Hypokalemic tubulopathy and deafness (1 variants)
• PMM2-congenital disorder of glycosylation (1 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNJ16 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				1	2	3
missense		1	1		1	3
nonsense	1	3				4
start loss						0
frameshift						0
inframe indel		1				1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				2	10	12
Total	1	5	1	3	13

Highest pathogenic variant AF is 0.0000591

Variants in KCNJ16

This is a list of pathogenic ClinVar variants found in the KCNJ16 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-70075206-C-T			Benign (Apr 09, 2019)
17-70100517-T-C			Benign (Apr 09, 2019)
17-70100767-G-G		not specified	Benign (Jan 22, 2018)
17-70108435-G-A			Benign (Apr 09, 2019)
17-70108499-A-C			Benign (Apr 09, 2019)
17-70130650-A-G			Benign (Mar 01, 2019)
17-70130715-A-G			Likely benign (Nov 25, 2020)
17-70131049-T-A			Benign (May 12, 2021)
17-70131052-C-T			Benign (May 12, 2021)
17-70131193-T-TA			Benign (Dec 11, 2021)
17-70131194-C-A			Likely benign (Nov 20, 2020)
17-70131194-CA-C			Benign (May 18, 2021)
17-70131194-C-CA			Benign (May 26, 2021)
17-70132099-C-G		Hypokalemic tubulopathy and deafness	Likely pathogenic (Jan 31, 2022)
17-70132118-A-G			Benign (May 04, 2021)
17-70132278-C-T		Hypokalemic tubulopathy and deafness	Pathogenic (Jun 28, 2021)
17-70132342-G-A		Hypokalemic tubulopathy and deafness	Pathogenic (Mar 27, 2024)
17-70132447-G-A		not specified	Likely benign (Mar 27, 2024)
17-70132482-T-G		Hypokalemic tubulopathy and deafness	Pathogenic (Jun 29, 2021)
17-70132482-T-TAGG		KCNJ16-related disorder	Likely pathogenic (Dec 05, 2023)
17-70132484-G-T		Hypokalemic tubulopathy and deafness	Likely pathogenic (Jan 31, 2022)
17-70132491-G-C		Hypokalemic tubulopathy and deafness	Pathogenic (Jun 28, 2021)
17-70132496-C-G			Likely pathogenic (Apr 01, 2023)
17-70132496-C-T		Hypokalemic tubulopathy and deafness	Pathogenic (Jun 28, 2021)
17-70132554-T-G		KCNJ16-related disorder	Likely pathogenic (Apr 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNJ16	protein_coding	protein_coding	ENST00000392670	1	82180

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.87e-12	0.0216	125562	0	186	125748	0.000740

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.00220	238	238	1.00	0.0000133	2767
Missense in Polyphen		116	111.32	1.042		1302
Synonymous	-0.117	89	87.6	1.02	0.00000511	810
Loss of Function	-0.414	16	14.3	1.12	0.00000103	152

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00255	0.00224
Ashkenazi Jewish	0.00	0.00
East Asian	0.000599	0.000598
Finnish	0.000370	0.000370
European (Non-Finnish)	0.000705	0.000703
Middle Eastern	0.000599	0.000598
South Asian	0.000686	0.000686
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:24561201). {ECO:0000305|PubMed:24561201}.
• Pathway: Gastric acid secretion - Homo sapiens (human);Neuronal System;Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits;Activation of GABAB receptors;GABA B receptor activation;GABA receptor activation;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Activation of G protein gated Potassium channels;G protein gated Potassium channels;Potassium transport channels;Inwardly rectifying K+ channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• rvis_EVS: -0.91
• rvis_percentile_EVS: 9.96

Haploinsufficiency Scores

• pHI: 0.152
• hipred: N
• hipred_score: 0.350
• ghis: 0.558

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.381

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnj16
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: potassium ion transport;regulation of ion transmembrane transport;potassium ion import across plasma membrane
• Cellular component: plasma membrane;voltage-gated potassium channel complex;basolateral plasma membrane
• Molecular function: inward rectifier potassium channel activity;G-protein activated inward rectifier potassium channel activity