KCNJ10

potassium inwardly rectifying channel subfamily J member 10, the group of Potassium inwardly rectifying channel subfamily J

Basic information

Region (hg38): 1:159998650-160070160

Links

ENSG00000177807 ∙ NCBI:3766 ∙ OMIM:602208 ∙ HGNC:6256 ∙ Uniprot:P78508 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• EAST syndrome (Strong), mode of inheritance: AR
• EAST syndrome (Definitive), mode of inheritance: AR
• EAST syndrome (Strong), mode of inheritance: AR
• Pendred syndrome (Supportive), mode of inheritance: AR
• EAST syndrome (Supportive), mode of inheritance: AR
• EAST syndrome (Strong), mode of inheritance: AR
• enlarged vestibular aqueduct syndrome (Disputed Evidence), mode of inheritance: AD
• EAST syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 4, with enlarged vestibular aqueduct; Pendred syndrome, digenic; Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SESAME syndrome)	AR/Digenic	Audiologic/Otolaryngologic; Renal	Individuals with Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalances display early-onset electrolyte abnormalities (eg, hypokalemia, metabolic alkalosis, and hypomagnesemia due to renal salt wasting), and treatment related to electrolyte imbalances may be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Neurologic; Renal	19420365; 19289823; 19289823; 19426954; 21849804
Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalances manifests with deafness, as well as electrolyte abnormalities; Digenic inheritance has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNJ10 gene.

• EAST syndrome (301 variants)
• Autosomal recessive nonsyndromic hearing loss 4 (93 variants)
• not provided (90 variants)
• Inborn genetic diseases (50 variants)
• not specified (33 variants)
• Autosomal recessive nonsyndromic hearing loss 4;Pendred syndrome;EAST syndrome (12 variants)
• Nonsyndromic Hearing Loss, Mixed (11 variants)
• Pendred syndrome (11 variants)
• Seizures, Sensorineural Deafness, Ataxia, Intellectual Disability, and Electrolyte Imbalance Syndrome (11 variants)
• Pendred syndrome;EAST syndrome;Autosomal recessive nonsyndromic hearing loss 4 (7 variants)
• Autosomal recessive nonsyndromic hearing loss 4;EAST syndrome;Pendred syndrome (6 variants)
• EAST syndrome;Autosomal recessive nonsyndromic hearing loss 4;Pendred syndrome (4 variants)
• Pendred syndrome;Autosomal recessive nonsyndromic hearing loss 4;EAST syndrome (3 variants)
• Intellectual disability (2 variants)
• EAST syndrome;Pendred syndrome;Autosomal recessive nonsyndromic hearing loss 4 (2 variants)
• KCNJ10-Related Disorders (2 variants)
• Autosomal recessive nonsyndromic hearing loss 4;EAST syndrome (2 variants)
• Peripheral neuropathy (1 variants)
• Abnormality of the nervous system (1 variants)
• SeSAME-like syndrome (1 variants)
• KCNJ10-related condition (1 variants)
• EAST syndrome;Autosomal recessive nonsyndromic hearing loss 4 (1 variants)
• Seizure;Intellectual disability (1 variants)
• Seizure;Autism;Intellectual disability (1 variants)
• Nonsyndromic Hearing Loss, Recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNJ10 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			3	72		75
missense	1	7	142	1		151
nonsense		1	1			2
start loss			1			1
frameshift	2	1				3
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region						0
non coding			56	17	9	82
Total	3	10	204	90	9

Highest pathogenic variant AF is 0.00000657

Variants in KCNJ10

This is a list of pathogenic ClinVar variants found in the KCNJ10 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-160030471-G-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Jun 25, 2023)
1-160030482-TTCTC-T		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency • PIGM-related disorder • not specified	Uncertain significance (Aug 18, 2023)
1-160030523-T-G		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Nov 15, 2022)
1-160030541-T-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Jul 12, 2022)
1-160030547-A-G		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Jun 23, 2023)
1-160030548-G-C		not specified	Uncertain significance (Mar 06, 2023)
1-160030590-T-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency • PIGM-related disorder	Benign (Jan 24, 2024)
1-160030597-T-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Likely benign (Oct 14, 2023)
1-160030640-C-A		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Feb 28, 2022)
1-160030645-A-T		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Benign (Jan 30, 2024)
1-160030647-A-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Sep 01, 2022)
1-160030650-A-G		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Sep 16, 2022)
1-160030698-G-A		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Benign (Apr 01, 2023)
1-160030698-G-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency • not specified	Uncertain significance (Oct 27, 2023)
1-160030723-G-A		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Likely benign (Jul 07, 2020)
1-160030739-T-G		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Jun 30, 2022)
1-160030741-G-A		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Benign/Likely benign (Aug 30, 2023)
1-160030758-T-A		not specified	Uncertain significance (Aug 13, 2021)
1-160030778-G-T		PIGM-related disorder	Uncertain significance (Aug 18, 2022)
1-160030779-T-C		not specified	Uncertain significance (Dec 19, 2023)
1-160030781-T-C		PIGM-related disorder	Uncertain significance (Dec 02, 2023)
1-160030790-C-T		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency • not specified	Uncertain significance (Jan 30, 2024)
1-160030802-AGGTCTCTGT-A		See cases	Uncertain significance (May 10, 2021)
1-160030873-G-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Likely benign (Aug 16, 2022)
1-160030877-A-G		not specified	Uncertain significance (Mar 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNJ10	protein_coding	protein_coding	ENST00000368089	1	32782

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.150	0.834	125725	0	9	125734	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.48	161	223	0.722	0.0000134	2458
Missense in Polyphen		56	101.63	0.55099		1212
Synonymous	-0.151	87	85.2	1.02	0.00000457	815
Loss of Function	2.09	3	10.2	0.294	6.23e-7	109

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000443	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be responsible for potassium buffering action of glial cells in the brain. 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. Can be blocked by extracellular barium and cesium (By similarity). In the kidney, together with KCNJ16, mediates basolateral K(+) recycling in distal tubules; this process is critical for Na(+) reabsorption at the tubules. {ECO:0000250, 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: 0.375

Intolerance Scores

• loftool: 0.0834
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.51

Haploinsufficiency Scores

• pHI: 0.185
• hipred: Y
• hipred_score: 0.655
• ghis: 0.530

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnj10
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; renal/urinary system phenotype; vision/eye 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); hearing/vestibular/ear phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: kcnj10b
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: potassium ion transport;visual perception;adult walking behavior;central nervous system myelination;regulation of ion transmembrane transport;regulation of long-term neuronal synaptic plasticity;glutamate reuptake;potassium ion homeostasis;regulation of resting membrane potential;potassium ion import across plasma membrane
• Cellular component: plasma membrane;integral component of plasma membrane;basolateral plasma membrane;presynapse
• Molecular function: inward rectifier potassium channel activity;protein binding;ATP binding;ATP-activated inward rectifier potassium channel activity;G-protein activated inward rectifier potassium channel activity