KCNU1

potassium calcium-activated channel subfamily U member 1, the group of Potassium calcium-activated channels

Basic information

Region (hg38): 8:36784323-36936125

Links

ENSG00000215262 ∙ NCBI:157855 ∙ OMIM:615215 ∙ HGNC:18867 ∙ Uniprot:A8MYU2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 79 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 79	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing	Genitourinary	34980136; 35551387

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNU1 gene.

• Inborn genetic diseases (45 variants)
• not provided (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNU1 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					4	4
missense			42	6	1	49
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	42	6	5

Variants in KCNU1

This is a list of pathogenic ClinVar variants found in the KCNU1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-36784478-T-A		not specified	Uncertain significance (May 31, 2023)
8-36784516-T-C		not specified	Uncertain significance (May 31, 2023)
8-36787341-T-A		not specified	Uncertain significance (Jun 02, 2023)
8-36804034-T-C		not specified	Uncertain significance (Dec 07, 2021)
8-36804079-A-G		not specified	Uncertain significance (Feb 21, 2024)
8-36804082-C-T		not specified	Uncertain significance (Sep 07, 2022)
8-36806320-G-A		not specified	Uncertain significance (Jun 29, 2023)
8-36806372-A-G		not specified	Uncertain significance (Sep 23, 2023)
8-36807438-C-T		not specified	Uncertain significance (Nov 12, 2021)
8-36808788-C-T		not specified	Uncertain significance (Feb 03, 2022)
8-36814300-A-G		not specified	Uncertain significance (Jun 22, 2022)
8-36814352-T-A		not specified	Uncertain significance (Apr 25, 2022)
8-36814358-T-C		not specified	Uncertain significance (Jan 26, 2022)
8-36814364-C-T		not specified	Uncertain significance (Jan 26, 2022)
8-36815633-T-A		not specified	Uncertain significance (Jan 23, 2023)
8-36815638-G-A		not specified	Uncertain significance (May 18, 2023)
8-36815682-A-C			Benign (Dec 31, 2019)
8-36817679-T-C		not specified	Uncertain significance (Oct 06, 2022)
8-36817714-C-T		not specified	Uncertain significance (May 04, 2023)
8-36817717-G-A		not specified	Uncertain significance (Dec 01, 2022)
8-36833658-C-T		not specified	Uncertain significance (Jun 22, 2023)
8-36834810-A-T		Spermatogenic failure 79	Pathogenic (Feb 02, 2023)
8-36834871-A-C		Spermatogenic failure 79	Pathogenic (Feb 02, 2023)
8-36836812-C-A		not specified	Uncertain significance (Oct 03, 2022)
8-36836864-A-G			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNU1	protein_coding	protein_coding	ENST00000399881	27	151805

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.79e-16	0.990	124383	0	261	124644	0.00105

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00508	598	598	0.999	0.0000308	7477
Missense in Polyphen		140	195.73	0.71526		2601
Synonymous	-1.23	248	225	1.10	0.0000119	2191
Loss of Function	2.70	34	55.7	0.610	0.00000291	686

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00113	0.00113
Ashkenazi Jewish	0.00	0.00
East Asian	0.000390	0.000389
Finnish	0.000791	0.000789
European (Non-Finnish)	0.00171	0.00170
Middle Eastern	0.000390	0.000389
South Asian	0.000365	0.000360
Other	0.00116	0.00116

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Testis-specific potassium channel activated by both intracellular pH and membrane voltage that mediates export of K(+). May represent the primary spermatozoan K(+) current. In contrast to KCNMA1/SLO1, it is not activated by Ca(2+) or Mg(2+). Critical for fertility. May play an important role in sperm osmoregulation required for the acquisition of normal morphology and motility when faced with osmotic challenges, such as those experienced after mixing with seminal fluid and entry into the vagina. {ECO:0000269|PubMed:23129643}.
• Pathway: Vascular smooth muscle contraction - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Fertilization;Reproduction;Sperm Motility And Taxes (Consensus)

Intolerance Scores

• loftool: 0.534
• rvis_EVS: -0.74
• rvis_percentile_EVS: 13.78

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.530
• ghis: 0.385

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.108

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnu1
• Phenotype: reproductive system phenotype; cellular phenotype

Gene ontology

• Biological process: reproductive process;regulation of ion transmembrane transport;sperm-egg recognition;regulation of membrane potential;potassium ion transmembrane transport
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: potassium channel activity;calcium-activated potassium channel activity;outward rectifier potassium channel activity;large conductance calcium-activated potassium channel activity