KCNU1

Chr 8AR

potassium calcium-activated channel subfamily U member 1

Also known as: KCNMC1, KCa5, KCa5.1, Kcnma3, SPGF79, Slo3

NCBI Gene: 157855 ENSG00000215262 UniProt: A8MYU2 OMIM: 615215

This gene encodes a member of the potassium channel family of proteins. The encoded voltage-gated ion channel allows the outward flow of potassium ions during plasma membrane hyperpolarization in sperm. Opening of this channel may be regulated by calcium ion levels. Homozygous knockout mice that lack the related mouse gene exhibit male sterility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spermatogenic failure 79MIM #620196

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Spermatogenic failure 79; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.81

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.000

Z-score 2.70

OE 0.61 (0.46–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.01Z-score

OE missense 1.00 (0.93–1.07)

598 obs / 598.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.61 (0.46–0.81)

0≤0.351.4

Missense OE?1.00 (0.93–1.07)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 34 / 55.7Missense obs/exp: 598 / 598.3Syn Z: -1.23

Background carrier burden — how many people carry a rare variant somewhere in KCNU1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 41

1,446 rare PASS variants

Rare truncating (LoF)

1 in 240

222 rare PASS variants

Rare synonymous (reference)

1 in 60

563 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KCNU1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 51	1 in 440
South Asian	~43k	1 in 33	1 in 590
Remaining (unassigned)	~30k	1 in 41	1 in 210
European (Finnish)	~27k	1 in 150	1 in 470
Admixed American	~22k	1 in 35	1 in 450
African / African American	~21k	1 in 46	1 in 320
East Asian	~20k	1 in 42	1 in 430
Ashkenazi Jewish	~13k	1 in 160	1 in 2,200
Middle Eastern	~2,884	1 in 45	1 in 480

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.