CATSPER1

Chr 11AR

cation channel sperm associated 1

Also known as: CATSPER, SPGF7

NCBI Gene: 117144 ENSG00000175294 UniProt: Q8NEC5 OMIM: 606389

The protein forms the pore-forming subunit of the CatSper complex, a sperm-specific voltage-gated calcium channel essential for sperm hyperactivation, acrosome reaction, and chemotaxis during fertilization. Autosomal recessive mutations cause spermatogenic failure, resulting in male infertility. This gene shows very low constraint against loss-of-function variants in the general population, consistent with its specialized reproductive function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Calcium ions play a primary role in the regulation of sperm motility. This gene belongs to a family of putative cation channels that are specific to spermatozoa and localize to the flagellum. The protein family features a single repeat with six membrane-spanning segments and a predicted calcium-selective pore region. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spermatogenic failure 7MIM #612997

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Spermatogenic failure 7; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.99

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.60

OE 0.69 (0.49–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.65Z-score

OE missense 0.92 (0.84–0.99)

430 obs / 469.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.49–0.99)

0≤0.351.4

Missense OE?0.92 (0.84–0.99)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 22 / 31.7Missense obs/exp: 430 / 469.7Syn Z: 0.41

Background carrier burden — how many people carry a rare variant somewhere in CATSPER1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

979 rare PASS variants

Rare truncating (LoF)

1 in 940

142 rare PASS variants

Rare synonymous (reference)

1 in 74

392 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CATSPER1. 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 69	1 in 1,100
South Asian	~43k	1 in 48	1 in 780
Remaining (unassigned)	~30k	1 in 45	1 in 1,300
European (Finnish)	~27k	1 in 180	1 in 1,900
Admixed American	~22k	1 in 50	1 in 1,400
African / African American	~21k	1 in 31	1 in 630
East Asian	~20k	1 in 51	1 in 160
Ashkenazi Jewish	~13k	1 in 230	1 in 1,400
Middle Eastern	~2,884	1 in 39	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓