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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CATSPER4
cation channel sperm associated 4
Chromosome 1 · 1p36.11
NCBI Gene: 378807Ensembl: ENSG00000188782.9HGNC: HGNC:23220UniProt: Q7RTX7
13PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsodium ion transportvoltage-gated calcium channel activityflagellated sperm motilitydiabetes mellitusdiabetic neuropathyazoospermiaspermatogenic failure 55
✦AI Summary

CATSPER4 encodes a pore-forming subunit of the CatSper (cation channel sperm-associated) complex, a sperm-specific voltage-gated calcium channel 1. The protein contains a single channel-forming domain with a conserved pore-loop sequence (TxDxW) and coiled-coil protein-protein interaction domains in its C-terminal tail, enabling assembly into a functional hetero-tetrameric channel with CATSPER1-3 1. CATSPER4 is primarily expressed in testis and ejaculated sperm 2, with expression increasing substantially from puberty onward during spermatogenesis 2. The channel mediates calcium-dependent physiological responses essential for fertilization, including sperm hyperactivation, acrosome reaction, and oocyte chemotaxis 3. CATSPER4 demonstrates particular involvement in sperm flagellum function 4. Clinically, CATSPER4 mutations have been identified in patients with asthenozoospermia (reduced sperm motility) 5, and the gene is imprinted, suggesting heterozygous mutations may impair function 5. CATSPER4 has been identified as a hub gene and potential biomarker for nonobstructive azoospermia diagnosis 6. A genome-wide association study identified a CATSPER4 locus associated with human adult height 7, though the biological relevance of this association remains unexplored.

Sources cited
1
CATSPER4 is a pore-forming subunit containing a channel-forming domain and coiled-coil interaction domains, predicted to form a hetero-tetrameric channel with other CatSper proteins
PMID: 12932298
2
CATSPER4 is primarily expressed in testis and mature sperm, with expression upregulated during sexual maturation
PMID: 21970684
3
CatSper channels regulate sperm hyperactivation, chemotaxis, and acrosome reaction essential for male fertility
PMID: 25457194
4
CATSPER4 heterozygous mutations were identified in asthenozoospermia patients; CATSPER4 is imprinted
PMID: 21255775
5
CATSPER4 is a hub gene with significant diagnostic value as a biomarker for nonobstructive azoospermia
PMID: 39506588
6
CATSPER4 protein shows strong functional relation with sperm flagellum structure and motility
PMID: 36472830
7
CATSPER4 is involved in sperm capacitation and male fertility through spermatozoal gene expression
PMID: 37815627
8
A CATSPER4 locus variant (rs11809207) shows genome-wide significant association with human adult height
PMID: 19343178
Disease Associationsⓘ20
diabetes mellitusOpen Targets
0.17Weak
diabetic neuropathyOpen Targets
0.16Weak
azoospermiaOpen Targets
0.11Weak
spermatogenic failure 3Open Targets
0.09Suggestive
spermatogenic failure 55Open Targets
0.09Suggestive
spermatogenic failure 83Open Targets
0.09Suggestive
spermatogenic failure, X-linked, 5Open Targets
0.09Suggestive
spermatogenic failure 19Open Targets
0.08Suggestive
spermatogenic failure 43Open Targets
0.08Suggestive
spermatogenic failure 45Open Targets
0.08Suggestive
spermatogenic failure 49Open Targets
0.08Suggestive
spermatogenic failure 82Open Targets
0.08Suggestive
spermatogenic failure 18Open Targets
0.08Suggestive
spermatogenic failure 27Open Targets
0.08Suggestive
spermatogenic failure 46Open Targets
0.08Suggestive
spermatogenic failure 72Open Targets
0.08Suggestive
spermatogenic failure 58Open Targets
0.08Suggestive
spermatogenic failure 7Open Targets
0.08Suggestive
spermatogenic failure 16Open Targets
0.08Suggestive
spermatogenic failure 21Open Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HSPA2Protein interaction99%CACNA1DProtein interaction96%CACNA1CProtein interaction91%CACNA1HProtein interaction82%CACNG2Protein interaction76%RYR1Protein interaction73%
Tissue Expression6 tissues
Lung
100%
Ovary
100%
Brain
0%
Heart
0%
Liver
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
CATSPER4HSPA2CACNA1DCACNA1CCACNA1HCACNG2RYR1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q7RTX7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.03LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.80 [0.63–1.03]
RankingsWhere CATSPER4 stands among ~20K protein-coding genes
  • #16,125of 20,598
    Most Researched13
  • #10,250of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedCATSPER4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identification of human and mouse CatSper3 and CatSper4 genes: characterisation of a common interaction domain and evidence for expression in testis.
PMID: 12932298
Reprod Biol Endocrinol · 2003
1.00
2
In Silico Analysis of CatSper Family Genes and APOB Gene Regulation in Male Infertility.
PMID: 36472830
Adv Exp Med Biol · 2022
0.90
3
Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size.
PMID: 19343178
PLoS Genet · 2009
0.80
4
Identification of Potential Biomarkers Associated with Spermatogenesis in Azoospermia.
PMID: 39506588
Clin Lab · 2024
0.70
5
CatSper channel, sperm function and male fertility.
PMID: 25457194
Reprod Biomed Online · 2015
0.60