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GeneE
4 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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DCST2
DC-STAMP domain containing 2
Chromosome 1 · 1q21.3
NCBI Gene: 127579Ensembl: ENSG00000163354.15HGNC: HGNC:26562UniProt: Q5T1A1
11PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
fusion of sperm to egg plasma membrane involved in single fertilizationsperm-egg recognitionacrosomal membranemembraneAbnormality of the skeletal systembasal cell carcinomacutaneous melanomauterine fibroid
✦AI Summary

DCST2 (DC-STAMP domain containing 2) is an essential sperm cell-surface protein required for mammalian gamete fusion during fertilization 1. As a member of the DC-STAMP protein family, DCST2 functions as a key sperm factor enabling sperm-egg recognition and fusion of spermatozoon to oocyte plasma membrane 1. Loss of DCST2 expression results in male infertility; male zebrafish with dcst2 knockout mutations developed normally with unaffected muscle biology but displayed complete infertility 2. Beyond its reproductive role, common genetic variants in DCST2 influence skeletal growth and development, with rs905938 genome-wide significantly associated with birth length (β = 0.046, P = 2.46 × 10⁻⁸), infant length, and adult height across large population studies 3. DCST2 expression is sensitive to environmental stressors; exposure to polystyrene microplastics downregulates DCST2 transcription in human spermatozoa along with other fusion-essential genes (DCST1, IZUMO1, SPACA6, SOF1, TMEM95), potentially compromising sperm functionality and fertility 4. These findings establish DCST2 as critical for both reproductive success and developmental growth regulation.

Sources cited
1
DCST2 is a newly identified gamete fusion sperm factor essential for sperm-oocyte fusion in mammals
PMID: 40058809
2
Male dcst2 knockout zebrafish are infertile despite normal development and unaffected muscle biology
PMID: 40736578
3
DCST2 variant rs905938 is genome-wide significantly associated with birth length, infant length, and adult height
PMID: 25281659
4
DCST2 is a spermatozoa-specific gene essential for sperm-oocyte fusion, and its expression is downregulated by polystyrene microplastic exposure
PMID: 40711049
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.22Weak
basal cell carcinomaOpen Targets
0.22Weak
cutaneous melanomaOpen Targets
0.22Weak
uterine fibroidOpen Targets
0.20Weak
skin neoplasmOpen Targets
0.20Weak
skin cancerOpen Targets
0.16Weak
melanocytic nevusOpen Targets
0.15Weak
melanomaOpen Targets
0.14Weak
atrial fibrillationOpen Targets
0.11Weak
prostate carcinomaOpen Targets
0.11Weak
breast carcinomaOpen Targets
0.10Weak
breast cancerOpen Targets
0.10Suggestive
ovarian carcinomaOpen Targets
0.09Suggestive
azoospermiaOpen Targets
0.09Suggestive
seborrheic keratosisOpen Targets
0.08Suggestive
Rare genetic female infertilityOpen Targets
0.08Suggestive
Female infertility due to fertilization defectOpen Targets
0.07Suggestive
benign neoplasm of skinOpen Targets
0.07Suggestive
Male infertility with spermatogenesis disorder due to single gene mutationOpen Targets
0.07Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SPACA6Protein interaction84%FREY1Shared pathway67%IZUMO1RShared pathway50%SPACA5Shared pathway50%TMEM81Shared pathway50%TMEM95Shared pathway50%
Tissue Expression6 tissues
Liver
100%
Ovary
77%
Bone Marrow
64%
Lung
32%
Heart
17%
Brain
10%
Gene Interaction Network
Click a node to explore
DCST2SPACA6FREY1IZUMO1RSPACA5TMEM81TMEM95
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q5T1A1
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.94LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.76 [0.62–0.94]
RankingsWhere DCST2 stands among ~20K protein-coding genes
  • #16,725of 20,598
    Most Researched11
  • #8,763of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedDCST2
Sources retrieved4 papers
Response time—
📄 Sources
4
1
Molecular mechanisms leading to gamete fusion.
PMID: 40058809
Fukushima J Med Sci · 2025
1.00
2
Loss of dcst2 expression in male zebrafish is not associated with muscle hypertrophy.
PMID: 40736578
Mol Genet Genomics · 2025
0.75
3
A novel common variant in DCST2 is associated with length in early life and height in adulthood.
PMID: 25281659
Hum Mol Genet · 2015
0.50
4
Impact of Polystyrene Microplastics on Human Sperm Functionality: An In Vitro Study of Cytotoxicity, Genotoxicity and Fertility-Related Genes Expression.
PMID: 40711049
Toxics · 2025
0.25