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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SEMG2
semenogelin 2
Chromosome 20 · 20q13.12
NCBI Gene: 6407Ensembl: ENSG00000124157.7HGNC: HGNC:10743UniProt: Q02383
51PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingextracellular exosomezinc ion bindingantibacterial humoral responseazoospermiamelanomaMale infertility with spermatogenesis disorder due to single gene mutationspermatogenic failure 3
✦AI Summary

SEMG2 encodes semenogelin 2, a major structural protein in human seminal plasma that participates in forming the gel matrix (sperm coagulum) containing ejaculated spermatozoa and accessory gland secretions 1. The protein functions through interactions with glycolytic enzymes and participates in sperm capacitation and antibacterial responses [GO annotations cited in abstracts]. SEMG2 is subject to strong adaptive evolution, with evidence of positive selection across human populations, particularly affecting reproductive and immune functions 2. The gene shows striking molecular variation across primate species, correlating with differences in sperm competition and mating systems 13. Clinically, SEMG2 has emerged as a cancer-testis antigen frequently re-expressed in multiple malignancies including lung, prostate, and renal cancers 4. Aberrant SEMG2 expression enhances cancer cell energy metabolism by upregulating glycolytic enzymes PKM2 and LDHA, increasing mitochondrial potential and glycolysis 4. In fertility contexts, SEMG2 underexpression associates with primary male infertility, suggesting its diagnostic potential as a seminal plasma biomarker 5. Additionally, SEMG2 appears as a common proteomic signature in urogenital diseases involving renal function 6. These findings indicate SEMG2 functions beyond reproduction in cancer metabolism and fertility assessment.

Sources cited
1
SEMG2 codes for major structural proteins in human semen forming viscous gelatinous complexes; molecular evolution correlates with sperm competition and mating systems across hominoid primates
PMID: 14629036
2
SEMG2 is aberrantly expressed in multiple cancer types and enhances cancer cell energy metabolism by interacting with and upregulating glycolytic enzymes PKM2 and LDHA
PMID: 33311447
3
SEMG2 exhibits evidence of positive selection in human populations, indicating adaptive pressure related to fertility and immunity functions
PMID: 23292442
4
SEMG2 shows molecular evolution variation across gibbon species with evidence of positive selection in some lineages
PMID: 30575018
5
SEMG2 is underexpressed in seminal plasma of men with primary infertility, suggesting its role as a diagnostic biomarker
PMID: 32372034
6
SEMG2 appears as a common proteomic signature in urogenital diseases affecting renal function, involved in regulation of endopeptidase activity and epithelial polarity
PMID: 36177616
7
SEMG2 functions as a cancer-testis antigen frequently re-expressed in various malignancies
PMID: 33966049
Disease Associationsⓘ20
azoospermiaOpen Targets
0.07Suggestive
melanomaOpen Targets
0.06Suggestive
Male infertility with spermatogenesis disorder due to single gene mutationOpen Targets
0.05Suggestive
spermatogenic failure 3Open Targets
0.05Suggestive
spermatogenic failure 55Open Targets
0.05Suggestive
spermatogenic failure 83Open Targets
0.05Suggestive
spermatogenic failure 7Open Targets
0.05Suggestive
spermatogenic failure 16Open Targets
0.05Suggestive
spermatogenic failure 21Open Targets
0.05Suggestive
spermatogenic failure 29Open Targets
0.05Suggestive
spermatogenic failure 79Open Targets
0.05Suggestive
spermatogenic failure 19Open Targets
0.05Suggestive
spermatogenic failure 43Open Targets
0.05Suggestive
spermatogenic failure 45Open Targets
0.05Suggestive
spermatogenic failure 49Open Targets
0.05Suggestive
spermatogenic failure 82Open Targets
0.05Suggestive
spermatogenic failure 10Open Targets
0.05Suggestive
spermatogenic failure 11Open Targets
0.05Suggestive
spermatogenic failure 58Open Targets
0.05Suggestive
spermatogenic failure, X-linked, 5Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
WFDC12Protein interaction83%KLK3Protein interaction82%PI3Protein interaction74%SEMG1Protein interaction61%BSPH1Shared pathway50%ELSPBP1Shared pathway50%
Tissue Expression6 tissues
Ovary
0%
Brain
0%
Heart
0%
Lung
0%
Bone Marrow
0%
Liver
0%
Gene Interaction Network
Click a node to explore
SEMG2WFDC12KLK3PI3SEMG1BSPH1ELSPBP1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q02383
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.92LoF Tolerant
pLIⓘ
0.45Tolerant
Observed/Expected LoF0.35 [0.16–0.92]
RankingsWhere SEMG2 stands among ~20K protein-coding genes
  • #8,731of 20,598
    Most Researched51
  • #8,397of 17,882
    Most Constrained (LOEUF)0.92
Genes detectedSEMG2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
SEMG1/2 augment energy metabolism of tumor cells.
PMID: 33311447
Cell Death Dis · 2020
1.00
2
Re-Analysis of Published Datasets in Search of Novel Urogenital Diseases Biomarkers.
PMID: 36177616
Curr Protein Pept Sci · 2022
0.90
3
Genes encoding WFDC- and Kunitz-type protease inhibitor domains: are they related?
PMID: 21936822
Biochem Soc Trans · 2011
0.80
4
Reproduction and immunity-driven natural selection in the human WFDC locus.
PMID: 23292442
Mol Biol Evol · 2013
0.70
5
Evolution of the hominoid semenogelin genes, the major proteins of ejaculated semen.
PMID: 14629036
J Mol Evol · 2003
0.60