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8 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PGAM4
phosphoglycerate mutase family member 4
Chromosome X · Xq21.1
NCBI Gene: 441531Ensembl: ENSG00000226784.3HGNC: HGNC:21731UniProt: Q8N0Y7
24PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
sperm principal pieceextracellular exosomephosphoglycerate mutase activityglycolytic processcancergliomaAutoimmune Hepatitischronic hepatitis B virus infection
✦AI Summary

PGAM4 (phosphoglycerate mutase family member 4) is an X-linked retrogene that catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate, a crucial step in glycolysis 1. The gene is predominantly expressed in testicular tissue, particularly in post-meiotic spermatids and spermatozoa, localizing to the sperm flagellar principal piece 1. PGAM4 plays a fundamental role in male reproduction; a G75C polymorphism associated with male infertility reduces enzymatic activity both in vitro and in vivo, present in 4.5% of infertile patients 1. However, in a Chinese Han population, the G75C polymorphism showed no significant association with non-obstructive azoospermia 2. Beyond reproduction, PGAM4 is upregulated in glioma and lung cancer, where it promotes cell viability, proliferation, and glycolytic activity 345. PGAM4 silencing in glioma cells suppresses glycolysis and chemoresistance to temozolomide 3, suggesting therapeutic potential in cancer treatment. The gene appears regulated by EP300-mediated histone acetylation modifications 3. Complete deletion of PGAM4 does not impair male fertility in carriers, indicating functional redundancy in this context 6.

Sources cited
1
PGAM4 is an X-linked testis-specific retrogene expressed in spermatids and spermatozoa; G75C polymorphism decreases enzymatic activity and is associated with male infertility
PMID: 22590500
2
G75C polymorphism shows no significant association with non-obstructive azoospermia in Chinese Han population
PMID: 23631659
3
PGAM4 is upregulated in glioma, promotes glycolysis and cell proliferation; silencing inhibits chemoresistance to temozolomide; regulated by EP300-mediated H3K27ac
PMID: 36576012
4
PGAM4 identified as differentially expressed gene regulated by MALAT1 in lung cancer cells, associated with survival and tumorigenesis
PMID: 37667226
5
PGAM4 included in prognostic exosomal gene signature for lung adenocarcinoma with predictive value for patient outcomes
PMID: 40179422
6
Complete deletion of PGAM4 does not disrupt male fertility in X-linked carriers
PMID: 26242992
Disease Associationsⓘ20
cancerOpen Targets
0.02Suggestive
gliomaOpen Targets
0.02Suggestive
Autoimmune HepatitisOpen Targets
0.02Suggestive
chronic hepatitis B virus infectionOpen Targets
0.02Suggestive
primary biliary cirrhosisOpen Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
cryohydrocytosisOpen Targets
0.01Suggestive
infertilityOpen Targets
0.01Suggestive
Menkes diseaseOpen Targets
0.01Suggestive
azoospermiaOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
chronic hepatitis C virus infectionOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
lung cancerOpen Targets
0.00Suggestive
head and neck squamous cell carcinomaOpen Targets
0.00Suggestive
squamous cell lung carcinomaOpen Targets
0.00Suggestive
strokeOpen Targets
0.00Suggestive
male infertilityOpen Targets
0.00Suggestive
malariaOpen Targets
0.00Suggestive
non-small cell lung carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GAPDHProtein interaction100%PHGDHProtein interaction99%ALDOAProtein interaction97%ALDOBProtein interaction97%ALDOCProtein interaction97%ENO1Protein interaction97%
Tissue Expression6 tissues
Liver
100%
Lung
100%
Ovary
100%
Heart
0%
Brain
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PGAM4GAPDHPHGDHALDOAALDOBALDOCENO1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q8N0Y7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.21LoF Tolerant
pLIⓘ
0.02Tolerant
Observed/Expected LoF0.65 [0.37–1.21]
RankingsWhere PGAM4 stands among ~20K protein-coding genes
  • #13,269of 20,598
    Most Researched24
  • #12,778of 17,882
    Most Constrained (LOEUF)1.21
Genes detectedPGAM4
Sources retrieved8 papers
Response time—
📄 Sources
8▼
1
A single nucleotide polymorphism within the novel sex-linked testis-specific retrotransposed PGAM4 gene influences human male fertility.
PMID: 22590500
PLoS One · 2012
1.00
2
MALAT1-regulated gene expression profiling in lung cancer cell lines.
PMID: 37667226
BMC Cancer · 2023
0.88
3
PGAM4 silencing inhibited glycolysis and chemoresistance to temozolomide in glioma cells.
PMID: 36576012
Cell Biol Int · 2023
0.75
4
The PGAM4 gene in non-obstructive azoospermia.
PMID: 23631659
Syst Biol Reprod Med · 2013
0.63
5
Identifying diagnostic markers and establishing prognostic model for lung cancer based on lung cancer-derived exosomal genes.
PMID: 40179422
Cancer Biomark · 2025
0.50