PGK2

Chr 6

phosphoglycerate kinase 2

Also known as: HEL-S-272, PGKB, PGKPS, dJ417L20.2

NCBI Gene: 5232ENSG00000170950UniProt: P07205

This gene is intronless, arose via retrotransposition of the phosphoglycerate kinase 1 gene, and is expressed specifically in the testis. Initially assumed to be a pseudogene, the encoded protein is actually a functional phosphoglycerate kinase that catalyzes the reversible conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate, during the Embden-Meyerhof-Parnas pathway of glycolysis, in the later stages of spermatogenesis.[provided by RefSeq, May 2010]

83
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PGK2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 75 VUS of 83 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.61LOEUF
pLI 0.000
Z-score 0.24
OE 0.91 (0.53–1.61)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.92Z-score
OE missense 1.18 (1.06–1.30)
257 obs / 218.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.91 (0.53–1.61)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.18 (1.06–1.30)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.24
0≤1.21.6
LoF obs/exp: 8 / 8.8Missense obs/exp: 257 / 218.7Syn Z: -1.68

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic3
VUS75
5
Pathogenic
3
Likely Pathogenic
75
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
3
0
3
VUS
0
69
6
0
75
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total06914083

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PGK2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men.
Fietz D et al.·Front Endocrinol (Lausanne)
2024
METTL5 deficiency induces oligoasthenoteratozoospermia via impaired 18S rRNA m(6)A methylation in humans and mice.
Zhang M et al.·Mol Ther
2025
Characteristics of testis-specific phosphoglycerate kinase 2 and its association with human sperm quality.
Liu XX et al.·Hum Reprod
2016
A cytoplasmic variant of the KH-type splicing regulatory protein serves as a decay-promoting factor for phosphoglycerate kinase 2 mRNA in murine male germ cells.
Xu M et al.·Nucleic Acids Res
2008
Effects of Intermittent Hypoxia on Expression of Glucose Metabolism Genes in MCF7 Breast Cancer Cell Line.
Jarrar Y et al.·Curr Cancer Drug Targets
2020
Comparative proteomic study between human normal motility sperm and idiopathic asthenozoospermia.
Shen S et al.·World J Urol
2013
A new variant of phosphoglycerate kinase deficiency (p.I371K) with multiple tissue involvement: molecular and functional characterization.
Fermo E et al.·Mol Genet Metab
2012Case report
An in silico analysis of human sperm genes associated with asthenozoospermia and its implication in male infertility.
Liu XX et al.·Medicine (Baltimore)
2018
Significant expression levels of transgenic PPP1CC2 in testis and sperm are required to overcome the male infertility phenotype of Ppp1cc null mice.
Sinha N et al.·PLoS One
2012
Three de novo losses and one insertion within a pericentric inversion of chromosome 6 in a patient with complete absence of expressive speech and reduced pain perception.
Poot M et al.·Eur J Med Genet
2009Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Seminal plasma PGK2 serves as a predictive biomarker for post-varicocelectomy sperm motility improvement in varicocele subjects.
Yang C et al.·Transl Androl Urol
2025🔓 Open Access
Evaluation of PGK2 and ACR proteins in seminal plasma: suggestion of potential new biomarkers for prediction of sperm retrieval in non-obstructive azoospermia patients.
Ghanami Gashti N et al.·Hum Fertil (Camb)
2023Cohort
The Germ Cell-Specific Markers ZPBP2 and PGK2 in Testicular Biopsies Can Predict the Presence as well as the Quality of Sperm in Non-obstructive Azoospermia Patients.
Ghanami Gashti N et al.·Reprod Sci
2021Cohort
Esculetin Inhibits Cancer Cell Glycolysis by Binding Tumor PGK2, GPD2, and GPI.
Wu ST et al.·Front Pharmacol
2020🔓 Open Access
Species-specific expression of phosphoglycerate kinase 2 (PGK2) in the developing porcine testis.
Park HJ et al.·Theriogenology
2018
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools