PGK1

Chr XXLR

phosphoglycerate kinase 1

Also known as: HEL-S-68p, MIG10, PGKA

NCBI Gene: 5230ENSG00000102144UniProt: P00558

The protein encoded by this gene is a glycolytic enzyme that catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate. The encoded protein may also act as a cofactor for polymerase alpha. Additionally, this protein is secreted by tumor cells where it participates in angiogenesis by functioning to reduce disulfide bonds in the serine protease, plasmin, which consequently leads to the release of the tumor blood vessel inhibitor angiostatin. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Deficiency of the enzyme is associated with a wide range of clinical phenotypes hemolytic anemia and neurological impairment. Pseudogenes of this gene have been defined on chromosomes 19, 21 and the X chromosome. [provided by RefSeq, Jan 2014]

Primary Disease Associations & Inheritance

Phosphoglycerate kinase 1 deficiencyMIM #300653
XLR
407
ClinVar variants
74
Pathogenic / LP
0.77
pLI score
0
Active trials
Clinical Summary— PGK1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
74 Pathogenic / Likely Pathogenic· 188 VUS of 407 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.47LOEUF
pLI 0.765
Z-score 2.91
OE 0.15 (0.06–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
0.34Z-score
OE missense 0.92 (0.81–1.06)
144 obs / 155.9 exp
Tolerant

Mild missense constraint

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.0.15 (0.06–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.81–1.06)
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.1.00
0≤1.21.6
LoF obs/exp: 2 / 13.5Missense obs/exp: 144 / 155.9Syn Z: 0.03

ClinVar Variant Classifications

407 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic68
Likely Pathogenic6
VUS188
Likely Benign101
Benign27
Conflicting17
68
Pathogenic
6
Likely Pathogenic
188
VUS
101
Likely Benign
27
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
11
57
0
68
Likely Pathogenic
0
4
2
0
6
VUS
2
146
39
1
188
Likely Benign
1
14
47
39
101
Benign
0
5
17
5
27
Conflicting
—17
Total318016245407

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

View in ClinVar →

Protein Context — Lollipop Plot

PGK1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PGK1-related phosphoglycerate kinase 1 deficiency

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Phosphoglycerate kinase 1 deficiency

MIM #300653

Molecular basis of disorder known

X-linked recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrative proteogenomic characterization of early esophageal cancer.
Li L et al.·Nat Commun
2023
Integrated proteogenomic characterization of urothelial carcinoma of the bladder.
Xu N et al.·J Hematol Oncol
2022
Novel PGK1 determines SKP2-dependent AR stability and reprograms granular cell glucose metabolism facilitating ovulation dysfunction.
Liu X et al.·EBioMedicine
2020
Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases.
Cai R et al.·J Clin Invest
2019Functional
Localisation of PGK1 determines metabolic phenotype to balance metastasis and proliferation in patients with SMAD4-negative pancreatic cancer.
Liang C et al.·Gut
2020Review
PGK deficiency.
Beutler E·Br J Haematol
2007Review
TRIM50 inhibits glycolysis and the malignant progression of gastric cancer by ubiquitinating PGK1.
Gu C et al.·Int J Biol Sci
2024
Inhibition of PGK1 ameliorates acute kidney injury through inactivating the PKM2/ALOX12/ferroptosis pathway in a study with male mice.
Zhu XX et al.·Nat Commun
2025
OXCT1 promotes triple negative breast cancer immune escape via modulating succinylation modification of PGK1.
Zhang H et al.·Commun Biol
2025
A novel glycolysis-related gene signature for predicting prognosis and immunotherapy efficacy in breast cancer.
Huang R et al.·Front Immunol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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