PGK1

Chr X

phosphoglycerate kinase 1

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

NCBI Gene: 5230 ENSG00000102144 UniProt: P00558

Phosphoglycerate kinase 1 catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate in the glycolytic pathway and acts as a polymerase alpha cofactor protein. Mutations cause phosphoglycerate kinase 1 deficiency, which presents with hemolytic anemia and neurological impairment. The condition follows X-linked recessive inheritance and the gene is highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.47

Clinical Summary— PGK1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.

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ClinVar Variants

21 unique Pathogenic / Likely Pathogenic· 169 VUS of 363 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.34Z-score

OE missense 0.92 (0.81–1.06)

144 obs / 155.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.06–0.47)

0≤0.351.4

Missense OE?0.92 (0.81–1.06)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 2 / 13.5Missense obs/exp: 144 / 155.9Syn Z: 0.03

ClinVar Variant Classifications

363 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16

Likely Pathogenic5

VUS169

Likely Benign101

Benign27

Conflicting17

Pathogenic

Likely Pathogenic

169

VUS

101

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	11	5	0	16
Likely Pathogenic	0	4	1	0	5
VUS	2	149	17	1	169
Likely Benign	1	14	47	39	101
Benign	0	5	17	5	27
Conflicting	—				17
Total	3	183	87	45	335

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

View in ClinVar →

61 pathogenic / likely-pathogenic (of 80) ClinVar copy-number / structural variants overlap PGK1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →