GDPGP1

Chr 15

GDP-D-glucose phosphorylase 1

Also known as: C15orf58, VTC2

NCBI Gene: 390637 ENSG00000183208 UniProt: Q6ZNW5 OMIM: 619240

The protein functions as a GDP-D-glucose phosphorylase that regulates cellular GDP-D-glucose levels and plays a key role in neuronal stress resistance by modulating neuronal glycogen levels and maintaining glucose balance. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in early infancy with seizures and severe developmental delay. The gene shows tolerance to loss-of-function variants (LOEUF 1.84), suggesting the pathogenic variants may have more complex effects on protein function.

OMIM ResearchSummary from RefSeq, UniProt

Enables GDP-D-glucose phosphorylase activity. Involved in glucose metabolic process. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.84

Clinical Summary— GDPGP1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

67 VUS of 72 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.84LOEUF

pLI 0.000

Z-score -0.63

OE 1.23 (0.76–1.84)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.18Z-score

OE missense 0.97 (0.87–1.08)

221 obs / 228.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.23 (0.76–1.84)

0≤0.351.4

Missense OE?0.97 (0.87–1.08)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 11 / 9.0Missense obs/exp: 221 / 228.5Syn Z: -0.88

ClinVar Variant Classifications

72 submitted variants in ClinVar

ClinVar

Classification Summary

VUS67

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	67	67
Likely Benign	4	4
Benign	0	0
Total	71	71

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

View in ClinVar →

41 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap GDPGP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →