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…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.84

LOEUF

—

Mechanism

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

Background carrier burden — how many people carry a rare variant somewhere in GDPGP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

479 rare PASS variants

Rare truncating (LoF)

1 in 950

65 rare PASS variants

Rare synonymous (reference)

1 in 180

231 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GDPGP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 2,100
South Asian	~43k	1 in 90	1 in 2,700
Remaining (unassigned)	~30k	1 in 75	1 in 1,700
European (Finnish)	~27k	1 in 680	≈ 1 in 8,900
Admixed American	~22k	1 in 130	1 in 2,000
African / African American	~21k	1 in 73	1 in 1,600
East Asian	~20k	1 in 75	1 in 550
Ashkenazi Jewish	~13k	1 in 290	none seen
Middle Eastern	~2,884	1 in 91	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓