UGP2

Chr 2AR

UDP-glucose pyrophosphorylase 2

Also known as: DEE83, EIEE83, SVUGP2, UDPG, UDPGP, UDPGP2, UGP1, UGPP1

NCBI Gene: 7360 ENSG00000169764 UniProt: Q16851 OMIM: 191760

UTP-glucose-1-phosphate uridylyltransferase catalyzes the conversion of glucose-1-phosphate to UDP-glucose, a crucial precursor for glycogen synthesis in liver and muscle. Mutations cause developmental and epileptic encephalopathy 83, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern where heterozygous carriers are unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The enzyme encoded by this gene is an important intermediary in mammalian carbohydrate interconversions. It transfers a glucose moiety from glucose-1-phosphate to MgUTP and forms UDP-glucose and MgPPi. In liver and muscle tissue, UDP-glucose is a direct precursor of glycogen; in lactating mammary gland it is converted to UDP-galactose which is then converted to lactose. The eukaryotic enzyme has no significant sequence similarity to the prokaryotic enzyme. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 83MIM #618744

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Developmental and epileptic encephalopathy 83; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.12

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.12LOEUF

pLI 0.000

Z-score 1.15

OE 0.73 (0.48–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.93Z-score

OE missense 0.67 (0.59–0.76)

180 obs / 269.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.73 (0.48–1.12)

0≤0.351.4

Missense OE?0.67 (0.59–0.76)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 15 / 20.7Missense obs/exp: 180 / 269.4Syn Z: -0.60

Background carrier burden — how many people carry a rare variant somewhere in UGP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

524 rare PASS variants

Rare truncating (LoF)

1 in 960

153 rare PASS variants

Rare synonymous (reference)

1 in 140

261 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UGP2. 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 190	1 in 1,100
South Asian	~43k	1 in 130	1 in 610
Remaining (unassigned)	~30k	1 in 190	1 in 730
European (Finnish)	~27k	1 in 590	1 in 2,000
Admixed American	~22k	1 in 160	1 in 760
African / African American	~21k	1 in 110	1 in 450
East Asian	~20k	1 in 390	1 in 960
Ashkenazi Jewish	~13k	1 in 630	1 in 930
Middle Eastern	~2,884	1 in 220	none seen

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 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓