UAP1

Chr 1

UDP-N-acetylglucosamine pyrophosphorylase 1

Also known as: AGX, AGX1, AGX2, SPAG2

NCBI Gene: 6675 ENSG00000117143 UniProt: Q16222 OMIM: 602862

UAP1 encodes UDP-N-acetylglucosamine pyrophosphorylase 1, which catalyzes the final step in UDP-N-acetylglucosamine biosynthesis and also pyrophosphorylates IRF3 to promote antiviral interferon responses. Mutations cause autosomal recessive intellectual disability with seizures and spasticity, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.54), suggesting some tolerance to haploinsufficiency.

OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity and protein serine pyrophosphorylase activity. Involved in antiviral innate immune response and positive regulation of type I interferon production. Located in nucleoplasm and plasma membrane. Is active in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.54

Clinical Summary— UAP1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

51 VUS of 76 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.54LOEUF

pLI 0.023

Z-score 3.37

OE 0.30 (0.17–0.54)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.02Z-score

OE missense 0.83 (0.74–0.92)

226 obs / 273.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.17–0.54)

0≤0.351.4

Missense OE?0.83 (0.74–0.92)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 8 / 26.8Missense obs/exp: 226 / 273.7Syn Z: -1.48

ClinVar Variant Classifications

76 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

Likely Benign5

Benign5

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	51	0	0	51
Likely Benign	2	0	3	5
Benign	2	1	2	5
Total	55	1	5	61

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap UAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →