POGLUT1

Chr 3ADAR

protein O-glucosyltransferase 1

NCBI Gene: 56983ENSG00000163389UniProt: Q8NBL1

Dual specificity glycosyltransferase that catalyzes the transfer of glucose and xylose from UDP-glucose and UDP-xylose, respectively, to a serine residue found in the consensus sequence of C-X-S-X-P-C (PubMed:21081508, PubMed:21490058, PubMed:21949356, PubMed:27807076, PubMed:28775322). Specifically targets extracellular EGF repeats of protein such as CRB2, F7, F9 and NOTCH2 (PubMed:21081508, PubMed:21490058, PubMed:21949356, PubMed:27807076, PubMed:28775322). Acts as a positive regulator of Notch signaling by mediating O-glucosylation of Notch, leading to regulate muscle development (PubMed:27807076). Notch glucosylation does not affect Notch ligand binding (PubMed:21490058). Required during early development to promote gastrulation: acts by mediating O-glucosylation of CRB2, which is required for CRB2 localization to the cell membrane (By similarity)

Primary Disease Associations & Inheritance

Dowling-Degos disease 4MIM #615696
AD
Muscular dystrophy, limb-girdle, autosomal recessive 21MIM #617232
AR
360
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— POGLUT1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
360 total variants — no pathogenic classifications of 360 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.89LOEUF
pLI 0.000
Z-score 2.00
OE 0.60 (0.41–0.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.15Z-score
OE missense 0.78 (0.68–0.89)
164 obs / 211.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.60 (0.41–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.68–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 17 / 28.6Missense obs/exp: 164 / 211.0Syn Z: -0.83

ClinVar Variant Classifications

360 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

POGLUT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

POGLUT1-related Dowling-Degos disease

strong
ADUndeterminedAbsent Gene Product
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dowling-Degos disease 4

MIM #615696

Molecular basis of disorder known

Autosomal dominant

Muscular dystrophy, limb-girdle, autosomal recessive 21

MIM #617232

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness.
Töpf A et al.·Genet Med
2020Cohort
Disseminated papular variant of Dowling-Degos disease: Histopathological features in POGLUT1 mutation.
Papadopoulou K et al.·J Dtsch Dermatol Ges
2022Review
Beneath the surface: delineating the subtypes of Dowling-Degos disease.
Kumar S et al.·Br J Dermatol
2025Review
The Notch signaling pathway in skeletal muscle health and disease.
Vargas-Franco D et al.·Muscle Nerve
2022Review
POGLUT1 biallelic mutations cause myopathy with reduced satellite cells, α-dystroglycan hypoglycosylation and a distinctive radiological pattern.
Servián-Morilla E et al.·Acta Neuropathol
2020
Potential Drug Targets for Diabetic Retinopathy Identified Through Mendelian Randomization Analysis.
Liu H et al.·Transl Vis Sci Technol
2024
Mutations in POGLUT1, encoding protein O-glucosyltransferase 1, cause autosomal-dominant Dowling-Degos disease.
Basmanav FB et al.·Am J Hum Genet
2014
Protein O-Glucosyltransferase 1 (POGLUT1) Promotes Mouse Gastrulation through Modification of the Apical Polarity Protein CRUMBS2.
Ramkumar N et al.·PLoS Genet
2015Functional
Sex-specific associations of Notch signaling with chronic HBV infection: a study from Taiwan Biobank.
Jen IA et al.·Biol Sex Differ
2024
Identification of a novel genetic locus associated with immune-mediated thrombotic thrombocytopenic purpura.
Stubbs MJ et al.·Haematologica
2022Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools