POMGNT1

Chr 1AR

protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-)

Also known as: GNTI.2, GnT I.2, LGMD2O, LGMDR15, MEB, MGAT1.2, RP76, gnT-I.2

NCBI Gene: 55624ENSG00000085998UniProt: Q8WZA1

This gene encodes a type II transmembrane protein that resides in the Golgi apparatus. It participates in O-mannosyl glycosylation and is specific for alpha linked terminal mannose. Mutations in this gene may be associated with muscle-eye-brain disease and several congenital muscular dystrophies. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Feb 2014]

Primary Disease Associations & Inheritance

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3MIM #253280
AR
Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3MIM #613151
AR
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3MIM #613157
AR
Retinitis pigmentosa 76MIM #617123
AR
479
ClinVar variants
73
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— POMGNT1
🧬
Gene-Disease Validity (ClinGen)
myopathy caused by variation in POMGNT1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 162 VUS of 479 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

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.
1.04LOEUF
pLI 0.000
Z-score 1.32
OE 0.79 (0.60–1.04)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.90Z-score
OE missense 0.88 (0.81–0.96)
373 obs / 425.2 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.0.79 (0.60–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.81–0.96)
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.1.02
0≤1.21.6
LoF obs/exp: 36 / 45.6Missense obs/exp: 373 / 425.2Syn Z: -0.24

ClinVar Variant Classifications

479 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic48
VUS162
Likely Benign239
Benign2
Conflicting3
25
Pathogenic
48
Likely Pathogenic
162
VUS
239
Likely Benign
2
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
0
10
0
25
Likely Pathogenic
29
2
17
0
48
VUS
4
132
16
10
162
Likely Benign
0
5
157
77
239
Benign
0
0
2
0
2
Conflicting
—3
Total4813920287479

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

View in ClinVar →

Protein Context — Lollipop Plot

POMGNT1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

POMGNT1-related muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

POMGNT1-related muscular dystrophy-dystroglycanopathy congenital with intellectual developmental disorder, type B, 3

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

POMGNT1-related muscular dystrophy-dystroglycanopathy limb-girdle

definitive
ARUndeterminedUncertain
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3

MIM #253280

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3

MIM #613151

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3

MIM #613157

Molecular basis of disorder known

Autosomal recessive

Retinitis pigmentosa 76

MIM #617123

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — POMGNT1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic variations and clinical spectrum of dystroglycanopathy in a large cohort of Chinese patients.
Song D et al.·Clin Genet
2021Cohort
Role of glycosyltransferase PomGnT1 in glioblastoma progression.
Lan J et al.·Neuro Oncol
2015
[Recent Advances in α-dystroglycanopathy].
Kuga A et al.·Brain Nerve
2011Review
Glycosyltransferase POMGNT1 deficiency strengthens N-cadherin-mediated cell-cell adhesion.
Noor SI et al.·J Biol Chem
2021
Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy.
Mohan S et al.·Ann Clin Transl Neurol
2024
Variable Ophthalmologic Phenotypes Associated with Biallelic Loss-of-Function Variants in POMGNT1.
Ziccardi L et al.·Int J Mol Sci
2025Case report
Clinical, radiological, and genetic survey of patients with muscle-eye-brain disease caused by mutations in POMGNT1.
Yiş U et al.·Pediatr Neurol
2014Cohort
Malformations of Core M3 on α-Dystroglycan Are the Leading Cause of Dystroglycanopathies.
Sharaf-Eldin W·J Mol Neurosci
2025Review
Muscular dystrophies due to glycosylation defects.
Muntoni F et al.·Neurotherapeutics
2008Review
Novel POMGnT1 mutations cause muscle-eye-brain disease in Chinese patients.
Jiao H et al.·Mol Genet Genomics
2013Cohort
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
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10
Congenital Muscular Dystrophy With ITGA7 (Integrin Alpha-7) DeficiencyAlpha-Dystroglycanopathy (Congenital Muscular Dystrophy and Abnormal Glycosylation of Dystroglycan With Severe Epilepsy)Alpha-Dystroglycanopathy (Congenital Muscular Dystrophy With Fatty Liver and Infantile-onset Cataract Caused by TRAPPC11 Mutations)

Congenital Muscle Disease Study of Patient and Family Reported Medical Information

RECRUITING
NCT01403402Cure CMDStarted 2009-09
Muscular Dystrophy

Clinical Trial Readiness for the Dystroglycanopathies

RECRUITING
NCT00313677Katherine MathewsStarted 2006-04

External Resources

Links to major genomics databases and tools