POMT1

Chr 9AR

protein O-mannosyltransferase 1

Also known as: LGMD2K, LGMDR11, MDDGA1, MDDGB1, MDDGC1, RT

NCBI Gene: 10585ENSG00000130714UniProt: Q9Y6A1

The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT2 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS) and limb-girdle muscular dystrophy type 2K (LGMD2K). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1MIM #236670
AR
Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 1MIM #613155
AR
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1MIM #609308
AR
576
ClinVar variants
112
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— POMT1
🧬
Gene-Disease Validity (ClinGen)
myopathy caused by variation in POMT1 · 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
112 Pathogenic / Likely Pathogenic· 196 VUS of 576 total submissions
💊
Clinical Trials
1 active or recruiting trial — 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.
0.93LOEUF
pLI 0.000
Z-score 1.92
OE 0.70 (0.53–0.93)
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.
0.62Z-score
OE missense 0.92 (0.84–1.00)
385 obs / 420.6 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.0.70 (0.53–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.84–1.00)
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.1.09
0≤1.21.6
LoF obs/exp: 33 / 47.3Missense obs/exp: 385 / 420.6Syn Z: -0.94

ClinVar Variant Classifications

576 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic62
VUS196
Likely Benign260
Benign4
Conflicting4
50
Pathogenic
62
Likely Pathogenic
196
VUS
260
Likely Benign
4
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
29
3
18
0
50
Likely Pathogenic
44
6
11
1
62
VUS
3
167
21
5
196
Likely Benign
0
18
135
107
260
Benign
1
1
2
0
4
Conflicting
—4
Total77195187113576

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

View in ClinVar →

Protein Context — Lollipop Plot

POMT1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

POMT1-related muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
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, 1

MIM #236670

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 1

MIM #613155

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1

MIM #609308

Molecular basis of disorder known

Autosomal recessive
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
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
Molecular genetics of the POMT1-related muscular dystrophy-dystroglycanopathies.
Hu P et al.·Mutat Res Rev Mutat Res
2018Review
Correlation of enzyme activity and clinical phenotype in POMT1-associated dystroglycanopathies.
Lommel M et al.·Neurology
2010Case report
Analysis of phenotype, enzyme activity and genotype of Chinese patients with POMT1 mutation.
Yang H et al.·J Hum Genet
2016Cohort
Clinical long-time course, novel mutations and genotype-phenotype correlation in a cohort of 27 families with POMT1-related disorders.
Geis T et al.·Orphanet J Rare Dis
2019Cohort
Glyc-O-genetics of Walker-Warburg syndrome.
van Reeuwijk J et al.·Clin Genet
2005Review
[Recent Advances in α-dystroglycanopathy].
Kuga A et al.·Brain Nerve
2011Review
Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy-dystroglycanopathy C1.
Hu P et al.·J Cell Mol Med
2017
Expanding the clinical spectrum of POMT1 phenotype.
D'Amico A et al.·Neurology
2006
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
Muscular Dystrophy

Clinical Trial Readiness for the Dystroglycanopathies

RECRUITING
NCT00313677Katherine MathewsStarted 2006-04

External Resources

Links to major genomics databases and tools