POMT2

Chr 14AR

protein O-mannosyltransferase 2

Also known as: LGMD2N, LGMDR14, MDDGA2, MDDGB2, MDDGC2

NCBI Gene: 29954ENSG00000009830UniProt: Q9UKY4

The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT1 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).[provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2MIM #613150
AR
Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 2MIM #613156
AR
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2MIM #613158
AR
1364
ClinVar variants
94
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— POMT2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
94 Pathogenic / Likely Pathogenic· 251 VUS of 1364 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.
0.80LOEUF
pLI 0.000
Z-score 2.65
OE 0.57 (0.41–0.80)
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.
0.08Z-score
OE missense 0.99 (0.91–1.07)
412 obs / 416.4 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.0.57 (0.41–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.91–1.07)
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.0.97
0≤1.21.6
LoF obs/exp: 25 / 43.9Missense obs/exp: 412 / 416.4Syn Z: 0.29

ClinVar Variant Classifications

1364 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic55
VUS251
Likely Benign310
Benign19
Conflicting8
39
Pathogenic
55
Likely Pathogenic
251
VUS
310
Likely Benign
19
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
0
17
0
39
Likely Pathogenic
36
7
12
0
55
VUS
1
195
52
3
251
Likely Benign
0
2
163
145
310
Benign
0
0
18
1
19
Conflicting
—8
Total59204262149682

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

View in ClinVar →

Protein Context — Lollipop Plot

POMT2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

POMT2-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, 2

MIM #613150

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 2

MIM #613156

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2

MIM #613158

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
Novel POMT2 variants associated with limb-girdle muscular dystrophy R14: genetic, histological and functional studies.
Yang G et al.·Orphanet J Rare Dis
2025Functional
Unique clinical presentations and follow-up outcomes from experience with congenital disorders of glycosylation: PMM2-PGM1-DPAGT1-MPI-POMT2-B3GALNT2-DPM1-SRD5A3-CDG.
Yoldas Celik M et al.·J Pediatr Endocrinol Metab
2023Natural history
The twisted abdomen phenotype of Drosophila POMT1 and POMT2 mutants coincides with their heterophilic protein O-mannosyltransferase activity.
Ichimiya T et al.·J Biol Chem
2004
Long-term clinical and MRI follow-up in two POMT2-related limb girdle muscular dystrophy (LGMDR14) patients.
Panicucci C et al.·Brain Dev
2023Case report
Cystic kidneys in fetal Walker-Warburg syndrome with POMT2 mutation: Intrafamilial phenotypic variability in four siblings and review of literature.
Nabhan MM et al.·Am J Med Genet A
2017Review
Novel cardiovascular findings in association with a POMT2 mutation: three siblings with α-dystroglycanopathy.
Martinez HR et al.·Eur J Hum Genet
2014
Limb girdle muscular dystrophy due to mutations in POMT2.
Østergaard ST et al.·J Neurol Neurosurg Psychiatry
2018
POMT1 and POMT2 gene mutations result in 2 cases of alpha-dystroglycanopathy.
Gan S et al.·Zhong Nan Da Xue Xue Bao Yi Xue Ban
2021Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A POMT2 missense substitution contributes to hypoxia adaptation in hibernating mammals.
Zhang J et al.·Mol Biol Evol
2026🔓 Open Access
Deletion of POMT2 in Zebrafish Causes Degeneration of Photoreceptors.
Liu Y et al.·Int J Mol Sci
2022🔓 Open AccessFunctional
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