POMGNT1

Chr 1

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: 55624 ENSG00000085998 UniProt: Q8WZA1

The encoded protein localizes to the Golgi apparatus and catalyzes O-mannosyl glycosylation by adding N-acetylglucosamine to alpha-linked terminal mannose residues on dystroglycan. Mutations cause autosomal recessive dystroglycanopathies ranging from severe congenital muscular dystrophy with brain and eye anomalies (muscle-eye-brain disease) to milder limb-girdle muscular dystrophy, as well as retinitis pigmentosa. The pathogenic mechanism involves defective glycosylation of alpha-dystroglycan, disrupting its binding to extracellular matrix proteins.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.04

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

269 unique Pathogenic / Likely Pathogenic· 557 VUS of 1608 total submissions

💊

Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — POMGNT1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.90Z-score

OE missense 0.88 (0.81–0.96)

373 obs / 425.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.60–1.04)

0≤0.351.4

Missense OE?0.88 (0.81–0.96)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 36 / 45.6Missense obs/exp: 373 / 425.2Syn Z: -0.24

ClinVar Variant Classifications

1608 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic85

Likely Pathogenic184

VUS557

Likely Benign636

Benign28

Conflicting97

Pathogenic

184

Likely Pathogenic

557

VUS

636

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	68	7	9	1	85
Likely Pathogenic	153	25	6	0	184
VUS	15	460	61	21	557
Likely Benign	0	19	347	270	636
Benign	0	2	24	2	28
Conflicting	—				97
Total	236	513	447	294	1,587

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap POMGNT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →