GNPTAB

Chr 12

N-acetylglucosamine-1-phosphate transferase subunits alpha and beta

Also known as: GNPTA, ICD

This gene encodes two of three subunit types of the membrane-bound enzyme N-acetylglucosamine-1-phosphotransferase, a heterohexameric complex composed of two alpha, two beta, and two gamma subunits. The encoded protein is proteolytically cleaved at the Lys928-Asp929 bond to yield mature alpha and beta polypeptides while the gamma subunits are the product of a distinct gene (GeneID 84572). In the Golgi apparatus, the heterohexameric complex catalyzes the first step in the synthesis of mannose 6-phosphate recognition markers on certain oligosaccharides of newly synthesized lysosomal enzymes. These recognition markers are essential for appropriate trafficking of lysosomal enzymes. Mutations in this gene have been associated with both mucolipidosis II and mucolipidosis IIIA.[provided by RefSeq, May 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMucolipidosis type II
UniProtMucolipidosis type III complementation group A

Clinical highlights

Gene-disease validity (ClinGen)
GNPTAB-mucolipidosis · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
27
Pubs (1 yr)
P/LP submissions
P/LP missense
0.82
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — GNPTAB
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

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.82LOEUF
pLI 0.000
Z-score 2.71
OE 0.63 (0.490.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.19Z-score
OE missense 0.87 (0.810.93)
572 obs / 657.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.63 (0.490.82)
00.351.4
Missense OE?0.87 (0.810.93)
00.61.4
Synonymous OE?1.06
01.21.6
LoF obs/exp: 39 / 62.0Missense obs/exp: 572 / 657.7Syn Z: -0.70

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GNPTAB · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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