GNPTG

Chr 16AR

N-acetylglucosamine-1-phosphate transferase subunit gamma

NCBI Gene: 84572ENSG00000090581UniProt: Q9UJJ9

Non-catalytic subunit of the N-acetylglucosamine-1-phosphotransferase complex, an enzyme that catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus. Binds and presents the high mannose glycans of the acceptor to the catalytic alpha and beta subunits (GNPTAB). Enhances the rate of N-acetylglucosamine-1-phosphate transfer to the oligosaccharides of acid hydrolase acceptors

Primary Disease Associations & Inheritance

Mucolipidosis III gammaMIM #252605
AR
UniProtMucolipidosis type III complementation group C
1065
ClinVar variants
77
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GNPTG
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
77 Pathogenic / Likely Pathogenic· 141 VUS of 1065 total submissions

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.
1.22LOEUF
pLI 0.000
Z-score 0.85
OE 0.79 (0.53–1.22)
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.
-2.06Z-score
OE missense 1.44 (1.30–1.60)
253 obs / 176.0 exp
Tolerant

Tolerant to missense variation

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 (0.53–1.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.44 (1.30–1.60)
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.1.70
0≤1.21.6
LoF obs/exp: 15 / 19.0Missense obs/exp: 253 / 176.0Syn Z: -4.86

ClinVar Variant Classifications

1065 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic30
VUS141
Likely Benign274
Conflicting1
47
Pathogenic
30
Likely Pathogenic
141
VUS
274
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
26
0
21
0
47
Likely Pathogenic
24
0
6
0
30
VUS
8
107
23
3
141
Likely Benign
0
2
169
103
274
Benign
0
0
0
0
0
Conflicting
—1
Total58109219106493

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

View in ClinVar →

Protein Context — Lollipop Plot

GNPTG · protein map & ClinVar variants

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

Gene2Phenotype Curations

GNPTG-related mucolipidosis type III complementation group C

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkinSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mucolipidosis III gamma

MIM #252605

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome.
Si S et al.·Genome Med
2024
Clinical, radiological and computational studies on two novel GNPTG variants causing mucolipidosis III gamma phenotypes with varying severity.
Doğan M et al.·Mol Biol Rep
2021
Pathogenic variants in GNPTAB and GNPTG encoding distinct subunits of GlcNAc-1-phosphotransferase differentially impact bone resorption in patients with mucolipidosis type II and III.
Di Lorenzo G et al.·Genet Med
2021Cohort
Mucolipidosis type II and III: clinical spectrum, genetic landscape, and longitudinal outcomes in a pediatric cohort with six novel mutations.
Erdem F et al.·J Pediatr Endocrinol Metab
2025Cohort
The lysosomal storage disorders mucolipidosis type II, type III alpha/beta, and type III gamma: Update on GNPTAB and GNPTG mutations.
Velho RV et al.·Hum Mutat
2019
Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III - identification of eight novel mutations.
Encarnação M et al.·Clin Genet
2009Cohort
Variants in GNPTAB, GNPTG and NAGPA genes are associated with stutterers.
Kazemi N et al.·Gene
2018
[Clinical and genetic analysis of mucolipidosis in 3 pedigrees and literature review].
Liu N et al.·Zhonghua Er Ke Za Zhi
2019Review
Mucolipidosis type II and type III: a systematic review of 843 published cases.
Dogterom EJ et al.·Genet Med
2021Review
Dilated cardiomyopathy in mucolipidosis type 2.
Carboni E et al.·J Biol Regul Homeost Agents
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Evaluation of recurrent GNPTAB, GNPTG, and NAGPA variants associated with stuttering.
Gunasekaran ND et al.·Adv Genet (Hoboken)
2021🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools