GNPTAB-mucolipidosis

Summary

GNPTAB-mucolipidosis (MONDO:0100122) is a disease caused by GNPTAB (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GNPTAB (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	GNPTAB-mucolipidosis
Mondo ID	MONDO:0100122
GARD	0026054
Is cancer (heuristic)	no

Also known as: GNPTAB-related disorder · UDP-N-acetylglucosamine-1-phosphotransferase subunit alpha/beta deficiency

Data availability: 4 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › mucolipidosis › GNPTAB-mucolipidosis

Related subtypes (1): familial mucolipidosis

Subtypes (2): mucolipidosis type II, mucolipidosis type III, alpha/beta

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2925502	NM_024312.5(GNPTAB):c.2269_2273del (p.Glu757fs)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
39061	NM_024312.5(GNPTAB):c.2866C>T (p.His956Tyr)	GNPTAB	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4081698	NM_024312.5(GNPTAB):c.118-1G>C	GNPTAB	Likely pathogenic	criteria provided, single submitter
2175778	NM_024312.5(GNPTAB):c.3431C>G (p.Pro1144Arg)	GNPTAB	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GNPTAB	Definitive	Autosomal recessive	mucolipidosis type II	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GNPTAB	Orphanet:423461	Mucolipidosis type III alpha/beta
GNPTAB	Orphanet:576	Mucolipidosis type II

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GNPTAB	HGNC:29670	ENSG00000111670	Q3T906	N-acetylglucosamine-1-phosphotransferase subunits alpha/beta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNPTAB	N-acetylglucosamine-1-phosphotransferase subunits alpha/beta	Catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GNPTAB	Enzyme (other)	yes	2.7.8.17	Notch_dom, EF_hand_dom, DMAP1-bd

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endothelial cell	1
sural nerve	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNPTAB	290	ubiquitous	marker	tibia, endothelial cell, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNPTAB	1,518

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNPTAB	Q3T906	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
N-glycan processing to lysosome	1	8426.0×	5e-04	GNPTAB
secretion of lysosomal enzymes	1	3370.4×	6e-04	GNPTAB
carbohydrate phosphorylation	1	2106.5×	6e-04	GNPTAB
lysosome organization	1	306.4×	0.003	GNPTAB

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GNPTAB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GNPTAB	2.7.8.17	UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	GNPTAB
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GNPTAB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.