GNPTG-mucolipidosis
disease diseaseOn this page
Also known as ML 3 gammaML III gammamucolipidosis type 3 gammamucolipidosis type III gamma
Summary
GNPTG-mucolipidosis (MONDO:0009652) is a disease caused by GNPTG (GenCC Definitive), with 2 cohort genes.
At a glance
- Prevalence: Unknown (Worldwide) [Orphanet-validated]
- Causal gene: GNPTG (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 288
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | GNPTG-mucolipidosis |
| Mondo ID | MONDO:0009652 |
| MeSH | C565367 |
| OMIM | 252605 |
| Orphanet | 423470 |
| DOID | DOID:0080678 |
| NCIT | C129978 |
| UMLS | C1854896 |
| MedGen | 340743 |
| GARD | 0017705 |
| Is cancer (heuristic) | no |
Also known as: GNPTG-mucolipidosis · ML 3 gamma · ML III gamma · mucolipidosis type 3 gamma · mucolipidosis type III gamma
Data availability: 288 ClinVar variants · 6 GenCC gene-disease records · 2 cell lines.
Disease family
Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › mucolipidosis › familial mucolipidosis › GNPTG-mucolipidosis
Related subtypes (4): mucolipidosis type IV, sialidosis type 2, mucolipidosis type III, alpha/beta, sialidosis type 1
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
288 retrieved; paginated sample, class counts are floors:
113 uncertain significance, 45 likely pathogenic, 42 likely benign, 31 conflicting classifications of pathogenicity, 26 pathogenic, 19 pathogenic/likely pathogenic, 5 benign/likely benign, 4 not provided, 3 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1069744 | NM_032520.5(GNPTG):c.739A>T (p.Lys247Ter) | GNPTG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1072459 | NM_032520.5(GNPTG):c.750_753del (p.Lys250fs) | GNPTG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1342959 | NM_032520.5(GNPTG):c.190_193dup (p.Phe65fs) | GNPTG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1354910 | NM_032520.5(GNPTG):c.203C>A (p.Ser68Ter) | GNPTG | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1450957 | NM_032520.5(GNPTG):c.607C>T (p.Gln203Ter) | GNPTG | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1526169 | NM_032520.5(GNPTG):c.638_639del (p.Leu212_Phe213insTer) | GNPTG | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1685858 | NM_032520.5(GNPTG):c.735C>A (p.Cys245Ter) | GNPTG | Pathogenic | criteria provided, single submitter |
| 2080282 | NM_032520.5(GNPTG):c.108del (p.Phe36fs) | GNPTG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2119911 | NM_032520.5(GNPTG):c.701del (p.Pro234fs) | GNPTG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 21713 | NM_032520.5(GNPTG):c.196C>T (p.Arg66Ter) | GNPTG | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 21714 | NM_032520.5(GNPTG):c.318-1G>C | GNPTG | Pathogenic | criteria provided, single submitter |
| 21715 | NM_032520.5(GNPTG):c.344ACA[1] (p.Asn116del) | GNPTG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 21719 | NM_032520.5(GNPTG):c.609+28_610-16del | GNPTG | Pathogenic | no assertion criteria provided |
| 21720 | NM_032520.5(GNPTG):c.610-1G>T | GNPTG | Pathogenic | no assertion criteria provided |
| 21721 | NM_032520.5(GNPTG):c.610-2A>G | GNPTG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 21723 | NM_032520.5(GNPTG):c.639del (p.Phe213fs) | GNPTG | Pathogenic | no assertion criteria provided |
| 2444155 | NM_032520.5(GNPTG):c.610-1G>A | GNPTG | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2731676 | NM_032520.5(GNPTG):c.384_385dup (p.Cys129fs) | GNPTG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2795 | NM_032520.4(GNPTG):c.611delG | GNPTG | Pathogenic | no assertion criteria provided |
| 2796 | NM_032520.5(GNPTG):c.640_667del (p.Glu214fs) | GNPTG | Pathogenic | no assertion criteria provided |
| 2797 | NM_032520.5(GNPTG):c.333G>A (p.Trp111Ter) | GNPTG | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2799 | NM_032520.5(GNPTG):c.316G>A (p.Gly106Ser) | GNPTG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3004658 | NM_032520.5(GNPTG):c.461_465del (p.Pro154fs) | GNPTG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 30685 | NM_032520.5(GNPTG):c.527-10G>A | GNPTG | Pathogenic | no assertion criteria provided |
| 3578452 | NM_032520.5(GNPTG):c.514dup (p.His172fs) | GNPTG | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 39080 | NM_032520.5(GNPTG):c.445del (p.Ala149fs) | GNPTG | Pathogenic | no assertion criteria provided |
| 437454 | NM_032520.4(GNPTG):c.499dup (p.Leu167Profs) | GNPTG | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 453175 | NM_032520.5(GNPTG):c.318-1G>A | GNPTG | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 4807182 | NM_032520.5(GNPTG):c.559C>T (p.Gln187Ter) | GNPTG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4816330 | NM_032520.5(GNPTG):c.13del (p.Leu5fs) | GNPTG | Pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 6 · Orphanet: 1 · 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 |
|---|---|---|---|---|
| GNPTG | Definitive | Autosomal recessive | GNPTG-mucolipidosis | 6 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| GNPTG | Orphanet:423470 | Mucolipidosis type III gamma |
Cohort genes → proteins
2 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| GNPTG | HGNC:23026 | ENSG00000090581 | Q9UJJ9 | N-acetylglucosamine-1-phosphotransferase subunit gamma | gencc,clinvar |
| UNKL | HGNC:14184 | ENSG00000059145 | Q9H9P5 | Putative E3 ubiquitin-protein ligase UNKL | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| GNPTG | N-acetylglucosamine-1-phosphotransferase subunit gamma | 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. |
| UNKL | Putative E3 ubiquitin-protein ligase UNKL | May participate in a protein complex showing an E3 ligase activity regulated by RAC1. |
Protein-family classification
Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5
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 | 6.0× | 0.228 |
| Transcription factor | 1 | 4.1× | 0.228 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| GNPTG | Enzyme (other) | yes | 2.7.8.17 | Man6P_isomerase_rcpt-bd_dom_sf, DMAP1-bd, OS9-like_dom |
| UNKL | Transcription factor | no | Znf_CCCH, Znf_RING, Znf_RING/FYVE/PHD |
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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| left adrenal gland | 1 |
| right adrenal gland | 1 |
| right adrenal gland cortex | 1 |
| oocyte | 1 |
| secondary oocyte | 1 |
| sural nerve | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| GNPTG | 255 | ubiquitous | marker | right adrenal gland cortex, right adrenal gland, left adrenal gland |
| UNKL | 259 | ubiquitous | yes | secondary oocyte, oocyte, sural nerve |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| GNPTG | 1,199 |
| UNKL | 675 |
Structural data
PDB: 0 · AlphaFold-only: 2 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| GNPTG | Q9UJJ9 | 80.63 |
| UNKL | Q9H9P5 | 67.86 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).
Pathways 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.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Antigen processing: Ubiquitination & Proteasome degradation | 1 | 37.2× | 0.027 | UNKL |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 | 4213.0× | 7e-04 | GNPTG |
| carbohydrate phosphorylation | 1 | 1053.2× | 0.001 | GNPTG |
| protein ubiquitination | 1 | 20.7× | 0.048 | UNKL |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 0 of 2 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 |
|---|---|---|
| GNPTG | 0 | 0 |
| UNKL | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| GNPTG | 2.7.8.17 | UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase |
Pharmacogenomics
Cohort genes with a PharmGKB record: 2; 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 | 0 | |
| D | Druggable family + AlphaFold only, no drug | 1 | GNPTG |
| E | Difficult family or no structure, no drug | 1 | UNKL |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| GNPTG | 0 | — |
| UNKL | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.