mucolipidosis type III, alpha/beta
disease diseaseOn this page
Also known as ML 3ML 3 AML 3 alpha/betaML III alpha/betaML3MLIIImucolipidosis 3mucolipidosis IIImucolipidosis type 3 alpha/betamucolipidosis type 3Amucolipidosis type IIIPseudo Hurler Polydystrophypseudo-Hurler polydystrophy
Summary
mucolipidosis type III, alpha/beta (MONDO:0018931) is a disease caused by GNPTAB (GenCC Definitive), with 1 cohort gene and 1 clinical trial.
At a glance
- Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
- Causal gene: GNPTAB (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 1,432
- Phenotypes (HPO): 36
- Clinical trials: 1
Clinical features
Epidemiology
Prevalence records
6 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Annual incidence | 1-9 / 1 000 000 | 0.985 | Europe | Validated |
| Point prevalence | 1-5 / 10 000 | 29.55 | Europe | Validated |
| Annual incidence | <1 / 1 000 000 | 0.08 | Netherlands | Validated |
| Annual incidence | 1-9 / 1 000 000 | 1.68 | Portugal | Validated |
| Point prevalence | 1-9 / 100 000 | 2.4 | Netherlands | Validated |
| Point prevalence | 1-5 / 10 000 | 50.4 | Portugal | Validated |
Signs & symptoms
Clinical features (HPO)
36 HPO clinical features (Orphanet curated; top 36 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000269 | Prominent occiput | Very frequent (80-99%) |
| HP:0000505 | Visual impairment | Very frequent (80-99%) |
| HP:0001387 | Joint stiffness | Very frequent (80-99%) |
| HP:0003264 | Deficiency of N-acetylglucosamine-1-phosphotransferase | Very frequent (80-99%) |
| HP:0003272 | Abnormality of the hip bone | Very frequent (80-99%) |
| HP:0003312 | Abnormal form of the vertebral bodies | Very frequent (80-99%) |
| HP:0004322 | Short stature | Very frequent (80-99%) |
| HP:0004493 | Craniofacial hyperostosis | Very frequent (80-99%) |
| HP:0008818 | Large iliac wings | Very frequent (80-99%) |
| HP:0008821 | Hypoplastic inferior ilia | Very frequent (80-99%) |
| HP:0025261 | Stiff finger | Very frequent (80-99%) |
| HP:0002857 | Genu valgum | Frequent (30-79%) |
| HP:0003307 | Hyperlordosis | Frequent (30-79%) |
| HP:0007957 | Corneal opacity | Frequent (30-79%) |
| HP:0000280 | Coarse facial features | Frequent (30-79%) |
| HP:0000938 | Osteopenia | Frequent (30-79%) |
| HP:0000943 | Dysostosis multiplex | Frequent (30-79%) |
| HP:0001385 | Hip dysplasia | Frequent (30-79%) |
| HP:0001634 | Mitral valve prolapse | Frequent (30-79%) |
| HP:0002650 | Scoliosis | Frequent (30-79%) |
| HP:0002758 | Osteoarthritis | Frequent (30-79%) |
| HP:0009837 | Bullet-shaped distal phalanges of the hand | Frequent (30-79%) |
| HP:0012185 | Constrictive median neuropathy | Frequent (30-79%) |
| HP:0012532 | Chronic pain | Frequent (30-79%) |
| HP:0030680 | Abnormal cardiovascular system morphology | Frequent (30-79%) |
| HP:0034337 | Claw hand deformity | Frequent (30-79%) |
| HP:0100543 | Cognitive impairment | Frequent (30-79%) |
| HP:0000885 | Broad ribs | Occasional (5-29%) |
| HP:0001072 | Thickened skin | Occasional (5-29%) |
| HP:0001653 | Mitral regurgitation | Occasional (5-29%) |
| HP:0001659 | Aortic regurgitation | Occasional (5-29%) |
| HP:0002091 | Restrictive ventilatory defect | Occasional (5-29%) |
| HP:0002176 | Spinal cord compression | Occasional (5-29%) |
| HP:0002515 | Waddling gait | Occasional (5-29%) |
| HP:0004349 | Reduced bone mineral density | Occasional (5-29%) |
| HP:0012378 | Fatigue | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | mucolipidosis type III, alpha/beta |
| Mondo ID | MONDO:0018931 |
| OMIM | 252600 |
| Orphanet | 423461, 577 |
| DOID | DOID:0080071 |
| SNOMED CT | 65764006 |
| UMLS | C0033788 |
| MedGen | 10988 |
| GARD | 0017704 |
| NORD | 1624 |
| Is cancer (heuristic) | no |
Also known as: ML 3 · ML 3 A · ML 3 alpha/beta · ML III alpha/beta · ML3 · MLIII · mucolipidosis 3 · mucolipidosis III · mucolipidosis type 3 alpha/beta · mucolipidosis type 3A · mucolipidosis type III · Pseudo Hurler Polydystrophy · pseudo-Hurler polydystrophy
Data availability: 1,432 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › mucolipidosis › familial mucolipidosis › mucolipidosis type III, alpha/beta
Related subtypes (4): GNPTG-mucolipidosis, mucolipidosis type IV, sialidosis type 2, 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
600 retrieved; paginated sample, class counts are floors:
353 likely benign, 100 uncertain significance, 61 pathogenic, 49 likely pathogenic, 15 pathogenic/likely pathogenic, 12 conflicting classifications of pathogenicity, 5 benign, 5 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1012255 | NM_024312.5(GNPTAB):c.2980_2983del (p.Ala994fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1069206 | NM_024312.5(GNPTAB):c.118-1G>A | GNPTAB | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1071081 | NM_024312.5(GNPTAB):c.1491del (p.Gly498fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1072768 | NM_024312.5(GNPTAB):c.2657_2660del (p.Asp886fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1072782 | NM_024312.5(GNPTAB):c.2423del (p.Leu808fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1072926 | NM_024312.5(GNPTAB):c.2868_2869del (p.Met957fs) | GNPTAB | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1072933 | NM_024312.5(GNPTAB):c.3345del (p.Met1116fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1073529 | NM_024312.5(GNPTAB):c.3300_3301del (p.Lys1100fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1074624 | NM_024312.5(GNPTAB):c.1906del (p.Arg636fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1075110 | NM_024312.5(GNPTAB):c.2737_2738del (p.Gln913fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1075885 | NM_024312.5(GNPTAB):c.178_179del (p.Ile60fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1362626 | NM_024312.5(GNPTAB):c.269del (p.Leu90fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1364183 | NM_024312.5(GNPTAB):c.3100del (p.Ala1034fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1382090 | NM_024312.5(GNPTAB):c.2675del (p.Leu892fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1385807 | NM_024312.5(GNPTAB):c.2334_2338del (p.Ser778fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1388742 | NM_024312.5(GNPTAB):c.3034C>T (p.Gln1012Ter) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1393484 | NM_024312.5(GNPTAB):c.29_32dup (p.Thr12fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1396985 | NM_024312.5(GNPTAB):c.1186G>T (p.Glu396Ter) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1398708 | NM_024312.5(GNPTAB):c.280C>T (p.Gln94Ter) | GNPTAB | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1399558 | NM_024312.5(GNPTAB):c.2654_2655del (p.Thr885fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1416350 | NM_024312.5(GNPTAB):c.88_89del (p.Thr30fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1424471 | NM_024312.5(GNPTAB):c.2303_2306del (p.Lys768fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1429731 | NM_024312.5(GNPTAB):c.1936dup (p.Gln646fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1431816 | NM_024312.5(GNPTAB):c.1503_1521dup (p.Gly508delinsCysLeuLeuLeuTer) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1437885 | NM_024312.5(GNPTAB):c.1122dup (p.Arg375fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1445251 | NM_024312.5(GNPTAB):c.1292T>A (p.Leu431Ter) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1451810 | NM_024312.5(GNPTAB):c.1499del (p.Asn500fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1451897 | NM_024312.5(GNPTAB):c.2923del (p.Glu975fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1452514 | NM_024312.5(GNPTAB):c.2098dup (p.Ile700fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
| 1452854 | NM_024312.5(GNPTAB):c.1871del (p.Glu624fs) | GNPTAB | Pathogenic | criteria provided, single submitter |
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: 1.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01891422 | Not specified | COMPLETED | Longitudinal Studies of the Glycoproteinoses |
Related Atlas pages
- Cohort genes: GNPTAB