mucolipidosis type II

Summary

mucolipidosis type II (MONDO:0009650) is a disease caused by GNPTAB (GenCC Definitive), with 1 cohort gene and 3 clinical trials. Top therapeutic interventions include alemtuzumab, clofarabine, and cyclophosphamide anhydrous.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: GNPTAB (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 1,587
• Phenotypes (HPO): 63
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

6 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Validated
Prevalence at birth	1-9 / 1 000 000	0.34	Europe	Validated
Prevalence at birth	1-9 / 1 000 000	0.81	Portugal	Validated
Prevalence at birth	1-9 / 1 000 000	0.16	Netherlands	Validated
Prevalence at birth	1-5 / 10 000	16.2	Specific population	Validated
Prevalence at birth	<1 / 1 000 000	0.05	Sweden	Validated

Signs & symptoms

Clinical features (HPO)

63 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000212	Gingival overgrowth	Very frequent (80-99%)
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0001072	Thickened skin	Very frequent (80-99%)
HP:0001270	Motor delay	Very frequent (80-99%)
HP:0001537	Umbilical hernia	Very frequent (80-99%)
HP:0001538	Protuberant abdomen	Very frequent (80-99%)
HP:0001609	Hoarse voice	Very frequent (80-99%)
HP:0002474	Expressive language delay	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0006596	Restricted chest movement	Very frequent (80-99%)
HP:0008897	Postnatal growth retardation	Very frequent (80-99%)
HP:0030680	Abnormal cardiovascular system morphology	Very frequent (80-99%)
HP:0031650	Abnormal atrioventricular valve physiology	Very frequent (80-99%)
HP:0000388	Otitis media	Frequent (30-79%)
HP:0000405	Conductive hearing impairment	Frequent (30-79%)
HP:0000774	Narrow chest	Frequent (30-79%)
HP:0001363	Craniosynostosis	Frequent (30-79%)
HP:0001376	Limitation of joint mobility	Frequent (30-79%)
HP:0001633	Abnormal mitral valve morphology	Frequent (30-79%)
HP:0001653	Mitral regurgitation	Frequent (30-79%)
HP:0002091	Restrictive ventilatory defect	Frequent (30-79%)
HP:0002465	Poor speech	Frequent (30-79%)
HP:0002540	Inability to walk	Frequent (30-79%)
HP:0002870	Obstructive sleep apnea	Frequent (30-79%)
HP:0005280	Depressed nasal bridge	Frequent (30-79%)
HP:0010444	Pulmonary insufficiency	Frequent (30-79%)
HP:0012368	Flat face	Frequent (30-79%)
HP:0045027	Abnormality of the thoracic cavity	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000286	Epicanthus	Occasional (5-29%)
HP:0000586	Shallow orbits	Occasional (5-29%)
HP:0001433	Hepatosplenomegaly	Occasional (5-29%)
HP:0001540	Diastasis recti	Occasional (5-29%)
HP:0001562	Oligohydramnios	Occasional (5-29%)
HP:0001638	Cardiomyopathy	Occasional (5-29%)
HP:0001646	Abnormal aortic valve morphology	Occasional (5-29%)
HP:0001655	Patent foramen ovale	Occasional (5-29%)
HP:0001659	Aortic regurgitation	Occasional (5-29%)
HP:0001712	Left ventricular hypertrophy	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0001824	Weight loss	Occasional (5-29%)
HP:0002205	Recurrent respiratory infections	Occasional (5-29%)
HP:0002213	Fine hair	Occasional (5-29%)
HP:0002808	Kyphosis	Occasional (5-29%)
HP:0002827	Hip dislocation	Occasional (5-29%)
HP:0003273	Hip contracture	Occasional (5-29%)
HP:0005487	Prominent metopic ridge	Occasional (5-29%)
HP:0006203	Decreased movement range in interphalangeal joints	Occasional (5-29%)
HP:0006248	Limited wrist movement	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	mucolipidosis type II
Mondo ID	MONDO:0009650
MeSH	C538602
OMIM	252500
Orphanet	576
DOID	DOID:0080070
NCIT	C61270
SNOMED CT	70199000
UMLS	C2673377
MedGen	435914
GARD	0006749
NORD	1279
Is cancer (heuristic)	no

Also known as: GNPTA · I Cell Disease · I cell disease · I-cell disease · inclusion cell disease · Leroy disease · ML 2 · ML disorder type 2 · mucolipidosis type II · mucolipidosis type II alpha/beta · N-acetylglucosamine 1-phosphotransferase deficiency · N-acetylglucosamine 1phosphotransferase deficiency

Data availability: 1,587 ClinVar variants · 4 GenCC gene-disease records · 12 cell lines.

Disease family

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

Related subtypes (1): 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

600 retrieved; paginated sample, class counts are floors:

349 likely benign, 102 uncertain significance, 62 pathogenic, 49 likely pathogenic, 15 pathogenic/likely pathogenic, 13 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
1252037	NM_024312.5(GNPTAB):c.3653del (p.Thr1218fs)	GNPTAB	Pathogenic	no assertion criteria provided
1323027	NM_024312.5(GNPTAB):c.1567T>C (p.Cys523Arg)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
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

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: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	2
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00176917	PHASE2	COMPLETED	Stem Cell Transplantation for Hurler
NCT00383448	PHASE2	COMPLETED	HSCT for High Risk Inherited Inborn Errors
NCT00005900	Not specified	UNKNOWN	Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALEMTUZUMAB	4	1
CLOFARABINE	4	1
CYCLOPHOSPHAMIDE ANHYDROUS	4	1
HYDROXYUREA	4	1