Mucolipidosis

Summary

Mucolipidosis (MONDO:0019248) is a disease caused by GNPTAB (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: GNPTAB (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 52

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mucolipidosis
Mondo ID	MONDO:0019248
MeSH	D009081
Orphanet	79212
DOID	DOID:0080488
ICD-11	714623911
NCIT	C61267
SNOMED CT	70528007
UMLS	C0026697
MedGen	7731
GARD	0018975
Is cancer (heuristic)	no

Data availability: 52 ClinVar variants · 1 GenCC gene-disease record · 11 cell lines.

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

Related subtypes (56): Neu-Laxova syndrome, inborn mitochondrial metabolism disorder, Ehlers-Danlos syndrome, spondylodysplastic type, MGAT2-congenital disorder of glycosylation, ALDH18A1-related de Barsy syndrome, classic homocystinuria, Larsen-like syndrome, B3GAT3 type, Nijmegen breakage syndrome, Peters plus syndrome, Wiedemann-Rautenstrauch syndrome, 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency, SHORT syndrome, mucosulfatidosis, CHIME syndrome, creatine transporter deficiency, multiple congenital anomalies-hypotonia-seizures syndrome 2, SLC35A2-congenital disorder of glycosylation, SSR4-congenital disorder of glycosylation, Fabry disease, occipital horn syndrome, Ehlers-Danlos syndrome, musculocontractural type, temtamy preaxial brachydactyly syndrome, B4GALT1-congenital disorder of glycosylation, AICA-ribosiduria, COG7-congenital disorder of glycosylation, permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome, Al-Gazali syndrome, COG1-congenital disorder of glycosylation, RFT1-congenital disorder of glycosylation, Nijmegen breakage syndrome-like disorder, multiple congenital anomalies-hypotonia-seizures syndrome 1, multiple congenital anomalies-hypotonia-seizures syndrome 3, autism spectrum disorder - epilepsy - arthrogryposis syndrome, cutis laxa, autosomal dominant 3, SLC39A8-CDG, transketolase deficiency, mucopolysaccharidosis-plus syndrome, Cockayne syndrome, pontocerebellar hypoplasia type 1, mandibuloacral dysplasia, hyperphosphatasia-intellectual disability syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, CADDS, XYLT1-congenital disorder of glycosylation, hypophosphatasia, sterol biosynthesis disorder, mucopolysaccharidosis, oligosaccharidosis, encephalopathy due to sulfite oxidase deficiency, Fanconi anemia, autosomal recessive cutis laxa type 2, Zellweger spectrum disorders, pseudohypoparathyroidism, developmental and epileptic encephalopathy, 77, glycosylphosphatidylinositol biosynthesis defect 15, progressive hypotonia-intellectual disability-facial dysmorphism syndrome due to FYVE-defective RBSN

Subtypes (2): familial mucolipidosis, GNPTAB-mucolipidosis

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

52 retrieved; paginated sample, class counts are floors:

27 pathogenic, 13 likely pathogenic, 12 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069206	NM_024312.5(GNPTAB):c.118-1G>A	GNPTAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1416350	NM_024312.5(GNPTAB):c.88_89del (p.Thr30fs)	GNPTAB	Pathogenic	criteria provided, single submitter
194787	NM_024312.5(GNPTAB):c.3326dup (p.Asn1109fs)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
194986	NM_024312.5(GNPTAB):c.3560_3561del (p.Glu1187fs)	GNPTAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
197858	NM_024312.5(GNPTAB):c.377T>A (p.Leu126Ter)	GNPTAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2501249	NM_024312.5(GNPTAB):c.2174T>A (p.Leu725Ter)	GNPTAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2582829	NM_024312.5(GNPTAB):c.1523del (p.Gly508fs)	GNPTAB	Pathogenic	no assertion criteria provided
2582835	NM_024312.5(GNPTAB):c.77G>A (p.Gly26Asp)	GNPTAB	Pathogenic	no assertion criteria provided
2582836	NM_024312.5(GNPTAB):c.196C>T (p.Gln66Ter)	GNPTAB	Pathogenic	no assertion criteria provided
2582837	NM_024312.5(GNPTAB):c.673C>T (p.Gln225Ter)	GNPTAB	Pathogenic	no assertion criteria provided
2582838	NM_024312.5(GNPTAB):c.2455G>T (p.Glu819Ter)	GNPTAB	Pathogenic	no assertion criteria provided
2764	NM_024312.5(GNPTAB):c.3565C>T (p.Arg1189Ter)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
2768	NM_024312.5(GNPTAB):c.2715+1G>A	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
2772	NM_024312.5(GNPTAB):c.3335+1G>A	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
38429	NM_024312.5(GNPTAB):c.3613C>T (p.Arg1205Ter)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
38432	NM_024312.5(GNPTAB):c.616_619del (p.Thr206fs)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
3895878	NM_024312.5(GNPTAB):c.336del (p.Asn114fs)	GNPTAB	Pathogenic	criteria provided, single submitter
39021	NM_024312.5(GNPTAB):c.1090C>T (p.Arg364Ter)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
39030	NM_024312.5(GNPTAB):c.1331dup (p.Ser445fs)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
39034	NM_024312.5(GNPTAB):c.1399del (p.Asp467fs)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
39040	NM_024312.5(GNPTAB):c.1759C>T (p.Arg587Ter)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
39041	NM_024312.5(GNPTAB):c.1959_1962del (p.Ser654fs)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
39055	NM_024312.5(GNPTAB):c.2550_2554del (p.Lys850fs)	GNPTAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39057	NM_024312.5(GNPTAB):c.2693dup (p.Tyr899fs)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
39058	NM_024312.5(GNPTAB):c.2693del (p.Lys898fs)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
39059	NM_024312.5(GNPTAB):c.2715+2T>G	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
39065	NM_024312.5(GNPTAB):c.3091C>T (p.Arg1031Ter)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
39073	NM_024312.5(GNPTAB):c.344_345del (p.Thr115fs)	GNPTAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39074	NM_024312.5(GNPTAB):c.3443_3446del (p.Val1148fs)	GNPTAB	Pathogenic	criteria provided, multiple submitters, no conflicts
39087	NM_024312.5(GNPTAB):c.749dup (p.Asn250fs)	GNPTAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 4 · 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
MCOLN1	Orphanet:578	Mucolipidosis type IV
GNPTG	Orphanet:423470	Mucolipidosis type III gamma

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GNPTAB	HGNC:29670	ENSG00000111670	Q3T906	N-acetylglucosamine-1-phosphotransferase subunits alpha/beta	gencc,clinvar
MCOLN1	HGNC:13356	ENSG00000090674	Q9GZU1	Mucolipin-1	clinvar
GNPTG	HGNC:23026	ENSG00000090581	Q9UJJ9	N-acetylglucosamine-1-phosphotransferase subunit gamma	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.
MCOLN1	Mucolipin-1	Nonselective cation channel probably playing a role in the regulation of membrane trafficking events and of metal homeostasis.
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.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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)	2	8.0×	0.039
Other/Unknown	1	0.6×	0.914

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
MCOLN1	Other/Unknown	no		PKD1_2_channel, Mucolipin, ML1_ELD
GNPTG	Enzyme (other)	yes	2.7.8.17	Man6P_isomerase_rcpt-bd_dom_sf, DMAP1-bd, OS9-like_dom

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right adrenal gland	2
right adrenal gland cortex	2
endothelial cell	1
sural nerve	1
tibia	1
spleen	1
left adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNPTAB	290	ubiquitous	marker	tibia, endothelial cell, sural nerve
MCOLN1	255	ubiquitous	marker	spleen, right adrenal gland cortex, right adrenal gland
GNPTG	255	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNPTAB	1,518
MCOLN1	1,412
GNPTG	1,199

Intra-cohort edges

A	B	Sources
GNPTAB	GNPTG	biogrid_interaction, intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MCOLN1	Q9GZU1	25
GNPTAB	Q3T906	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GNPTG	Q9UJJ9	80.63

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 3 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
TRP channels	1	407.9×	0.006	MCOLN1
Transferrin endocytosis and recycling	1	368.4×	0.006	MCOLN1
Iron uptake and transport	1	346.1×	0.006	MCOLN1
Stimuli-sensing channels	1	135.9×	0.011	MCOLN1
Ion channel transport	1	96.0×	0.013	MCOLN1
Transport of small molecules	1	25.1×	0.040	MCOLN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 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	2	5617.3×	4e-07	GNPTAB, GNPTG
carbohydrate phosphorylation	2	1404.3×	5e-06	GNPTAB, GNPTG
calcium ion export	1	1404.3×	0.003	MCOLN1
positive regulation of lysosome organization	1	1404.3×	0.003	MCOLN1
secretion of lysosomal enzymes	1	1123.5×	0.003	GNPTAB
iron ion transmembrane transport	1	802.5×	0.004	MCOLN1
cellular response to pH	1	702.2×	0.004	MCOLN1
transferrin transport	1	510.7×	0.004	MCOLN1
phagosome maturation	1	401.2×	0.005	MCOLN1
monoatomic cation transport	1	255.3×	0.007	MCOLN1
intracellular zinc ion homeostasis	1	160.5×	0.010	MCOLN1
autophagosome maturation	1	117.0×	0.012	MCOLN1
release of sequestered calcium ion into cytosol	1	114.6×	0.012	MCOLN1
lysosome organization	1	102.1×	0.013	GNPTAB
protein homotetramerization	1	79.1×	0.015	MCOLN1
calcium ion transmembrane transport	1	70.2×	0.016	MCOLN1
cellular response to calcium ion	1	66.9×	0.016	MCOLN1
adaptive immune response	1	28.1×	0.035	MCOLN1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
MCOLN1	0	0
GNPTG	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MCOLN1	9	Binding:9

Cohort enzymes (BRENDA EC)

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

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	GNPTG
E	Difficult family or no structure, no drug	1	MCOLN1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GNPTAB	0	—
MCOLN1	9	—
GNPTG	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.