Lisch epithelial corneal dystrophy

Summary

Lisch epithelial corneal dystrophy (MONDO:0010425) is a disease caused by MCOLN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MCOLN1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 26

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		36	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Lisch epithelial corneal dystrophy
Mondo ID	MONDO:0010425
MeSH	C567588
OMIM	300778, 620763
Orphanet	98955
DOID	DOID:0060450
ICD-11	1571503165
SNOMED CT	724175002
UMLS	C2749050
MedGen	411737
GARD	0016877
Is cancer (heuristic)	no

Also known as: band-shaped and whorled microcystic dystrophy of the corneal epithelium · corneal dystrophy, Lisch epithelial · corneal dystrophy, Lisch epithelial, X-linked dominant · LECD · Lisch epithelial corneal dystrophy

Data availability: 26 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › corneal disorder › corneal dystrophy › epithelial and subepithelial corneal dystrophy › Lisch epithelial corneal dystrophy

Related subtypes (4): epithelial basement membrane dystrophy, Meesmann corneal dystrophy, gelatinous drop-like corneal dystrophy, subepithelial mucinous corneal dystrophy

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

26 retrieved; paginated sample, class counts are floors:

12 pathogenic/likely pathogenic, 7 likely pathogenic, 4 conflicting classifications of pathogenicity, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072635	NM_020533.3(MCOLN1):c.169C>T (p.Arg57Ter)	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074644	NM_020533.3(MCOLN1):c.499C>T (p.Gln167Ter)	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454517	NM_020533.3(MCOLN1):c.1627C>T (p.Gln543Ter)	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1997684	NM_020533.3(MCOLN1):c.1005G>A (p.Trp335Ter)	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208021	NM_020533.3(MCOLN1):c.694A>C (p.Thr232Pro)	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208028	NM_020533.3(MCOLN1):c.1210dup (p.Tyr404fs)	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208029	NM_020533.3(MCOLN1):c.1453_1463dup (p.Ser488fs)	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208030	NM_020533.3(MCOLN1):c.514C>T (p.Arg172Ter)	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208039	NM_020533.3(MCOLN1):c.920del (p.Leu307fs)	MCOLN1	Pathogenic	criteria provided, multiple submitters, no conflicts
3062182	NM_020533.3(MCOLN1):c.576C>A (p.Cys192Ter)	MCOLN1	Pathogenic	criteria provided, single submitter
3584205	NM_020533.3(MCOLN1):c.777+1G>T	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371019	NM_020533.3(MCOLN1):c.984+1G>A	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5131	NM_020533.3(MCOLN1):c.406-2A>G	MCOLN1	Pathogenic	criteria provided, multiple submitters, no conflicts
5135	NM_020533.3(MCOLN1):c.1084G>T (p.Asp362Tyr)	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
554026	NM_020533.3(MCOLN1):c.571+2T>C	MCOLN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3584202	NM_020533.3(MCOLN1):c.31+1_31+2delinsTC	LOC130063376	Likely pathogenic	criteria provided, single submitter
208033	NM_020533.3(MCOLN1):c.1336G>T (p.Val446Leu)	MCOLN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3584203	NM_020533.3(MCOLN1):c.238-1G>C	MCOLN1	Likely pathogenic	criteria provided, single submitter
3584204	NM_020533.3(MCOLN1):c.643dup (p.Ser215fs)	MCOLN1	Likely pathogenic	criteria provided, single submitter
3584206	NM_020533.3(MCOLN1):c.778-2A>G	MCOLN1	Likely pathogenic	criteria provided, single submitter
3584207	NM_020533.3(MCOLN1):c.878-2A>T	MCOLN1	Likely pathogenic	criteria provided, single submitter
3584208	NM_020533.3(MCOLN1):c.1446dup (p.Gln483fs)	MCOLN1	Likely pathogenic	criteria provided, single submitter
283177	NM_020533.3(MCOLN1):c.782C>T (p.Thr261Met)	MCOLN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
727013	NM_020533.3(MCOLN1):c.707G>A (p.Arg236Gln)	MCOLN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
780173	NM_020533.3(MCOLN1):c.305G>A (p.Arg102Gln)	MCOLN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
991186	NM_020533.3(MCOLN1):c.338C>T (p.Ala113Val)	MCOLN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
MCOLN1	Strong	Autosomal dominant	Lisch epithelial corneal dystrophy	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MCOLN1	Orphanet:578	Mucolipidosis type IV

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
MCOLN1	HGNC:13356	ENSG00000090674	Q9GZU1	Mucolipin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MCOLN1	Mucolipin-1	Nonselective cation channel probably playing a role in the regulation of membrane trafficking events and of metal homeostasis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MCOLN1	Other/Unknown	no		PKD1_2_channel, Mucolipin, ML1_ELD

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
right adrenal gland	1
right adrenal gland cortex	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MCOLN1	255	ubiquitous	marker	spleen, right adrenal gland cortex, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MCOLN1	1,412

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MCOLN1	Q9GZU1	25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
calcium ion export	1	4213.0×	0.002	MCOLN1
positive regulation of lysosome organization	1	4213.0×	0.002	MCOLN1
iron ion transmembrane transport	1	2407.4×	0.002	MCOLN1
cellular response to pH	1	2106.5×	0.002	MCOLN1
transferrin transport	1	1532.0×	0.002	MCOLN1
phagosome maturation	1	1203.7×	0.002	MCOLN1
monoatomic cation transport	1	766.0×	0.003	MCOLN1
intracellular zinc ion homeostasis	1	481.5×	0.004	MCOLN1
autophagosome maturation	1	351.1×	0.004	MCOLN1
release of sequestered calcium ion into cytosol	1	343.9×	0.004	MCOLN1
protein homotetramerization	1	237.3×	0.005	MCOLN1
calcium ion transmembrane transport	1	210.7×	0.005	MCOLN1
cellular response to calcium ion	1	200.6×	0.005	MCOLN1
adaptive immune response	1	84.3×	0.012	MCOLN1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MCOLN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MCOLN1	9	Binding:9

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MCOLN1

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)
MCOLN1	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.