Gelatinous drop-like corneal dystrophy

Summary

Gelatinous drop-like corneal dystrophy (MONDO:0008777) is a disease caused by TACSTD2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 1 000 000 (Japan) [Orphanet-validated]
• Causal gene: TACSTD2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 56
• Phenotypes (HPO): 11

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.33	Japan	Validated
Point prevalence	1-9 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0000613	Photophobia	Very frequent (80-99%)
HP:0000622	Blurred vision	Very frequent (80-99%)
HP:0000643	Blepharospasm	Frequent (30-79%)
HP:0007663	Reduced visual acuity	Frequent (30-79%)
HP:0008039	Subepithelial corneal opacities	Frequent (30-79%)
HP:0009926	Epiphora	Frequent (30-79%)
HP:0010637	Conjunctival amyloidosis	Frequent (30-79%)
HP:0011496	Corneal neovascularization	Frequent (30-79%)
HP:0034804	Corneal foreign body sensation	Frequent (30-79%)
HP:0200026	Ocular pain	Frequent (30-79%)
HP:0011493	Central opacification of the cornea	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	gelatinous drop-like corneal dystrophy
Mondo ID	MONDO:0008777
MeSH	C535480
OMIM	204870
Orphanet	98957
DOID	DOID:0060449
ICD-11	1062815669
NCIT	C142805
UMLS	C0339273
MedGen	90939
GARD	0009647
Is cancer (heuristic)	no

Also known as: amyloid corneal dystrophy, Japanese type · amyloidosis corneal · CDGDL · corneal amyloidosis · corneal dystrophy, gelatinous drop-like · corneal dystrophy, lattice type 3 · GDCD · GDLD · gelatinous drop-like corneal dystrophy · lattice corneal dystrophy type 3 · primary familial amyloidosis of the cornea · subepithelial amyloidosis of the cornea

Data availability: 56 ClinVar variants · 5 GenCC gene-disease records · 2 cell lines.

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 › gelatinous drop-like corneal dystrophy

Related subtypes (4): epithelial basement membrane dystrophy, Meesmann corneal dystrophy, Lisch epithelial 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

56 retrieved; paginated sample, class counts are floors:

21 uncertain significance, 16 benign, 10 pathogenic, 4 likely benign, 3 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16182	NM_002353.3(TACSTD2):c.352C>T (p.Gln118Ter)	TACSTD2	Pathogenic	no assertion criteria provided
16183	NM_002353.3(TACSTD2):c.619C>T (p.Gln207Ter)	TACSTD2	Pathogenic	no assertion criteria provided
16184	NM_002353.3(TACSTD2):c.509C>A (p.Ser170Ter)	TACSTD2	Pathogenic	no assertion criteria provided
16185	NM_002353.3(TACSTD2):c.632del (p.Gln211fs)	TACSTD2	Pathogenic	no assertion criteria provided
16186	NM_002353.3(TACSTD2):c.2T>G (p.Met1Arg)	TACSTD2	Pathogenic	no assertion criteria provided
16187	NM_002353.3(TACSTD2):c.355T>A (p.Cys119Ser)	TACSTD2	Pathogenic	no assertion criteria provided
16188	NM_002353.3(TACSTD2):c.772_783delinsT (p.Leu257_Ile258insTer)	TACSTD2	Pathogenic	no assertion criteria provided
16189	NM_002353.3(TACSTD2):c.557T>C (p.Leu186Pro)	TACSTD2	Pathogenic	no assertion criteria provided
1699935	NM_002353.3(TACSTD2):c.653del (p.Asp218fs)	TACSTD2	Pathogenic	criteria provided, single submitter
4082113	NM_002353.3(TACSTD2):c.588C>A (p.Tyr196Ter)	TACSTD2	Pathogenic	criteria provided, single submitter
3248623	NM_002353.3(TACSTD2):c.679G>A (p.Glu227Lys)	TACSTD2	Likely pathogenic	no assertion criteria provided
297771	NM_002353.3(TACSTD2):c.257C>G (p.Ala86Gly)	TACSTD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
715494	NM_002353.3(TACSTD2):c.735C>T (p.Arg245=)	TACSTD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
873846	NM_002353.3(TACSTD2):c.899G>A (p.Arg300Gln)	TACSTD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297751	NM_002353.3(TACSTD2):c.*656T>A	TACSTD2	Uncertain significance	criteria provided, single submitter
297761	NM_002353.3(TACSTD2):c.*94G>A	TACSTD2	Uncertain significance	criteria provided, single submitter
297762	NM_002353.3(TACSTD2):c.*59A>C	TACSTD2	Uncertain significance	criteria provided, single submitter
297766	NM_002353.3(TACSTD2):c.827G>A (p.Gly276Asp)	TACSTD2	Uncertain significance	criteria provided, multiple submitters, no conflicts
297772	NM_002353.3(TACSTD2):c.175G>A (p.Gly59Ser)	TACSTD2	Uncertain significance	criteria provided, multiple submitters, no conflicts
297775	NM_002353.3(TACSTD2):c.-56C>T	TACSTD2	Uncertain significance	criteria provided, single submitter
297776	NM_002353.3(TACSTD2):c.-56C>G	TACSTD2	Uncertain significance	criteria provided, multiple submitters, no conflicts
297777	NM_002353.2(TACSTD2):c.-104C>G	TACSTD2	Uncertain significance	criteria provided, single submitter
297779	NM_002353.2(TACSTD2):c.-269G>C	TACSTD2	Uncertain significance	criteria provided, single submitter
3067889	NM_002353.3(TACSTD2):c.140_148del (p.Asp47_Pro49del)	TACSTD2	Uncertain significance	criteria provided, single submitter
873847	NM_002353.3(TACSTD2):c.720C>A (p.Gly240=)	TACSTD2	Uncertain significance	criteria provided, single submitter
874743	NM_002353.3(TACSTD2):c.*645T>C	TACSTD2	Uncertain significance	criteria provided, single submitter
874796	NM_002353.3(TACSTD2):c.8G>C (p.Arg3Pro)	TACSTD2	Uncertain significance	criteria provided, single submitter
875684	NM_002353.3(TACSTD2):c.*298A>C	TACSTD2	Uncertain significance	criteria provided, single submitter
875685	NM_002353.3(TACSTD2):c.*281A>C	TACSTD2	Uncertain significance	criteria provided, single submitter
875686	NM_002353.3(TACSTD2):c.*236C>G	TACSTD2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
TACSTD2	Definitive	Autosomal recessive	gelatinous drop-like corneal dystrophy	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TACSTD2	Orphanet:98957	Gelatinous drop-like corneal dystrophy

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
TACSTD2	HGNC:11530	ENSG00000184292	P09758	Tumor-associated calcium signal transducer 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TACSTD2	Tumor-associated calcium signal transducer 2	May function as a growth factor receptor.

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)
TACSTD2	Other/Unknown	no		Thyroglobulin_1, Thyroglobulin_1_sf, EpCAM_N

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
palpebral conjunctiva	1
pharyngeal mucosa	1
tongue squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TACSTD2	234	broad	marker	palpebral conjunctiva, tongue squamous epithelium, pharyngeal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TACSTD2	1,378

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TACSTD2	P09758	7

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
negative regulation of branching involved in ureteric bud morphogenesis	1	8426.0×	9e-04	TACSTD2
ureteric bud morphogenesis	1	5617.3×	9e-04	TACSTD2
negative regulation of ruffle assembly	1	2407.4×	0.001	TACSTD2
negative regulation of cell motility	1	1296.3×	0.001	TACSTD2
positive regulation of stem cell differentiation	1	1296.3×	0.001	TACSTD2
negative regulation of substrate adhesion-dependent cell spreading	1	1123.5×	0.001	TACSTD2
negative regulation of epithelial cell migration	1	1053.2×	0.001	TACSTD2
regulation of epithelial cell proliferation	1	936.2×	0.001	TACSTD2
negative regulation of stress fiber assembly	1	581.1×	0.002	TACSTD2
visual perception	1	79.5×	0.013	TACSTD2

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
TACSTD2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	TACSTD2

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)
TACSTD2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.