TACSTD2

Summary

TACSTD2 (tumor associated calcium signal transducer 2, HGNC:11530) is a protein-coding gene on chromosome 1p32.1, encoding Tumor-associated calcium signal transducer 2 (P09758). May function as a growth factor receptor.

This intronless gene encodes a carcinoma-associated antigen. This antigen is a cell surface receptor that transduces calcium signals. Mutations of this gene have been associated with gelatinous drop-like corneal dystrophy.

Source: NCBI Gene 4070 — RefSeq curated summary.

At a glance

• Gene–disease (curated): gelatinous drop-like corneal dystrophy (Definitive, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 119 total — 10 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 15
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_002353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11530
Approved symbol	TACSTD2
Name	tumor associated calcium signal transducer 2
Location	1p32.1
Locus type	gene with protein product
Status	Approved
Aliases	TROP2, GA733-1, EGP-1
Ensembl gene	ENSG00000184292
Ensembl biotype	protein_coding
OMIM	137290
Entrez	4070

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000371225

RefSeq mRNA: 1 — MANE Select: NM_002353 NM_002353

CCDS: CCDS609

Canonical transcript exons

ENST00000371225 — 1 exons

Exon	Start	End
ENSE00001454677	58575433	58577252

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 99.89.

FANTOM5 (CAGE): breadth broad, TPM avg 80.3263 / max 3388.5931, expressed in 628 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12566	80.3263	628

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	99.89	gold quality
tongue squamous epithelium	UBERON:0006919	99.87	gold quality
pharyngeal mucosa	UBERON:0000355	99.86	gold quality
bronchial epithelial cell	CL:0002328	99.85	gold quality
nasal cavity epithelium	UBERON:0005384	99.85	gold quality
oral cavity	UBERON:0000167	99.84	gold quality
amniotic fluid	UBERON:0000173	99.84	gold quality
gingiva	UBERON:0001828	99.84	gold quality
gingival epithelium	UBERON:0001949	99.84	gold quality
squamous epithelium	UBERON:0006914	99.84	gold quality
esophagus squamous epithelium	UBERON:0006920	99.84	gold quality
epithelium of bronchus	UBERON:0002031	99.81	gold quality
upper leg skin	UBERON:0004262	99.81	gold quality
bronchus	UBERON:0002185	99.80	gold quality
cervix squamous epithelium	UBERON:0006922	99.80	gold quality
penis	UBERON:0000989	99.75	gold quality
epithelium of nasopharynx	UBERON:0001951	99.75	gold quality
parotid gland	UBERON:0001831	99.74	gold quality
mammalian vulva	UBERON:0000997	99.73	gold quality
body of tongue	UBERON:0011876	99.68	gold quality
lower esophagus mucosa	UBERON:0035834	99.68	gold quality
cervix epithelium	UBERON:0004801	99.66	gold quality
tongue	UBERON:0001723	99.64	gold quality
nasal cavity mucosa	UBERON:0001826	99.64	gold quality
trachea	UBERON:0003126	99.63	gold quality
nipple	UBERON:0002030	99.58	gold quality
superior surface of tongue	UBERON:0007371	99.58	gold quality
skin of hip	UBERON:0001554	99.57	gold quality
upper arm skin	UBERON:0004263	99.57	gold quality
seminal vesicle	UBERON:0000998	99.56	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	17233.78
E-HCAD-13	yes	7081.77
E-MTAB-8142	yes	5348.59
E-HCAD-38	yes	4262.64
E-HCAD-1	yes	3603.01
E-MTAB-8221	yes	3301.75
E-GEOD-130473	yes	2252.56
E-MTAB-10287	yes	1683.10
E-HCAD-10	yes	1397.70
E-CURD-126	yes	1271.56
E-GEOD-114530	yes	1127.39
E-GEOD-124472	yes	1108.58
E-MTAB-6308	yes	909.45
E-MTAB-8530	yes	840.37
E-MTAB-6653	yes	708.99

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

22 targeting TACSTD2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-5094	98.63	67.11	1062
HSA-MIR-4535	97.27	65.17	469
HSA-MIR-550B-2-5P	96.56	64.61	646
HSA-MIR-5704	94.82	67.46	448
HSA-MIR-933	93.25	68.68	76

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The Q118X mutation of the M1S1 gene can produce either a gelatinous drop-like region or band-shaped opacities. (PMID:12036680)
• Allelic and locus heterogeneity in autosomal recessive gelatinous drop-like corneal dystrophy. Seven novel mutations (M1R, 8-bp ins., Q118 E, V194 E, C119 S, 870delC, and 1117delA) were identified in six families and two unrelated individuals. (PMID:12107443)
• A novel mutation of M1S1 gene found in a Vietnamese patient with gelatinous droplike corneal dystrophy. (PMID:12614764)
• Because the compound heterozygote mutations Q118X and Y184C cosegregated with the phenotype, they are likely the cause of GDLD (gelatinous droplike corneal dystrophy) in this patient. (PMID:15013888)
• The affected members had compound heterozygous mutations consisting of a nonsense change at codon 84 (K84X) and a missense mutation resulting in a substitution of arginine for cysteine at codon 108 (C108R). (PMID:15295654)
• The results confirm that the missense mutation L186P in the TACSTD2 gene is also responsible for the GDLD (gelatinous droplike dystrophy) phenotype. (PMID:15652848)
• abnormal transcription of TACSTD2 and S100A2 are thought to be unique molecular markers of the preinvasive stage of lung adenocarcinoma (PMID:16232198)
• TROP2 mRNA and protein were overexpressed in colorectal cancer cells, and high TROP2 expression status correlated with liver metastasis and poor prognosis (PMID:16707602)
• Newly identified mutation is predicted to generate shortened protein product, thereby completely altering COOH-terminal region and deleting transmembrane domain, required for anchoring at cell membranes and phosphatidylinosyol2-binding site. (PMID:17167402)
• study reports two novel mutations in two gelatinous drop-like corneal dystrophy families and expands the spectrum of mutations in TACSTD2 gene that may cause pathological corneal amyloidosis (PMID:17653040)
• This is the first report, to our knowledge, of a homozygous mutation (L186P) in the M1S1 gene found in a Turkish patient. (PMID:17721311)
• It is concluded that Gelatinous Drop-like Corneal Dystrophy (GDLD) in the pedigree is probably not caused by mutations in TACSTD2, supporting evidence for the existence of at least one other locus for GDLD. (PMID:17768381)
• Detection of GA733 mRNA by qualitative RT-PCR is highly specific for diagnosis of malignant pleural and peritoneal effusions. (PMID:17878632)
• Although mutations in TACSTD2 among Iranian patients with GDLD were heterogeneous, E227K was found to be a common mutation. It is suggested that E227K may be a founder mutation in this population (PMID:17898270)
• TROP2 overexpression is an independent prognostic marker in patients with oral squamous cell carcinoma. (PMID:18084248)
• Trop-2 is an oncogene that has potential as a therapeutic target in colon cancer. (PMID:18281513)
• TROP2 could be a novel prognostic biomarker for pancreatic cancer. (PMID:18813308)
• The chimeric mRNA is a bicistronic transcript of post transcriptional origin that independently translates the Cyclin D1 and Trop-2 proteins in cancer cells. (PMID:18829570)
• Trop2 identifies a subpopulation of murine and human prostate basal cells with stem cell characteristics.( (PMID:19088204)
• Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer. (PMID:19421758)
• TROP2 is a differentially expressed gene between left-sided and right-sided colon cancer, and high expression is closely related to factors indicating poor prognosis. (PMID:19434540)
• The newly identified mutation expands the spectrum of mutations in TACSTD2 that may cause pathological corneal amyloidosis. (PMID:19693293)
• Trop-2 protein overexpression correlates with an aggressive malignant phenotype and may constitute a novel prognostic factor for epithelial ovarian cancer (PMID:20060709)
• Novel TACSTD2 C119Y mutation leading to amino acid substitution was identified in two affected siblings. Protein modeling studies revealed an exposed cysteine residue. (PMID:20454699)
• TROP2 overexpression and lymph node metastasis were independent prognostic markers in pulmonary adenocarcinoma (PMID:20473768)
• loss of function of the TACSTD2 gene impairs epithelial barrier function through decreased expression and altered subcellular localization of tight junction-related proteins in Gelatinous drop-like dystrophy corneas (PMID:20651236)
• Study also provides the first indication of a molecular signaling pathway activated by Trop2 which has important implications for cancer cell growth and survival. (PMID:20858281)
• Genetic analysis revealed that all the patients possessed a homozygous Q118X mutation in TACSTD2, a major founder mutation in Japanese gelatinous drop-like corneal dystrophy. (PMID:21052915)
• Trop-2 was highly expressed in uterine serous carcinoma at mRNA and protein levels (PMID:21246534)
• The expression of Trop-2 is correlated with the development and malignancy of pancreatic cancer. (PMID:21418992)
• Two novel mutations of TACSTD2 are found in three Japanese gelatinous drop-like corneal dystrophy families with their aberrant subcellular localization. (PMID:21541270)
• In human and mouse, Trop2 is highly expressed at both the transcript and protein levels on several essential normal tissues. (PMID:21551320)
• TROP2 (TACSTD2), an EpCAM-like molecule, is a specific marker for TGF-beta1-dependent human epidermal Langerhans cells (PMID:21677668)
• Trop-2 is overexpressed in a proportion of human uterine (UMMT) and ovarian (OMMT) carcinosarcoma. (PMID:22075385)
• TACSTD2 expression was inversely correlated with methylation (P=0.016), and both measures were associated with fat mass (expression, P=0.049; methylation, P=0.037) (PMID:22190649)
• Our data support a model where above-baseline expression of wild-type Trop-2 is a key driver of human cancer growth. (PMID:22349828)
• our data demonstrate that the transmembrane receptor Trop-2 is a regulator of PrCa cell adhesion to fibronectin through activation of the beta(1) integrin-RACK1-FAK-Src signaling axis (PMID:22378065)
• Inactivation of TROP2 due to loss of heterozygosity or by DNA methylation may play an important role in lung cancer tumourigenicity through losing its suppressive effect on IGF-1R signalling and tumour growth. (PMID:22419550)
• Network hubs and interacting partners are co-expressed with Trop-2 in primary human tumours, supporting a role of this signalling network in cancer growth. (PMID:22562244)
• TROP2 gene expression can be used as an independent prognostic indicator for squamous cell carcinoma of the larynx. (PMID:22987366)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	epcam	ENSDARG00000040534
mus_musculus	Tacstd2	ENSMUSG00000051397
rattus_norvegicus	Tacstd2	ENSRNOG00000078917

Paralogs (1): EPCAM (ENSG00000119888)

Protein

Protein identifiers

Tumor-associated calcium signal transducer 2 — P09758 (reviewed: P09758)

Alternative names: Cell surface glycoprotein Trop-2, Membrane component chromosome 1 surface marker 1, Pancreatic carcinoma marker protein GA733-1

All UniProt accessions (1): P09758

UniProt curated annotations — full annotation on UniProt →

Function. May function as a growth factor receptor.

Subcellular location. Membrane.

Tissue specificity. Placenta, pancreatic carcinoma cell lines.

Post-translational modifications. The N-terminus is blocked.

Disease relevance. Corneal dystrophy, gelatinous drop-like (GDLD) [MIM:204870] A form of lattice corneal dystrophy, a class of inherited stromal amyloidoses characterized by pathognomonic branching lattice figures in the cornea. GDLD is an autosomal recessive disorder characterized by severe corneal amyloidosis leading to blindness. Clinical manifestations, which appear in the first decade of life, include blurred vision, photophobia, and foreign-body sensation. By the third decade, raised, yellowish-gray, gelatinous masses severely impair visual acuity. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the EPCAM family.

RefSeq proteins (1): NP_002344* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000716	Thyroglobulin_1	Domain
IPR036857	Thyroglobulin_1_sf	Homologous_superfamily
IPR041630	EpCAM_N	Domain
IPR043406	EPCAM/Trop-2	Family
IPR049420	EPCAM-Trop-2_C	Domain

Pfam: PF00086, PF18635, PF21283

UniProt features (37 total): strand 11, helix 7, glycosylation site 4, disulfide bond 3, sequence variant 3, topological domain 2, turn 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9PI9	X-RAY DIFFRACTION	1.56
7PEE	X-RAY DIFFRACTION	2.81
7E5M	X-RAY DIFFRACTION	3.2
7E5N	X-RAY DIFFRACTION	3.2
2MAE	SOLUTION NMR
2MVK	SOLUTION NMR
2MVL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09758-F1	83.11	0.61

Antibody-complex structures (SAbDab): 1 — 9PI9

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (3): 73–108, 119–125, 127–145

Glycosylation sites (4): 33, 120, 168, 208

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 355 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, JAEGER_METASTASIS_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_64, MODULE_418, GOZGIT_ESR1_TARGETS_DN, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_REGULATION_OF_RUFFLE_ASSEMBLY

GO Biological Process (10): visual perception (GO:0007601), negative regulation of epithelial cell migration (GO:0010633), regulation of epithelial cell proliferation (GO:0050678), negative regulation of stress fiber assembly (GO:0051497), ureteric bud morphogenesis (GO:0060675), negative regulation of branching involved in ureteric bud morphogenesis (GO:0090191), negative regulation of substrate adhesion-dependent cell spreading (GO:1900025), negative regulation of ruffle assembly (GO:1900028), negative regulation of cell motility (GO:2000146), positive regulation of stem cell differentiation (GO:2000738)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytosol (GO:0005829), basal plasma membrane (GO:0009925), membrane (GO:0016020), lateral plasma membrane (GO:0016328), extracellular exosome (GO:0070062), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
negative regulation of multicellular organismal process	2
sensory perception of light stimulus	1
epithelial cell migration	1
regulation of epithelial cell migration	1
negative regulation of cell migration	1
regulation of cell population proliferation	1
epithelial cell proliferation	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
ureteric bud development	1
mesonephric tubule morphogenesis	1
branching involved in ureteric bud morphogenesis	1
regulation of branching involved in ureteric bud morphogenesis	1
negative regulation of morphogenesis of an epithelium	1
negative regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
ruffle assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of ruffle assembly	1
negative regulation of locomotion	1
negative regulation of cellular process	1
cell motility	1
regulation of cell motility	1
positive regulation of cell differentiation	1
stem cell differentiation	1
regulation of stem cell differentiation	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
basal part of cell	1
plasma membrane region	1
plasma membrane	1
extracellular vesicle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TACSTD2	CLDN7	O95471	925
TACSTD2	CLDN1	O95832	822
TACSTD2	IGF1	P01343	815
TACSTD2	ZNF92	Q03936	725
TACSTD2	TG	P01266	722
TACSTD2	ERBB2	P04626	719
TACSTD2	MDK	P21741	681
TACSTD2	EGFR	P00533	621
TACSTD2	CCND1	P24385	612
TACSTD2	NECTIN4	Q96NY8	582
TACSTD2	CEACAM6	P40199	507
TACSTD2	CHST6	Q9GZX3	507
TACSTD2	NRG1	P98202	496
TACSTD2	KRT8	P05787	482
TACSTD2	EPHA2	P29317	476

IntAct

35 interactions, top by confidence:

A	B	Type	Score
CLDN7	TACSTD2	psi-mi:“MI:0914”(association)	0.570
TACSTD2	CLDN7	psi-mi:“MI:0914”(association)	0.570
CLDN7	TACSTD2	psi-mi:“MI:2364”(proximity)	0.570
TACSTD2	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	TACSTD2	psi-mi:“MI:0915”(physical association)	0.560
TACSTD2	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
TACSTD2	KRTAP5-2	psi-mi:“MI:0915”(physical association)	0.560
CYP8B1	TACSTD2	psi-mi:“MI:0914”(association)	0.530
CLDN1	TACSTD2	psi-mi:“MI:2364”(proximity)	0.420
TACSTD2	HNRNPAB	psi-mi:“MI:0915”(physical association)	0.400
TACSTD2		psi-mi:“MI:0915”(physical association)	0.370
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATP6V1A		psi-mi:“MI:0914”(association)	0.350
TACSTD2	RIMOC1	psi-mi:“MI:0914”(association)	0.350
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
ST6GALNAC6	A2ML1	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
MBNL1	A2ML1	psi-mi:“MI:0914”(association)	0.350
ATF2	CLIC1	psi-mi:“MI:0914”(association)	0.350
ERF	DVL2	psi-mi:“MI:0914”(association)	0.350
RSRP1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
CLDN4	TACSTD2	psi-mi:“MI:2364”(proximity)	0.270
TACSTD2	TJP1	psi-mi:“MI:2364”(proximity)	0.270
TACSTD2	KRTAP1-3	psi-mi:“MI:0915”(physical association)	0.000
TACSTD2	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (131): TACSTD2 (Affinity Capture-MS), TACSTD2 (Affinity Capture-MS), TACSTD2 (Affinity Capture-MS), TACSTD2 (Proximity Label-MS), KRTAP10-8 (Two-hybrid), KRTAP5-2 (Two-hybrid), KRTAP1-3 (Two-hybrid), TACSTD2 (Affinity Capture-MS), HNRNPAB (Proximity Label-MS), TACSTD2 (Affinity Capture-MS), INTS5 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), USP27X (Affinity Capture-MS), TNPO2 (Affinity Capture-MS), KIAA1244 (Affinity Capture-MS)

ESM2 similar proteins: A1YVX4, A2ALW5, A3KMI0, A5DTG8, F4JIN3, O13633, O88379, P09758, P34454, P41229, P43613, P70302, P83093, P84903, P92029, Q0WT48, Q13586, Q149L6, Q17433, Q19293, Q28056, Q28I38, Q2QUP1, Q38JA7, Q3UZP0, Q58CP9, Q58E03, Q5BJW9, Q5EA26, Q5HZT9, Q61712, Q6PGC1, Q7XVN7, Q7Z478, Q7ZXQ8, Q8GUN6, Q8IMZ9, Q90830, Q91WT4, Q95KD5

Diamond homologs: O55159, P09758, P16422, Q1WER1, Q3T0L5, Q5F381, Q6P9Z6, Q75QW1, Q8BGV3, Q99JW5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKCD	“down-regulates activity”	TACSTD2	phosphorylation
PRKCA	“down-regulates activity”	TACSTD2	phosphorylation
TACSTD2	“up-regulates quantity”	CLDN7	binding

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

119 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	1
Uncertain significance	78
Likely benign	9
Benign	16

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
16182	NM_002353.3(TACSTD2):c.352C>T (p.Gln118Ter)	Pathogenic
16183	NM_002353.3(TACSTD2):c.619C>T (p.Gln207Ter)	Pathogenic
16184	NM_002353.3(TACSTD2):c.509C>A (p.Ser170Ter)	Pathogenic
16185	NM_002353.3(TACSTD2):c.632del (p.Gln211fs)	Pathogenic
16186	NM_002353.3(TACSTD2):c.2T>G (p.Met1Arg)	Pathogenic
16187	NM_002353.3(TACSTD2):c.355T>A (p.Cys119Ser)	Pathogenic
16188	NM_002353.3(TACSTD2):c.772_783delinsT (p.Leu257_Ile258insTer)	Pathogenic
16189	NM_002353.3(TACSTD2):c.557T>C (p.Leu186Pro)	Pathogenic
1699935	NM_002353.3(TACSTD2):c.653del (p.Asp218fs)	Pathogenic
4082113	NM_002353.3(TACSTD2):c.588C>A (p.Tyr196Ter)	Pathogenic
3248623	NM_002353.3(TACSTD2):c.679G>A (p.Glu227Lys)	Likely pathogenic

SpliceAI

27 predictions. Top by Δscore:

Variant	Effect	Δscore
1:58576927:T:TG	acceptor_gain	0.5100
1:58575663:A:C	acceptor_gain	0.4600
1:58576928:T:A	acceptor_gain	0.4600
1:58575671:A:T	acceptor_gain	0.4300
1:58575943:GTTGT:G	acceptor_gain	0.3400
1:58575944:TTGTT:T	acceptor_gain	0.3400
1:58577037:CT:C	acceptor_gain	0.3300
1:58577038:TT:T	acceptor_gain	0.3300
1:58575953:C:CT	acceptor_gain	0.3200
1:58577038:T:C	acceptor_gain	0.3200
1:58575984:T:G	acceptor_gain	0.3100
1:58575946:GTT:G	acceptor_gain	0.2900
1:58576245:C:A	donor_gain	0.2800
1:58575941:CTGT:C	acceptor_gain	0.2600
1:58575942:TGTT:T	acceptor_gain	0.2600
1:58575945:TGTT:T	acceptor_gain	0.2600
1:58577172:C:CT	acceptor_gain	0.2600
1:58575951:ACC:A	acceptor_gain	0.2500
1:58575650:C:CT	acceptor_gain	0.2400
1:58576934:G:GA	acceptor_gain	0.2400
1:58575651:A:T	acceptor_gain	0.2300
1:58575650:C:T	acceptor_gain	0.2200
1:58576932:C:A	acceptor_gain	0.2200
1:58576665:G:T	acceptor_gain	0.2100
1:58577038:T:TC	acceptor_gain	0.2100
1:58576458:C:CA	acceptor_gain	0.2000
1:58576931:GC:G	acceptor_gain	0.2000

AlphaMissense

2075 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:58576779:C:A	W126C	0.998
1:58576779:C:G	W126C	0.998
1:58576770:G:C	N129K	0.997
1:58576770:G:T	N129K	0.997
1:58576815:G:C	F114L	0.997
1:58576815:G:T	F114L	0.997
1:58576817:A:G	F114L	0.997
1:58576816:A:C	F114C	0.996
1:58576771:T:A	N129I	0.995
1:58576816:A:G	F114S	0.994
1:58576834:C:G	C108S	0.994
1:58576835:A:T	C108S	0.994
1:58576763:C:A	G132C	0.993
1:58576777:C:G	C127S	0.993
1:58576778:A:T	C127S	0.993
1:58576781:A:G	W126R	0.993
1:58576781:A:T	W126R	0.993
1:58576941:C:A	K72N	0.993
1:58576941:C:G	K72N	0.993
1:58576723:C:G	C145S	0.992
1:58576724:A:T	C145S	0.992
1:58576762:C:A	G132V	0.992
1:58576762:C:T	G132D	0.992
1:58576939:C:G	C73S	0.992
1:58576940:A:T	C73S	0.992
1:58576803:C:A	Q118H	0.991
1:58576803:C:G	Q118H	0.991
1:58576723:C:T	C145Y	0.990
1:58576763:C:G	G132R	0.990
1:58576834:C:T	C108Y	0.990

dbSNP variants (sampled 300 via entrez): RS1000334974 (1:58575154 C>T), RS1001337662 (1:58577224 C>G,T), RS1002017751 (1:58577499 G>A), RS1003412954 (1:58579139 C>A,T), RS1003841345 (1:58577406 TCAGAA>T), RS1003902231 (1:58579126 G>A,C,T), RS1003952717 (1:58578544 A>G), RS1003956004 (1:58577208 C>A,G,T), RS1004956958 (1:58575943 G>A), RS1005533848 (1:58578993 C>G), RS1005650049 (1:58578704 C>CG), RS1006746840 (1:58575509 C>A,T), RS1008163872 (1:58576799 T>G), RS1009990083 (1:58577991 A>G), RS1010034094 (1:58575445 A>G)

Disease associations

OMIM: gene MIM:137290 | disease phenotypes: MIM:204870

GenCC curated gene-disease

Disease	Classification	Inheritance
gelatinous drop-like corneal dystrophy	Definitive	Autosomal recessive

Mondo (1): gelatinous drop-like corneal dystrophy (MONDO:0008777)

Orphanet (1): Gelatinous drop-like corneal dystrophy (Orphanet:98957)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000613	Photophobia
HP:0000622	Blurred vision
HP:0000643	Blepharospasm
HP:0001131	Corneal dystrophy
HP:0007663	Reduced visual acuity
HP:0008039	Subepithelial corneal opacities
HP:0009926	Epiphora
HP:0010637	Conjunctival amyloidosis
HP:0011463	Childhood onset
HP:0011493	Central opacification of the cornea
HP:0011496	Corneal neovascularization
HP:0034804	Corneal foreign body sensation
HP:0200026	Ocular pain

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002928_28	Nickel levels	8.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535480	Corneal dystrophy, gelatinous drop-like (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3856163 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Tumour-associated antigens

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
sacituzumab govitecan	Binding	9.54	pKd
sacituzumab tirumotecan	Binding	9.51	pKd
hIMB1636-MMAE	Binding	9.15	pKd

CTD chemical–gene interactions

74 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
trichostatin A	affects cotreatment, increases expression, decreases expression	4
Estradiol	affects cotreatment, decreases expression, increases expression	4
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
methylmercuric chloride	increases expression	2
bisphenol A	increases expression	2
sodium arsenite	decreases expression, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
belinostat	affects cotreatment, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Calcitriol	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression	2
Tretinoin	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
TL8-506	affects cotreatment, increases expression	1
methylselenic acid	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
afimoxifene	decreases expression, decreases reaction	1
tetrathiomolybdate	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
cupric chloride	decreases expression	1
1-nitropyrene	decreases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1

Cellosaurus cell lines

17 cell lines: 7 cancer cell line, 7 spontaneously immortalized cell line, 3 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7JP	MCF7/TROP2-KO	Cancer cell line	Female
CVCL_B7JS	CHO/PA16-TROP2-RAP-MAP	Spontaneously immortalized cell line	Female
CVCL_B7JT	CHO/TROP2-PA	Spontaneously immortalized cell line	Female
CVCL_B7JU	Lec1/TROP2	Spontaneously immortalized cell line	Female
CVCL_B7JV	Lec2/TROP2	Spontaneously immortalized cell line	Female
CVCL_B7JW	Lec8/TROP2	Spontaneously immortalized cell line	Female
CVCL_B8QG	Abcam HCT 116 TACSTD2 KO	Cancer cell line	Male
CVCL_B9C4	Abcam MCF-7 TACSTD2 KO	Cancer cell line	Female
CVCL_B9SX	Abcam A-549 TACSTD2 KO	Cancer cell line	Male
CVCL_D8WT	Ubigene HCT 116 TACSTD2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.