Amyloidosis, hereditary systemic 1
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Summary
Amyloidosis, hereditary systemic 1 (MONDO:0971004) is a disease caused by TTR (GenCC Definitive), with 9 cohort genes. The dominant Reactome pathway is Striated Muscle Contraction (4 cohort genes).
At a glance
- Causal gene: TTR (GenCC Definitive)
- Cohort genes: 9
- ClinVar variants: 387
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | amyloidosis, hereditary systemic 1 |
| Mondo ID | MONDO:0971004 |
| OMIM | 105210 |
| UMLS | C2751492 |
| MedGen | 414031 |
| GARD | 0027098 |
| Is cancer (heuristic) | no |
Data availability: 387 ClinVar variants · 2 GenCC gene-disease records.
Disease family
An umbrella term covering 2 Mondo subtypes.
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › hereditary amyloidosis › familial amyloid neuropathy › amyloidosis, hereditary systemic 1
Related subtypes (3): amyloidosis, hereditary systemic 3, amyloidosis, hereditary systemic 5, amyloidosis, hereditary systemic 6
Subtypes (2): ATTRV122I amyloidosis, ATTRV30M amyloidosis
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
387 retrieved; paginated sample, class counts are floors:
111 uncertain significance, 90 likely benign, 53 pathogenic, 43 conflicting classifications of pathogenicity, 43 pathogenic/likely pathogenic, 32 likely pathogenic, 10 benign/likely benign, 5 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1012273 | NM_000371.4(TTR):c.[239C>T];[424G>A] | Pathogenic | no assertion criteria provided | |
| 1066429 | NM_000371.4(TTR):c.179C>A (p.Thr60Asn) | TTR | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1067499 | NM_000371.4(TTR):c.217G>A (p.Gly73Arg) | TTR | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1067500 | NM_000371.4(TTR):c.251T>C (p.Phe84Ser) | TTR | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1068392 | NM_000371.4(TTR):c.186G>C (p.Glu62Asp) | TTR | Pathogenic | criteria provided, single submitter |
| 1073324 | NM_000371.4(TTR):c.325G>A (p.Glu109Lys) | TTR | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1073325 | NM_000371.4(TTR):c.381T>G (p.Ile127Met) | TTR | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1075407 | NM_000371.4(TTR):c.94C>G (p.Leu32Val) | TTR | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1075408 | NM_000371.4(TTR):c.182G>T (p.Trp61Leu) | TTR | Pathogenic | criteria provided, single submitter |
| 1178327 | NM_000371.4(TTR):c.214T>C (p.Ser72Pro) | TTR | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1294424 | NM_000371.4(TTR):c.293A>T (p.Tyr98Phe) | TTR | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1333466 | NM_000371.4(TTR):c.425T>C (p.Val142Ala) | TTR | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13417 | NM_000371.4(TTR):c.148G>A (p.Val50Met) | TTR | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13418 | NM_000371.4(TTR):c.157T>A (p.Phe53Ile) | TTR | Pathogenic | no assertion criteria provided |
| 13419 | NM_000371.4(TTR):c.401A>G (p.Tyr134Cys) | TTR | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13420 | NM_000371.4(TTR):c.233T>A (p.Leu78His) | TTR | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13421 | NM_000371.4(TTR):c.238A>G (p.Thr80Ala) | TTR | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13422 | NM_000371.4(TTR):c.290C>A (p.Ser97Tyr) | TTR | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13423 | NM_000371.4(TTR):c.311T>G (p.Ile104Ser) | TTR | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13426 | NM_000371.4(TTR):c.424G>A (p.Val142Ile) | TTR | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13428 | NM_000371.4(TTR):c.185A>G (p.Glu62Gly) | TTR | Pathogenic | no assertion criteria provided |
| 13429 | NM_000371.4(TTR):c.210T>G (p.Ser70Arg) | TTR | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13430 | NM_000371.4(TTR):c.149T>C (p.Val50Ala) | TTR | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13432 | NM_000371.4(TTR):c.166G>C (p.Ala56Pro) | TTR | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13435 | NM_000371.4(TTR):c.233T>G (p.Leu78Arg) | TTR | Pathogenic | no assertion criteria provided |
| 13436 | NM_000371.4(TTR):c.199G>C (p.Gly67Arg) | TTR | Pathogenic | no assertion criteria provided |
| 13437 | NM_000371.4(TTR):c.133G>A (p.Ala45Thr) | TTR | Pathogenic | no assertion criteria provided |
| 13438 | NM_000371.4(TTR):c.224T>C (p.Leu75Pro) | TTR | Pathogenic | no assertion criteria provided |
| 13439 | NM_000371.4(TTR):c.209G>T (p.Ser70Ile) | TTR | Pathogenic | no assertion criteria provided |
| 13440 | NM_000371.4(TTR):c.148G>C (p.Val50Leu) | TTR | Pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 8 · Orphanet: 30 · 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 |
|---|---|---|---|---|
| TTR | Definitive | Autosomal dominant | amyloidosis, hereditary systemic 1 | 8 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TTR | Orphanet:597939 | Euthyroid dysprealbuminemic hyperthyroxinemia |
| TTR | Orphanet:85447 | ATTRV30M amyloidosis |
| TTR | Orphanet:85451 | ATTRV122I amyloidosis |
| TNNI3 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| TNNI3 | Orphanet:75249 | Familial isolated restrictive cardiomyopathy |
| TTN | Orphanet:140922 | Titin-related limb-girdle muscular dystrophy R10 |
| TTN | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| TTN | Orphanet:169186 | Autosomal recessive centronuclear myopathy |
| TTN | Orphanet:178464 | Hereditary myopathy with early respiratory failure |
| TTN | Orphanet:289377 | Early-onset myopathy with fatal cardiomyopathy |
| TTN | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| TTN | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| TTN | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| TTN | Orphanet:324604 | Classic multiminicore myopathy |
| TTN | Orphanet:334 | Hereditary atrial fibrillation |
| TTN | Orphanet:466921 | Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome |
| TTN | Orphanet:609 | Tibial muscular dystrophy |
| TTN | Orphanet:707983 | Early-onset autosomal recessive TTN-related distal myopathy |
| DSC3 | Orphanet:217407 | Hereditary hypotrichosis with recurrent skin vesicles |
| DSG2 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| DSG2 | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| DSG2 | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| DSG2 | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| MYBPC3 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| MYBPC3 | Orphanet:54260 | Left ventricular noncompaction |
| PKP2 | Orphanet:130 | Brugada syndrome |
| PKP2 | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| PKP2 | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| PKP2 | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| PKP2 | Orphanet:54260 | Left ventricular noncompaction |
Cohort genes → proteins
9 cohort genes, 9 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 9 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TTR | HGNC:12405 | ENSG00000118271 | P02766 | Transthyretin | gencc,clinvar |
| TNNI3 | HGNC:11947 | ENSG00000129991 | P19429 | Troponin I, cardiac muscle | clinvar |
| TTN | HGNC:12403 | ENSG00000155657 | Q8WZ42 | Titin | clinvar |
| DSC1 | HGNC:3035 | ENSG00000134765 | Q08554 | Desmocollin-1 | clinvar |
| DSC3 | HGNC:3037 | ENSG00000134762 | Q14574 | Desmocollin-3 | clinvar |
| DSG2 | HGNC:3049 | ENSG00000046604 | Q14126 | Desmoglein-2 | clinvar |
| MYBPC3 | HGNC:7551 | ENSG00000134571 | Q14896 | Myosin-binding protein C, cardiac-type | clinvar |
| MYL3 | HGNC:7584 | ENSG00000160808 | P08590 | Myosin light chain 3 | clinvar |
| PKP2 | HGNC:9024 | ENSG00000057294 | Q99959 | Plakophilin-2 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TTR | Transthyretin | Thyroid hormone-binding protein. |
| TNNI3 | Troponin I, cardiac muscle | Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. |
| TTN | Titin | Key component in the assembly and functioning of vertebrate striated muscles. |
| DSC1 | Desmocollin-1 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. |
| DSC3 | Desmocollin-3 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. |
| DSG2 | Desmoglein-2 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. |
| MYBPC3 | Myosin-binding protein C, cardiac-type | Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. |
| MYL3 | Myosin light chain 3 | Regulatory light chain of myosin. |
| PKP2 | Plakophilin-2 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. |
Protein-family classification
Druggable: 2 · Difficult: 0 · Unknown: 7 · Druggable fraction: 0.22
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 |
|---|---|---|---|
| Antibody/Immunoglobulin | 1 | 3.2× | 0.282 |
| Kinase | 1 | 3.1× | 0.282 |
| Other/Unknown | 7 | 1.4× | 0.282 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TTR | Other/Unknown | no | Transthyretin/HIU_hydrolase, Transthyretin/HIU_hydrolase_d, Thyroxine_BS | |
| TNNI3 | Other/Unknown | no | Troponin, Troponin-I_N, Troponin_sf | |
| TTN | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, Ig_sub2, Ig_sub |
| DSC1 | Other/Unknown | no | Cadherin-like_dom, Desmosomal_cadherin, Cadherin_pro_dom | |
| DSC3 | Other/Unknown | no | Cadherin_Y-type_LIR, Cadherin-like_dom, Desmosomal_cadherin | |
| DSG2 | Other/Unknown | no | Cadherin-like_dom, Desmosomal_cadherin, Cadherin-like_sf | |
| MYBPC3 | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, FN3_dom | |
| MYL3 | Other/Unknown | no | EF_hand_dom, EF-hand-dom_pair, CALM/Myosin/TropC-like | |
| PKP2 | Other/Unknown | no | Armadillo, ARM-like, ARM-type_fold |
Expression context
Cohort genes with no expression data: 0.
9 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) | 9 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| apex of heart | 4 |
| left ventricle myocardium | 2 |
| right atrium auricular region | 2 |
| upper leg skin | 2 |
| heart right ventricle | 2 |
| choroid plexus epithelium | 1 |
| right lobe of liver | 1 |
| type B pancreatic cell | 1 |
| biceps brachii | 1 |
| gluteal muscle | 1 |
| skeletal muscle tissue of biceps brachii | 1 |
| skin of hip | 1 |
| upper arm skin | 1 |
| gingiva | 1 |
| gingival epithelium | 1 |
| colonic mucosa | 1 |
| jejunal mucosa | 1 |
| mucosa of sigmoid colon | 1 |
| cardiac atrium | 1 |
| hindlimb stylopod muscle | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TTR | 185 | broad | marker | choroid plexus epithelium, type B pancreatic cell, right lobe of liver |
| TNNI3 | 169 | broad | marker | apex of heart, left ventricle myocardium, right atrium auricular region |
| TTN | 223 | broad | marker | biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii |
| DSC1 | 102 | tissue_specific | marker | upper leg skin, skin of hip, upper arm skin |
| DSC3 | 177 | broad | marker | upper leg skin, gingival epithelium, gingiva |
| DSG2 | 238 | ubiquitous | marker | mucosa of sigmoid colon, colonic mucosa, jejunal mucosa |
| MYBPC3 | 149 | tissue_specific | marker | apex of heart, right atrium auricular region, cardiac atrium |
| MYL3 | 198 | broad | marker | apex of heart, heart right ventricle, hindlimb stylopod muscle |
| PKP2 | 237 | ubiquitous | marker | heart right ventricle, apex of heart, left ventricle myocardium |
Protein interactions among cohort
Intra-cohort edges: 11.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TTR | 4,528 |
| TTN | 4,237 |
| MYL3 | 2,255 |
| DSG2 | 2,033 |
| PKP2 | 1,861 |
| TNNI3 | 1,836 |
| MYBPC3 | 1,800 |
| DSC3 | 1,474 |
| DSC1 | 831 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| DSC1 | DSG2 | intact |
| DSC3 | DSG2 | intact, string_interaction |
| DSC3 | PKP2 | string_interaction |
| DSG2 | MYBPC3 | string_interaction |
| DSG2 | PKP2 | string_interaction |
| MYBPC3 | MYL3 | string_interaction |
| MYBPC3 | TNNI3 | string_interaction |
| MYBPC3 | TTN | string_interaction |
| MYL3 | TNNI3 | string_interaction |
| MYL3 | TTN | string_interaction |
| TNNI3 | TTN | string_interaction |
Structural data
PDB: 8 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TTR | P02766 | 462 |
| TTN | Q8WZ42 | 64 |
| TNNI3 | P19429 | 39 |
| MYBPC3 | Q14896 | 17 |
| DSG2 | Q14126 | 12 |
| MYL3 | P08590 | 3 |
| DSC1 | Q08554 | 1 |
| PKP2 | Q99959 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| DSC3 | Q14574 | 75.53 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 9 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Striated Muscle Contraction | 4 | 137.2× | 2e-07 | TNNI3, TTN, MYBPC3, MYL3 |
| Formation of the cornified envelope | 4 | 39.0× | 2e-05 | DSC1, DSC3, DSG2, PKP2 |
| Keratinization | 4 | 24.8× | 6e-05 | DSC1, DSC3, DSG2, PKP2 |
| Defective visual phototransduction due to STRA6 loss of function | 1 | 423.0× | 0.009 | TTR |
| Muscle contraction | 2 | 17.1× | 0.018 | MYBPC3, MYL3 |
| Apoptotic cleavage of cell adhesion proteins | 1 | 115.3× | 0.023 | DSG2 |
| The canonical retinoid cycle in rods (twilight vision) | 1 | 57.7× | 0.039 | TTR |
| Retinoid metabolism and transport | 1 | 27.6× | 0.071 | TTR |
| Ion homeostasis | 1 | 22.7× | 0.077 | TNNI3 |
| Non-integrin membrane-ECM interactions | 1 | 17.1× | 0.079 | TTR |
| RHOG GTPase cycle | 1 | 16.5× | 0.079 | DSG2 |
| Neutrophil degranulation | 2 | 5.1× | 0.079 | TTR, DSC1 |
| RAC2 GTPase cycle | 1 | 14.1× | 0.084 | DSG2 |
| RAC3 GTPase cycle | 1 | 13.2× | 0.084 | DSG2 |
| Amyloid fiber formation | 1 | 11.4× | 0.090 | TTR |
| Platelet degranulation | 1 | 9.8× | 0.098 | TTN |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| ventricular cardiac muscle tissue morphogenesis | 4 | 312.1× | 3e-08 | TNNI3, MYBPC3, MYL3, PKP2 |
| cardiac muscle contraction | 4 | 178.3× | 2e-07 | TNNI3, TTN, MYBPC3, MYL3 |
| cell-cell adhesion | 4 | 45.1× | 3e-05 | DSC1, DSC3, DSG2, PKP2 |
| bundle of His cell-Purkinje myocyte adhesion involved in cell communication | 2 | 535.0× | 9e-05 | DSG2, PKP2 |
| desmosome organization | 2 | 468.1× | 9e-05 | DSG2, PKP2 |
| regulation of striated muscle contraction | 2 | 468.1× | 9e-05 | MYBPC3, MYL3 |
| regulation of ventricular cardiac muscle cell action potential | 2 | 312.1× | 2e-04 | DSG2, PKP2 |
| muscle filament sliding | 2 | 234.1× | 3e-04 | TNNI3, TTN |
| homophilic cell-cell adhesion | 3 | 46.8× | 3e-04 | DSC1, DSC3, DSG2 |
| skeletal muscle contraction | 2 | 113.5× | 0.001 | TNNI3, TTN |
| sarcomere organization | 2 | 85.1× | 0.002 | TTN, MYBPC3 |
| regulation of heart rate by cardiac conduction | 2 | 83.2× | 0.002 | DSG2, PKP2 |
| maintenance of protein localization at cell tip | 1 | 1872.4× | 0.003 | PKP2 |
| muscle contraction | 2 | 46.2× | 0.004 | TTN, MYL3 |
| regulation of systemic arterial blood pressure by ischemic conditions | 1 | 936.2× | 0.005 | TNNI3 |
| desmosome maintenance | 1 | 936.2× | 0.005 | DSC1 |
| Purkinje myocyte development | 1 | 936.2× | 0.005 | DSG2 |
| regulation of muscle filament sliding | 1 | 936.2× | 0.005 | MYBPC3 |
| regulation of cell-substrate adhesion | 1 | 624.1× | 0.005 | PKP2 |
| skeletal muscle myosin thick filament assembly | 1 | 624.1× | 0.005 | TTN |
| sarcomerogenesis | 1 | 624.1× | 0.005 | TTN |
| positive regulation of protein localization to cell-cell junction | 1 | 624.1× | 0.005 | DSG2 |
| cell adhesion | 3 | 12.5× | 0.005 | DSC3, DSG2, MYBPC3 |
| negative regulation of glomerular filtration | 1 | 468.1× | 0.007 | TTR |
| negative regulation of endothelial cell differentiation | 1 | 374.5× | 0.008 | DSG2 |
| maintenance of animal organ identity | 1 | 374.5× | 0.008 | PKP2 |
| regulation of substrate adhesion-dependent cell spreading | 1 | 374.5× | 0.008 | PKP2 |
| skeletal muscle thin filament assembly | 1 | 312.1× | 0.008 | TTN |
| intermediate filament bundle assembly | 1 | 312.1× | 0.008 | PKP2 |
| desmosome assembly | 1 | 267.5× | 0.009 | PKP2 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 7
Druggability breadth: 5 of 9 evidence-associated genes (56%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| TTR | TRICLABENDAZOLE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| TTR | 29 | 4 |
| DSC1 | 1 | 2 |
| TNNI3 | 0 | 0 |
| TTN | 0 | 0 |
| DSC3 | 0 | 0 |
| DSG2 | 0 | 0 |
| MYBPC3 | 0 | 0 |
| MYL3 | 0 | 0 |
| PKP2 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| TRICLABENDAZOLE | 4 | TTR |
| AMLEXANOX | 4 | TTR |
| TOLCAPONE | 4 | TTR |
| DICLOFENAC | 4 | TTR |
| LEVOTHYROXINE | 4 | TTR |
| TAFAMIDIS | 4 | TTR |
| BENZIODARONE | 4 | TTR |
| BITHIONOL | 4 | TTR |
| BENZBROMARONE | 4 | TTR |
| ACORAMIDIS | 4 | TTR |
| GEMFIBROZIL | 4 | TTR |
| MECLOFENAMIC ACID | 4 | TTR |
| DASATINIB | 4 | TTR |
| DEXTROTHYROXINE | 4 | TTR |
| TRICLOSAN | 4 | TTR |
| DIFLUNISAL | 4 | TTR |
| CAFFEIC ACID | 3 | TTR |
| RESVERATROL | 3 | TTR |
| EPIGALOCATECHIN GALLATE | 3 | TTR |
| DIACEREIN | 3 | TTR |
| TOLFENAMIC ACID | 2 | TTR |
| LUTEOLIN | 2 | TTR |
| FLUFENAMIC ACID | 2 | TTR |
| XANTHOHUMOL | 2 | TTR |
| GENISTEIN | 2 | TTR |
| NIFLUMIC ACID | 2 | TTR |
| DAIDZEIN | 2 | TTR |
| PTEROSTILBENE | 2 | TTR |
| ACECLOFENAC | 2 | TTR |
| MOLIBRESIB | 2 | DSC1 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| TTR | 423 | Binding:391, Functional:32 |
| DSC1 | 6 | Binding:6 |
| TNNI3 | 2 | Binding:2 |
| TTN | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| TTN | 2.7.11.1 | non-specific serine/threonine protein kinase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| TTR | 423 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
30 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| TRICLABENDAZOLE | 4 | TTR |
| AMLEXANOX | 4 | TTR |
| TOLCAPONE | 4 | TTR |
| DICLOFENAC | 4 | TTR |
| LEVOTHYROXINE | 4 | TTR |
| TAFAMIDIS | 4 | TTR |
| BENZIODARONE | 4 | TTR |
| BITHIONOL | 4 | TTR |
| BENZBROMARONE | 4 | TTR |
| ACORAMIDIS | 4 | TTR |
| GEMFIBROZIL | 4 | TTR |
| MECLOFENAMIC ACID | 4 | TTR |
| DASATINIB | 4 | TTR |
| DEXTROTHYROXINE | 4 | TTR |
| TRICLOSAN | 4 | TTR |
| DIFLUNISAL | 4 | TTR |
| CAFFEIC ACID | 3 | TTR |
| RESVERATROL | 3 | TTR |
| EPIGALOCATECHIN GALLATE | 3 | TTR |
| DIACEREIN | 3 | TTR |
| TOLFENAMIC ACID | 2 | TTR |
| LUTEOLIN | 2 | TTR |
| FLUFENAMIC ACID | 2 | TTR |
| XANTHOHUMOL | 2 | TTR |
| GENISTEIN | 2 | TTR |
| NIFLUMIC ACID | 2 | TTR |
| DAIDZEIN | 2 | TTR |
| PTEROSTILBENE | 2 | TTR |
| ACECLOFENAC | 2 | TTR |
| MOLIBRESIB | 2 | DSC1 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | TTR |
| B | Phased (≥1) drug, not yet approved | 1 | DSC1 |
| C | Druggable family + PDB, no drug | 2 | TTN, MYBPC3 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 5 | TNNI3, DSC3, DSG2, MYL3, PKP2 |
Undrugged target profiles
7 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| TNNI3 | 2 | — |
| TTN | 1 | — |
| DSC3 | 0 | — |
| DSG2 | 0 | — |
| MYBPC3 | 0 | — |
| MYL3 | 0 | — |
| PKP2 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.