autosomal recessive limb-girdle muscular dystrophy type 2J
diseaseOn this page
Also known as autosomal recessive limb-girdle muscular dystrophy caused by mutation in TTNLGMD2Jlimb-girdle muscular dystrophy type 2Jmuscular dystrophy, limb-girdle, autosomal recessive 10muscular dystrophy, limb-girdle, type 2JTTN autosomal recessive limb-girdle muscular dystrophy
Summary
autosomal recessive limb-girdle muscular dystrophy type 2J (MONDO:0012127) is a disease caused by TTN (GenCC Strong), with 8 cohort genes and 1 clinical trial.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: TTN (GenCC Strong)
- Cohort genes: 8
- ClinVar variants: 26,352
- Clinical trials: 1
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 1 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | autosomal recessive limb-girdle muscular dystrophy type 2J |
| Mondo ID | MONDO:0012127 |
| MeSH | C563854 |
| OMIM | 608807 |
| Orphanet | 140922 |
| DOID | DOID:0110283 |
| UMLS | C1837342 |
| MedGen | 324741 |
| GARD | 0012534 |
| Is cancer (heuristic) | no |
Also known as: autosomal recessive limb-girdle muscular dystrophy caused by mutation in TTN · LGMD2J · limb-girdle muscular dystrophy type 2J · muscular dystrophy, limb-girdle, autosomal recessive 10 · muscular dystrophy, limb-girdle, type 2J · TTN autosomal recessive limb-girdle muscular dystrophy
Data availability: 26,352 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive limb-girdle muscular dystrophy › autosomal recessive limb-girdle muscular dystrophy type 2J
Related subtypes (31): epidermolysis bullosa simplex 5B, with muscular dystrophy, autosomal recessive limb-girdle muscular dystrophy type 2A, autosomal recessive limb-girdle muscular dystrophy type 2B, autosomal recessive limb-girdle muscular dystrophy type 2C, autosomal recessive limb-girdle muscular dystrophy type 2H, autosomal recessive limb-girdle muscular dystrophy type 2F, autosomal recessive limb-girdle muscular dystrophy type 2G, autosomal recessive limb-girdle muscular dystrophy type 2E, autosomal recessive limb-girdle muscular dystrophy type 2I, autosomal recessive limb-girdle muscular dystrophy type 2D, autosomal recessive limb-girdle muscular dystrophy type 2K, autosomal recessive limb-girdle muscular dystrophy type 2L, autosomal recessive limb-girdle muscular dystrophy type 2M, autosomal recessive limb-girdle muscular dystrophy type 2O, autosomal recessive limb-girdle muscular dystrophy type 2N, autosomal recessive limb-girdle muscular dystrophy type 2Q, autosomal recessive limb-girdle muscular dystrophy type 2P, autosomal recessive limb-girdle muscular dystrophy type 2T, autosomal recessive limb-girdle muscular dystrophy type R18, autosomal recessive limb-girdle muscular dystrophy type 2U, limb-girdle muscular dystrophy due to POMK deficiency, autosomal recessive limb-girdle muscular dystrophy type 2X, autosomal recessive limb-girdle muscular dystrophy type 2W, autosomal recessive limb-girdle muscular dystrophy type 2Y, autosomal recessive limb-girdle muscular dystrophy type 2R1, muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8, muscular dystrophy, limb-girdle, autosomal recessive 23, muscular dystrophy, limb-girdle, autosomal recessive 26, muscular dystrophy, limb-girdle, autosomal recessive 27, muscular dystrophy, limb-girdle, autosomal recessive 28, muscular dystrophy, limb-girdle, autosomal recessive 29
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
600 retrieved; paginated sample, class counts are floors:
230 likely pathogenic, 163 likely benign, 161 uncertain significance, 21 conflicting classifications of pathogenicity, 13 pathogenic/likely pathogenic, 11 pathogenic, 1 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1011266 | NM_001267550.2(TTN):c.6825del (p.Asp2275fs) | TTN | Pathogenic | criteria provided, single submitter |
| 1015906 | NM_001267550.2(TTN):c.26287G>T (p.Glu8763Ter) | TTN | Pathogenic | criteria provided, single submitter |
| 1016464 | NM_001267550.2(TTN):c.32312-1G>C | TTN | Pathogenic | criteria provided, single submitter |
| 1030169 | NM_001267550.2(TTN):c.107224-1G>C | TTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1035316 | NM_001267550.2(TTN):c.6570dup (p.Met2191fs) | TTN | Pathogenic | criteria provided, single submitter |
| 1057336 | NM_001267550.2(TTN):c.3344G>A (p.Trp1115Ter) | TTN | Pathogenic | criteria provided, single submitter |
| 1065903 | NM_001267550.2(TTN):c.47314C>T (p.Arg15772Ter) | TTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1066283 | NM_001267550.2(TTN):c.93088del (p.Arg31030fs) | TTN | Pathogenic | criteria provided, single submitter |
| 1066477 | NM_001267550.2(TTN):c.101687C>A (p.Ser33896Ter) | TTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1066644 | NM_001267550.2(TTN):c.96849del (p.Gly32284fs) | TTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1066907 | NM_001267550.2(TTN):c.51667C>T (p.Arg17223Ter) | TTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1067013 | NM_001267550.2(TTN):c.69421_69422insAAAAG (p.Gly23141fs) | TTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1067751 | NM_001267550.2(TTN):c.66968del (p.Asn22323fs) | TTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1069899 | NM_001267550.2(TTN):c.77646del (p.Ile25883fs) | TTN | Pathogenic | criteria provided, single submitter |
| 1071779 | NM_001267550.2(TTN):c.88462dup (p.Cys29488fs) | TTN | Pathogenic | criteria provided, single submitter |
| 1074124 | NM_001267550.2(TTN):c.67348C>T (p.Gln22450Ter) | TTN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1076903 | NM_001267550.2(TTN):c.85011_85014del (p.Glu28338fs) | TTN | Pathogenic | criteria provided, single submitter |
| 1030165 | NM_001267550.2(TTN):c.91920G>A (p.Trp30640Ter) | TTN-AS1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1061173 | NM_001267550.2(TTN):c.46603C>T (p.Arg15535Ter) | TTN-AS1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1066067 | NM_001267550.2(TTN):c.53206C>T (p.Arg17736Ter) | TTN-AS1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1067228 | NM_001267550.2(TTN):c.95872C>T (p.Arg31958Ter) | TTN-AS1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1067472 | NM_001267550.2(TTN):c.83971C>T (p.Gln27991Ter) | TTN-AS1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1068107 | NM_001267550.2(TTN):c.47797A>T (p.Arg15933Ter) | TTN-AS1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1068361 | NM_001267550.2(TTN):c.96669G>A (p.Trp32223Ter) | TTN-AS1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1018433 | NM_001267550.2(TTN):c.4537C>T (p.Gln1513Ter) | LOC101927055 | Likely pathogenic | criteria provided, single submitter |
| 1020457 | NM_001267550.2(TTN):c.4880G>A (p.Trp1627Ter) | LOC101927055 | Likely pathogenic | criteria provided, single submitter |
| 1022898 | NM_001267550.2(TTN):c.4413del (p.Gln1472fs) | LOC101927055 | Likely pathogenic | criteria provided, single submitter |
| 1052992 | NM_001267550.2(TTN):c.4216_4219del (p.Ser1406fs) | LOC101927055 | Likely pathogenic | criteria provided, single submitter |
| 1066247 | NM_001267550.2(TTN):c.96682dup (p.Tyr32228fs) | LOC126806421 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1066881 | NM_001267550.2(TTN):c.96937C>T (p.Gln32313Ter) | LOC126806421 | Likely pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 21 · Orphanet: 18 · 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 |
|---|---|---|---|---|
| TTN | Strong | Autosomal dominant | tibial muscular dystrophy | 21 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| 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 |
| CORIN | Orphanet:275555 | Preeclampsia |
| LRP4 | Orphanet:3152 | Sclerosteosis |
| LRP4 | Orphanet:3258 | Cenani-Lenz syndrome |
| LRP4 | Orphanet:98913 | Postsynaptic congenital myasthenic syndrome |
| PRKRA | Orphanet:210571 | Dystonia 16 |
Cohort genes → proteins
8 cohort genes, 7 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 8 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TTN | HGNC:12403 | ENSG00000155657 | Q8WZ42 | Titin | gencc,clinvar |
| SRPK3 | HGNC:11402 | ENSG00000184343 | Q9UPE1 | SRSF protein kinase 3 | clinvar |
| PLEKHA3 | HGNC:14338 | ENSG00000116095 | Q9HB20 | Pleckstrin homology domain-containing family A member 3 | clinvar |
| CORIN | HGNC:19012 | ENSG00000145244 | Q9Y5Q5 | Atrial natriuretic peptide-converting enzyme | clinvar |
| FKBP7 | HGNC:3723 | ENSG00000079150 | Q9Y680 | Peptidyl-prolyl cis-trans isomerase FKBP7 | clinvar |
| TTN-AS1 | HGNC:44124 | ENSG00000237298 | TTN antisense RNA 1 | clinvar | |
| LRP4 | HGNC:6696 | ENSG00000134569 | O75096 | Low-density lipoprotein receptor-related protein 4 | clinvar |
| PRKRA | HGNC:9438 | ENSG00000180228 | O75569 | Interferon-inducible double-stranded RNA-dependent protein kinase activator A | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TTN | Titin | Key component in the assembly and functioning of vertebrate striated muscles. |
| SRPK3 | SRSF protein kinase 3 | Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains. |
| PLEKHA3 | Pleckstrin homology domain-containing family A member 3 | Plays a role in regulation of vesicular cargo transport from the trans-Golgi network (TGN) to the plasma membrane. |
| CORIN | Atrial natriuretic peptide-converting enzyme | Serine-type endopeptidase involved in atrial natriuretic peptide (NPPA) and brain natriuretic peptide (NPPB) processing. |
| FKBP7 | Peptidyl-prolyl cis-trans isomerase FKBP7 | PPIases accelerate the folding of proteins during protein synthesis. |
| LRP4 | Low-density lipoprotein receptor-related protein 4 | Mediates SOST-dependent inhibition of bone formation. |
| PRKRA | Interferon-inducible double-stranded RNA-dependent protein kinase activator A | Activates EIF2AK2/PKR in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. |
Protein-family classification
Druggable: 3 · Difficult: 1 · Unknown: 4 · Druggable fraction: 0.38
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 |
|---|---|---|---|
| Kinase | 2 | 6.9× | 0.126 |
| Protease | 1 | 4.6× | 0.398 |
| Scaffold/PPI | 1 | 2.2× | 0.506 |
| Other/Unknown | 4 | 0.9× | 0.755 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TTN | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, Ig_sub2, Ig_sub |
| SRPK3 | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf |
| PLEKHA3 | Scaffold/PPI | no | PH_domain, PH-like_dom_sf, Boi1/Boi2-like | |
| CORIN | Protease | yes | SRCR, Trypsin_dom, LDrepeatLR_classA_rpt | |
| FKBP7 | Other/Unknown | no | PPIase_FKBP_dom, EF_hand_dom, EF-hand-dom_pair | |
| TTN-AS1 | Other/Unknown | no | ||
| LRP4 | Other/Unknown | no | LDLR_classB_rpt, EGF, EGF-like_Ca-bd_dom | |
| PRKRA | Other/Unknown | no | dsRBD_dom, PRKRA_DSRM_1, PRKRA_DSRM_2 |
Expression context
Cohort genes with no expression data: 0.
8 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) | 8 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| biceps brachii | 2 |
| gluteal muscle | 2 |
| skeletal muscle tissue of biceps brachii | 2 |
| gastrocnemius | 2 |
| hindlimb stylopod muscle | 2 |
| endothelial cell | 1 |
| epithelial cell of pancreas | 1 |
| oviduct epithelium | 1 |
| cardiac muscle of right atrium | 1 |
| heart right ventricle | 1 |
| myocardium | 1 |
| calcaneal tendon | 1 |
| left ovary | 1 |
| stromal cell of endometrium | 1 |
| right atrium auricular region | 1 |
| dorsal motor nucleus of vagus nerve | 1 |
| medial globus pallidus | 1 |
| ventricular zone | 1 |
| sperm | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TTN | 223 | broad | marker | biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii |
| SRPK3 | 202 | broad | marker | hindlimb stylopod muscle, gluteal muscle, gastrocnemius |
| PLEKHA3 | 259 | ubiquitous | marker | epithelial cell of pancreas, oviduct epithelium, endothelial cell |
| CORIN | 176 | tissue_specific | marker | cardiac muscle of right atrium, heart right ventricle, myocardium |
| FKBP7 | 230 | ubiquitous | marker | stromal cell of endometrium, calcaneal tendon, left ovary |
| TTN-AS1 | 174 | ubiquitous | marker | hindlimb stylopod muscle, gastrocnemius, right atrium auricular region |
| LRP4 | 242 | ubiquitous | marker | ventricular zone, dorsal motor nucleus of vagus nerve, medial globus pallidus |
| PRKRA | 294 | ubiquitous | marker | sperm, skeletal muscle tissue of biceps brachii, biceps brachii |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TTN | 4,237 |
| PRKRA | 2,410 |
| FKBP7 | 2,058 |
| SRPK3 | 1,561 |
| CORIN | 1,291 |
| LRP4 | 1,250 |
| PLEKHA3 | 810 |
| TTN-AS1 | 0 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| FKBP7 | PLEKHA3 | string_interaction |
Structural data
PDB: 4 · AlphaFold-only: 3 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TTN | Q8WZ42 | 64 |
| PLEKHA3 | Q9HB20 | 3 |
| PRKRA | O75569 | 2 |
| LRP4 | O75096 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| FKBP7 | Q9Y680 | 86.12 |
| SRPK3 | Q9UPE1 | 80.61 |
| CORIN | Q9Y5Q5 | 70.20 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 8 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Small interfering RNA (siRNA) biogenesis | 1 | 228.4× | 0.033 | PRKRA |
| Physiological factors | 1 | 134.3× | 0.033 | CORIN |
| MicroRNA (miRNA) biogenesis | 1 | 91.4× | 0.033 | PRKRA |
| Striated Muscle Contraction | 1 | 61.7× | 0.036 | TTN |
| Synthesis of PIPs at the plasma membrane | 1 | 42.3× | 0.042 | PLEKHA3 |
| ECM proteoglycans | 1 | 30.1× | 0.045 | LRP4 |
| PKR-mediated signaling | 1 | 28.2× | 0.045 | PRKRA |
| Platelet degranulation | 1 | 17.6× | 0.063 | TTN |
| Extracellular matrix organization | 1 | 12.6× | 0.077 | LRP4 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| positive regulation of presynaptic membrane organization | 1 | 2808.7× | 0.013 | LRP4 |
| regulation of systemic arterial blood pressure by atrial natriuretic peptide | 1 | 936.2× | 0.013 | CORIN |
| skeletal muscle myosin thick filament assembly | 1 | 936.2× | 0.013 | TTN |
| sarcomerogenesis | 1 | 936.2× | 0.013 | TTN |
| synaptic assembly at neuromuscular junction | 1 | 936.2× | 0.013 | LRP4 |
| regulation of regulatory ncRNA processing | 1 | 936.2× | 0.013 | PRKRA |
| regulation of renal sodium excretion | 1 | 702.2× | 0.013 | CORIN |
| muscle tissue development | 1 | 561.7× | 0.013 | SRPK3 |
| skeletal muscle thin filament assembly | 1 | 468.1× | 0.013 | TTN |
| detection of muscle stretch | 1 | 401.2× | 0.013 | TTN |
| postsynaptic membrane assembly | 1 | 401.2× | 0.013 | LRP4 |
| amyloid-beta clearance by cellular catabolic process | 1 | 351.1× | 0.013 | LRP4 |
| siRNA processing | 1 | 312.1× | 0.013 | PRKRA |
| skeletal muscle acetylcholine-gated channel clustering | 1 | 312.1× | 0.013 | LRP4 |
| positive regulation of skeletal muscle acetylcholine-gated channel clustering | 1 | 312.1× | 0.013 | LRP4 |
| cardiac muscle hypertrophy | 1 | 280.9× | 0.013 | TTN |
| presynaptic membrane assembly | 1 | 280.9× | 0.013 | LRP4 |
| outer ear morphogenesis | 1 | 255.3× | 0.013 | PRKRA |
| generation of neurons | 1 | 255.3× | 0.013 | LRP4 |
| RISC complex assembly | 1 | 255.3× | 0.013 | PRKRA |
| obsolete protein kinase A signaling | 1 | 234.1× | 0.013 | TTN |
| cardiac muscle tissue morphogenesis | 1 | 234.1× | 0.013 | TTN |
| receptor recycling | 1 | 216.1× | 0.013 | PLEKHA3 |
| enzyme-linked receptor protein signaling pathway | 1 | 216.1× | 0.013 | LRP4 |
| negative regulation of axonogenesis | 1 | 216.1× | 0.013 | LRP4 |
| cardiac myofibril assembly | 1 | 216.1× | 0.013 | TTN |
| pre-miRNA processing | 1 | 187.2× | 0.015 | PRKRA |
| muscle filament sliding | 1 | 175.5× | 0.015 | TTN |
| miRNA processing | 1 | 175.5× | 0.015 | PRKRA |
| mitotic chromosome condensation | 1 | 165.2× | 0.015 | TTN |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 7
Druggability breadth: 2 of 8 evidence-associated genes (25%) 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 |
|---|---|
| SRPK3 | FEDRATINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| SRPK3 | 18 | 4 |
| TTN | 0 | 0 |
| PLEKHA3 | 0 | 0 |
| CORIN | 0 | 0 |
| FKBP7 | 0 | 0 |
| TTN-AS1 | 0 | 0 |
| LRP4 | 0 | 0 |
| PRKRA | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| FEDRATINIB | 4 | SRPK3 |
| AXITINIB | 4 | SRPK3 |
| RUXOLITINIB | 4 | SRPK3 |
| BOSUTINIB | 4 | SRPK3 |
| NINTEDANIB | 4 | SRPK3 |
| SUNITINIB | 4 | SRPK3 |
| ERLOTINIB | 4 | SRPK3 |
| CRIZOTINIB | 4 | SRPK3 |
| MIDOSTAURIN | 4 | SRPK3 |
| DOVITINIB | 3 | SRPK3 |
| LESTAURTINIB | 3 | SRPK3 |
| RUBOXISTAURIN | 3 | SRPK3 |
| SU-014813 | 2 | SRPK3 |
| TG100-115 | 2 | SRPK3 |
| R-406 | 2 | SRPK3 |
| TOZASERTIB | 2 | SRPK3 |
| GSK-461364 | 1 | SRPK3 |
| KW-2449 | 1 | SRPK3 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| SRPK3 | 229 | Binding:229 |
| TTN | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| TTN | 2.7.11.1 | non-specific serine/threonine protein kinase |
| SRPK3 | 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 |
|---|---|
| SRPK3 | 229 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
18 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) |
|---|---|---|
| FEDRATINIB | 4 | SRPK3 |
| AXITINIB | 4 | SRPK3 |
| RUXOLITINIB | 4 | SRPK3 |
| BOSUTINIB | 4 | SRPK3 |
| NINTEDANIB | 4 | SRPK3 |
| SUNITINIB | 4 | SRPK3 |
| ERLOTINIB | 4 | SRPK3 |
| CRIZOTINIB | 4 | SRPK3 |
| MIDOSTAURIN | 4 | SRPK3 |
| DOVITINIB | 3 | SRPK3 |
| LESTAURTINIB | 3 | SRPK3 |
| RUBOXISTAURIN | 3 | SRPK3 |
| SU-014813 | 2 | SRPK3 |
| TG100-115 | 2 | SRPK3 |
| R-406 | 2 | SRPK3 |
| TOZASERTIB | 2 | SRPK3 |
| GSK-461364 | 1 | SRPK3 |
| KW-2449 | 1 | SRPK3 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | SRPK3 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | TTN |
| D | Druggable family + AlphaFold only, no drug | 1 | CORIN |
| E | Difficult family or no structure, no drug | 5 | PLEKHA3, FKBP7, TTN-AS1, LRP4, PRKRA |
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) |
|---|---|---|
| TTN | 1 | — |
| PLEKHA3 | 0 | — |
| CORIN | 0 | — |
| FKBP7 | 0 | — |
| TTN-AS1 | 0 | — |
| LRP4 | 0 | — |
| PRKRA | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 1.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05989620 | Not specified | RECRUITING | Long-Term Development of Muscular Dystrophy Outcome Assessments |