◎ Sugi Atlas

Atlas / Disease / Specific language impairment

Specific language impairment

disease
On this page

Also known as language impairment (disease)

Summary

Specific language impairment (MONDO:0000724) is a disease (an umbrella term covering 5 Mondo subtypes) with 21 cohort genes (30 GWAS associations across 6 studies) and 12 clinical trials.

At a glance

  • Umbrella term: 5 Mondo subtypes
  • Cohort genes: 21
  • GWAS associations: 30
  • Clinical trials: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namespecific language impairment
Mondo IDMONDO:0000724
EFOEFO:1001510
OMIM606711
Orphanet458713
DOIDDOID:0060244
ICD-11862918022
UMLSC0454651
MedGen627772
Is cancer (heuristic)no

Also known as: language impairment (disease)

Data availability: 30 GWAS associations (6 studies).

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › developmental disorder of mental health › specific developmental disorder › communication disorder › language disorder › specific language impairment

Related subtypes (5): aphasia, stutter disorder, expressive language disorder, mixed receptive-expressive language disorder, articulation disorder

Subtypes (5): specific language impairment 1, specific language impairment 2, specific language impairment 3, specific language impairment 4, specific language impairment 5

Genetics & variants

GWAS landscape

30 GWAS associations across 6 studies. Top hits map to 17 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs1838265467e-09RPL6P22 - RPL10AP3A2.73
rs37877512e-07HLCS?0.39
rs591970853e-07CCDC136A5.12
rs105042294e-07LINC00588?0.51
rs59951775e-07RBFOX2A5.03
rs121218647e-07MIR34AHG?0.64
rs107745471e-06RPS27P25 - COX6A1T4.85
rs17117451e-06INIPA4.89
rs57616182e-06TPST2 - CRYBB1?0.35
rs7222083e-06ESR1G0.22
rs37898673e-06TNC, DELEC1?0.34
rs286553873e-06PMFBP1 - LINC01572T4.65
rs10253703e-06MIR4268 - EPHA4A4.67
rs15598314e-06LINC02694T0.34
rs64960124e-06LINC02694G0.34
rs37898684e-06DELEC1, TNCG
rs48959705e-06TARID?0.35
rs47966045e-06HAP1?0.36
rs726265816e-06ZFP64T4.53
rs21803867e-06MIR493HG, RTL1, MEG8A0.21
rs1419948687e-06STK24T4.51
rs133844699e-06LINC02973 - RNU6ATAC37PT4.45
rs67374179e-06MIR4268 - EPHA4A4.45

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90271931Nudel R202361017,770Developmental language disorder - a comprehensive study of more than 46,000 individuals.
GCST003396Kornilov SA20161490Genome-Wide Association and Exome Sequencing Study of Language Disorder in an Isolated Population.
GCST003397Kornilov SA20161490Genome-Wide Association and Exome Sequencing Study of Language Disorder in an Isolated Population.
GCST003398Kornilov SA20161490Genome-Wide Association and Exome Sequencing Study of Language Disorder in an Isolated Population.
GCST004401Gialluisi A201400Genome-wide screening for DNA variants associated with reading and language traits.
GCST004402Gialluisi A201400Genome-wide screening for DNA variants associated with reading and language traits.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding1
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic22

MAF distribution

BucketVariants
common (>=0.05)22
low_freq (0.01-0.05)1
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant19
intergenic_variant3
missense_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs183826546834217842G>A0.05intron_variantRPL6P22 - RPL10AP37e-09Tier 4: intronic/intergenic
rs37877512136787862T>A,C0.448intron_variantHLCS2e-07Tier 4: intronic/intergenic
rs591970857128820702G>A0.08intron_variantCCDC1363e-07Tier 4: intronic/intergenic
rs10504229857283936A>G0.162intron_variantLINC005884e-07Tier 4: intronic/intergenic
rs59951772235913505G>A,C0.08intron_variantRBFOX25e-07Tier 4: intronic/intergenic
rs1212186419145273C>A0.088intron_variantMIR34AHG7e-07Tier 4: intronic/intergenic
rs1077454712120424913T>A,C0.33intergenic_variantRPS27P25 - COX6A11e-06Tier 4: intronic/intergenic
rs17117459112690629C>A,T0.091intron_variantINIP1e-06Tier 4: intronic/intergenic
rs57616182226597742T>G0.494intron_variantTPST2 - CRYBB12e-06Tier 4: intronic/intergenic
rs7222086152001750A>G0.35intron_variantESR13e-06Tier 4: intronic/intergenic
rs37898679115113409A>C,G,T0.469intron_variantTNC, DELEC13e-06Tier 4: intronic/intergenic
rs286553871672225293T>A,G0.054intergenic_variantPMFBP1 - LINC015723e-06Tier 4: intronic/intergenic
rs10253702221346292G>A0.462intron_variantMIR4268 - EPHA43e-06Tier 4: intronic/intergenic
rs15598311538844103G>A,C,T0.06intron_variantLINC026944e-06Tier 4: intronic/intergenic
rs64960121538858723G>A0.06intron_variantLINC026944e-06Tier 4: intronic/intergenic
rs37898689115113402T>A,C,G0.47intron_variantDELEC1, TNC4e-06Tier 4: intronic/intergenic
rs48959706133543112T>A,C,G0.497intron_variantTARID5e-06Tier 4: intronic/intergenic
rs47966041741734624T>A,C,G0.444missense_variantHAP15e-06Tier 1: coding
rs726265812052166910T>A,C,G0.254intron_variantZFP646e-06Tier 4: intronic/intergenic
rs218038614100898928C>A,G,T0.38intron_variantMIR493HG, RTL1, MEG87e-06Tier 4: intronic/intergenic
rs1419948681398570168C>G,T0.027intron_variantSTK247e-06Tier 4: intronic/intergenic
rs1338446927509390G>T0.118intergenic_variantLINC02973 - RNU6ATAC37P9e-06Tier 4: intronic/intergenic
rs67374172221348323A>G0.462intron_variantMIR4268 - EPHA49e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
OPN1SWOrphanet:88629Tritanopia
COX6A1Orphanet:435998Autosomal recessive intermediate Charcot-Marie-Tooth disease type D
ESR1Orphanet:785Estrogen resistance syndrome
FLNCOrphanet:171445Muscle filaminopathy
FLNCOrphanet:63273FLNC-related handgrip and calf weakness-distal myopathy
FLNCOrphanet:75249Familial isolated restrictive cardiomyopathy
HLCSOrphanet:79242Holocarboxylase synthetase deficiency
TNCOrphanet:90635Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

Cohort genes → proteins

21 cohort genes, 20 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only21

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
OPN1SWHGNC:1012ENSG00000128617P03999Short-wave-sensitive opsin 1gwas
SRSF9HGNC:10791ENSG00000111786Q13242Serine/arginine-rich splicing factor 9gwas
STK24HGNC:11403ENSG00000102572Q9Y6E0Serine/threonine-protein kinase 24gwas
MEG8HGNC:14574ENSG00000225746maternally expressed 8, small nucleolar RNA host genegwas
CALUHGNC:1458ENSG00000128595O43852Calumeningwas
DYNLL1HGNC:15476ENSG00000088986P63167Dynein light chain 1, cytoplasmicgwas
ZFP64HGNC:15940ENSG00000020256Q9NTW7Zinc finger protein 64gwas
ATP6V1FHGNC:16832ENSG00000128524Q16864V-type proton ATPase subunit Fgwas
CCDC136HGNC:22225ENSG00000128596Q96JN2Coiled-coil domain-containing protein 136gwas
COX6A1HGNC:2277ENSG00000111775P12074Cytochrome c oxidase subunit 6A1, mitochondrialgwas
KIAA1958HGNC:23427ENSG00000165185Q8N8K9Uncharacterized protein KIAA1958gwas
LINC00588HGNC:24494ENSG00000215117Q9Y4M8Putative uncharacterized protein encoded by LINC00588gwas
INIPHGNC:24994ENSG00000148153Q9NRY2SOSS complex subunit Cgwas
GATCHGNC:25068ENSG00000257218O43716Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrialgwas
TRIAP1HGNC:26937ENSG00000170855O43715TP53-regulated inhibitor of apoptosis 1gwas
ESR1HGNC:3467ENSG00000091831P03372Estrogen receptorgwas
FLNCHGNC:3756ENSG00000128591Q14315Filamin-Cgwas
HLCSHGNC:4976ENSG00000159267P50747Biotin–protein ligasegwas
TNCHGNC:5318ENSG00000041982P24821Tenascingwas
APEX1HGNC:587ENSG00000100823P27695DNA repair nuclease/redox regulator APEX1gwas
RBFOX2HGNC:9906ENSG00000100320O43251RNA binding protein fox-1 homolog 2gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
OPN1SWShort-wave-sensitive opsin 1Visual pigments are the light-absorbing molecules that mediate vision.
SRSF9Serine/arginine-rich splicing factor 9Plays a role in constitutive splicing and can modulate the selection of alternative splice sites.
STK24Serine/threonine-protein kinase 24Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation.
CALUCalumeninInvolved in regulation of vitamin K-dependent carboxylation of multiple N-terminal glutamate residues.
DYNLL1Dynein light chain 1, cytoplasmicComponent of dynein, a family of motor proteins essential for movement along microtubules.
ZFP64Zinc finger protein 64May be involved in the regulation of mesenchymal cell differentiation through transactivation of NOTCH1 target genes.
ATP6V1FV-type proton ATPase subunit FSubunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
CCDC136Coiled-coil domain-containing protein 136May play a role in acrosome formation in spermatogenesis and in fertilization.
COX6A1Cytochrome c oxidase subunit 6A1, mitochondrialComponent of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.
INIPSOSS complex subunit CComponent of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint.
GATCGlutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrialAllows the formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria.
TRIAP1TP53-regulated inhibitor of apoptosis 1Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes.
ESR1Estrogen receptorNuclear hormone receptor.
FLNCFilamin-CMuscle-specific filamin, which plays a central role in sarcomere assembly and organization.
HLCSBiotin–protein ligaseBiotin–protein ligase catalyzing the biotinylation of the 4 biotin-dependent carboxylases acetyl-CoA-carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase.
TNCTenascinExtracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration.
APEX1DNA repair nuclease/redox regulator APEX1Multifunctional protein that plays a central role in the cellular response to oxidative stress.
RBFOX2RNA binding protein fox-1 homolog 2RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.

Protein-family classification

Druggable: 7 · Difficult: 1 · Unknown: 13 · Druggable fraction: 0.33

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.

FamilyGenesFoldFDR
Nuclear receptor118.4×0.424
Phosphatase14.0×0.594
Antibody/Immunoglobulin22.8×0.594
Other/Unknown131.1×0.739
Kinase11.3×0.789
GPCR11.1×0.789
Enzyme (other)10.6×0.934
Transcription factor10.4×0.934

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
OPN1SWGPCRyesGPCR_Rhodpsn, Opsin_blue, Opsin
SRSF9Other/UnknownnoRRM_dom, Nucleotide-bd_a/b_plait_sf, SRSF9_RRM1
STK24KinaseyesProt_kinase_dom, Kinase-like_dom_sf, Protein_kinase_ATP_BS
MEG8Other/Unknownno
CALUOther/UnknownnoEF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
DYNLL1Other/UnknownnoDynein_light_chain_typ-1/2, Dynein_light_1/2_CS, DLC_sf
ZFP64Transcription factornoZnf_C2H2_type, Znf_C2H2_sf, C2H2-ZF_domain-containing
ATP6V1FOther/UnknownnoATPase_V1-cplx_fsu_euk, ATPase_V1-cplx_f_g_su, ATPase_V1_fsu_sf
CCDC136Other/UnknownnoCent_Immune-Sig_Mod
COX6A1Other/UnknownnoCyt_c_oxidase_su6a, Cyt_c_oxidase_su6a_CS, Cyt_c_oxidase_su6a_sf
KIAA1958Other/UnknownnoZMYM2-like_C, KIAA1958
LINC00588Other/Unknownno
INIPOther/UnknownnoSOSSC
GATCEnzyme (other)yes6.3.5.7GatC, Asp/Glu-ADT_sf_sub_c
TRIAP1Other/UnknownnoMDM35_apoptosis
ESR1Nuclear receptoryesNucl_hrmn_rcpt_lig-bd, Estr_rcpt, Znf_hrmn_rcpt
FLNCAntibody/ImmunoglobulinyesFilamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
HLCSOther/UnknownnoBPL_C, BPL_LPL_catalytic, Biotin_CoA_COase_ligase
TNCAntibody/ImmunoglobulinyesEGF, Fibrinogen_a/b/g_C_dom, FN3_dom
APEX1Phosphataseyes4.2.99.18AP_endonuc_1, Endo/exonuclease/phosphatase, AP_endonuclease_F1_BS
RBFOX2Other/UnknownnoRRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3

Expression context

Cohort genes with no expression data: 0.

18 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)21
unknown0

Top tissues across cohort

TissueCohort genes
tendon of biceps brachii3
prefrontal cortex3
secondary oocyte2
frontal pole2
gingival epithelium2
left testis2
right testis2
kidney epithelium2
male germ line stem cell (sensu Vertebrata) in testis2
embryo2
ganglionic eminence2
Brodmann (1909) area 461
sural nerve1
vena cava1
body of pancreas1
endometrium epithelium1
monocyte1
amniotic fluid1
esophagus squamous epithelium1
adenohypophysis1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
OPN1SW95tissue_specificyesvena cava, sural nerve, Brodmann (1909) area 46
SRSF9302ubiquitousmarkerendometrium epithelium, monocyte, body of pancreas
STK24295ubiquitousmarkersecondary oocyte, esophagus squamous epithelium, amniotic fluid
MEG8163tissue_specificmarkeradrenal tissue, calcaneal tendon, adenohypophysis
CALU303ubiquitousmarkerstromal cell of endometrium, smooth muscle tissue, tendon of biceps brachii
DYNLL1295ubiquitousmarkerprefrontal cortex, frontal pole, gingival epithelium
ZFP64288ubiquitousyesgerminal epithelium of ovary, gingival epithelium, secondary oocyte
ATP6V1F294ubiquitousmarkerprefrontal cortex, left testis, right testis
CCDC136215ubiquitousmarkersperm, left testis, right testis
COX6A1145ubiquitousmarkerprefrontal cortex, primary visual cortex, frontal cortex
KIAA1958200ubiquitousmarkerkidney epithelium, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
LINC0058826yesmale germ line stem cell (sensu Vertebrata) in testis, cortex of kidney, testis
INIP256ubiquitousmarkerileal mucosa, kidney epithelium, pons
GATC258ubiquitousmarkertendon of biceps brachii, medial globus pallidus, globus pallidus
TRIAP1291ubiquitousmarkertendon of biceps brachii, tongue squamous epithelium, triceps brachii
ESR1216broadmarkeroviduct epithelium, cervix epithelium, mammalian vulva
FLNC255ubiquitousmarkergastrocnemius, hindlimb stylopod muscle, tibialis anterior
HLCS205ubiquitousmarkerparaflocculus, frontal pole, middle frontal gyrus
TNC272ubiquitousmarkersaphenous vein, tibial artery, popliteal artery
APEX1294ubiquitousmarkerganglionic eminence, embryo, ventricular zone
RBFOX2144ubiquitousmarkercortical plate, embryo, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

SymbolInteractor count
ESR112,382
APEX15,100
DYNLL14,541
FLNC3,174
SRSF92,949
HLCS2,554
RBFOX22,274
ATP6V1F2,214
STK242,041
CALU2,013

Intra-cohort edges

ABSources
CCDC136DYNLL1intact
CCDC136RBFOX2string_interaction
COX6A1ESR1intact
ESR1RBFOX2string_interaction

Structural data

PDB: 13 · AlphaFold-only: 7 · No structure: 1

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
ESR1P03372478
APEX1P2769567
STK24Q9Y6E040
DYNLL1P6316721
TNCP2482121
FLNCQ1431514
ATP6V1FQ168648
TRIAP1O437156
COX6A1P120743
INIPQ9NRY23
ZFP64Q9NTW72
OPN1SWP039991
RBFOX2O432511

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
CALUO4385279.82
GATCO4371678.61
HLCSP5074777.33
SRSF9Q1324269.97
CCDC136Q96JN269.24
KIAA1958Q8N8K960.57
LINC00588Q9Y4M849.41

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 105. Enrichment computed across 21 evidence-associated genes (14 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 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Defective visual phototransduction due to OPN1SW loss of function1815.7×0.082OPN1SW
Abasic sugar-phosphate removal via the single-nucleotide replacement pathway1271.9×0.082APEX1
Resolution of AP sites via the multiple-nucleotide patch replacement pathway1203.9×0.082APEX1
Activation of BIM and translocation to mitochondria1203.9×0.082DYNLL1
Resolution of AP sites via the single-nucleotide replacement pathway1163.1×0.082APEX1
Defects in biotin (Btn) metabolism1163.1×0.082HLCS
RUNX1 regulates estrogen receptor mediated transcription1135.9×0.082ESR1
RUNX1 regulates transcription of genes involved in WNT signaling1135.9×0.082ESR1
The retinoid cycle in cones (daylight vision)1116.5×0.082OPN1SW
Defective HLCS causes multiple carboxylase deficiency1116.5×0.082HLCS
Post-translational protein phosphorylation214.3×0.082CALU, TNC
POLB-Dependent Long Patch Base Excision Repair190.6×0.083APEX1
Opsins190.6×0.083OPN1SW
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)212.4×0.083CALU, TNC
Resolution of Abasic Sites (AP sites)181.6×0.083APEX1
Displacement of DNA glycosylase by APEX1174.2×0.083APEX1
Biotin transport and metabolism174.2×0.083HLCS
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors154.4×0.101ESR1
Base Excision Repair151.0×0.101APEX1
Cell-extracellular matrix interactions148.0×0.101FLNC
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy148.0×0.101ATP6V1F
Developmental Lineage of Mammary Gland Alveolar Cells145.3×0.101ESR1
Defects in vitamin and cofactor metabolism142.9×0.101HLCS
Mitochondrial unfolded protein response (UPRmt)142.9×0.101ESR1
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release138.8×0.107TRIAP1
PCNA-Dependent Long Patch Base Excision Repair137.1×0.108APEX1
Apoptotic cleavage of cellular proteins134.0×0.109STK24
Apoptotic execution phase134.0×0.109STK24
Developmental Lineage of Mammary Gland Luminal Epithelial Cells132.6×0.109ESR1
Syndecan interactions130.2×0.110TNC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 17 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
estrogen receptor signaling pathway286.2×0.035ESR1, RBFOX2
regulation of epithelial cell apoptotic process1991.3×0.038ESR1
mesenchymal-epithelial cell signaling involved in prostate gland development1495.6×0.038TNC
response to biotin1495.6×0.038HLCS
telomere maintenance via base-excision repair1495.6×0.038APEX1
negative regulation of DNA strand resection involved in replication fork processing1495.6×0.038DYNLL1
positive regulation of nitric-oxide synthase activity1330.4×0.038ESR1
bud outgrowth involved in lung branching1330.4×0.038TNC
prostate epithelial cord elongation1330.4×0.038ESR1
glutaminyl-tRNAGln biosynthesis via transamidation1330.4×0.038GATC
biotin metabolic process1247.8×0.038HLCS
mammary gland branching involved in pregnancy1247.8×0.038ESR1
antral ovarian follicle growth1198.3×0.038ESR1
regulation of translational fidelity1198.3×0.038GATC
steroid hormone receptor signaling pathway1198.3×0.038ESR1
regulation of branching involved in prostate gland morphogenesis1198.3×0.038ESR1
absorption of visible light1165.2×0.038OPN1SW
RNA metabolic process1165.2×0.038RBFOX2
negative regulation of phosphorylation1165.2×0.038DYNLL1
epithelial cell proliferation involved in mammary gland duct elongation1165.2×0.038ESR1
regulation of membrane lipid distribution1165.2×0.038TRIAP1
regulation of axon regeneration1141.6×0.038STK24
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis1141.6×0.038ESR1
cellular response to prostaglandin D stimulus1141.6×0.038TNC
positive regulation of phospholipid transport1141.6×0.038TRIAP1
peripheral nervous system axon regeneration1123.9×0.038TNC
nuclear receptor-mediated steroid hormone signaling pathway1123.9×0.038ESR1
mesenchymal cell differentiation1123.9×0.038ZFP64
response to fibroblast growth factor1123.9×0.038TNC
regulation of alternative mRNA splicing, via spliceosome228.7×0.038SRSF9, RBFOX2

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 4 · Undrugged: 17

Druggability breadth: 9 of 21 evidence-associated genes (43%) 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.

SymbolExample approved molecule
STK24NERATINIB
ESR1CANDESARTAN CILEXETIL
APEX1CEFOTAXIME SODIUM

Top cohort targets by molecule count

SymbolMoleculesMax phase
ESR11624
APEX1534
STK24184
DYNLL112
OPN1SW00
SRSF900
MEG800
CALU00
ZFP6400
ATP6V1F00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
NERATINIB4STK24
BOSUTINIB4STK24
GILTERITINIB4STK24
NINTEDANIB4STK24
SUNITINIB4STK24
QUIZARTINIB4STK24
CANDESARTAN CILEXETIL4ESR1
DIENESTROL4ESR1
BEXAROTENE4ESR1
VARENICLINE4ESR1
ACETOPHENAZINE4ESR1
ARIPIPRAZOLE4ESR1
RALOXIFENE HYDROCHLORIDE4ESR1
NORETHINDRONE4ESR1
TRIMETREXATE4ESR1
ESTRADIOL ACETATE4ESR1
ETHYLESTRENOL4ESR1
ETHYNODIOL DIACETATE4ESR1
CHLOROTRIANISENE4ESR1
ESTRADIOL CYPIONATE4ESR1
MESTRANOL4ESR1
QUINESTROL4ESR1
RIBOFLAVIN 5’-PHOSPHATE4ESR1
ESTETROL ANHYDROUS4ESR1
OXYBUTYNIN4ESR1
MILTEFOSINE4ESR1
MIFEPRISTONE4ESR1
LENVATINIB4ESR1
CLOFAZIMINE4ESR1
BUTOCONAZOLE4ESR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

SymbolAssaysType breakdown
ESR12,435Binding:2037, Functional:363, ADMET:35
STK24314Binding:314
APEX149Binding:45, Functional:4
HLCS8Binding:8
DYNLL17Binding:7
SRSF92Binding:2
CALU1Binding:1
COX6A11Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
GATC6.3.5.7glutaminyl-tRNA synthase (glutamine-hydrolysing)
APEX14.2.99.18DNA-(apurinic or apyrimidinic site) lyase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
STK24314
ESR12,435

Pharmacogenomics

Cohort genes with a PharmGKB record: 21; 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.

CompoundMax phaseCohort target (bioactivity)
NERATINIB4STK24
BOSUTINIB4STK24
GILTERITINIB4STK24
NINTEDANIB4STK24
SUNITINIB4STK24
QUIZARTINIB4STK24
CANDESARTAN CILEXETIL4ESR1
DIENESTROL4ESR1
BEXAROTENE4ESR1
VARENICLINE4ESR1
ACETOPHENAZINE4ESR1
ARIPIPRAZOLE4ESR1
RALOXIFENE HYDROCHLORIDE4ESR1
NORETHINDRONE4ESR1
TRIMETREXATE4ESR1
ESTRADIOL ACETATE4ESR1
ETHYLESTRENOL4ESR1
ETHYNODIOL DIACETATE4ESR1
CHLOROTRIANISENE4ESR1
ESTRADIOL CYPIONATE4ESR1
MESTRANOL4ESR1
QUINESTROL4ESR1
RIBOFLAVIN 5’-PHOSPHATE4ESR1
ESTETROL ANHYDROUS4ESR1
OXYBUTYNIN4ESR1
MILTEFOSINE4ESR1
MIFEPRISTONE4ESR1
LENVATINIB4ESR1
CLOFAZIMINE4ESR1
BUTOCONAZOLE4ESR1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)3STK24, ESR1, APEX1
BPhased (≥1) drug, not yet approved1DYNLL1
CDruggable family + PDB, no drug3OPN1SW, FLNC, TNC
DDruggable family + AlphaFold only, no drug1GATC
EDifficult family or no structure, no drug13SRSF9, MEG8, CALU, ZFP64, ATP6V1F, CCDC136, COX6A1, KIAA1958, LINC00588, INIP (+3 more)

Undrugged target profiles

17 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
OPN1SW0—
SRSF92—
MEG80—
CALU1—
ZFP640—
ATP6V1F0—
CCDC1360—
COX6A11—
KIAA19580—
LINC005880—
INIP0—
GATC0—
TRIAP10—
FLNC0—
HLCS8—
TNC0—
RBFOX20—

Clinical trials & evidence

Clinical trials

Clinical trials: 12.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified12

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04558541Not specifiedRECRUITINGA Developmental Framework For Linking Phonological And Morpho-syntactic Sequential Pattern Rules In DLD: Production
NCT06995014Not specifiedRECRUITINGRetrieval-based Word Learning in Developmental Language Disorder: Adaptive Retrieval Schedule
NCT07048392Not specifiedRECRUITINGRetrieval-Based Word Learning in Developmental Language Disorder During Book Reading II
NCT07136636Not specifiedRECRUITINGSpeech of Kids After Neonatal Encephalopathy
NCT01829360Not specifiedCOMPLETEDAccelerating Word Learning in Children With Language Impairment
NCT03438760Not specifiedTERMINATEDImproving STEM Outcomes for Young Children With Language Learning Disabilities
NCT04141332Not specifiedCOMPLETEDSpecific Language Impairment (SLI) in Children May Caused by Epileptic Brain Activity
NCT04531514Not specifiedCOMPLETEDA Framework For Linking Sequential Pattern Rules in DLD: Perception in Toddlers
NCT04996472Not specifiedCOMPLETEDA Framework For Linking Sequential Pattern Rules in DLD: Perception in Adults
NCT05325333Not specifiedCOMPLETEDRetrieval-Based Word Learning in Developmental Language Disorder
NCT06001866Not specifiedCOMPLETEDRetrieval-Based Word Learning in Developmental Language Disorder: Verb Learning
NCT06026124Not specifiedCOMPLETEDRetrieval-Based Word Learning in Developmental Language Disorder During Book Reading

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 70

This page pulls from 70 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd11intactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot