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Language disorder

disease
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Summary

Language disorder (MONDO:0004750) is a disease (an umbrella term covering 6 Mondo subtypes) with 4 cohort genes and 29 clinical trials. Top therapeutic interventions include leucovorin, levoleucovorin calcium, and rotigotine.

At a glance

  • Umbrella term: 6 Mondo subtypes
  • Cohort genes: 4
  • ClinVar variants: 4
  • Clinical trials: 29

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namelanguage disorder
Mondo IDMONDO:0004750
MeSHD007806
DOIDDOID:93
NCITC97155
UMLSC0023015
MedGen44069
Is cancer (heuristic)no

Data availability: 4 ClinVar variants · 1 HPO phenotype.

Disease family

An umbrella term covering 6 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

Related subtypes (1): speech disorder

Subtypes (6): aphasia, stutter disorder, specific language impairment, expressive language disorder, mixed receptive-expressive language disorder, articulation disorder

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

4 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance, 1 pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
983496NM_001382637.1(OTUD7A):c.697C>T (p.Leu233Phe)OTUD7APathogenicno assertion criteria provided
1332903NM_173354.5(SIK1):c.1153C>T (p.Arg385Ter)SIK1Likely pathogeniccriteria provided, single submitter
242909NM_001197104.2(KMT2A):c.2633G>A (p.Arg878Gln)KMT2AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
373900NM_183357.3(ADCY5):c.649del (p.Arg217fs)ADCY5Uncertain significanceno assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SIK1Orphanet:1934Early infantile developmental and epileptic encephalopathy
SIK1Orphanet:697160Infantile epileptic spasms syndrome
ADCY5Orphanet:1429Benign hereditary chorea
ADCY5Orphanet:324588Familial dyskinesia and facial myokymia
KMT2AOrphanet:319182Wiedemann-Steiner syndrome
KMT2AOrphanet:402017Acute myeloid leukemia with t(9;11)(p22;q23)
KMT2AOrphanet:585918B-lymphoblastic leukemia/lymphoma with t(v;11q23.3)
KMT2AOrphanet:589534Mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2)
KMT2AOrphanet:589595Mixed phenotype acute leukemia with t(v;11q23.3)
KMT2AOrphanet:98831Acute myeloid leukemia with 11q23 abnormalities
KMT2AOrphanet:98835Acute undifferentiated leukemia

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence4

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SIK1HGNC:11142ENSG00000142178P57059Serine/threonine-protein kinase SIK1clinvar
OTUD7AHGNC:20718ENSG00000169918Q8TE49OTU domain-containing protein 7Aclinvar
ADCY5HGNC:236ENSG00000173175O95622Adenylate cyclase type 5clinvar
KMT2AHGNC:7132ENSG00000118058Q03164Histone-lysine N-methyltransferase 2Aclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SIK1Serine/threonine-protein kinase SIK1Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression.
OTUD7AOTU domain-containing protein 7ADeubiquitinase, which cleaves ‘Lys-11’-linked polyubiquitin chains.
ADCY5Adenylate cyclase type 5Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.
KMT2AHistone-lysine N-methyltransferase 2AHistone methyltransferase that plays an essential role in early development and hematopoiesis.

Protein-family classification

Druggable: 2 · Difficult: 2 · Unknown: 0 · Druggable fraction: 0.5

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
Kinase16.9×0.205
Transcription factor24.1×0.205
Enzyme (other)13.0×0.294

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SIK1KinaseyesProt_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
OTUD7ATranscription factornoZnf_A20, OTU_dom, OTU_Deubiquitinase
ADCY5Enzyme (other)yes4.6.1.1A/G_cyclase, Adcy_conserved_dom, A/G_cyclase_CS
KMT2ATranscription factornoSET_dom, Bromodomain, Znf_PHD

Expression context

Cohort genes with no expression data: 0.

3 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)4
unknown0

Top tissues across cohort

TissueCohort genes
mucosa of stomach1
skin of abdomen1
zone of skin1
Brodmann (1909) area 231
endothelial cell1
middle temporal gyrus1
apex of heart1
lower esophagus1
lower esophagus muscularis layer1
colonic epithelium1
sural nerve1
ventricular zone1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SIK1138not_expressedmarkermucosa of stomach, skin of abdomen, zone of skin
OTUD7A178broadyesendothelial cell, Brodmann (1909) area 23, middle temporal gyrus
ADCY5193broadmarkerapex of heart, lower esophagus muscularis layer, lower esophagus
KMT2A285ubiquitousmarkerventricular zone, colonic epithelium, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
KMT2A4,314
ADCY51,992
SIK11,840
OTUD7A1,098

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
KMT2AQ0316460
ADCY5O956222
OTUD7AQ8TE491

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
SIK1P5705961.31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 70. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes2237.9×0.002SIK1, KMT2A
Adenylate cyclase activating pathway1285.5×0.034ADCY5
Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters1219.6×0.034KMT2A
Adenylate cyclase inhibitory pathway1190.3×0.034ADCY5
The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex1178.4×0.034KMT2A
PKA activation in glucagon signalling1167.9×0.034ADCY5
PKA activation1158.6×0.034ADCY5
Activation of GABAB receptors1150.3×0.034ADCY5
PKA-mediated phosphorylation of CREB1142.8×0.034ADCY5
GABA B receptor activation1135.9×0.034ADCY5
Adrenaline,noradrenaline inhibits insulin secretion198.5×0.034ADCY5
Anti-inflammatory response favouring Leishmania parasite infection198.5×0.034ADCY5
Leishmania parasite growth and survival198.5×0.034ADCY5
Calmodulin induced events195.2×0.034ADCY5
CaM pathway195.2×0.034ADCY5
Ca-dependent events192.1×0.034ADCY5
Aquaporin-mediated transport192.1×0.034ADCY5
Glucagon signaling in metabolic regulation186.5×0.034ADCY5
R-HSA-400253186.5×0.034SIK1
G-protein mediated events181.6×0.034ADCY5
DAG and IP3 signaling179.3×0.034ADCY5
GABA receptor activation179.3×0.034ADCY5
Response of endothelial cells to shear stress175.1×0.034ADCY5
FCGR3A-mediated IL10 synthesis173.2×0.034ADCY5
Ovarian tumor domain proteases169.6×0.034OTUD7A
Opioid Signalling166.4×0.034ADCY5
PLC beta mediated events166.4×0.034ADCY5
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion166.4×0.034ADCY5
Vasopressin regulates renal water homeostasis via Aquaporins166.4×0.034ADCY5
Formation of WDR5-containing histone-modifying complexes166.4×0.034KMT2A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
negative regulation of DNA methylation-dependent heterochromatin formation12106.5×0.011KMT2A
negative regulation of triglyceride biosynthetic process11053.2×0.011SIK1
obsolete negative regulation of CREB transcription factor activity11053.2×0.011SIK1
adenylate cyclase-inhibiting dopamine receptor signaling pathway1842.6×0.011ADCY5
regulation of myotube differentiation1842.6×0.011SIK1
G protein-coupled adenosine receptor signaling pathway1601.9×0.011ADCY5
response to potassium ion1526.6×0.011KMT2A
T-helper 2 cell differentiation1468.1×0.011KMT2A
positive regulation of anoikis1468.1×0.011SIK1
adenylate cyclase-activating dopamine receptor signaling pathway1383.0×0.011ADCY5
protein K11-linked deubiquitination1383.0×0.011OTUD7A
cAMP biosynthetic process1351.1×0.011ADCY5
anoikis1324.1×0.011SIK1
protein deubiquitination involved in ubiquitin-dependent protein catabolic process1324.1×0.011OTUD7A
regulation of short-term neuronal synaptic plasticity1280.9×0.011KMT2A
cellular response to forskolin1280.9×0.011ADCY5
embryonic hemopoiesis1247.8×0.011KMT2A
regulation of sodium ion transport1234.1×0.011SIK1
definitive hemopoiesis1234.1×0.011KMT2A
regulation of insulin secretion involved in cellular response to glucose stimulus1234.1×0.011ADCY5
intracellular signal transduction219.1×0.011SIK1, ADCY5
cellular response to glucagon stimulus1210.7×0.012ADCY5
negative regulation of gluconeogenesis1200.6×0.012SIK1
entrainment of circadian clock by photoperiod1183.2×0.012SIK1
vascular endothelial cell response to laminar fluid shear stress1183.2×0.012ADCY5
cardiac muscle cell differentiation1168.5×0.013SIK1
exploration behavior1162.0×0.013KMT2A
renal water homeostasis1127.7×0.015ADCY5
membrane depolarization1127.7×0.015KMT2A
negative regulation of fibroblast proliferation1123.9×0.015KMT2A

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
MethylprednisolonePhase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 3 of 4 evidence-associated genes (75%) 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
SIK1FEDRATINIB
KMT2AFLUORESCEIN

Top cohort targets by molecule count

SymbolMoleculesMax phase
KMT2A5354
SIK1194
OTUD7A00
ADCY500

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
FEDRATINIB4SIK1
AXITINIB4SIK1
NERATINIB4SIK1
VANDETANIB4SIK1
BOSUTINIB4SIK1
PAZOPANIB4SIK1
NINTEDANIB4SIK1
SUNITINIB4KMT2A, SIK1
DASATINIB4SIK1
MIDOSTAURIN4SIK1
FLUORESCEIN4KMT2A
METHYSERGIDE4KMT2A
OXCARBAZEPINE4KMT2A
TRYPAN BLUE FREE ACID4KMT2A
RALOXIFENE HYDROCHLORIDE4KMT2A
IDARUBICIN4KMT2A
DULOXETINE4KMT2A
PYRITHIONE ZINC4KMT2A
HYDROCORTISONE VALERATE4KMT2A
PROMETHAZINE HYDROCHLORIDE4KMT2A
THIORIDAZINE HYDROCHLORIDE4KMT2A
METHYSERGIDE MALEATE4KMT2A
THIOTHIXENE4KMT2A
METHANTHELINE4KMT2A
ROSE BENGAL FREE ACID4KMT2A
BENZYL BENZOATE4KMT2A
NOMIFENSINE MALEATE4KMT2A
ANTAZOLINE4KMT2A
CARBOPLATIN4KMT2A
FLUVOXAMINE MALEATE4KMT2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
SIK1210Binding:205, Toxicity:4, ADMET:1
KMT2A188Binding:180, Functional:8
ADCY543Binding:33, Functional:9, ADMET:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
ADCY54.6.1.1adenylate cyclase

Cohort genes with high screening signal

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

SymbolChEMBL assays
SIK1210
KMT2A188

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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)
FEDRATINIB4SIK1
AXITINIB4SIK1
NERATINIB4SIK1
VANDETANIB4SIK1
BOSUTINIB4SIK1
PAZOPANIB4SIK1
NINTEDANIB4SIK1
SUNITINIB4KMT2A, SIK1
DASATINIB4SIK1
MIDOSTAURIN4SIK1
FLUORESCEIN4KMT2A
METHYSERGIDE4KMT2A
OXCARBAZEPINE4KMT2A
TRYPAN BLUE FREE ACID4KMT2A
RALOXIFENE HYDROCHLORIDE4KMT2A
IDARUBICIN4KMT2A
DULOXETINE4KMT2A
PYRITHIONE ZINC4KMT2A
HYDROCORTISONE VALERATE4KMT2A
PROMETHAZINE HYDROCHLORIDE4KMT2A
THIORIDAZINE HYDROCHLORIDE4KMT2A
METHYSERGIDE MALEATE4KMT2A
THIOTHIXENE4KMT2A
METHANTHELINE4KMT2A
ROSE BENGAL FREE ACID4KMT2A
BENZYL BENZOATE4KMT2A
NOMIFENSINE MALEATE4KMT2A
ANTAZOLINE4KMT2A
CARBOPLATIN4KMT2A
FLUVOXAMINE MALEATE4KMT2A

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2SIK1, KMT2A
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1ADCY5
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1OTUD7A

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
OTUD7A0—
ADCY543—

Clinical trials & evidence

Clinical trials

Clinical trials: 29.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified23
PHASE24
PHASE31
PHASE2/PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00033150PHASE3COMPLETEDA Comparison of Language Intervention Programs
NCT02909088PHASE2/PHASE3UNKNOWNEfficacy and Tolerability of Ecopipam in Adults With Childhood Onset Fluency Disorder (Stuttering).
NCT04060017PHASE2ACTIVE_NOT_RECRUITINGEarly Treatment of Language Impairment in Young Children With Autism Spectrum Disorder With Leucovorin Calcium
NCT04060030PHASE2RECRUITINGTreatment of Social and Language Deficits With Leucovorin for Young Children With Autism
NCT00840060PHASE2COMPLETEDEfficacy of AMALS in Treating Language Impairment in Children
NCT04937452PHASE2COMPLETEDDopaminergic Therapy for Frontotemporal Dementia Patients
NCT05283265Not specifiedRECRUITINGNeurophysiological Mechanisms of Language Comprehension
NCT05443633Not specifiedRECRUITINGEnhancing Language Function in Aphasia
NCT05741853Not specifiedRECRUITINGCognitive Reserve and Response to Speech-Language Intervention in Bilingual Speakers With Primary Progressive Aphasia
NCT06036316Not specifiedRECRUITINGStudy of Language Disorders and Interactions Between Mnesic Capabilities and Semantic Competencies in Patients With Psychosis
NCT07518576Not specifiedRECRUITINGDevelopment and Validation of Language and Communication Assessment Scales
NCT00004570Not specifiedTERMINATEDHereditary Deficits in Auditory Processing Leading to Language Impairment
NCT00016796Not specifiedCOMPLETEDLanguage Stimuli Screening in Children
NCT00125216Not specifiedCOMPLETEDEvaluation of the Effects of Response Elaboration Training for Aphasia
NCT00125242Not specifiedCOMPLETEDWord-Retrieval Treatment for Aphasia: Semantic Feature Analysis
NCT00156221Not specifiedCOMPLETEDMR Scanning of Very Young Children With Severe Developmental Disorders
NCT00547833Not specifiedCOMPLETEDPartial Word Knowledge Growth in Children With LLD
NCT01375595Not specifiedTERMINATEDBrain Areas Involved in Sound and Spoken Word Memory
NCT01844609Not specifiedCOMPLETEDChina Obstetrics and Gynecology Journal Club
NCT01988623Not specifiedCOMPLETEDPivotal Response Treatment for Individuals With Intellectual Disabilities
NCT03974659Not specifiedUNKNOWNEnhanced Recovery After Surgery Using TMS on Cerebellar Language Area for Brain Tumor Patients
NCT04204356Not specifiedCOMPLETEDThe Effect of Non-invasive Brain Stimulation on Language Production in Post-stroke Aphasia
NCT04260815Not specifiedCOMPLETEDThe Effect of Non-invasive Brian Stimulation on Language Production in Healthy Older Adults
NCT04465084Not specifiedCOMPLETEDAssessment of Language Disorders in Multiple Sclerosis Patients
NCT04511767Not specifiedCOMPLETEDReliability and Validity of CCISO for Diagnosis of Autism Spectrum Disorder
NCT05909787Not specifiedUNKNOWNPrevalence of Oral Disorders in Children in ENT Pathologies
NCT05980897Not specifiedCOMPLETEDInner Speech and Naming Treatment for Individuals with Aphasia
NCT06025890Not specifiedUNKNOWNClinical Evaluation and Intervention of Developmental Behavioral Diseases Based on Multicenter Cohort Study(CEIDBDBMCS)
NCT07128810Not specifiedCOMPLETEDParent Child Interaction Therapy vs Conventional Parent Led Therapy in Down Syndrome

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
LEUCOVORIN42
LEVOLEUCOVORIN CALCIUM42
ROTIGOTINE41
ECOPIPAM31
CHEMBL10438301

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
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This page pulls from 69 datasets indexed by BioBTree:

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