Specific language impairment 5
disease diseaseOn this page
Also known as SLI5specific language impairment type 5
Summary
Specific language impairment 5 (MONDO:0014184) is a disease with 14 cohort genes (13 GWAS associations across 6 studies).
At a glance
- Cohort genes: 14
- GWAS associations: 13
- ClinVar variants: 6
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | specific language impairment 5 |
| Mondo ID | MONDO:0014184 |
| EFO | EFO:0005425 |
| OMIM | 615432 |
| UMLS | C3809483 |
| MedGen | 815813 |
| Is cancer (heuristic) | no |
Also known as: SLI5 · specific language impairment 5 · specific language impairment type 5
Data availability: 6 ClinVar variants · 13 GWAS associations (6 studies) · 2 GenCC gene-disease records.
Disease family
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 › specific language impairment 5
Related subtypes (4): specific language impairment 1, specific language impairment 2, specific language impairment 3, specific language impairment 4
Genetics & variants
GWAS landscape
13 GWAS associations across 6 studies. Top hits map to 6 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| rs4280164 | 4e-08 | NOP9 | G | 3.87 |
| rs80304372 | 5e-08 | SYNPR-AS1 | ? | |
| rs7801303 | 4e-07 | SUGCT - LINC01450 | ? | |
| rs61835453 | 8e-07 | LINC02645 - PFKP-DT | C | 2.17 |
| rs10222981 | 1e-06 | BLOC1S4 - KIAA0232 | T | 2.06 |
| rs365521 | 1e-06 | MIR633 - TRMT112P3 | G | 1.59 |
| rs13374908 | 2e-06 | FAM163A | A | 1.59 |
| rs12671090 | 4e-06 | MNX1-AS1 - UBE3C | G | 2.27 |
| rs28715896 | 4e-06 | ERBB4 | G | 1.59 |
| rs16924016 | 5e-06 | PTCSC2 | ? | |
| rs75337321 | 5e-06 | CACNA2D3 | T | 2.21 |
| rs2209852 | 6e-06 | SOX21-AS1 - LINC00557 | ? | |
| rs10959548 | 6e-06 | DMRT2 - RPS27AP14 | T | 2.12 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST007334 | Mukherjee S | 2018 | 510 | 3,447 | Genetic data and cognitively defined late-onset Alzheimer’s disease subgroups. |
| GCST90651689 | Liu TY | 2025 | 404 | 231,742 | Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population. |
| GCST002175 | Eicher JD | 2013 | 174 | 4,117 | Genome-wide association study of shared components of reading disability and language impairment. |
| GCST006152 | Pottier C | 2018 | 169 | 0 | Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study. |
| GCST002369 | Nudel R | 2014 | 0 | 0 | Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment. |
| GCST002371 | Nudel R | 2014 | 0 | 0 | Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 1 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 12 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 13 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|---|
| intron_variant | 6 |
| intergenic_variant | 5 |
| missense_variant | 1 |
| non_coding_transcript_exon_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| rs4280164 | 14 | 24302079 | G>A | 0.233 | missense_variant | NOP9 | 4e-08 | Tier 1: coding |
| rs80304372 | 3 | 63634852 | T>C | 0.05 | intron_variant | SYNPR-AS1 | 5e-08 | Tier 4: intronic/intergenic |
| rs7801303 | 7 | 40878471 | A>C,G,T | 0.05 | intergenic_variant | SUGCT - LINC01450 | 4e-07 | Tier 4: intronic/intergenic |
| rs61835453 | 10 | 2717604 | T>C | 0.06 | intergenic_variant | LINC02645 - PFKP-DT | 8e-07 | Tier 4: intronic/intergenic |
| rs10222981 | 4 | 6759326 | G>T | 0.08 | intergenic_variant | BLOC1S4 - KIAA0232 | 1e-06 | Tier 4: intronic/intergenic |
| rs365521 | 17 | 62944934 | A>G,T | 0.47 | intron_variant | MIR633 - TRMT112P3 | 1e-06 | Tier 4: intronic/intergenic |
| rs13374908 | 1 | 179780639 | G>A,C,T | 0.24 | intron_variant | FAM163A | 2e-06 | Tier 4: intronic/intergenic |
| rs12671090 | 7 | 157088226 | G>A,C,T | 0.4 | non_coding_transcript_exon_variant | MNX1-AS1 - UBE3C | 4e-06 | Tier 4: intronic/intergenic |
| rs28715896 | 2 | 211695376 | C>A,G,T | 0.43 | intron_variant | ERBB4 | 4e-06 | Tier 4: intronic/intergenic |
| rs16924016 | 9 | 97749049 | C>T | 0.05 | intron_variant | PTCSC2 | 5e-06 | Tier 4: intronic/intergenic |
| rs75337321 | 3 | 54550560 | C>A,T | 0.06 | intron_variant | CACNA2D3 | 5e-06 | Tier 4: intronic/intergenic |
| rs2209852 | 13 | 94865368 | A>G | 0.05 | intergenic_variant | SOX21-AS1 - LINC00557 | 6e-06 | Tier 4: intronic/intergenic |
| rs10959548 | 9 | 1121085 | C>T | 0.3 | intergenic_variant | DMRT2 - RPS27AP14 | 6e-06 | Tier 4: intronic/intergenic |
ClinVar germline variants
6 retrieved; paginated sample, class counts are floors:
3 uncertain significance, 2 pathogenic, 1 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 625777 | GRCh37/hg19 2q36.3(chr2:227939002-227943108) | COL4A4 | Pathogenic | criteria provided, single submitter |
| 243063 | TM4SF20, 4-KB DEL | TM4SF20 | Pathogenic | criteria provided, single submitter |
| 1701771 | NM_024795.4(TM4SF20):c.271A>G (p.Ser91Gly) | TM4SF20 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2665075 | NM_024795.4(TM4SF20):c.510G>A (p.Trp170Ter) | TM4SF20 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 4086129 | NM_024795.4(TM4SF20):c.571G>T (p.Val191Leu) | TM4SF20 | Uncertain significance | criteria provided, single submitter |
| 1065577 | NM_024795.4(TM4SF20):c.559A>G (p.Ile187Val) | TM4SF20 | Likely benign | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 2 · Orphanet: 9 · 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 |
|---|---|---|---|---|
| TM4SF20 | Limited | Autosomal dominant | specific language impairment 5 | 2 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SUGCT | Orphanet:35706 | Glutaric acidemia type 3 |
| COL4A4 | Orphanet:653722 | Digenic Alport syndrome |
| COL4A4 | Orphanet:88918 | Autosomal dominant Alport syndrome |
| COL4A4 | Orphanet:88919 | Autosomal recessive Alport syndrome |
| FOXE1 | Orphanet:1226 | Bamforth-Lazarus syndrome |
| FOXE1 | Orphanet:146 | Differentiated thyroid carcinoma |
| FOXE1 | Orphanet:319487 | Familial papillary or follicular thyroid carcinoma |
| FOXE1 | Orphanet:95713 | Athyreosis |
| INHBA | Orphanet:213504 | Adenocarcinoma of ovary |
Cohort genes → proteins
14 cohort genes, 13 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| gwas_only | 12 |
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TM4SF20 | HGNC:26230 | ENSG00000168955 | Q53R12 | Transmembrane 4 L6 family member 20 | gencc,clinvar |
| SUGCT | HGNC:16001 | ENSG00000175600 | Q9HAC7 | Succinyl-CoA:glutarate CoA-transferase | gwas |
| DHRS1 | HGNC:16445 | ENSG00000157379 | Q96LJ7 | Dehydrogenase/reductase SDR family member 1 | gwas |
| UBE3C | HGNC:16803 | ENSG00000009335 | Q15386 | Ubiquitin-protein ligase E3C | gwas |
| CIDEB | HGNC:1977 | ENSG00000136305 | Q9UHD4 | Lipid transferase CIDEB | gwas |
| NOP9 | HGNC:19826 | ENSG00000196943 | Q86U38 | Nucleolar protein 9 | gwas |
| COL4A4 | HGNC:2206 | ENSG00000081052 | P53420 | Collagen alpha-4(IV) chain | clinvar |
| ADCY4 | HGNC:235 | ENSG00000129467 | Q8NFM4 | Adenylate cyclase type 4 | gwas |
| DMRT2 | HGNC:2935 | ENSG00000173253 | Q9Y5R5 | Doublesex- and mab-3-related transcription factor 2 | gwas |
| FOXE1 | HGNC:3806 | ENSG00000178919 | O00358 | Forkhead box protein E1 | gwas |
| ABCC4 | HGNC:55 | ENSG00000125257 | O15439 | ATP-binding cassette sub-family C member 4 | gwas |
| INHBA | HGNC:6066 | ENSG00000122641 | P08476 | Inhibin beta A chain | gwas |
| KRT18P13 | HGNC:6432 | ENSG00000214417 | keratin 18 pseudogene 13 | gwas | |
| LTB4R | HGNC:6713 | ENSG00000213903 | Q15722 | Leukotriene B4 receptor 1 | gwas |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TM4SF20 | Transmembrane 4 L6 family member 20 | Polytopic transmembrane protein that inhibits regulated intramembrane proteolysis (RIP) of CREB3L1, inhibiting its activation and the induction of collagen synthesis. |
| SUGCT | Succinyl-CoA:glutarate CoA-transferase | Coenzyme A (CoA) transferase that reversibly catalyzes the transfer of a CoA moiety from a dicarboxyl-CoA to a dicarboxylate in a metabolite recycling process. |
| DHRS1 | Dehydrogenase/reductase SDR family member 1 | NADPH-dependent oxidoreductase which catalyzes the reduction of steroids (estrone, androstene-3,17-dione and cortisone) as well as prostaglandin E1, isatin and xenobiotics in vitro. |
| UBE3C | Ubiquitin-protein ligase E3C | E3 ubiquitin-protein ligase that specifically catalyzes ‘Lys-29’- and ‘Lys-48’-linked polyubiquitin chains. |
| CIDEB | Lipid transferase CIDEB | Lipid transferase specifically expressed in hepatocytes, which promotes unilocular lipid droplet formation by mediating lipid droplet fusion. |
| COL4A4 | Collagen alpha-4(IV) chain | Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen. |
| ADCY4 | Adenylate cyclase type 4 | Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. |
| DMRT2 | Doublesex- and mab-3-related transcription factor 2 | Transcriptional activator that directly regulates early activation of the myogenic determination gene MYF5 by binding in a sequence-specific manner to the early epaxial enhancer element of it. |
| FOXE1 | Forkhead box protein E1 | Transcription factor that binds consensus sites on a variety of gene promoters and activate their transcription. |
| ABCC4 | ATP-binding cassette sub-family C member 4 | ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. |
| INHBA | Inhibin beta A chain | Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion,… |
| LTB4R | Leukotriene B4 receptor 1 | Receptor for extracellular ATP > UTP and ADP. |
Protein-family classification
Druggable: 4 · Difficult: 1 · Unknown: 9 · Druggable fraction: 0.29
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 |
|---|---|---|---|
| Transporter | 1 | 5.6× | 0.562 |
| Enzyme (other) | 2 | 1.7× | 0.562 |
| GPCR | 1 | 1.7× | 0.562 |
| Other/Unknown | 9 | 1.1× | 0.562 |
| Transcription factor | 1 | 0.6× | 0.836 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TM4SF20 | Other/Unknown | no | L6_membrane | |
| SUGCT | Enzyme (other) | yes | 2.8.3.13 | CoA-Trfase_fam_III, CoA-Trfase_III_dom_1_sf, CoA-Trfase_III_dom3_sf |
| DHRS1 | Other/Unknown | no | SDR_fam, NAD(P)-bd_dom_sf | |
| UBE3C | Enzyme (other) | yes | 2.3.2.26 | IQ_motif_EF-hand-BS, HECT_dom, Hect_E3_ubiquitin_ligase |
| CIDEB | Other/Unknown | no | CIDE-N_dom | |
| NOP9 | Other/Unknown | no | Pumilio_RNA-bd_rpt, ARM-like, ARM-type_fold | |
| COL4A4 | Other/Unknown | no | Collagen_IV_NC, Collagen, CTDL_fold | |
| ADCY4 | Other/Unknown | no | A/G_cyclase, Adcy_conserved_dom, A/G_cyclase_CS | |
| DMRT2 | Other/Unknown | no | DM_DNA-bd, DMRT, DM_DNA-bd_sf | |
| FOXE1 | Transcription factor | no | Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2 | |
| ABCC4 | Transporter | yes | 7.6.2.2 | ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom |
| INHBA | Other/Unknown | no | Inhibin_betaA, TGF-b_propeptide, TGF-b_C | |
| KRT18P13 | Other/Unknown | no | ||
| LTB4R | GPCR | yes | GPCR_Rhodpsn, Formyl_rcpt-rel, Leukotriene_B4_rcpt |
Expression context
Cohort genes with no expression data: 0.
13 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) | 1 |
| broad (>20) | 13 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| esophagus mucosa | 2 |
| lower esophagus mucosa | 2 |
| right lobe of liver | 2 |
| metanephros cortex | 2 |
| left lobe of thyroid gland | 2 |
| right lobe of thyroid gland | 2 |
| thyroid gland | 2 |
| ileal mucosa | 1 |
| ileum | 1 |
| jejunal mucosa | 1 |
| oocyte | 1 |
| right adrenal gland cortex | 1 |
| right coronary artery | 1 |
| calcaneal tendon | 1 |
| islet of Langerhans | 1 |
| sural nerve | 1 |
| duodenum | 1 |
| liver | 1 |
| gastrocnemius | 1 |
| muscle of leg | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TM4SF20 | 77 | tissue_specific | marker | jejunal mucosa, ileal mucosa, ileum |
| SUGCT | 191 | ubiquitous | marker | right adrenal gland cortex, oocyte, right coronary artery |
| DHRS1 | 138 | ubiquitous | marker | lower esophagus mucosa, esophagus mucosa, right lobe of liver |
| UBE3C | 291 | ubiquitous | marker | sural nerve, calcaneal tendon, islet of Langerhans |
| CIDEB | 134 | broad | marker | right lobe of liver, liver, duodenum |
| NOP9 | 134 | ubiquitous | marker | skeletal muscle tissue, gastrocnemius, muscle of leg |
| COL4A4 | 187 | broad | marker | renal medulla, metanephros cortex, pigmented layer of retina |
| ADCY4 | 142 | broad | marker | apex of heart, subcutaneous adipose tissue, adipose tissue |
| DMRT2 | 174 | broad | marker | kidney epithelium, metanephros cortex, adult mammalian kidney |
| FOXE1 | 94 | tissue_specific | marker | right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland |
| ABCC4 | 230 | ubiquitous | marker | palpebral conjunctiva, secondary oocyte, buccal mucosa cell |
| INHBA | 235 | ubiquitous | marker | cartilage tissue, saphenous vein, vena cava |
| KRT18P13 | 8 | marker | right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland | |
| LTB4R | 133 | broad | yes | lower esophagus mucosa, skin of abdomen, esophagus mucosa |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| DHRS1 | 3,093 |
| ABCC4 | 2,497 |
| INHBA | 2,212 |
| NOP9 | 2,075 |
| UBE3C | 1,923 |
| FOXE1 | 1,606 |
| ADCY4 | 1,430 |
| CIDEB | 1,249 |
| COL4A4 | 1,243 |
| SUGCT | 1,164 |
Structural data
PDB: 8 · AlphaFold-only: 5 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| ABCC4 | O15439 | 25 |
| INHBA | P08476 | 16 |
| SUGCT | Q9HAC7 | 2 |
| COL4A4 | P53420 | 2 |
| LTB4R | Q15722 | 2 |
| DHRS1 | Q96LJ7 | 1 |
| UBE3C | Q15386 | 1 |
| CIDEB | Q9UHD4 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| NOP9 | Q86U38 | 86.53 |
| ADCY4 | Q8NFM4 | 79.03 |
| TM4SF20 | Q53R12 | 73.10 |
| FOXE1 | O00358 | 62.02 |
| DMRT2 | Q9Y5R5 | 54.37 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 84. Enrichment computed across 14 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Antagonism of Activin by Follistatin | 1 | 475.8× | 0.041 | INHBA |
| TGFBR3 regulates activin signaling | 1 | 475.8× | 0.041 | INHBA |
| Eicosanoid ligand-binding receptors | 1 | 380.7× | 0.041 | LTB4R |
| Leukotriene receptors | 1 | 317.2× | 0.041 | LTB4R |
| Peptide hormone biosynthesis | 1 | 237.9× | 0.041 | INHBA |
| Adenylate cyclase activating pathway | 1 | 190.3× | 0.041 | ADCY4 |
| Glycoprotein hormones | 1 | 158.6× | 0.041 | INHBA |
| Signaling by Activin | 1 | 126.9× | 0.041 | INHBA |
| Adenylate cyclase inhibitory pathway | 1 | 126.9× | 0.041 | ADCY4 |
| Anchoring fibril formation | 1 | 126.9× | 0.041 | COL4A4 |
| PKA activation in glucagon signalling | 1 | 112.0× | 0.041 | ADCY4 |
| PKA activation | 1 | 105.7× | 0.041 | ADCY4 |
| Activation of GABAB receptors | 1 | 100.2× | 0.041 | ADCY4 |
| PKA-mediated phosphorylation of CREB | 1 | 95.2× | 0.041 | ADCY4 |
| Fibronectin matrix formation | 1 | 95.2× | 0.041 | COL4A4 |
| Crosslinking of collagen fibrils | 1 | 95.2× | 0.041 | COL4A4 |
| GABA B receptor activation | 1 | 90.6× | 0.041 | ADCY4 |
| Attachment of bacteria to epithelial cells | 1 | 82.8× | 0.041 | COL4A4 |
| Azathioprine ADME | 1 | 82.8× | 0.041 | ABCC4 |
| Paracetamol ADME | 1 | 70.5× | 0.041 | ABCC4 |
| Anti-inflammatory response favouring Leishmania parasite infection | 1 | 65.6× | 0.041 | ADCY4 |
| Leishmania parasite growth and survival | 1 | 65.6× | 0.041 | ADCY4 |
| Calmodulin induced events | 1 | 63.4× | 0.041 | ADCY4 |
| CaM pathway | 1 | 63.4× | 0.041 | ADCY4 |
| Laminin interactions | 1 | 63.4× | 0.041 | COL4A4 |
| Ca-dependent events | 1 | 61.4× | 0.041 | ADCY4 |
| Aquaporin-mediated transport | 1 | 61.4× | 0.041 | ADCY4 |
| Signaling by TGFBR3 | 1 | 61.4× | 0.041 | INHBA |
| Signaling by BMP | 1 | 59.5× | 0.041 | INHBA |
| Glucagon signaling in metabolic regulation | 1 | 57.7× | 0.041 | ADCY4 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| kynurenic acid metabolic process | 1 | 1532.0× | 0.016 | ABCC4 |
| regulation of follicle-stimulating hormone secretion | 1 | 1532.0× | 0.016 | INHBA |
| cardiac fibroblast cell development | 1 | 1532.0× | 0.016 | INHBA |
| androst-4-ene-3,17-dione biosynthetic process | 1 | 1532.0× | 0.016 | INHBA |
| positive regulation of myotome development | 1 | 1532.0× | 0.016 | DMRT2 |
| progesterone secretion | 1 | 766.0× | 0.018 | INHBA |
| positive regulation of ovulation | 1 | 766.0× | 0.018 | INHBA |
| cAMP transport | 1 | 766.0× | 0.018 | ABCC4 |
| obsolete L-tryptophan metabolic process | 1 | 510.7× | 0.018 | ABCC4 |
| negative regulation of follicle-stimulating hormone secretion | 1 | 510.7× | 0.018 | INHBA |
| chordate pharynx development | 1 | 510.7× | 0.018 | FOXE1 |
| striatal medium spiny neuron differentiation | 1 | 383.0× | 0.018 | INHBA |
| embryonic organ morphogenesis | 1 | 383.0× | 0.018 | FOXE1 |
| myotome development | 1 | 383.0× | 0.018 | DMRT2 |
| cellular response to oxygen-glucose deprivation | 1 | 383.0× | 0.018 | INHBA |
| endonucleolytic cleavage to generate mature 5’-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) | 1 | 306.4× | 0.018 | NOP9 |
| platelet degranulation | 1 | 306.4× | 0.018 | ABCC4 |
| prostaglandin secretion | 1 | 306.4× | 0.018 | ABCC4 |
| negative regulation of B cell differentiation | 1 | 306.4× | 0.018 | INHBA |
| soft palate development | 1 | 306.4× | 0.018 | FOXE1 |
| GABAergic neuron differentiation | 1 | 306.4× | 0.018 | INHBA |
| lipid droplet fusion | 1 | 306.4× | 0.018 | CIDEB |
| regulation of somitogenesis | 1 | 255.3× | 0.018 | DMRT2 |
| negative regulation of phosphorylation | 1 | 255.3× | 0.018 | INHBA |
| hemoglobin biosynthetic process | 1 | 255.3× | 0.018 | INHBA |
| positive regulation of follicle-stimulating hormone secretion | 1 | 255.3× | 0.018 | INHBA |
| testosterone biosynthetic process | 1 | 255.3× | 0.018 | INHBA |
| urate transport | 1 | 218.9× | 0.020 | ABCC4 |
| leukotriene transport | 1 | 218.9× | 0.020 | ABCC4 |
| ribosomal small subunit export from nucleus | 1 | 191.5× | 0.020 | NOP9 |
Therapeutics
Drugs indicated or in trials for this disease
No drug has an approved disease-direct ChEMBL indication for this disease.
1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.
| Drug | Highest phase |
|---|---|
| OMEGA-3-ACID ETHYL ESTERS | Phase 3 |
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 12
Druggability breadth: 6 of 14 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.
| Symbol | Example approved molecule |
|---|---|
| ABCC4 | CEFOTAXIME SODIUM |
| LTB4R | ZILEUTON |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| ABCC4 | 102 | 4 |
| LTB4R | 7 | 4 |
| TM4SF20 | 0 | 0 |
| SUGCT | 0 | 0 |
| DHRS1 | 0 | 0 |
| UBE3C | 0 | 0 |
| CIDEB | 0 | 0 |
| NOP9 | 0 | 0 |
| COL4A4 | 0 | 0 |
| ADCY4 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| CEFOTAXIME SODIUM | 4 | ABCC4 |
| TELMISARTAN | 4 | ABCC4 |
| OXAPROZIN | 4 | ABCC4 |
| CEFUROXIME AXETIL | 4 | ABCC4 |
| AMLEXANOX | 4 | ABCC4 |
| VALRUBICIN | 4 | ABCC4 |
| RIMONABANT | 4 | ABCC4 |
| ACITRETIN | 4 | ABCC4 |
| TELITHROMYCIN | 4 | ABCC4 |
| SAQUINAVIR | 4 | ABCC4 |
| FEBUXOSTAT | 4 | ABCC4 |
| CEFAZOLIN SODIUM | 4 | ABCC4 |
| DOXAZOSIN MESYLATE | 4 | ABCC4 |
| GEMIFLOXACIN MESYLATE | 4 | ABCC4 |
| OLMESARTAN MEDOXOMIL | 4 | ABCC4 |
| TRAVOPROST | 4 | ABCC4 |
| DINOPROST TROMETHAMINE | 4 | ABCC4 |
| KETOROLAC TROMETHAMINE | 4 | ABCC4 |
| TEMSIROLIMUS | 4 | ABCC4 |
| ROSIGLITAZONE | 4 | ABCC4 |
| REPAGLINIDE | 4 | ABCC4 |
| CLOFAZIMINE | 4 | ABCC4 |
| QUINIDINE | 4 | ABCC4 |
| CARPROFEN | 4 | ABCC4 |
| TOLCAPONE | 4 | ABCC4 |
| BUDESONIDE | 4 | ABCC4 |
| MYCOPHENOLATE MOFETIL | 4 | ABCC4 |
| GLIMEPIRIDE | 4 | ABCC4 |
| NICARDIPINE | 4 | ABCC4 |
| DROSPIRENONE | 4 | ABCC4 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| LTB4R | 240 | Binding:166, Functional:73, ADMET:1 |
| ABCC4 | 97 | Functional:71, ADMET:21, Binding:5 |
| ADCY4 | 16 | Binding:14, Functional:2 |
| INHBA | 3 | Binding:3 |
| UBE3C | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| SUGCT | 2.8.3.13 | succinate-hydroxymethylglutarate CoA-transferase |
| UBE3C | 2.3.2.26 | HECT-type E3 ubiquitin transferase |
| ABCC4 | 7.6.2.2, 7.6.2.3 | ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| LTB4R | 240 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 13; 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) |
|---|---|---|
| CEFOTAXIME SODIUM | 4 | ABCC4 |
| TELMISARTAN | 4 | ABCC4 |
| OXAPROZIN | 4 | ABCC4 |
| CEFUROXIME AXETIL | 4 | ABCC4 |
| AMLEXANOX | 4 | ABCC4 |
| VALRUBICIN | 4 | ABCC4 |
| RIMONABANT | 4 | ABCC4 |
| ACITRETIN | 4 | ABCC4 |
| TELITHROMYCIN | 4 | ABCC4 |
| SAQUINAVIR | 4 | ABCC4 |
| FEBUXOSTAT | 4 | ABCC4 |
| CEFAZOLIN SODIUM | 4 | ABCC4 |
| DOXAZOSIN MESYLATE | 4 | ABCC4 |
| GEMIFLOXACIN MESYLATE | 4 | ABCC4 |
| OLMESARTAN MEDOXOMIL | 4 | ABCC4 |
| TRAVOPROST | 4 | ABCC4 |
| DINOPROST TROMETHAMINE | 4 | ABCC4 |
| KETOROLAC TROMETHAMINE | 4 | ABCC4 |
| TEMSIROLIMUS | 4 | ABCC4 |
| ROSIGLITAZONE | 4 | ABCC4 |
| REPAGLINIDE | 4 | ABCC4 |
| CLOFAZIMINE | 4 | ABCC4 |
| QUINIDINE | 4 | ABCC4 |
| CARPROFEN | 4 | ABCC4 |
| TOLCAPONE | 4 | ABCC4 |
| BUDESONIDE | 4 | ABCC4 |
| MYCOPHENOLATE MOFETIL | 4 | ABCC4 |
| GLIMEPIRIDE | 4 | ABCC4 |
| NICARDIPINE | 4 | ABCC4 |
| DROSPIRENONE | 4 | ABCC4 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | ABCC4, LTB4R |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 2 | SUGCT, UBE3C |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 10 | TM4SF20, DHRS1, CIDEB, NOP9, COL4A4, ADCY4, DMRT2, FOXE1, INHBA, KRT18P13 |
Undrugged target profiles
12 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| TM4SF20 | 0 | — |
| SUGCT | 0 | — |
| DHRS1 | 0 | — |
| UBE3C | 1 | — |
| CIDEB | 0 | — |
| NOP9 | 0 | — |
| COL4A4 | 0 | — |
| ADCY4 | 16 | — |
| DMRT2 | 0 | — |
| FOXE1 | 0 | — |
| INHBA | 3 | — |
| KRT18P13 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.