Migraine without aura, susceptibility to, 4
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Also known as MGOAMGR4migraine without aura, susceptibility to, type 4
Summary
Migraine without aura, susceptibility to, 4 (MONDO:0011847) is a disease with 14 cohort genes (25 GWAS associations across 6 studies).
At a glance
- Cohort genes: 14
- GWAS associations: 25
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | migraine without aura, susceptibility to, 4 |
| Mondo ID | MONDO:0011847 |
| OMIM | 607501 |
| UMLS | C1843773 |
| MedGen | 336040 |
| Is cancer (heuristic) | no |
Also known as: MGOA · MGR4 · migraine without aura, susceptibility to, 4 · migraine without aura, susceptibility to, type 4
Data availability: 25 GWAS associations (6 studies) · 1 HPO phenotype.
Disease family
Classification path: disease susceptibility › inherited disease susceptibility › migraine with or without aura, susceptibility to › migraine without aura, susceptibility to, 4
Related subtypes (12): migraine with or without aura, susceptibility to, 1, migraine, familial typical, susceptibility to, 2, migraine with or without aura, susceptibility to, 3, migraine with or without aura, susceptibility to, 5, migraine with or without aura, susceptibility to, 6, migraine with aura, susceptibility to, 7, migraine with or without aura, susceptibility to, 8, migraine with aura, susceptibility to, 9, migraine with or without aura, susceptibility to, 10, migraine with or without aura, susceptibility to, 11, migraine with or without aura, susceptibility to, 12, migraine, with or without aura, susceptibility to, 13
Genetics & variants
GWAS landscape
25 GWAS associations across 6 studies. Top hits map to 11 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| rs78378222 | 7e-36 | TP53 | ? | |
| rs1332844 | 3e-28 | PHACTR1 | ? | |
| rs2983896 | 1e-24 | FHL5 | ? | |
| rs4141663 | 5e-22 | ITGB5 | ? | |
| rs11172113 | 2e-17 | LRP1 | ? | |
| rs3798293 | 8e-15 | FHL5 | ? | |
| rs7454157 | 1e-13 | PHACTR1 | ? | |
| rs12631961 | 8e-13 | ITGB5 | ? | |
| rs7775721 | 1e-12 | FHL5 | T | 1.15 |
| rs655484 | 1e-12 | DLG2 | C | 2.42 |
| rs80080721 | 3e-11 | SPOP - SLC35B1 | ? | |
| rs6478241 | 1e-10 | ASTN2 | A | 1.14 |
| rs2274319 | 8e-10 | MEF2D | ? | |
| rs6724624 | 1e-09 | MSL3B - TRPM8 | ? | 1.16 |
| rs9349379 | 2e-09 | PHACTR1 | A | 1.14 |
| rs1024905 | 3e-09 | FGF23 - FGF6 | G | 1.12 |
| rs2078371 | 7e-09 | LINC01765 - NGF-AS1 | C | 1.18 |
| rs34995334 | 4e-08 | RNU4-35P - RNU4-76P | ? | |
| rs181024055 | 5e-08 | NRAP | ? | 23.74 |
| rs3781545 | 1e-07 | GFRA1 | G | 1.38 |
| rs17470570 | 3e-06 | HPSE2 | G | 1.2 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST011056 | Guo Y | 2020 | 59,674 | 316,078 | A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine. |
| GCST011057 | Guo Y | 2020 | 59,674 | 316,078 | A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine. |
| GCST011058 | Guo Y | 2020 | 59,674 | 316,078 | A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine. |
| GCST003721 | Gormley P | 2016 | 8,348 | 139,622 | Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. |
| GCST002078 | Anttila V | 2013 | 7,107 | 69,427 | Genome-wide meta-analysis identifies new susceptibility loci for migraine. |
| GCST004900 | Chen SP | 2017 | 1,005 | 1,053 | Genome-wide association study identifies novel susceptibility loci for migraine in Han Chinese resided in Taiwan. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 1 |
| Tier 2: splice/UTR | 1 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 19 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 19 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 2 |
Functional consequences
| Consequence | Count |
|---|---|
| intron_variant | 15 |
| intergenic_variant | 4 |
| 3_prime_UTR_variant | 1 |
| missense_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| rs78378222 | 17 | 7668434 | T>A,G | 3_prime_UTR_variant | TP53 | 7e-36 | Tier 2: splice/UTR | |
| rs1332844 | 6 | 12888772 | C>T | 0.05 | intron_variant | PHACTR1 | 3e-28 | Tier 4: intronic/intergenic |
| rs2983896 | 6 | 96581995 | G>A | 0.05 | intron_variant | FHL5 | 1e-24 | Tier 4: intronic/intergenic |
| rs4141663 | 3 | 124833120 | C>T | 0.05 | intron_variant | ITGB5 | 5e-22 | Tier 4: intronic/intergenic |
| rs11172113 | 12 | 57133500 | T>C,G | 0.05 | intron_variant | LRP1 | 2e-17 | Tier 4: intronic/intergenic |
| rs3798293 | 6 | 96585494 | A>G | 0.05 | intron_variant | FHL5 | 8e-15 | Tier 4: intronic/intergenic |
| rs7454157 | 6 | 12909642 | G>A,C | 0.05 | intron_variant | PHACTR1 | 1e-13 | Tier 4: intronic/intergenic |
| rs12631961 | 3 | 124843001 | C>A,G,T | 0.05 | intron_variant | ITGB5 | 8e-13 | Tier 4: intronic/intergenic |
| rs7775721 | 6 | 96609103 | C>T | 0.33 | intron_variant | FHL5 | 1e-12 | Tier 4: intronic/intergenic |
| rs655484 | 11 | 84472392 | T>A,C,G | 0.059 | intron_variant | DLG2 | 1e-12 | Tier 4: intronic/intergenic |
| rs80080721 | 17 | 49700178 | G>A,T | 0.05 | intron_variant | SPOP - SLC35B1 | 3e-11 | Tier 4: intronic/intergenic |
| rs6478241 | 9 | 116490350 | A>G,T | 0.35 | intron_variant | ASTN2 | 1e-10 | Tier 4: intronic/intergenic |
| rs2274319 | 1 | 156481081 | T>C | 0.05 | intron_variant | MEF2D | 8e-10 | Tier 4: intronic/intergenic |
| rs6724624 | 2 | 233911933 | C>G | 0.2 | intergenic_variant | MSL3B - TRPM8 | 1e-09 | Tier 4: intronic/intergenic |
| rs9349379 | 6 | 12903725 | A>C,G,T | 0.41 | intron_variant | PHACTR1 | 2e-09 | Tier 4: intronic/intergenic |
| rs1024905 | 12 | 4408974 | G>A,C | 0.48 | intergenic_variant | FGF23 - FGF6 | 3e-09 | Tier 4: intronic/intergenic |
| rs2078371 | 1 | 115134562 | T>A,C,G | 0.11 | intergenic_variant | LINC01765 - NGF-AS1 | 7e-09 | Tier 4: intronic/intergenic |
| rs34995334 | 6 | 121524533 | A>G | 0.05 | intergenic_variant | RNU4-35P - RNU4-76P | 4e-08 | Tier 4: intronic/intergenic |
| rs181024055 | 10 | 113595726 | C>A,T | missense_variant | NRAP | 5e-08 | Tier 1: coding | |
| rs3781545 | 10 | 116189948 | G>A | 0.216 | intron_variant | GFRA1 | 1e-07 | Tier 4: intronic/intergenic |
| rs17470570 | 10 | 98820366 | A>G | 0.08 | intron_variant | HPSE2 | 3e-06 | Tier 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)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| STAT6 | Orphanet:2126 | Solitary fibrous tumor |
| PHACTR1 | Orphanet:697160 | Infantile epileptic spasms syndrome |
| SDR9C7 | Orphanet:313 | Lamellar ichthyosis |
| SDR9C7 | Orphanet:79394 | Congenital ichthyosiform erythroderma |
| GFRA1 | Orphanet:1848 | Renal agenesis, bilateral |
| LRP1 | Orphanet:2340 | Keratosis follicularis spinulosa decalvans |
| LRP1 | Orphanet:79100 | Atrophoderma vermiculata |
| NGF | Orphanet:64752 | Hereditary sensory and autonomic neuropathy type 5 |
Cohort genes → proteins
14 cohort genes, 14 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| gwas_only | 14 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| STAT6 | HGNC:11368 | ENSG00000166888 | P42226 | Signal transducer and activator of transcription 6 | gwas |
| ASTN2 | HGNC:17021 | ENSG00000148219 | O75129 | Astrotactin-2 | gwas |
| FHL5 | HGNC:17371 | ENSG00000112214 | Q5TD97 | Four and a half LIM domains protein 5 | gwas |
| TRPM8 | HGNC:17961 | ENSG00000144481 | Q7Z2W7 | Transient receptor potential cation channel subfamily M member 8 | gwas |
| TSPAN2 | HGNC:20659 | ENSG00000134198 | O60636 | Tetraspanin-2 | gwas |
| PHACTR1 | HGNC:20990 | ENSG00000112137 | Q9C0D0 | Phosphatase and actin regulator 1 | gwas |
| UFL1 | HGNC:23039 | ENSG00000014123 | O94874 | E3 UFM1-protein ligase 1 | gwas |
| HJURP | HGNC:25444 | ENSG00000123485 | Q8NCD3 | Holliday junction recognition protein | gwas |
| SDR9C7 | HGNC:29958 | ENSG00000170426 | Q8NEX9 | Short-chain dehydrogenase/reductase family 9C member 7 | gwas |
| FGF6 | HGNC:3684 | ENSG00000111241 | P10767 | Fibroblast growth factor 6 | gwas |
| GFRA1 | HGNC:4243 | ENSG00000151892 | P56159 | GDNF family receptor alpha-1 | gwas |
| LRP1 | HGNC:6692 | ENSG00000123384 | Q07954 | Prolow-density lipoprotein receptor-related protein 1 | gwas |
| MPP2 | HGNC:7220 | ENSG00000108852 | Q14168 | MAGUK p55 subfamily member 2 | gwas |
| NGF | HGNC:7808 | ENSG00000134259 | P01138 | Beta-nerve growth factor | gwas |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| STAT6 | Signal transducer and activator of transcription 6 | Carries out a dual function: signal transduction and activation of transcription. |
| ASTN2 | Astrotactin-2 | Mediates recycling of the neuronal cell adhesion molecule ASTN1 to the anterior pole of the cell membrane in migrating neurons. |
| FHL5 | Four and a half LIM domains protein 5 | May be involved in the regulation of spermatogenesis. |
| TRPM8 | Transient receptor potential cation channel subfamily M member 8 | Non-selective ion channel permeable to monovalent and divalent cations, including Na(+), K(+), and Ca(2+), with higher permeability for Ca(2+). |
| TSPAN2 | Tetraspanin-2 | May play a role in signalling in oligodendrocytes in the early stages of their terminal differentiation into myelin-forming glia and may also function in stabilizing the mature sheath. |
| PHACTR1 | Phosphatase and actin regulator 1 | Binds actin monomers (G actin) and plays a role in multiple processes including the regulation of actin cytoskeleton dynamics, actin stress fibers formation, cell motility and survival, formation of tubules by endothelial cells, and regula… |
| UFL1 | E3 UFM1-protein ligase 1 | E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins, and which plays a key role in various processes, such as ribosome recycling, response to DNA dam… |
| HJURP | Holliday junction recognition protein | Centromeric protein that plays a central role in the incorporation and maintenance of histone H3-like variant CENPA at centromeres. |
| SDR9C7 | Short-chain dehydrogenase/reductase family 9C member 7 | Plays a crucial role in the formation of the epidermal permeability barrier. |
| FGF6 | Fibroblast growth factor 6 | Plays an important role in the regulation of cell proliferation, cell differentiation, angiogenesis and myogenesis, and is required for normal muscle regeneration. |
| GFRA1 | GDNF family receptor alpha-1 | Coreceptor for GDNF, a neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake. |
| LRP1 | Prolow-density lipoprotein receptor-related protein 1 | Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. |
| MPP2 | MAGUK p55 subfamily member 2 | Postsynaptic MAGUK scaffold protein that links CADM1 cell adhesion molecules to core components of the postsynaptic density. |
| NGF | Beta-nerve growth factor | Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. |
Protein-family classification
Druggable: 3 · Difficult: 2 · Unknown: 9 · Druggable fraction: 0.21
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 |
|---|---|---|---|
| Complement | 1 | 19.1× | 0.255 |
| Ion channel | 1 | 8.0× | 0.296 |
| Kinase | 1 | 2.0× | 0.503 |
| Other/Unknown | 9 | 1.1× | 0.503 |
| Transcription factor | 2 | 1.2× | 0.519 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| STAT6 | Transcription factor | no | SH2, STAT, p53-like_TF_DNA-bd_sf | |
| ASTN2 | Complement | yes | MACPF, Astrotactin, FN3_sf | |
| FHL5 | Transcription factor | no | Znf_LIM, FHL5_LIM2, LIM_FHL1/2/3/5_N | |
| TRPM8 | Ion channel | yes | Ion_trans_dom, TRPM_SLOG, TRPM | |
| TSPAN2 | Other/Unknown | no | Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin | |
| PHACTR1 | Other/Unknown | no | RPEL_repeat | |
| UFL1 | Other/Unknown | no | Ufl1, Ufl1_N, Ufl1_dom | |
| HJURP | Other/Unknown | no | Scm3/HJURP, HJURP_central_dom, HJURP_C | |
| SDR9C7 | Other/Unknown | no | SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf | |
| FGF6 | Other/Unknown | no | Fibroblast_GF_fam, IL1/FGF | |
| GFRA1 | Other/Unknown | no | GDNF_rcpt, GDNF_rcpt_A1, GDNF/GAS1 | |
| LRP1 | Other/Unknown | no | LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF | |
| MPP2 | Kinase | yes | SH3_domain, PDZ, L27_dom | |
| NGF | Other/Unknown | no | Nerve_growth_factor-rel, Nerve_growth_factor_CS, Nerve_growth_factor-like |
Expression context
Cohort genes with no expression data: 0.
11 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) | 14 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| right ovary | 2 |
| dorsal root ganglion | 2 |
| trigeminal ganglion | 2 |
| popliteal artery | 2 |
| granulocyte | 1 |
| left ovary | 1 |
| buccal mucosa cell | 1 |
| right coronary artery | 1 |
| tibial artery | 1 |
| liver | 1 |
| prostate gland | 1 |
| right lobe of liver | 1 |
| body of uterus | 1 |
| muscle layer of sigmoid colon | 1 |
| cortical plate | 1 |
| nucleus accumbens | 1 |
| postcentral gyrus | 1 |
| calcaneal tendon | 1 |
| caput epididymis | 1 |
| corpus epididymis | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| STAT6 | 292 | ubiquitous | marker | granulocyte, right ovary, left ovary |
| ASTN2 | 236 | ubiquitous | marker | buccal mucosa cell, trigeminal ganglion, dorsal root ganglion |
| FHL5 | 210 | tissue_specific | marker | popliteal artery, tibial artery, right coronary artery |
| TRPM8 | 122 | tissue_specific | marker | right lobe of liver, liver, prostate gland |
| TSPAN2 | 228 | broad | marker | body of uterus, muscle layer of sigmoid colon, popliteal artery |
| PHACTR1 | 210 | ubiquitous | marker | cortical plate, postcentral gyrus, nucleus accumbens |
| UFL1 | 295 | ubiquitous | marker | caput epididymis, corpus epididymis, calcaneal tendon |
| HJURP | 164 | ubiquitous | marker | ventricular zone, oocyte, secondary oocyte |
| SDR9C7 | 113 | tissue_specific | yes | skin of leg, skin of abdomen, zone of skin |
| FGF6 | 60 | tissue_specific | yes | type B pancreatic cell, olfactory bulb, hindlimb stylopod muscle |
| GFRA1 | 231 | broad | marker | endometrium epithelium, trigeminal ganglion, dorsal root ganglion |
| LRP1 | 293 | ubiquitous | marker | stromal cell of endometrium, descending thoracic aorta, ascending aorta |
| MPP2 | 210 | ubiquitous | yes | C1 segment of cervical spinal cord, prefrontal cortex, spinal cord |
| NGF | 158 | broad | marker | cartilage tissue, left uterine tube, right ovary |
Protein interactions among cohort
Intra-cohort edges: 7.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| NGF | 3,968 |
| UFL1 | 3,840 |
| FGF6 | 3,615 |
| STAT6 | 3,345 |
| MPP2 | 2,939 |
| LRP1 | 2,662 |
| HJURP | 1,616 |
| ASTN2 | 1,610 |
| GFRA1 | 1,492 |
| FHL5 | 1,346 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ASTN2 | TRPM8 | string_interaction |
| ASTN2 | TSPAN2 | string_interaction |
| FHL5 | UFL1 | string_interaction |
| GFRA1 | NGF | string_interaction |
| NGF | TRPM8 | string_interaction |
| PHACTR1 | TRPM8 | string_interaction |
| PHACTR1 | TSPAN2 | string_interaction |
Structural data
PDB: 11 · AlphaFold-only: 3 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| NGF | P01138 | 10 |
| UFL1 | O94874 | 9 |
| STAT6 | P42226 | 7 |
| LRP1 | Q07954 | 7 |
| TRPM8 | Q7Z2W7 | 6 |
| PHACTR1 | Q9C0D0 | 6 |
| ASTN2 | O75129 | 3 |
| FHL5 | Q5TD97 | 1 |
| HJURP | Q8NCD3 | 1 |
| GFRA1 | P56159 | 1 |
| MPP2 | Q14168 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| SDR9C7 | Q8NEX9 | 93.41 |
| TSPAN2 | O60636 | 87.26 |
| FGF6 | P10767 | 79.20 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 77. Enrichment computed across 14 evidence-associated genes (9 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| TRKA activation by NGF | 1 | 634.4× | 0.030 | NGF |
| NFG and proNGF binds to p75NTR | 1 | 634.4× | 0.030 | NGF |
| PLC-gamma1 signalling | 1 | 423.0× | 0.030 | NGF |
| Ceramide signalling | 1 | 423.0× | 0.030 | NGF |
| Signalling to STAT3 | 1 | 423.0× | 0.030 | NGF |
| STAT6-mediated induction of chemokines | 1 | 423.0× | 0.030 | STAT6 |
| NGF processing | 1 | 317.2× | 0.030 | NGF |
| Axonal growth stimulation | 1 | 317.2× | 0.030 | NGF |
| Signalling to p38 via RIT and RIN | 1 | 253.8× | 0.033 | NGF |
| p75NTR negatively regulates cell cycle via SC1 | 1 | 211.5× | 0.033 | NGF |
| NADE modulates death signalling | 1 | 211.5× | 0.033 | NGF |
| ARMS-mediated activation | 1 | 181.3× | 0.035 | NGF |
| PI3K/AKT activation | 1 | 141.0× | 0.035 | NGF |
| STING mediated induction of host immune responses | 1 | 115.3× | 0.035 | STAT6 |
| Frs2-mediated activation | 1 | 105.7× | 0.035 | NGF |
| Signaling by activated point mutants of FGFR1 | 1 | 105.7× | 0.035 | FGF6 |
| FGFR2c ligand binding and activation | 1 | 97.6× | 0.035 | FGF6 |
| p75NTR recruits signalling complexes | 1 | 97.6× | 0.035 | NGF |
| NF-kB is activated and signals survival | 1 | 97.6× | 0.035 | NGF |
| Scavenging of heme from plasma | 1 | 97.6× | 0.035 | LRP1 |
| Retrograde neurotrophin signalling | 1 | 90.6× | 0.035 | NGF |
| FGFR4 ligand binding and activation | 1 | 90.6× | 0.035 | FGF6 |
| FGFR1c ligand binding and activation | 1 | 84.6× | 0.035 | FGF6 |
| Phospholipase C-mediated cascade; FGFR4 | 1 | 84.6× | 0.035 | FGF6 |
| NRIF signals cell death from the nucleus | 1 | 79.3× | 0.035 | NGF |
| Signalling to RAS | 1 | 74.6× | 0.035 | NGF |
| Activated point mutants of FGFR2 | 1 | 74.6× | 0.035 | FGF6 |
| Phospholipase C-mediated cascade: FGFR1 | 1 | 74.6× | 0.035 | FGF6 |
| Phospholipase C-mediated cascade; FGFR2 | 1 | 70.5× | 0.035 | FGF6 |
| PI-3K cascade:FGFR4 | 1 | 63.4× | 0.035 | FGF6 |
GO biological processes 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.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| regulation of mast cell proliferation | 1 | 1203.7× | 0.030 | STAT6 |
| positive regulation of transcytosis | 1 | 1203.7× | 0.030 | LRP1 |
| positive regulation of lipid transport | 1 | 601.9× | 0.030 | LRP1 |
| regulation of DNA binding | 1 | 601.9× | 0.030 | HJURP |
| mammary gland morphogenesis | 1 | 601.9× | 0.030 | STAT6 |
| positive regulation of reverse cholesterol transport | 1 | 601.9× | 0.030 | LRP1 |
| positive regulation of neuron maturation | 1 | 401.2× | 0.030 | NGF |
| isotype switching to IgE isotypes | 1 | 401.2× | 0.030 | STAT6 |
| positive regulation of reticulophagy | 1 | 401.2× | 0.030 | UFL1 |
| astrocyte activation involved in immune response | 1 | 300.9× | 0.030 | LRP1 |
| T-helper 1 cell lineage commitment | 1 | 300.9× | 0.030 | STAT6 |
| microglia development | 1 | 300.9× | 0.030 | TSPAN2 |
| positive regulation of isotype switching to IgE isotypes | 1 | 300.9× | 0.030 | STAT6 |
| thermoception | 1 | 300.9× | 0.030 | TRPM8 |
| obsolete positive regulation of proteolysis involved in protein catabolic process | 1 | 300.9× | 0.030 | UFL1 |
| negative regulation of platelet-derived growth factor receptor-beta signaling pathway | 1 | 300.9× | 0.030 | LRP1 |
| positive regulation of cold-induced thermogenesis | 2 | 23.4× | 0.030 | STAT6, TRPM8 |
| regulation of extracellular matrix disassembly | 1 | 240.7× | 0.030 | LRP1 |
| establishment of body hair planar orientation | 1 | 240.7× | 0.030 | ASTN2 |
| positive regulation of lysosomal protein catabolic process | 1 | 240.7× | 0.030 | LRP1 |
| protein K69-linked ufmylation | 1 | 240.7× | 0.030 | UFL1 |
| negative regulation of type 2 immune response | 1 | 200.6× | 0.033 | STAT6 |
| negative regulation of IRE1-mediated unfolded protein response | 1 | 200.6× | 0.033 | UFL1 |
| interleukin-4-mediated signaling pathway | 1 | 172.0× | 0.034 | STAT6 |
| protein ufmylation | 1 | 172.0× | 0.034 | UFL1 |
| amyloid-beta clearance by transcytosis | 1 | 172.0× | 0.034 | LRP1 |
| negative regulation of T cell mediated immune response to tumor cell | 1 | 150.5× | 0.035 | UFL1 |
| amyloid-beta clearance by cellular catabolic process | 1 | 150.5× | 0.035 | LRP1 |
| positive regulation of amyloid-beta clearance | 1 | 150.5× | 0.035 | LRP1 |
| regulation of intracellular estrogen receptor signaling pathway | 1 | 133.8× | 0.035 | UFL1 |
Therapeutics
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 |
|---|---|
| STAT6 | THIORIDAZINE HYDROCHLORIDE |
| TRPM8 | CLOTRIMAZOLE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| TRPM8 | 15 | 4 |
| STAT6 | 11 | 4 |
| ASTN2 | 0 | 0 |
| FHL5 | 0 | 0 |
| TSPAN2 | 0 | 0 |
| PHACTR1 | 0 | 0 |
| UFL1 | 0 | 0 |
| HJURP | 0 | 0 |
| SDR9C7 | 0 | 0 |
| FGF6 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| THIORIDAZINE HYDROCHLORIDE | 4 | STAT6 |
| DOXORUBICIN HYDROCHLORIDE | 4 | STAT6 |
| AMSACRINE | 4 | STAT6 |
| ADENOSINE | 4 | STAT6 |
| AMANTADINE | 4 | STAT6 |
| BISACODYL | 4 | STAT6 |
| CLOTRIMAZOLE | 4 | TRPM8 |
| CANNABIDIOL | 4 | TRPM8 |
| MENTHOL | 4 | TRPM8 |
| CAPSAICIN | 4 | TRPM8 |
| DRONABINOL | 4 | TRPM8 |
| ECONAZOLE | 4 | TRPM8 |
| QUERCETIN | 3 | STAT6 |
| TIAPRIDE | 3 | STAT6 |
| ICILLIN | 3 | TRPM8 |
| LEVOMENTHOL | 3 | TRPM8 |
| HYCANTHONE | 2 | STAT6 |
| SANGUINARIUM | 2 | STAT6 |
| IODOQUINOL | 2 | STAT6 |
| SB-705498 | 2 | TRPM8 |
| TETRAHYDROCANNABIVARIN | 2 | TRPM8 |
| CANNABIDIVARIN | 2 | TRPM8 |
| ACOLTREMON | 2 | TRPM8 |
| ELISMETREP | 2 | TRPM8 |
| CANNABIGEROL | 2 | TRPM8 |
| PF-05105679 | 1 | TRPM8 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| TRPM8 | 160 | Binding:148, Functional:12 |
| STAT6 | 81 | Binding:77, Functional:4 |
| NGF | 4 | Binding:4 |
| GFRA1 | 2 | Binding:2 |
| UFL1 | 1 | Binding:1 |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| TRPM8 | 160 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 14; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
26 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) |
|---|---|---|
| THIORIDAZINE HYDROCHLORIDE | 4 | STAT6 |
| DOXORUBICIN HYDROCHLORIDE | 4 | STAT6 |
| AMSACRINE | 4 | STAT6 |
| ADENOSINE | 4 | STAT6 |
| AMANTADINE | 4 | STAT6 |
| BISACODYL | 4 | STAT6 |
| CLOTRIMAZOLE | 4 | TRPM8 |
| CANNABIDIOL | 4 | TRPM8 |
| MENTHOL | 4 | TRPM8 |
| CAPSAICIN | 4 | TRPM8 |
| DRONABINOL | 4 | TRPM8 |
| ECONAZOLE | 4 | TRPM8 |
| QUERCETIN | 3 | STAT6 |
| TIAPRIDE | 3 | STAT6 |
| ICILLIN | 3 | TRPM8 |
| LEVOMENTHOL | 3 | TRPM8 |
| HYCANTHONE | 2 | STAT6 |
| SANGUINARIUM | 2 | STAT6 |
| IODOQUINOL | 2 | STAT6 |
| SB-705498 | 2 | TRPM8 |
| TETRAHYDROCANNABIVARIN | 2 | TRPM8 |
| CANNABIDIVARIN | 2 | TRPM8 |
| ACOLTREMON | 2 | TRPM8 |
| ELISMETREP | 2 | TRPM8 |
| CANNABIGEROL | 2 | TRPM8 |
| PF-05105679 | 1 | TRPM8 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | STAT6, TRPM8 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 2 | ASTN2, MPP2 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 10 | FHL5, TSPAN2, PHACTR1, UFL1, HJURP, SDR9C7, FGF6, GFRA1, LRP1, NGF |
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) |
|---|---|---|
| ASTN2 | 0 | — |
| FHL5 | 0 | — |
| TSPAN2 | 0 | — |
| PHACTR1 | 0 | — |
| UFL1 | 1 | — |
| HJURP | 0 | — |
| SDR9C7 | 0 | — |
| FGF6 | 0 | — |
| GFRA1 | 2 | — |
| LRP1 | 0 | — |
| MPP2 | 0 | — |
| NGF | 4 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.