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Sporadic amyotrophic lateral sclerosis

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Summary

Sporadic amyotrophic lateral sclerosis (MONDO:0005145) is a disease with 75 cohort genes (192 GWAS associations across 7 studies) and 3 clinical trials. Top therapeutic interventions include mexiletine.

At a glance

  • Cohort genes: 75
  • GWAS associations: 192
  • Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namesporadic amyotrophic lateral sclerosis
Mondo IDMONDO:0005145
EFOEFO:0001357
DOIDDOID:0080917
UMLSC1862941
MedGen400171
GARD0024156
Is cancer (heuristic)no

Data availability: 192 GWAS associations (7 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › spinal cord disorder › anterior horn disorder › amyotrophic lateral sclerosis › sporadic amyotrophic lateral sclerosis

Related subtypes (3): familial amyotrophic lateral sclerosis, amyotrophic lateral sclerosis with polyglucosan bodies, progressive muscular atrophy

Genetics & variants

GWAS landscape

192 GWAS associations across 7 studies. Top hits map to 21 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs38499433e-23C9orf72, EMICERI?0.04
kgp222725278e-11?
kgp80877712e-10?3.03
rs126089323e-10UNC13A?0.02
rs357146953e-10SARM1?0.03
rs110612698e-10ADGRD1?3.78
rs16050702e-09IQCF5-AS1 - IQCF1?3.95
rs93293002e-09LINC02645 - PFKP-DT?3.1
rs99770182e-09PCSEAT - LINC00111?
rs1395505382e-09IDE?0.48
rs93278815e-09MACIR - PDZPH1P?
rs117382095e-09FGF1, SPRY4-AS1A2.36
kgp75692586e-09?
rs71170828e-09OPCML?2.79
rs345176139e-09KRT18P55T1.2
kgp123173559e-09?
rs38499421e-08EMICERI, C9orf72?
kgp153272562e-08?17.44
kgp88511852e-08?
rs6161472e-08MOBP?0.02
rs23549522e-08THSD7AG1.38
rs605652452e-08LRP1G2.18
rs98254203e-08ITGA9?3.03
rs117448763e-08CTNND2?
kgp58194353e-08?
rs26850564e-08EZRP1 - ALCAM?2.58
kgp105571684e-08?
rs24122084e-08CAMTA1?0.16
rs24571747e-08FSTL4 - WSPAR?
kgp129705147e-08?

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST002283Fogh I20136,1007,125A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis.
GCST003632Fogh I20164,2560Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis.
GCST004901Benyamin B20171,2342,850Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.
GCST008472Benyamin B20171,2342,850Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.
GCST000482Sha Q20092760Genome-wide association reveals three SNPs associated with sporadic amyotrophic lateral sclerosis through a two-locus analysis.
GCST002337Xie T20142500Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.
GCST90833033Nakamura R202300Genetic factors affecting survival in Japanese patients with sporadic amyotrophic lateral sclerosis: a genome-wide association study and verification in iPSC-derived motor neurons from patients.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR2
Tier 3: regulatory1
Tier 4: intronic/intergenic47

MAF distribution

BucketVariants
common (>=0.05)35
low_freq (0.01-0.05)3
rare (<0.01)0
unknown12

Functional consequences

ConsequenceCount
unknown19
intron_variant18
intergenic_variant7
non_coding_transcript_exon_variant3
regulatory_region_variant1
3_prime_UTR_variant1
5_prime_UTR_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs3849943927543384C>A,G,T0.05non_coding_transcript_exon_variantC9orf72, EMICERI3e-23Tier 4: intronic/intergenic
kgp222725278e-11Tier 4: intronic/intergenic
kgp80877710.22e-10Tier 4: intronic/intergenic
rs126089321917641880A>C,T0.05intron_variantUNC13A3e-10Tier 4: intronic/intergenic
rs357146951728392769G>A,C,T0.05intron_variantSARM13e-10Tier 4: intronic/intergenic
rs1106126912130971904G>A0.08intron_variantADGRD18e-10Tier 4: intronic/intergenic
rs1605070351882999C>A,G,T0.14intergenic_variantIQCF5-AS1 - IQCF12e-09Tier 4: intronic/intergenic
rs9329300102747402A>C,G,T0.19intergenic_variantLINC02645 - PFKP-DT2e-09Tier 4: intronic/intergenic
rs99770182141616809T>G0.05regulatory_region_variantPCSEAT - LINC001112e-09Tier 3: regulatory
rs1395505381092524312T>A,C0.05intron_variantIDE2e-09Tier 4: intronic/intergenic
rs93278815103389394G>A0.14intron_variantMACIR - PDZPH1P5e-09Tier 4: intronic/intergenic
rs117382095142636127T>A0.03intron_variantFGF1, SPRY4-AS15e-09Tier 4: intronic/intergenic
kgp75692580.36e-09Tier 4: intronic/intergenic
rs711708211133522399G>T0.21intron_variantOPCML8e-09Tier 4: intronic/intergenic
rs345176131728283226C>T0.05intron_variantKRT18P559e-09Tier 4: intronic/intergenic
kgp123173550.079e-09Tier 4: intronic/intergenic
rs3849942927543283T>A,C,G0.237non_coding_transcript_exon_variantEMICERI, C9orf721e-08Tier 4: intronic/intergenic
kgp153272560.022e-08Tier 4: intronic/intergenic
kgp88511850.092e-08Tier 4: intronic/intergenic
rs616147339492990A>G0.05intron_variantMOBP2e-08Tier 4: intronic/intergenic
rs2354952711529255A>C,G,T0.448intron_variantTHSD7A2e-08Tier 4: intronic/intergenic
rs605652451257136403C>A,G,T0.049intron_variantLRP12e-08Tier 4: intronic/intergenic
rs9825420337562521T>C,G0.33intron_variantITGA93e-08Tier 4: intronic/intergenic
rs11744876511084600G>A0.17intron_variantCTNND23e-08Tier 4: intronic/intergenic
kgp58194350.123e-08Tier 4: intronic/intergenic
rs26850563104699729G>A,C,T0.35intron_variantEZRP1 - ALCAM4e-08Tier 4: intronic/intergenic
kgp105571680.124e-08Tier 4: intronic/intergenic
rs241220817032722T>G0.05intron_variantCAMTA14e-08Tier 4: intronic/intergenic
rs24571745133843389C>A,G,T0.05intergenic_variantFSTL4 - WSPAR7e-08Tier 4: intronic/intergenic
kgp129705147e-08Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 38 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BMPR1BOrphanet:2098Acromesomelic dysplasia, Grebe type
BMPR1BOrphanet:2639Fibular aplasia-complex brachydactyly syndrome
BMPR1BOrphanet:93384Brachydactyly type C
BMPR1BOrphanet:93388Brachydactyly type A1
BMPR1BOrphanet:93396Brachydactyly type A2
SLCO2A1Orphanet:2796Pachydermoperiostosis
SLCO2A1Orphanet:468641Chronic enteropathy associated with SLCO2A1 gene
SLC25A12Orphanet:353217Epileptic encephalopathy with global cerebral demyelination
SMARCA2Orphanet:3051Nicolaides-Baraitser syndrome
SMARCA2Orphanet:637013SMARCA2-related blepharophimosis-intellectual disability syndrome
TBXAS1Orphanet:1802Ghosal hematodiaphyseal dysplasia
TFAP2AOrphanet:1297Branchio-oculo-facial syndrome
THRBOrphanet:566243Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta
TLL1Orphanet:99103Atrial septal defect, ostium secundum type
TLL1Orphanet:99106Atrial septal defect, ostium primum type
TYRP1Orphanet:79433Oculocutaneous albinism type 3
CD2APOrphanet:656Hereditary steroid-resistant nephrotic syndrome
AUTS2Orphanet:352490Autism spectrum disorder due to AUTS2 deficiency
AUTS2Orphanet:641372B-lymphoblastic leukemia/lymphoma with t(7;9)(q11.2;p13.2)
LPIN2Orphanet:77297Majeed syndrome
ADAMTSL1Orphanet:521445Microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome
RP1L1Orphanet:247834Occult macular dystrophy
RP1L1Orphanet:791Retinitis pigmentosa
ADAMTS18Orphanet:369970Microcornea-myopic chorioretinal atrophy-telecanthus syndrome
RAB3GAP2Orphanet:1387Cataract-intellectual disability-hypogonadism syndrome
RAB3GAP2Orphanet:2510Micro syndrome
RAB3GAP2Orphanet:401830Autosomal recessive spastic paraplegia type 69
MYO18BOrphanet:447974Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome
CAMTA1Orphanet:157791Epithelioid hemangioendothelioma
CAMTA1Orphanet:314647Non-progressive cerebellar ataxia with intellectual disability
CHD2Orphanet:1942Epilepsy with myoclonic-atonic seizures
CHD2Orphanet:2382Lennox-Gastaut syndrome
GLRX5Orphanet:255132Adult-onset autosomal recessive sideroblastic anemia
GLRX5Orphanet:401866Childhood-onset spasticity with hyperglycinemia
ZFYVE26Orphanet:100996Kjellin syndrome
IFT74Orphanet:110Bardet-Biedl syndrome
IFT74Orphanet:137893Male infertility due to large-headed multiflagellar polyploid spermatozoa
IFT74Orphanet:475Isolated Joubert syndrome

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only75

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
RGS6HGNC:10002ENSG00000182732P49758Regulator of G-protein signaling 6gwas
RPS6KA1HGNC:10430ENSG00000117676Q15418Ribosomal protein S6 kinase alpha-1gwas
RYR3HGNC:10485ENSG00000198838Q15413Ryanodine receptor 3gwas
SDC1HGNC:10658ENSG00000115884P18827Syndecan-1gwas
BMPR1BHGNC:1077ENSG00000138696O00238Bone morphogenetic protein receptor type-1Bgwas
SLC10A2HGNC:10906ENSG00000125255Q12908Ileal sodium/bile acid cotransportergwas
SLCO2A1HGNC:10955ENSG00000174640Q92959Solute carrier organic anion transporter family member 2A1gwas
SLC25A12HGNC:10982ENSG00000115840O75746Electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrialgwas
SMARCA2HGNC:11098ENSG00000080503P51531SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2gwas
SP4HGNC:11209ENSG00000105866Q02446Transcription factor Sp4gwas
SREBF2HGNC:11290ENSG00000198911Q12772Sterol regulatory element-binding protein 2gwas
SSTR4HGNC:11333ENSG00000132671P31391Somatostatin receptor type 4gwas
TBC1D1HGNC:11578ENSG00000065882Q86TI0TBC1 domain family member 1gwas
TBXAS1HGNC:11609ENSG00000059377P24557Thromboxane-A synthasegwas
ZNF354AHGNC:11628ENSG00000169131O60765Zinc finger protein 354Agwas
TFAP2AHGNC:11742ENSG00000137203P05549Transcription factor AP-2-alphagwas
THRBHGNC:11799ENSG00000151090P10828Thyroid hormone receptor betagwas
TLL1HGNC:11843ENSG00000038295O43897Tolloid-like protein 1gwas
TMPRSS2HGNC:11876ENSG00000184012O15393Transmembrane protease serine 2gwas
TYRP1HGNC:12450ENSG00000107165P176435,6-dihydroxyindole-2-carboxylic acid oxidasegwas
ZNF28HGNC:13073ENSG00000198538P17035Zinc finger protein 28gwas
CALN1HGNC:13248ENSG00000183166Q9BXU9Calcium-binding protein 8gwas
RNF19AHGNC:13432ENSG00000034677Q9NV58E3 ubiquitin-protein ligase RNF19Agwas
FBXO15HGNC:13617ENSG00000141665Q8NCQ5F-box only protein 15gwas
NEUROG2HGNC:13805ENSG00000178403Q9H2A3Neurogenin-2gwas
CELF4HGNC:14015ENSG00000101489Q9BZC1CUGBP Elav-like family member 4gwas
CSMD1HGNC:14026ENSG00000183117Q96PZ7CUB and sushi domain-containing protein 1gwas
CD2APHGNC:14258ENSG00000198087Q9Y5K6CD2-associated proteingwas
AUTS2HGNC:14262ENSG00000158321Q8WXX7Autism susceptibility gene 2 proteingwas
ETNPPLHGNC:14404ENSG00000164089Q8TBG4Ethanolamine-phosphate phospho-lyasegwas
LPIN2HGNC:14450ENSG00000101577Q92539Phosphatidate phosphatase LPIN2gwas
ADAMTSL1HGNC:14632ENSG00000178031Q8N6G6ADAMTS-like protein 1gwas
ADAMTSL3HGNC:14633ENSG00000156218P82987ADAMTS-like protein 3gwas
ABCC12HGNC:14640ENSG00000140798Q96J65ATP-binding cassette sub-family C member 12gwas
INTS6HGNC:14879ENSG00000102786Q9UL03Integrator complex subunit 6gwas
FAM167AHGNC:15549ENSG00000154319Q96KS9Protein FAM167Agwas
RP1L1HGNC:15946ENSG00000183638Q8IWN7Retinitis pigmentosa 1-like 1 proteingwas
MACROD2HGNC:16126ENSG00000172264A1Z1Q3ADP-ribose glycohydrolase MACROD2gwas
C20orf173HGNC:16166ENSG00000125975Q96LM9Uncharacterized protein C20orf173gwas
SLC28A3HGNC:16484ENSG00000197506Q9HAS3Solute carrier family 28 member 3gwas
TP53I11HGNC:16842ENSG00000175274O14683Tumor protein p53-inducible protein 11gwas
STON1HGNC:17003ENSG00000243244Q9Y6Q2Stonin-1gwas
MGLLHGNC:17038ENSG00000074416Q99685Monoglyceride lipasegwas
SARM1HGNC:17074ENSG00000004139Q6SZW1NAD(+) hydrolase SARM1gwas
ADAMTS18HGNC:17110ENSG00000140873Q8TE60A disintegrin and metalloproteinase with thrombospondin motifs 18gwas
RAB3GAP2HGNC:17168ENSG00000118873Q9H2M9Rab3 GTPase-activating protein non-catalytic subunitgwas
OLFM4HGNC:17190ENSG00000102837Q6UX06Olfactomedin-4gwas
SYNPO2HGNC:17732ENSG00000172403Q9UMS6Synaptopodin-2gwas
CHODLHGNC:17807ENSG00000154645Q9H9P2Chondrolectingwas
TRPM8HGNC:17961ENSG00000144481Q7Z2W7Transient receptor potential cation channel subfamily M member 8gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
RGS6Regulator of G-protein signaling 6Regulates G protein-coupled receptor signaling cascades.
RPS6KA1Ribosomal protein S6 kinase alpha-1Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation thr…
RYR3Ryanodine receptor 3Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm in muscle and thereby plays a role in triggering muscle contraction.
SDC1Syndecan-1Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix.
BMPR1BBone morphogenetic protein receptor type-1BOn ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
SLC10A2Ileal sodium/bile acid cotransporterPlays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine.
SLCO2A1Solute carrier organic anion transporter family member 2A1Mediates the transport of prostaglandins (PGs, mainly PGE2, PGE1, PGE3, PGF2alpha, PGD2, PGH2) and thromboxanes (thromboxane B2) across the cell membrane.
SLC25A12Electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrialMitochondrial electrogenic aspartate/glutamate antiporter that favors efflux of aspartate and entry of glutamate and proton within the mitochondria as part of the malate-aspartate shuttle.
SMARCA2SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
SP4Transcription factor Sp4Binds to GT and GC boxes promoters elements.
SREBF2Sterol regulatory element-binding protein 2Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 2), which is embedded in the endoplasmic reticulum membrane.
SSTR4Somatostatin receptor type 4Receptor for somatostatin-14.
TBC1D1TBC1 domain family member 1May act as a GTPase-activating protein for Rab family protein(s).
TBXAS1Thromboxane-A synthaseCatalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation.
TFAP2ATranscription factor AP-2-alphaSequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
THRBThyroid hormone receptor betaNuclear hormone receptor that can act as a repressor or activator of transcription.
TLL1Tolloid-like protein 1Protease which processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase.
TMPRSS2Transmembrane protease serine 2Plasma membrane-anchored serine protease that cleaves at arginine residues.
TYRP15,6-dihydroxyindole-2-carboxylic acid oxidasePlays a role in melanin biosynthesis.
ZNF28Zinc finger protein 28May be involved in transcriptional regulation.
CALN1Calcium-binding protein 8Negatively regulates Golgi-to-plasma membrane trafficking by interacting with PI4KB and inhibiting its activity.
RNF19AE3 ubiquitin-protein ligase RNF19AE3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates, such as SNCAIP or CASR.
FBXO15F-box only protein 15Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
NEUROG2Neurogenin-2Transcriptional regulator.
CELF4CUGBP Elav-like family member 4RNA-binding protein implicated in the regulation of pre-mRNA alternative splicing.
CSMD1CUB and sushi domain-containing protein 1Potential suppressor of squamous cell carcinomas.
CD2APCD2-associated proteinSeems to act as an adapter protein between membrane proteins and the actin cytoskeleton.
AUTS2Autism susceptibility gene 2 proteinComponent of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.
ETNPPLEthanolamine-phosphate phospho-lyaseCatalyzes the pyridoxal-phosphate-dependent breakdown of phosphoethanolamine, converting it to ammonia, inorganic phosphate and acetaldehyde.
LPIN2Phosphatidate phosphatase LPIN2Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis in the endoplasmic reti…
ABCC12ATP-binding cassette sub-family C member 12Probable transporter, its substrate specificity is unknown.
INTS6Integrator complex subunit 6Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes.
RP1L1Retinitis pigmentosa 1-like 1 proteinRequired for the differentiation of photoreceptor cells.
MACROD2ADP-ribose glycohydrolase MACROD2Removes ADP-ribose from aspartate and glutamate residues in proteins bearing a single ADP-ribose moiety.
SLC28A3Solute carrier family 28 member 3Sodium-dependent, pyrimidine- and purine-selective.
STON1Stonin-1May be involved in the endocytic machinery.
MGLLMonoglyceride lipaseConverts monoacylglycerides to free fatty acids and glycerol.
SARM1NAD(+) hydrolase SARM1NAD(+) hydrolase, which plays a key role in axonal degeneration following injury by regulating NAD(+) metabolism.
RAB3GAP2Rab3 GTPase-activating protein non-catalytic subunitRegulatory subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of RAB3GAP1 and RAB3GAP2, which accelerates the otherwise slow GTP hydrolysis catalyzed by Rab proteins.
OLFM4Olfactomedin-4May promote proliferation of pancreatic cancer cells by favoring the transition from the S to G2/M phase.
SYNPO2Synaptopodin-2Has an actin-binding and actin-bundling activity.
CHODLChondrolectinMay play a role in the development of the nervous system such as in neurite outgrowth and elongation.
TRPM8Transient receptor potential cation channel subfamily M member 8Non-selective ion channel permeable to monovalent and divalent cations, including Na(+), K(+), and Ca(2+), with higher permeability for Ca(2+).
RTCARNA 3’-terminal phosphate cyclaseCatalyzes the conversion of 3’-phosphate to a 2’,3’-cyclic phosphodiester at the end of RNA.
MYO18BUnconventional myosin-XVIIIbMay be involved in intracellular trafficking of the muscle cell when in the cytoplasm, whereas entering the nucleus, may be involved in the regulation of muscle specific genes.
CEP250Centrosome-associated protein CEP250Plays an important role in centrosome cohesion during interphase.
CAMTA1Calmodulin-binding transcription activator 1Transcriptional activator.
NUDT12NAD-capped RNA hydrolase NUDT12mRNA decapping enzyme that specifically removes the nicotinamide adenine dinucleotide (NAD) cap from a subset of mRNAs by hydrolyzing the diphosphate linkage to produce nicotinamide mononucleotide (NMN) and 5’ monophosphate mRNA.
PSD3PH and SEC7 domain-containing protein 3Guanine nucleotide exchange factor for ARF6.
SLC5A8Sodium-coupled monocarboxylate transporter 1Acts as an electrogenic sodium (Na(+)) and chloride (Cl-)-dependent sodium-coupled solute transporter, including transport of monocarboxylates (short-chain fatty acids including L-lactate, D-lactate, pyruvate, acetate, propionate, valerate…

Protein-family classification

Druggable: 23 · Difficult: 15 · Unknown: 37 · Druggable fraction: 0.31

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 receptor15.2×0.532
Complement13.6×0.532
Transporter33.1×0.532
Ion channel23.0×0.532
Antibody/Immunoglobulin41.6×0.532
Scaffold/PPI61.4×0.532
Protease31.5×0.577
Kinase31.1×0.753
Transcription factor91.0×0.753
Other/Unknown370.9×0.894
Enzyme (other)40.6×0.894
GPCR20.6×0.894

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
RGS6Other/UnknownnoDEP_dom, G-protein_gamma-like_dom, RGS
RPS6KA1Kinaseyes2.7.11.1Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
RYR3Ion channelyesRIH_dom, B30.2/SPRY, EF_hand_dom
SDC1Other/UnknownnoSyndecan, Neurexin-like, Syndecan/Neurexin_dom
BMPR1BKinaseyes2.7.10.2TGFB_receptor, Activin_recp, Prot_kinase_dom
SLC10A2Other/UnknownnoBilAc:Na_symport/Acr3, Bilac:Na_transpt, Na+/solute_symporter_sf
SLCO2A1TransporteryesKazal_dom, OATP, MFS_dom
SLC25A12TransporteryesEF_hand_dom, MCP, EF-hand-dom_pair
SMARCA2Other/UnknownnoSNF2_N, Bromodomain, Helicase_C-like
SP4Transcription factornoZnf_C2H2_type, Znf_C2H2_sf, Sp4-like
SREBF2Transcription factornobHLH_dom, HLH_DNA-bd_sf
SSTR4GPCRyesGPCR_Rhodpsn, Somatstn_rcpt, Somatstn_rcpt_4
TBC1D1Other/UnknownnoRab-GAP-TBC_dom, PTB/PI_dom, PH-like_dom_sf
TBXAS1Other/UnknownnoCyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
ZNF354ATranscription factornoKRAB, Znf_C2H2_type, KRAB_dom_sf
TFAP2ATranscription factornoTF_AP2, TF_AP2_alpha_N, TF_AP2_C
THRBNuclear receptoryesNucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
TLL1ProteaseyesEGF-type_Asp/Asn_hydroxyl_site, EGF, CUB_dom
TMPRSS2Proteaseyes3.4.21.B60SRCR, Trypsin_dom, Peptidase_S1A
TYRP1Other/UnknownnoTyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
ZNF28Transcription factornoKRAB, Znf_C2H2_type, KRAB_dom_sf
CALN1Other/UnknownnoS100/CaBP7/8-like_CS, EF_hand_dom, EF-hand-dom_pair
RNF19ATranscription factornoZnf_RING, IBR_dom, Znf_RING/FYVE/PHD
FBXO15Other/UnknownnoF-box_dom, F-box-like_dom_sf
NEUROG2Transcription factornobHLH_dom, Ngn-2_bHLH, HLH_DNA-bd_sf
CELF4Other/UnknownnoRRM_dom, Nucleotide-bd_a/b_plait_sf, CELF3/4/5/6_RRM1
CSMD1ComplementyesSushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
CD2APScaffold/PPInoSH3_domain, CD2AP_SH3_1, CD2AP_SH_2
AUTS2Other/UnknownnoAUTS2
ETNPPLOther/UnknownnoAminotrans_3, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small
LPIN2Other/UnknownnoLipin_N, LNS2, LIPIN
ADAMTSL1Antibody/ImmunoglobulinyesTSP1_rpt, Ig_sub2, Ig_sub
ADAMTSL3Antibody/ImmunoglobulinyesTSP1_rpt, Ig_sub2, Ig_sub
ABCC12TransporteryesABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
INTS6Other/UnknownnoVWF_A, INT_SG_DDX_CT_C, vWFA_dom_sf
FAM167AOther/UnknownnoFAM167, FAM167_domain
RP1L1Other/UnknownnoDoublecortin_dom, Doublecortin_dom_sf
MACROD2Enzyme (other)yes3.1.1.106Macro_dom, Macro_dom-like
C20orf173Other/UnknownnoGT29-like_sf, Beta-gal_alpha2-3_sialyltrans
SLC28A3Other/UnknownnoCNT_N_dom, C_nuclsd_transpt, Gate_dom
TP53I11Other/UnknownnoTP53I11
STON1Other/UnknownnoSHD_dom, Stonin, MHD
MGLLEnzyme (other)yes3.1.1.23AB_hydrolase_1, ABHD17C-like, AB_hydrolase_fold
SARM1Other/UnknownnoTIR_dom, SAM, ARM-like
ADAMTS18ProteaseyesTSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
RAB3GAP2Other/UnknownnoRab3GAP2, RAB3GAP2_C, RAB3GAP_N
OLFM4Other/UnknownnoOlfac-like_dom, Quinoprot_gluc/sorb_DH_b-prop, Olfactomedin-like_domain
SYNPO2Scaffold/PPInoPDZ, PDZ_sf, Synaptopodin_domain
CHODLOther/UnknownnoC-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold
TRPM8Ion channelyesIon_trans_dom, TRPM_SLOG, TRPM

Expression context

Cohort genes with no expression data: 0.

69 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)1
broad (>20)74
unknown0

Top tissues across cohort

TissueCohort genes
cortical plate11
calcaneal tendon8
secondary oocyte7
sural nerve6
jejunal mucosa6
primordial germ cell in gonad6
islet of Langerhans5
bronchial epithelial cell4
cerebellar vermis4
ventricular zone4
prefrontal cortex4
Brodmann (1909) area 234
endothelial cell4
middle temporal gyrus3
mucosa of transverse colon3
cauda epididymis3
duodenum3
colonic epithelium3
germinal epithelium of ovary3
ganglionic eminence3

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
RGS6185broadmarkercortical plate, sural nerve, middle temporal gyrus
RPS6KA1134ubiquitousmarkerblood, granulocyte, mucosa of transverse colon
RYR3233broadmarkerdiaphragm, sural nerve, right hemisphere of cerebellum
SDC1240ubiquitousmarkerlower esophagus mucosa, skin of abdomen, pharyngeal mucosa
BMPR1B239broadmarkercalcaneal tendon, bronchial epithelial cell, cauda epididymis
SLC10A249tissue_specificmarkerileal mucosa, jejunal mucosa, duodenum
SLCO2A1252broadmarkerright lung, upper lobe of left lung, upper lobe of lung
SLC25A12295ubiquitousmarkerbiceps brachii, skeletal muscle tissue of biceps brachii, triceps brachii
SMARCA2301ubiquitousmarkercalcaneal tendon, colonic epithelium, cortical plate
SP4265ubiquitousmarkercerebellar vermis, germinal epithelium of ovary, superficial temporal artery
SREBF2287ubiquitousmarkerganglionic eminence, cortical plate, ventricular zone
SSTR435yesendometrium epithelium, metanephric glomerulus, prefrontal cortex
TBC1D1280ubiquitousmarkerventricular zone, body of uterus, muscle layer of sigmoid colon
TBXAS1180ubiquitousmarkermonocyte, mononuclear cell, leukocyte
ZNF354A253ubiquitousmarkersecondary oocyte, oocyte, cortical plate
TFAP2A220ubiquitousmarkerupper leg skin, gingival epithelium, gingiva
THRB267ubiquitousmarkerBrodmann (1909) area 23, middle temporal gyrus, tibia
TLL1162broadmarkersecondary oocyte, buccal mucosa cell, primordial germ cell in gonad
TMPRSS2198broadmarkermucosa of transverse colon, mucosa of sigmoid colon, colonic mucosa
TYRP1206broadmarkerpigmented layer of retina, upper leg skin, mammalian vulva
ZNF28136broadmarkerislet of Langerhans, adrenal tissue, primordial germ cell in gonad
CALN1140broadmarkercerebellar vermis, pons, cerebellum
RNF19A270ubiquitousmarkercalcaneal tendon, sperm, colonic epithelium
FBXO15197broadmarkerbronchial epithelial cell, bronchus, right uterine tube
NEUROG243tissue_specificmarkerganglionic eminence, ventricular zone, primordial germ cell in gonad
CELF4183broadmarkercerebellar cortex, cerebellar hemisphere, Brodmann (1909) area 9
CSMD1179broadmarkerBrodmann (1909) area 23, middle temporal gyrus, primary visual cortex
CD2AP275ubiquitousmarkerjejunal mucosa, esophagus squamous epithelium, colonic mucosa
AUTS2292ubiquitousmarkercortical plate, tibia, ganglionic eminence
ETNPPL204tissue_specificmarkercranial nerve II, lateral globus pallidus, putamen

Protein interactions among cohort

Intra-cohort edges: 11.

Hub genes (top 10 by interactor count)

SymbolInteractor count
DOCK44,803
SMARCA24,237
SDC13,387
SREBF23,073
TMPRSS23,048
RPS6KA12,833
MGLL2,776
RTCA2,745
TFAP2A2,734
CEP2502,707

Intra-cohort edges

ABSources
ADAMTSL1TYRP1string_interaction
AUTS2CALN1string_interaction
AUTS2SLC9A9string_interaction
C6orf132LRFN2string_interaction
CEP250FAM167Abiogrid_interaction
DOCK4SYNPO2intact
DPF1SMARCA2intact
IFT74RNF19Astring_interaction
INTS6OLFM4biogrid_interaction
LRRTM4SDC1intact
SARM1SDC1intact

Structural data

PDB: 35 · AlphaFold-only: 39 · No structure: 1

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
SARM1Q6SZW155
THRBP1082834
TMPRSS2O1539334
SMARCA2P5153132
MGLLQ9968530
RPS6KA1Q1541823
TYRP1P1764313
CD2APQ9Y5K612
RYR3Q1541310
INTS6Q9UL039
ADGRD1Q6QNK28
SLCO2A1Q929597
TRPM8Q7Z2W76
MACROD2A1Z1Q34
SDC1P188273
TFAP2AP055493
SLC25A12O757462
SSTR4P313912
CELF4Q9BZC12
GLRX5Q86SX62
SLITRK1Q96PX82
RGS6P497581
BMPR1BO002381
SREBF2Q127721
TBC1D1Q86TI01
TLL1O438971
CSMD1Q96PZ71
ETNPPLQ8TBG41
SLC28A3Q9HAS31
RAB3GAP2Q9H2M91

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
RTCAO0044295.90
CSNK1A1LQ8N75292.06
ASB13Q8WXK391.60
TBXAS1P2455791.50
OLFM4Q6UX0683.34
SLC10A2Q1290882.88
ST6GALNAC5Q9BVH781.83
IFT74Q96LB381.21
ABCC12Q96J6578.09
FBXO15Q8NCQ577.42
CHODLQ9H9P276.83
DOCK4Q8N1I076.47
TP53I11O1468375.77
LRRTM4Q86VH474.45
ADAMTS18Q8TE6073.83
SLC9A9Q8IVB473.46
FAM167AQ96KS971.98
ADAMTSL1Q8N6G671.26
LRFN2Q9ULH470.36
ZNF28P1703569.35
ZNF354AO6076568.73
DPF1Q9278267.41
ADAMTSL3P8298765.99
STON1Q9Y6Q265.75
NEUROG2Q9H2A364.98
SNX19Q9254361.47
LPIN2Q9253961.12
CHD2O1464760.81
MYO18BQ8IUG560.66
C5orf15Q8NC5457.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 541. Enrichment computed across 165 evidence-associated genes (100 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 100 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Defective TBXAS1 causes GHDD1114.2×0.194TBXAS1
Defective SLC9A9 causes autism 16 (AUTS16)1114.2×0.194SLC9A9
Defective SLCO2A1 causes primary, autosomal recessive hypertrophic osteoarthropathy 2 (PHOAR2)1114.2×0.194SLCO2A1
Synthesis of PE217.6×0.194ETNPPL, LPIN2
Synthesis of IP2, IP, and Ins in the cytosol215.2×0.194INPP4B, INPP5B
TRAF6-mediated induction of TAK1 complex within TLR4 complex214.3×0.194SARM1, MAP3K7
ERK/MAPK targets213.4×0.194RPS6KA1, PPP2R5D
Triglyceride metabolism213.4×0.194LPIN2, MGLL
Specification of the neural plate border212.7×0.194TFAP2A, PAX3
Formation of the canonical BAF (cBAF) complex212.7×0.194SMARCA2, DPF1
Regulation of MITF-M-dependent genes involved in pigmentation410.6×0.194SMARCA2, TFAP2A, TYRP1, DPF1
Glycerophospholipid biosynthesis310.1×0.194ETNPPL, LPIN2, MGLL
MAP kinase activation39.3×0.194RPS6KA1, MAP3K7, PPP2R5D
Defective B3GALTL causes PpS39.3×0.194ADAMTSL1, ADAMTSL3, ADAMTS18
O-glycosylation of TSR domain-containing proteins39.0×0.194ADAMTSL1, ADAMTSL3, ADAMTS18
Platelet homeostasis38.4×0.194KCNMB2, ATP2B2, PPP2R5D
Phospholipid metabolism48.0×0.194ETNPPL, LPIN2, MGLL, INPP4B
Protein-protein interactions at synapses38.0×0.194LRRTM4, SLITRK1, LRFN2
Toll Like Receptor 3 (TLR3) Cascade47.7×0.194RPS6KA1, SARM1, MAP3K7, PPP2R5D
Interleukin-17 signaling37.6×0.194RPS6KA1, MAP3K7, PPP2R5D
MyD88-independent TLR4 cascade47.4×0.194RPS6KA1, SARM1, MAP3K7, PPP2R5D
Toll Like Receptor 10 (TLR10) Cascade36.5×0.194RPS6KA1, MAP3K7, PPP2R5D
Toll Like Receptor 5 (TLR5) Cascade36.5×0.194RPS6KA1, MAP3K7, PPP2R5D
Diseases associated with O-glycosylation of proteins36.5×0.194ADAMTSL1, ADAMTSL3, ADAMTS18
Diseases of glycosylation45.2×0.194SDC1, ADAMTSL1, ADAMTSL3, ADAMTS18
Constitutive Signaling by Aberrant PI3K in Cancer45.1×0.194ERBB4, FGF9, FYN, NTRK3
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling54.8×0.194ERBB4, FGF9, FYN, NTRK3, PPP2R5D
L1CAM interactions44.8×0.194RPS6KA1, ALCAM, ANK3, ITGA9
Diseases of metabolism54.0×0.194SDC1, TBXAS1, ADAMTSL1, ADAMTSL3, ADAMTS18
Transport of small molecules102.5×0.194RYR3, SLCO2A1, SLC28A3, SLC5A8, SLC9A9, LRRC8C, ABCG1, NEDD4L (+2 more)

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 143 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
optic cup structural organization1117.8×0.182TFAP2A
acetate transport1117.8×0.182SLC5A8
pyruvate transport1117.8×0.182SLC5A8
propanoate transmembrane transport1117.8×0.182SLC5A8
pyrimidine nucleoside transport1117.8×0.182SLC28A3
negative regulation of MyD88-independent toll-like receptor signaling pathway1117.8×0.182SARM1
posterior lateral line neuromast hair cell development1117.8×0.182TMEM132E
obsolete acetoacetic acid metabolic process1117.8×0.182TYRP1
positive regulation of axon extension involved in regeneration1117.8×0.182NTRK3
striated muscle cell development1117.8×0.182SDC1
negative regulation of cardiac epithelial to mesenchymal transition1117.8×0.182NOG
receptor diffusion trapping1117.8×0.182TSPAN9
multiple spine synapse organization, single dendrite1117.8×0.182CX3CR1
regulation of retina development in camera-type eye1117.8×0.182CELF4
positive regulation of cyclin-dependent protein kinase activity1117.8×0.182STOX1
positive regulation of otic vesicle morphogenesis1117.8×0.182STOX1
negative regulation of microglial cell mediated cytotoxicity1117.8×0.182CX3CR1
ceramide phosphoethanolamine catabolic process1117.8×0.182ETNPPL
negative regulation of optical nerve axon regeneration1117.8×0.182RTCA
obsolete regulation of Rho-dependent protein serine/threonine kinase activity1117.8×0.182SYNPO2
response to singlet oxygen158.9×0.182FYN
regulation of systemic arterial blood pressure by aortic arch baroreceptor feedback158.9×0.182ASIC2
optic vesicle morphogenesis158.9×0.182TFAP2A
NADP+ catabolic process158.9×0.182NUDT12
positive regulation of cell communication by electrical coupling158.9×0.182ANK3
lactate transport158.9×0.182SLC5A8
pyruvate fermentation to lactate158.9×0.182LDHC
central nervous system morphogenesis158.9×0.182ERBB4
oculomotor nerve formation158.9×0.182TFAP2A
central nervous system maturation158.9×0.182CX3CR1

Therapeutics

Drug target analysis

Approved (phase 4): 13 · Phase ≥3: 13 · Phased (≥1): 15 · Undrugged: 60

Druggability breadth: 52 of 165 evidence-associated genes (32%) 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
RPS6KA1FEDRATINIB
BMPR1BMOMELOTINIB
SLC10A2URSODIOL
SLCO2A1DINOPROST
SSTR4OCTREOTIDE
TBXAS1CLOTRIMAZOLE
THRBAMINOCAPROIC ACID
TMPRSS2DEBRISOQUIN
SLC28A3ADENOSINE
MGLLDISULFIRAM
SARM1NIACINAMIDE
TRPM8CLOTRIMAZOLE
CSNK1A1LBOSUTINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
THRB1174
TBXAS1464
RPS6KA1374
BMPR1B284
TRPM8154
SLC10A294
TMPRSS294
SARM174
CSNK1A1L74
SSTR464

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
FEDRATINIB4BMPR1B, RPS6KA1
RUXOLITINIB4BMPR1B, RPS6KA1
NERATINIB4RPS6KA1
TOFACITINIB CITRATE4RPS6KA1
TOFACITINIB4RPS6KA1
CERITINIB4RPS6KA1
VANDETANIB4BMPR1B, RPS6KA1
GILTERITINIB4BMPR1B, RPS6KA1
BRIGATINIB4RPS6KA1
NINTEDANIB4RPS6KA1
SUNITINIB4BMPR1B, CSNK1A1L, RPS6KA1
MIDOSTAURIN4RPS6KA1
MOMELOTINIB4BMPR1B
AXITINIB4BMPR1B
PAZOPANIB4BMPR1B
DASATINIB4BMPR1B
QUIZARTINIB4BMPR1B
CRIZOTINIB4BMPR1B
URSODIOL4SLC10A2
CYCLOSPORINE4SLC10A2
MARALIXIBAT CHLORIDE4SLC10A2
CHENODIOL4SLC10A2
TAURURSODIOL4SLC10A2
MARALIXIBAT4SLC10A2
DEOXYCHOLIC ACID4SLC10A2
DINOPROST4SLCO2A1
OCTREOTIDE4SSTR4
GALLIUM OXODOTREOTIDE4SSTR4
CLOTRIMAZOLE4TBXAS1, TRPM8
CISPLATIN4TBXAS1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

SymbolAssaysType breakdown
RPS6KA1785Binding:784, ADMET:1
MGLL334Binding:329, ADMET:3, Functional:2
SMARCA2311Binding:274, Functional:25, ADMET:12
TBXAS1210Binding:138, Functional:72
SSTR4174Binding:153, Functional:19, ADMET:2
THRB169Binding:129, Functional:40
BMPR1B166Binding:164, ADMET:2
TRPM8160Binding:148, Functional:12
CSNK1A1L93Binding:93
SLC10A247Binding:28, Functional:19
TMPRSS228Binding:28
SARM125Binding:25
SREBF222Binding:22
INTS66Binding:6
TLL15Binding:5
SLCO2A14Functional:4
MACROD24Binding:2, Toxicity:2
TYRP13Binding:3
SLC28A33ADMET:2, Binding:1
RYR32Binding:2
ADGRD12Binding:2
SDC11Binding:1
CD2AP1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
RPS6KA12.7.11.1non-specific serine/threonine protein kinase
BMPR1B2.7.10.2non-specific protein-tyrosine kinase
TMPRSS23.4.21.B60
MACROD23.1.1.106O-acetyl-ADP-ribose deacetylase
MGLL3.1.1.23acylglycerol lipase
RTCA6.5.1.4RNA 3’-terminal-phosphate cyclase (ATP)
ST6GALNAC52.4.99.7alpha-N-acetylneuraminyl-2,3-beta-galactosyl-1,3-N-acetylgalactosaminide 6-alpha-sialyltransferase

Cohort genes with high screening signal

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

SymbolChEMBL assays
RPS6KA1785
BMPR1B166
SMARCA2311
SSTR4174
TBXAS1210
THRB169
MGLL334
TRPM8160

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; 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)
FEDRATINIB4BMPR1B, RPS6KA1
RUXOLITINIB4BMPR1B, RPS6KA1
NERATINIB4RPS6KA1
TOFACITINIB CITRATE4RPS6KA1
TOFACITINIB4RPS6KA1
CERITINIB4RPS6KA1
VANDETANIB4BMPR1B, RPS6KA1
GILTERITINIB4BMPR1B, RPS6KA1
BRIGATINIB4RPS6KA1
NINTEDANIB4RPS6KA1
SUNITINIB4BMPR1B, CSNK1A1L, RPS6KA1
MIDOSTAURIN4RPS6KA1
MOMELOTINIB4BMPR1B
AXITINIB4BMPR1B
PAZOPANIB4BMPR1B
DASATINIB4BMPR1B
QUIZARTINIB4BMPR1B
CRIZOTINIB4BMPR1B
URSODIOL4SLC10A2
CYCLOSPORINE4SLC10A2
MARALIXIBAT CHLORIDE4SLC10A2
CHENODIOL4SLC10A2
TAURURSODIOL4SLC10A2
MARALIXIBAT4SLC10A2
DEOXYCHOLIC ACID4SLC10A2
DINOPROST4SLCO2A1
OCTREOTIDE4SSTR4
GALLIUM OXODOTREOTIDE4SSTR4
CLOTRIMAZOLE4TBXAS1, TRPM8
CISPLATIN4TBXAS1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)13RPS6KA1, BMPR1B, SLC10A2, SLCO2A1, SSTR4, TBXAS1, THRB, TMPRSS2, SLC28A3, MGLL (+3 more)
BPhased (≥1) drug, not yet approved2SMARCA2, INTS6
CDruggable family + PDB, no drug7RYR3, SLC25A12, TLL1, CSMD1, MACROD2, CAMTA1, ADGRD1
DDruggable family + AlphaFold only, no drug7ADAMTSL1, ADAMTSL3, ABCC12, ADAMTS18, RTCA, ST6GALNAC5, LRFN2
EDifficult family or no structure, no drug46RGS6, SDC1, SP4, SREBF2, TBC1D1, ZNF354A, TFAP2A, TYRP1, ZNF28, CALN1 (+36 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
RGS60—
RYR32—
SDC11—
SLC25A120—
SP40—
SREBF222—
TBC1D10—
ZNF354A0—
TFAP2A0—
TLL15—
TYRP13—
ZNF280—
CALN10—
RNF19A0—
FBXO150—
NEUROG20—
CELF40—
CSMD10—
CD2AP1—
AUTS20—
ETNPPL0—
LPIN20—
ADAMTSL10—
ADAMTSL30—
ABCC120—
FAM167A0—
RP1L10—
MACROD24—
C20orf1730—
TP53I110—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE22
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT01849770PHASE2COMPLETEDMexiletine in Sporadic Amyotrophic Lateral Sclerosis (SALS)
NCT02781454PHASE2COMPLETEDMexiletine in Sporadic Amyotrophic Lateral Sclerosis
NCT02969759EARLY_PHASE1UNKNOWNBioenergetics and Protein Metabolism in Sporadic Amyotrophic Lateral Sclerosis

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
MEXILETINE42

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
v1.1.4
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_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot