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Atlas / Disease / Congenital left-sided heart lesions

Congenital left-sided heart lesions

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Summary

Congenital left-sided heart lesions (MONDO:0005584) is a disease with 20 cohort genes (35 GWAS associations across 7 studies).

At a glance

  • Cohort genes: 20
  • GWAS associations: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namecongenital left-sided heart lesions
Mondo IDMONDO:0005584
EFOEFO:0005938
UMLSC4022397
MedGen868006
GARD0024207
Is cancer (heuristic)no

Data availability: 35 GWAS associations (7 studies).

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › congenital anomaly of cardiovascular system › congenital heart malformation › congenital left-sided heart lesions

Related subtypes (25): transposition of the great arteries, interventricular septum aneurysm, congenital heart defects, multiple types, 2, coronary artery congenital malformation, criss-cross heart, triatrial heart, familial idiopathic dilatation of the right atrium, cardiac diverticulum, conotruncal heart malformations, congenital mitral malformation, congenital pericardium anomaly, ectopia cordis, visceral heterotaxy, mesocardia, univentricular cardiopathy, congenital anomaly of the great arteries, Laubry-Pezzi syndrome, congenital Gerbode defect, juxtaposition of the atrial appendages, ectasia of the right atrial appendage, ectasia of the left appendage, atrial septal aneurysm, congenital acardia, congenital right-sided heart lesions, congenital heart defects, multiple types, 1, X-linked

Subtypes (1): hypoplastic left heart syndrome

Genetics & variants

GWAS landscape

35 GWAS associations across 7 studies. Top hits map to 27 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs80611214e-09C16orf95?2.65
rs13053931956e-09SUMF1?11.02
rs37464461e-08MYH7BG1.23
rs728202642e-08HULC?2.05
rs350461433e-08LINC01708?0.17
rs354371214e-08ARHGEF4?2.27
rs1145036845e-08TFDP2?3.53
rs557884146e-08PKD1L2?5.82
rs20460607e-08LINC01991 - LPP-AS2?1.57
rs118949321e-07MGAT4A?2.25
rs19756493e-07SYNPR-AS1, SYNPR?1.65
rs110082226e-07LINC02644 - ZNF438?1.64
rs16426458e-07HIVEP3 - HNRNPFP1?1.88
rs120458079e-07ENSAC1.61
rs774711499e-07RN7SKP188 - ANXA10?2
rs743773012e-06ASB15, ASB15-AS1?1.63
rs111598402e-06HISLA?1.61
rs125092812e-06FRAS1?2.21
rs76071402e-06UPP2?2.51
rs117550543e-06LINC03005, CASC15?1.56
rs6721493e-06FLI1?1.6
rs25679924e-06P2RX4?1.81
rs13791344e-06ZMAT4 - RNU6-356P?2.7
rs68118025e-06HNRNPA1P56 - FRAS1?2.01
rs15722025e-06RPL9P21 - TMEM72-AS1?1.77
rs76232916e-06KCNMB2-AS1, KCNMB2?1.57
rs115142956e-06PRANCR?1.98
rs7333177e-06GHRHR - ADCYAP1R1?1.64
rs14684987e-06AFAP1L2?2
rs117665247e-06LINC02476?1.92

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90570533Broberg M20242,382392,503Genome-wide association studies highlight novel risk loci for septal defects and left-sided congenital heart defects.
GCST003419Hanchard NA20165922,676A genome-wide association study of congenital cardiovascular left-sided lesions shows association with a locus on chromosome 20.
GCST011986Lahm H20203268,486Congenital heart disease risk loci identified by genome-wide association study in European patients.
GCST004719Agopian AJ201700Genome-Wide Association Studies and Meta-Analyses for Congenital Heart Defects.
GCST004722Agopian AJ201700Genome-Wide Association Studies and Meta-Analyses for Congenital Heart Defects.
GCST002572Mitchell LE201400Genome-wide association study of maternal and inherited effects on left-sided cardiac malformations.
GCST002574Mitchell LE201400Genome-wide association study of maternal and inherited effects on left-sided cardiac malformations.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory1
Tier 4: intronic/intergenic34

MAF distribution

BucketVariants
common (>=0.05)32
low_freq (0.01-0.05)0
rare (<0.01)0
unknown3

Functional consequences

ConsequenceCount
intron_variant22
intergenic_variant11
synonymous_variant1
regulatory_region_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs80611211687159478T>A,C,G0.11intergenic_variantC16orf954e-09Tier 4: intronic/intergenic
rs130539319533995049T>Gintron_variantSUMF16e-09Tier 4: intronic/intergenic
rs37464462034986962T>C0.18synonymous_variantMYH7B1e-08Tier 4: intronic/intergenic
rs7282026469291650T>C0.05intergenic_variantHULC2e-08Tier 4: intronic/intergenic
rs35046143199567757TAA>T,TA,TAAA0.05intron_variantLINC017083e-08Tier 4: intronic/intergenic
rs354371212131011875C>A,T0.05intron_variantARHGEF44e-08Tier 4: intronic/intergenic
rs1145036843142116127C>G,Tintron_variantTFDP25e-08Tier 4: intronic/intergenic
rs557884141681151334C>T0.05intron_variantPKD1L26e-08Tier 4: intronic/intergenic
rs20460603188134698A>C,G,T0.05intron_variantLINC01991 - LPP-AS27e-08Tier 4: intronic/intergenic
rs11894932298648723A>C,G0.05intron_variantMGAT4A1e-07Tier 4: intronic/intergenic
rs1975649363453210T>A,C0.33intron_variantSYNPR-AS1, SYNPR3e-07Tier 4: intronic/intergenic
rs110082221030753565G>A,C0.49intergenic_variantLINC02644 - ZNF4386e-07Tier 4: intronic/intergenic
rs1642645142036610A>C,T0.05intron_variantHIVEP3 - HNRNPFP18e-07Tier 4: intronic/intergenic
rs120458071150612358T>C0.089regulatory_region_variantENSA9e-07Tier 3: regulatory
rs774711494167914184A>C,G,T0.05intergenic_variantRN7SKP188 - ANXA109e-07Tier 4: intronic/intergenic
rs743773017123592441intron_variantASB15, ASB15-AS12e-06Tier 4: intronic/intergenic
rs111598401488090181G>A,T0.05intron_variantHISLA2e-06Tier 4: intronic/intergenic
rs12509281478480280A>G0.05intron_variantFRAS12e-06Tier 4: intronic/intergenic
rs76071402157946200G>A0.05intron_variantUPP22e-06Tier 4: intronic/intergenic
rs11755054622656836A>C,T0.05intron_variantLINC03005, CASC153e-06Tier 4: intronic/intergenic
rs67214911128759487T>C,G0.05intron_variantFLI13e-06Tier 4: intronic/intergenic
rs256799212121228050A>G0.05intron_variantP2RX44e-06Tier 4: intronic/intergenic
rs1379134841028059T>A,C,G0.05intergenic_variantZMAT4 - RNU6-356P4e-06Tier 4: intronic/intergenic
rs6811802478011684G>C,T0.05intergenic_variantHNRNPA1P56 - FRAS15e-06Tier 4: intronic/intergenic
rs15722021044514712G>A,T0.05intron_variantRPL9P21 - TMEM72-AS15e-06Tier 4: intronic/intergenic
rs76232913178638449C>G,T0.05intron_variantKCNMB2-AS1, KCNMB26e-06Tier 4: intronic/intergenic
rs115142951269984473T>C,G0.05intron_variantPRANCR6e-06Tier 4: intronic/intergenic
rs733317731017952A>G0.05intergenic_variantGHRHR - ADCYAP1R17e-06Tier 4: intronic/intergenic
rs146849810114306461A>C,G0.05intron_variantAFAP1L27e-06Tier 4: intronic/intergenic
rs117665247119948217C>T0.05intergenic_variantLINC024767e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

GeneHGNCEvidence routes
MYH7BMYH7BGWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
MYH7BOrphanet:54260Left ventricular noncompaction
FRAS1Orphanet:2052Fraser syndrome
FRAS1Orphanet:93100Renal agenesis, unilateral
CTSKOrphanet:763Pycnodysostosis
CFAP43Orphanet:276234Non-syndromic male infertility due to sperm motility disorder

Cohort genes → proteins

20 cohort genes, 20 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only20

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
TFDP2HGNC:11751ENSG00000114126Q14188Transcription factor Dp-2gwas
HIVEP3HGNC:13561ENSG00000127124Q5T1R4Transcription factor HIVEP3gwas
CAMKK2HGNC:1470ENSG00000110931Q96RR4Calcium/calmodulin-dependent protein kinase kinase 2gwas
MYH7BHGNC:15906ENSG00000078814A7E2Y1Myosin-7Bgwas
SYNPRHGNC:16507ENSG00000163630Q8TBG9Synaptoporingwas
GJD2HGNC:19154ENSG00000159248Q9UKL4Gap junction delta-2 proteingwas
FRAS1HGNC:19185ENSG00000138759Q86XX4Extracellular matrix organizing protein FRAS1gwas
ASB15HGNC:19767ENSG00000146809Q8WXK1Ankyrin repeat and SOCS box protein 15gwas
ZNF438HGNC:21029ENSG00000183621Q7Z4V0Zinc finger protein 438gwas
PKD1L2HGNC:21715ENSG00000166473Q7Z442Polycystin-1-like protein 2gwas
CTSKHGNC:2536ENSG00000143387P43235Cathepsin Kgwas
CTSSHGNC:2545ENSG00000163131P25774Cathepsin Sgwas
AFAP1L2HGNC:25901ENSG00000169129Q8N4X5Actin filament-associated protein 1-like 2gwas
CFAP43HGNC:26684ENSG00000197748Q8NDM7Cilia- and flagella-associated protein 43gwas
FLIIHGNC:3750ENSG00000177731Q13045Protein flightless-1 homologgwas
KCNMB2HGNC:6286ENSG00000197584Q9Y691Calcium-activated potassium channel subunit beta-2gwas
ARHGEF4HGNC:684ENSG00000136002Q9NR80Rho guanine nucleotide exchange factor 4gwas
ARNTHGNC:700ENSG00000143437P27540Aryl hydrocarbon receptor nuclear translocatorgwas
MGAT4AHGNC:7047ENSG00000071073Q9UM21Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase Agwas
P2RX4HGNC:8535ENSG00000135124Q99571P2X purinoceptor 4gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
TFDP2Transcription factor Dp-2Can stimulate E2F-dependent transcription.
HIVEP3Transcription factor HIVEP3Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Also binds to the kappa-B motif of gene such as S100A4, involved in c…
CAMKK2Calcium/calmodulin-dependent protein kinase kinase 2Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes.
MYH7BMyosin-7BInvolved in muscle contraction.
SYNPRSynaptoporinIntrinsic membrane protein of small synaptic vesicles.
GJD2Gap junction delta-2 proteinOne gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
FRAS1Extracellular matrix organizing protein FRAS1Involved in extracellular matrix organization.
ASB15Ankyrin repeat and SOCS box protein 15May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
ZNF438Zinc finger protein 438Isoform 1 acts as a transcriptional repressor.
PKD1L2Polycystin-1-like protein 2May function as a G-protein-coupled receptor.
CTSKCathepsin KThiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling.
CTSSCathepsin SThiol protease.
AFAP1L2Actin filament-associated protein 1-like 2May play a role in a signaling cascade by enhancing the kinase activity of SRC.
CFAP43Cilia- and flagella-associated protein 43Flagellar protein involved in sperm flagellum axoneme organization and function.
FLIIProtein flightless-1 homologIs a regulator of actin polymerization, required for proper myofibril organization and regulation of the length of sarcomeric thin filaments.
KCNMB2Calcium-activated potassium channel subunit beta-2Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel.
ARHGEF4Rho guanine nucleotide exchange factor 4Acts as a guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases.
ARNTAryl hydrocarbon receptor nuclear translocatorRequired for activity of the AHR.
MGAT4AAlpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase AGlycosyltransferase that catalyze the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans through a beta1-4 linkage and participates in the production of tri- and tetra-antennary…
P2RX4P2X purinoceptor 4ATP-gated nonselective transmembrane cation channel permeable to potassium, sodium and calcium.

Protein-family classification

Druggable: 5 · Difficult: 9 · Unknown: 6 · Druggable fraction: 0.25

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
Scaffold/PPI54.3×0.034
Protease23.7×0.358
Ion channel15.6×0.381
Transcription factor41.6×0.381
Kinase11.4×0.729
Enzyme (other)10.6×0.962
Other/Unknown60.5×0.995

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
TFDP2Transcription factornoE2F_WHTH_DNA-bd_dom, Transc_factor_DP_C, Transcrpt_fac_DP
HIVEP3Transcription factornoZnf_C2H2_type, Znf_CCHC_HIVEP, Znf_C2H2_sf
CAMKK2Kinaseyes2.7.11.17Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
MYH7BScaffold/PPInoMyosin_head_motor_dom-like, Myosin_tail, SH3_Myosin
SYNPROther/UnknownnoSynaptophysin/porin, Marvel
GJD2Other/UnknownnoConnexin, Connexin36, Connexin_N
FRAS1Other/UnknownnoEGF, VWF_dom, Calx_beta
ASB15Scaffold/PPInoSOCS_box, Ankyrin_rpt, SOCS_box-like_dom_sf
ZNF438Transcription factornoZnf_C2H2_type, Znf_C2H2_sf
PKD1L2Other/UnknownnoGPS, Lectin_gal-bd_dom, PLAT/LH2_dom
CTSKProteaseyes3.4.22.38Pept_cys_AS, Peptidase_C1A_C, Peptidase_C1A
CTSSProteaseyes3.4.22.27Pept_cys_AS, Peptidase_C1A_C, Peptidase_C1A
AFAP1L2Scaffold/PPInoPH_domain, PH-like_dom_sf, AFAP
CFAP43Scaffold/PPInoWD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
FLIIOther/UnknownnoLeu-rich_rpt, Leu-rich_rpt_typical-subtyp, Villin/Gelsolin
KCNMB2Ion channelyesK_chnl_Ca-activ_BK_bsu, KCNMB2_ball_chain_dom, KCNMB2_ball/chain_dom_sf
ARHGEF4Scaffold/PPInoDH_dom, GDS_CDC24_CS, SH3_domain
ARNTTranscription factornoPAS, Nuc_translocat, PAC
MGAT4AEnzyme (other)yes2.4.1.145Glyco_transf_54, MGAT4_A/B/C_C, MGAT4
P2RX4Other/UnknownnoP2X_purnocptor, P2X4_purnocptor, P2X_extracellular_dom_sf

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

TissueCohort genes
apex of heart4
hindlimb stylopod muscle3
calcaneal tendon2
cerebellar hemisphere2
right hemisphere of cerebellum2
nucleus accumbens2
islet of Langerhans2
renal medulla2
monocyte2
sural nerve2
right uterine tube2
left testis1
right testis1
Brodmann (1909) area 231
buccal mucosa cell1
endothelial cell1
cerebellar cortex1
heart left ventricle1
cerebellar vermis1
lateral nuclear group of thalamus1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
TFDP2276ubiquitousmarkercalcaneal tendon, left testis, right testis
HIVEP3234ubiquitousmarkerbuccal mucosa cell, endothelial cell, Brodmann (1909) area 23
CAMKK2283ubiquitousmarkercerebellar cortex, cerebellar hemisphere, right hemisphere of cerebellum
MYH7B195broadyesapex of heart, hindlimb stylopod muscle, heart left ventricle
SYNPR156broadmarkerlateral nuclear group of thalamus, cerebellar vermis, nucleus accumbens
GJD270tissue_specificmarkerislet of Langerhans, primordial germ cell in gonad, tongue squamous epithelium
FRAS1212ubiquitousmarkergerminal epithelium of ovary, parietal pleura, renal medulla
ASB1568tissue_specificyeshindlimb stylopod muscle, apex of heart, muscle of leg
ZNF438209ubiquitousmarkertibialis anterior, monocyte, deltoid
PKD1L2156broadmarkerseminal vesicle, apex of heart, subcutaneous adipose tissue
CTSK254ubiquitousmarkerperiodontal ligament, stromal cell of endometrium, skin of hip
CTSS260ubiquitousmarkermonocyte, mononuclear cell, leukocyte
AFAP1L2213broadmarkersural nerve, left lobe of thyroid gland, right lobe of thyroid gland
CFAP43190broadmarkerright uterine tube, bronchial epithelial cell, mucosa of paranasal sinus
FLII134ubiquitousmarkerlower esophagus mucosa, apex of heart, hindlimb stylopod muscle
KCNMB2156tissue_specificmarkerislet of Langerhans, right uterine tube, male germ line stem cell (sensu Vertebrata) in testis
ARHGEF4239ubiquitousmarkerright frontal lobe, nucleus accumbens, prefrontal cortex
ARNT281ubiquitousmarkercolonic epithelium, calcaneal tendon, sural nerve
MGAT4A266ubiquitousmarkerjejunal mucosa, colonic mucosa, renal medulla
P2RX4238ubiquitousmarkermucosa of transverse colon, cerebellar hemisphere, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CTSS4,897
ARNT2,894
CTSK2,790
FRAS12,552
FLII2,364
SYNPR2,165
MYH7B1,770
CAMKK21,736
HIVEP31,464
ARHGEF41,460

Structural data

PDB: 12 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CTSKP4323570
CTSSP2577462
ARNTP2754044
CAMKK2Q96RR424
GJD2Q9UKL424
ARHGEF4Q9NR804
P2RX4Q995714
TFDP2Q141881
AFAP1L2Q8N4X51
CFAP43Q8NDM71
KCNMB2Q9Y6911
MGAT4AQ9UM211

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
ASB15Q8WXK187.39
FLIIQ1304581.20
SYNPRQ8TBG975.98
MYH7BA7E2Y173.79
PKD1L2Q7Z44271.44
ZNF438Q7Z4V049.71
HIVEP3Q5T1R437.25
FRAS1Q86XX4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 141. Enrichment computed across 20 evidence-associated genes (12 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 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Trafficking and processing of endosomal TLR2135.9×0.013CTSK, CTSS
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)282.8×0.018CTSS, ARHGEF4
Platelet homeostasis246.4×0.038KCNMB2, P2RX4
Activation of NOXA and translocation to mitochondria1158.6×0.078TFDP2
Electric Transmission Across Gap Junctions1158.6×0.078GJD2
Aryl hydrocarbon receptor signalling1158.6×0.078ARNT
E2F mediated regulation of DNA replication1135.9×0.078TFDP2
CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde1119.0×0.078CAMKK2
Activation of RAC1 downstream of NMDARs1119.0×0.078CAMKK2
CaMK IV-mediated phosphorylation of CREB195.2×0.078CAMKK2
Ca2+ activated K+ channels195.2×0.078KCNMB2
Activation of PUMA and translocation to mitochondria195.2×0.078TFDP2
RUNX1 regulates transcription of genes involved in differentiation of keratinocytes195.2×0.078CTSK
Endosomal/Vacuolar pathway186.5×0.078CTSS
Regulation of gene expression by Hypoxia-inducible Factor179.3×0.078ARNT
Cellular response to hypoxia173.2×0.078ARNT
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects173.2×0.078TFDP2
Inhibition of replication initiation of damaged DNA by RB1/E2F1168.0×0.078TFDP2
Nitric oxide stimulates guanylate cyclase168.0×0.078KCNMB2
N-Glycan antennae elongation163.4×0.078MGAT4A
Elevation of cytosolic Ca2+ levels159.5×0.078P2RX4
Cytochrome P450 - arranged by substrate type159.5×0.078ARNT
cGMP effects159.5×0.078KCNMB2
Toll-like Receptor Cascades220.7×0.078CTSK, CTSS
Degradation of the extracellular matrix219.6×0.078CTSK, CTSS
MHC class II antigen presentation214.9×0.078CTSK, CTSS
Class I MHC mediated antigen processing & presentation211.7×0.078ASB15, CTSS
Extracellular matrix organization210.5×0.078CTSK, CTSS
Adaptive Immune System37.5×0.078ASB15, CTSK, CTSS
RNA Polymerase II Transcription35.6×0.078TFDP2, CTSK, ARNT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 19 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
obsolete proteolysis involved in protein catabolic process255.4×0.038CTSK, CTSS
neuronal action potential250.7×0.038GJD2, KCNMB2
collagen catabolic process241.2×0.038CTSK, CTSS
extracellular matrix disassembly238.6×0.038CTSK, CTSS
sensory perception of touch1443.5×0.040P2RX4
regulation of antigen processing and presentation1295.6×0.040CTSS
basement membrane disassembly1295.6×0.040CTSS
positive regulation of hormone biosynthetic process1295.6×0.040ARNT
antigen processing and presentation of peptide antigen1295.6×0.040CTSS
metanephros morphogenesis1221.7×0.040FRAS1
purinergic nucleotide receptor signaling pathway1221.7×0.040P2RX4
positive regulation of autophagy of mitochondrion1221.7×0.040CAMKK2
regulation of CAMKK-AMPK signaling cascade1221.7×0.040MYH7B
positive regulation of cation channel activity1221.7×0.040CTSS
calcium-mediated signaling219.3×0.040CAMKK2, P2RX4
glyoxylate metabolic process1147.8×0.045MGAT4A
regulation of chemotaxis1147.8×0.045P2RX4
CAMKK-AMPK signaling cascade1147.8×0.045CAMKK2
positive regulation of microglial cell migration1147.8×0.045P2RX4
regulation of protein kinase activity1126.7×0.050CAMKK2
regulation of cilium beat frequency1110.9×0.052CFAP43
negative regulation of cartilage development1110.9×0.052CTSK
positive regulation of prostaglandin secretion198.5×0.053P2RX4
response to fluid shear stress198.5×0.053P2RX4
regulation of interleukin-6 production188.7×0.055AFAP1L2
endothelial cell activation188.7×0.055P2RX4
cellular response to thyroid hormone stimulus180.6×0.056CTSS
response to acidic pH168.2×0.056CTSS
positive regulation of protein sumoylation168.2×0.056ARNT
relaxation of cardiac muscle168.2×0.056P2RX4

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 4 · Undrugged: 16

Druggability breadth: 8 of 20 evidence-associated genes (40%) 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
CAMKK2PONATINIB
CTSKBOCEPREVIR
CTSSBOCEPREVIR
P2RX4DULOXETINE

Top cohort targets by molecule count

SymbolMoleculesMax phase
CAMKK2424
CTSS124
CTSK84
P2RX454
TFDP200
HIVEP300
MYH7B00
SYNPR00
GJD200
FRAS100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
PONATINIB4CAMKK2
FEDRATINIB4CAMKK2
AXITINIB4CAMKK2
ALECTINIB4CAMKK2
PACRITINIB4CAMKK2
CERITINIB4CAMKK2
BOSUTINIB4CAMKK2
FILGOTINIB4CAMKK2
ABEMACICLIB4CAMKK2
GILTERITINIB4CAMKK2
BRIGATINIB4CAMKK2
NINTEDANIB4CAMKK2
SUNITINIB4CAMKK2
CRIZOTINIB4CAMKK2
MIDOSTAURIN4CAMKK2
BOCEPREVIR4CTSK, CTSS
TELAPREVIR4CTSK, CTSS
NIRMATRELVIR4CTSK, CTSS
SIMEPREVIR4CTSS
DULOXETINE4P2RX4
PAROXETINE4P2RX4
VOLASERTIB3CAMKK2
CRENOLANIB3CAMKK2
ENZASTAURIN3CAMKK2
ALVOCIDIB3CAMKK2
DOVITINIB3CAMKK2
LESTAURTINIB3CAMKK2
RUBOXISTAURIN3CAMKK2
ODANACATIB3CTSK, CTSS
VANIPREVIR3CTSS

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

SymbolAssaysType breakdown
CTSK376Binding:365, ADMET:5, Toxicity:5, Functional:1
CTSS328Binding:313, ADMET:9, Functional:5, Toxicity:1
CAMKK2320Binding:319, Functional:1
P2RX4106Binding:94, Functional:12
ARNT16Binding:16
TFDP22Binding:2
ARHGEF42Binding:2

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CAMKK22.7.11.17Ca2+/calmodulin-dependent protein kinase
CTSK3.4.22.38cathepsin K
CTSS3.4.22.27cathepsin S
MGAT4A2.4.1.145alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase

Cohort genes with high screening signal

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

SymbolChEMBL assays
CAMKK2320
CTSK376
CTSS328
P2RX4106

Pharmacogenomics

Cohort genes with a PharmGKB record: 20; 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)
PONATINIB4CAMKK2
FEDRATINIB4CAMKK2
AXITINIB4CAMKK2
ALECTINIB4CAMKK2
PACRITINIB4CAMKK2
CERITINIB4CAMKK2
BOSUTINIB4CAMKK2
FILGOTINIB4CAMKK2
ABEMACICLIB4CAMKK2
GILTERITINIB4CAMKK2
BRIGATINIB4CAMKK2
NINTEDANIB4CAMKK2
SUNITINIB4CAMKK2
CRIZOTINIB4CAMKK2
MIDOSTAURIN4CAMKK2
BOCEPREVIR4CTSK, CTSS
TELAPREVIR4CTSK, CTSS
NIRMATRELVIR4CTSK, CTSS
SIMEPREVIR4CTSS
DULOXETINE4P2RX4
PAROXETINE4P2RX4
VOLASERTIB3CAMKK2
CRENOLANIB3CAMKK2
ENZASTAURIN3CAMKK2
ALVOCIDIB3CAMKK2
DOVITINIB3CAMKK2
LESTAURTINIB3CAMKK2
RUBOXISTAURIN3CAMKK2
ODANACATIB3CTSK, CTSS
VANIPREVIR3CTSS

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)4CAMKK2, CTSK, CTSS, P2RX4
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug2KCNMB2, MGAT4A
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug14TFDP2, HIVEP3, MYH7B, SYNPR, GJD2, FRAS1, ASB15, ZNF438, PKD1L2, AFAP1L2 (+4 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
TFDP22—
HIVEP30—
MYH7B0—
SYNPR0—
GJD20—
FRAS10—
ASB150—
ZNF4380—
PKD1L20—
AFAP1L20—
CFAP430—
FLII0—
KCNMB20—
ARHGEF42—
ARNT16—
MGAT4A0—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

About this page

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

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 69

This page pulls from 69 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot