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Atlas / Disease / Autosomal recessive non-syndromic intellectual disability

Autosomal recessive non-syndromic intellectual disability

disease
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Also known as AR-NSIDautosomal recessive intellectual disabilityintellectual disability, autosomal recessivemental retardation, autosomal recessivenon-syndromic intellectual disability, autosomal recessiveNS-ARID

Summary

Autosomal recessive non-syndromic intellectual disability (MONDO:0019502) is a disease (an umbrella term covering 68 Mondo subtypes) with 51 cohort genes. The dominant Reactome pathway is Maturation of spike protein (3 cohort genes).

At a glance

  • Umbrella term: 68 Mondo subtypes
  • Cohort genes: 51
  • ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameautosomal recessive non-syndromic intellectual disability
Mondo IDMONDO:0019502
OMIM249500
Orphanet88616
DOIDDOID:0060308
UMLSC5680181
MedGen1826073
GARD0018643
Is cancer (heuristic)no

Also known as: AR-NSID · autosomal recessive intellectual disability · autosomal recessive non-syndromic intellectual disability · intellectual disability, autosomal recessive · mental retardation, autosomal recessive · non-syndromic intellectual disability, autosomal recessive · NS-ARID

Data availability: 9 ClinVar variants · 44 GenCC gene-disease records · 2 cell lines.

Disease family

An umbrella term covering 68 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › autosomal recessive non-syndromic intellectual disability

Related subtypes (2): autosomal dominant non-syndromic intellectual disability, non-syndromic X-linked intellectual disability

Subtypes (68): intellectual disability, autosomal recessive 1, intellectual disability, autosomal recessive 2, intellectual disability, autosomal recessive 3, intellectual disability, autosomal recessive 12, intellectual disability, autosomal recessive 5, intellectual disability, autosomal recessive 6, intellectual disability, autosomal recessive 7, intellectual disability, autosomal recessive 9, intellectual disability, autosomal recessive 10, intellectual disability, autosomal recessive 11, intellectual disability, autosomal recessive 4, intellectual disability, autosomal recessive 13, intellectual disability, autosomal recessive 14, Rafiq syndrome, intellectual disability, autosomal recessive 16, intellectual disability, autosomal recessive 18, intellectual disability, autosomal recessive 31, intellectual disability, autosomal recessive 29, intellectual disability, autosomal recessive 27, intellectual disability, autosomal recessive 33, intellectual disability, autosomal recessive 30, intellectual disability, autosomal recessive 19, intellectual disability, autosomal recessive 23, intellectual disability, autosomal recessive 24, intellectual disability, autosomal recessive 25, intellectual disability, autosomal recessive 28, intellectual disability, autosomal recessive 34, intellectual disability, autosomal recessive 42, intellectual disability, autosomal recessive 43, intellectual disability, autosomal recessive 44, intellectual disability, autosomal recessive 45, intellectual disability, autosomal recessive 46, intellectual disability, autosomal recessive 47, Al-Raqad syndrome, intellectual disability, autosomal recessive 50, intellectual disability, autosomal recessive 51, intellectual disability, autosomal recessive 52, intellectual disability, autosomal recessive 54, intellectual disability, autosomal recessive 56, intellectual developmental disorder, autosomal recessive 74, intellectual disability, autosomal recessive 57, intellectual disability, autosomal recessive 58, intellectual disability, autosomal recessive 59, pontocerebellar hypoplasia type 1, intellectual disability, autosomal recessive 64, intellectual disability, autosomal recessive 65, intellectual developmental disorder, autosomal recessive 73, intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, intellectual disability, autosomal recessive 61, intellectual developmental disorder, autosomal recessive 76, intellectual developmental disorder, autosomal recessive 77, intellectual disability, autosomal recessive 66, intellectual developmental disorder, autosomal recessive 67, intellectual developmental disorder, autosomal recessive 68, intellectual developmental disorder, autosomal recessive 69, intellectual developmental disorder, autosomal recessive 70, intellectual developmental disorder, autosomal recessive 71, intellectual developmental disorder, autosomal recessive 72, glycosylphosphatidylinositol biosynthesis defect 16, intellectual disability, autosomal recessive 60, intellectual disability, autosomal recessive 63, adenosine kinase deficiency, intellectual developmental disorder, autosomal recessive 78, intellectual developmental disorder, autosomal recessive 79, intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, intellectual developmental disorder, autosomal recessive 81, intellectual developmental disorder, autosomal recessive 82, intellectual developmental disorder, autosomal recessive 83

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

4 pathogenic, 2 pathogenic/likely pathogenic, 2 uncertain significance, 1 likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
1699097NM_017721.5(CC2D1A):c.2347C>T (p.Arg783Ter)CC2D1APathogeniccriteria provided, single submitter
599374NM_001130053.5(EEF1D):c.948G>A (p.Trp316Ter)EEF1DPathogenicno assertion criteria provided
375705NM_182548.4(LHFPL5):c.575T>C (p.Leu192Pro)LHFPL5Pathogeniccriteria provided, single submitter
1030591NM_017755.6(NSUN2):c.1165C>T (p.Arg389Ter)NSUN2Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1203937NM_017755.6(NSUN2):c.790C>T (p.Arg264Ter)NSUN2Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1683498NM_001160372.4(TRAPPC9):c.1994dup (p.Val666fs)TRAPPC9Pathogenicno assertion criteria provided
3067138NM_021937.5(EEFSEC):c.1169A>C (p.Asp390Ala)EEFSECLikely pathogeniccriteria provided, single submitter
599375NM_001100878.2(MROH6):c.1904A>T (p.Asn635Ile)MROH6Uncertain significanceno assertion criteria provided
599376NC_000008.11:g.144464447G>TZFTRAF1Uncertain significanceno assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 242 · Orphanet: 59 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

GeneClassificationInheritanceDiseaseRecords
ALKBH8DefinitiveAutosomal recessiveintellectual developmental disorder, autosomal recessive 715
CC2D1ADefinitiveAutosomal recessiveintellectual disability, autosomal recessive 35
GRIK2DefinitiveAutosomal recessiveintellectual disability, autosomal recessive 68
MED25DefinitiveAutosomal recessivecongenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome7
MED9DefinitiveAutosomal recessivecongenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome7
METTL23DefinitiveAutosomal recessiveintellectual disability, autosomal recessive 445
PRSS12DefinitiveAutosomal recessiveintellectual disability, autosomal recessive 15
RSRC1DefinitiveAutosomal recessiveintellectual developmental disorder, autosomal recessive 705
TRAPPC9DefinitiveAutosomal recessiveintellectual disability, autosomal recessive 136
TUSC3DefinitiveAutosomal recessiveintellectual disability5
CRADDStrongAutosomal recessiveintellectual disability, autosomal recessive 343
FBXO31StrongAutosomal recessiveintellectual disability, autosomal recessive6
FBXO5StrongAutosomal recessiveintellectual disability, autosomal recessive6
FMN2StrongAutosomal recessiveintellectual disability, autosomal recessive 475
HNMTStrongAutosomal recessiveintellectual disability, autosomal recessive 514
IQSEC1StrongAutosomal recessiveintellectual developmental disorder with short stature and behavioral abnormalities6
KDM5BStrongAutosomal recessiveintellectual disability, autosomal recessive 655
LINS1StrongAutosomal recessiveintellectual disability, autosomal recessive 274
MBOAT7StrongAutosomal recessiveintellectual disability, autosomal recessive 575
MED23StrongAutosomal recessiveintellectual disability, autosomal recessive 186
NDST1StrongAutosomal recessiveintellectual disability, autosomal recessive 464
NSUN2StrongAutosomal recessiveintellectual disability, autosomal recessive 57
PGAP1StrongAutosomal recessiveintellectual disability, autosomal recessive 425
SLC45A1StrongAutosomal recessiveintellectual developmental disorder with neuropsychiatric features5
ST3GAL3StrongAutosomal recessiveintellectual disability, autosomal recessive 127
WASHC4StrongAutosomal recessiveintellectual disability, autosomal recessive 434
LMAN2LModerateAutosomal recessiveintellectual disability, autosomal recessive 528
TNIKModerateAutosomal recessiveintellectual disability, autosomal recessive 545
ZC3H14ModerateAutosomal recessiveintellectual disability, autosomal recessive 564
AIMP1SupportiveAutosomal recessiveautosomal recessive non-syndromic intellectual disability6

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
NSUN2Orphanet:235Dubowitz syndrome
NSUN2Orphanet:88616Autosomal recessive non-syndromic intellectual disability
CC2D1AOrphanet:88616Autosomal recessive non-syndromic intellectual disability
TRAPPC9Orphanet:352530Intellectual disability-obesity-brain malformations-facial dysmorphism syndrome
TRAPPC9Orphanet:88616Autosomal recessive non-syndromic intellectual disability
CLIP1Orphanet:88616Autosomal recessive non-syndromic intellectual disability
SARS1Orphanet:2512Autosomal recessive primary microcephaly
SARS1Orphanet:88616Autosomal recessive non-syndromic intellectual disability
AIMP1Orphanet:280293Pelizaeus-Merzbacher-like disease due to AIMP1 mutation
AIMP1Orphanet:88616Autosomal recessive non-syndromic intellectual disability
ST3GAL3Orphanet:697734ST3GAL3-CDG
SLC12A2Orphanet:633021SLC12A2-related autosomal recessive neonatal-developmental delay-intellectual disability-feeding difficulty-sensorineural deafness syndrome
SLC12A2Orphanet:633024SLC12A2-related autosomal dominant infantile-developmental delay-intellectual disability-sensorineural deafness syndrome
UBE4AOrphanet:88616Autosomal recessive non-syndromic intellectual disability
EZROrphanet:88616Autosomal recessive non-syndromic intellectual disability
FRRS1LOrphanet:725Developmental and epileptic encephalopathy with spike-wave activation in sleep
FRRS1LOrphanet:88616Autosomal recessive non-syndromic intellectual disability
FMN2Orphanet:88616Autosomal recessive non-syndromic intellectual disability
MBOAT7Orphanet:88616Autosomal recessive non-syndromic intellectual disability
FBXO31Orphanet:88616Autosomal recessive non-syndromic intellectual disability
NCDNOrphanet:88616Autosomal recessive non-syndromic intellectual disability
SLC45A1Orphanet:88616Autosomal recessive non-syndromic intellectual disability
KDM5BOrphanet:178469Autosomal dominant non-syndromic intellectual disability
KDM5BOrphanet:88616Autosomal recessive non-syndromic intellectual disability
LMAN2LOrphanet:88616Autosomal recessive non-syndromic intellectual disability
TTC5Orphanet:88616Autosomal recessive non-syndromic intellectual disability
ZC3H14Orphanet:88616Autosomal recessive non-syndromic intellectual disability
CRADDOrphanet:88616Autosomal recessive non-syndromic intellectual disability
MED23Orphanet:88616Autosomal recessive non-syndromic intellectual disability
RSRC1Orphanet:88616Autosomal recessive non-syndromic intellectual disability
ALKBH8Orphanet:88616Autosomal recessive non-syndromic intellectual disability
UFSP2Orphanet:2114Hip dysplasia, Beukes type
UFSP2Orphanet:442835Non-specific early-onset epileptic encephalopathy
PGAP1Orphanet:401820Autosomal recessive spastic paraplegia type 67
PGAP1Orphanet:88616Autosomal recessive non-syndromic intellectual disability
EDC3Orphanet:88616Autosomal recessive non-syndromic intellectual disability
METTL23Orphanet:88616Autosomal recessive non-syndromic intellectual disability
B3GALNT2Orphanet:588Muscle-eye-brain disease
B3GALNT2Orphanet:88616Autosomal recessive non-syndromic intellectual disability
B3GALNT2Orphanet:899Walker-Warburg syndrome
MED25Orphanet:464738Basel-Vanagaite-Smirin-Yosef syndrome
MED25Orphanet:88616Autosomal recessive non-syndromic intellectual disability
IQSEC1Orphanet:88616Autosomal recessive non-syndromic intellectual disability
WASHC4Orphanet:88616Autosomal recessive non-syndromic intellectual disability
DCPSOrphanet:88616Autosomal recessive non-syndromic intellectual disability
CRBNOrphanet:88616Autosomal recessive non-syndromic intellectual disability
TUSC3Orphanet:88616Autosomal recessive non-syndromic intellectual disability
TNIKOrphanet:88616Autosomal recessive non-syndromic intellectual disability
LINS1Orphanet:88616Autosomal recessive non-syndromic intellectual disability
TECROrphanet:88616Autosomal recessive non-syndromic intellectual disability

Cohort genes → proteins

51 cohort genes, 51 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence51

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
NSUN2HGNC:25994ENSG00000037474Q08J23RNA cytosine C(5)-methyltransferase NSUN2gencc,clinvar
CC2D1AHGNC:30237ENSG00000132024Q6P1N0Coiled-coil and C2 domain-containing protein 1Agencc,clinvar
TRAPPC9HGNC:30832ENSG00000167632Q96Q05Trafficking protein particle complex subunit 9gencc,clinvar
CLIP1HGNC:10461ENSG00000130779P30622CAP-Gly domain-containing linker protein 1gencc
SARS1HGNC:10537ENSG00000031698P49591Serine–tRNA ligase, cytoplasmicgencc
AIMP1HGNC:10648ENSG00000164022Q12904Aminoacyl tRNA synthase complex-interacting multifunctional protein 1gencc
ST3GAL3HGNC:10866ENSG00000126091Q11203CMP-N-acetylneuraminate-beta-1,4-galactoside alpha-2,3-sialyltransferasegencc
SLC12A2HGNC:10911ENSG00000064651P55011Solute carrier family 12 member 2gencc
UBE4AHGNC:12499ENSG00000110344Q14139Ubiquitin conjugation factor E4 Agencc
EZRHGNC:12691ENSG00000092820P15311Ezringencc
FBXO5HGNC:13584ENSG00000112029Q9UKT4F-box only protein 5gencc
FRRS1LHGNC:1362ENSG00000260230Q9P0K9DOMON domain-containing protein FRRS1Lgencc
FMN2HGNC:14074ENSG00000155816Q9NZ56Formin-2gencc
MBOAT7HGNC:15505ENSG00000125505Q96N66Membrane-bound acylglycerophosphatidylinositol O-acyltransferase MBOAT7gencc
FBXO31HGNC:16510ENSG00000103264Q5XUX0F-box only protein 31gencc
NCDNHGNC:17597ENSG00000020129Q9UBB6Neurochondringencc
SLC45A1HGNC:17939ENSG00000162426Q9Y2W3Proton-associated sugar transporter Agencc
KDM5BHGNC:18039ENSG00000117139Q9UGL1Lysine-specific demethylase 5Bgencc
LMAN2LHGNC:19263ENSG00000114988Q9H0V9VIP36-like proteingencc
TTC5HGNC:19274ENSG00000136319Q8N0Z6Tetratricopeptide repeat protein 5gencc
ZC3H14HGNC:20509ENSG00000100722Q6PJT7Zinc finger CCCH domain-containing protein 14gencc
CRADDHGNC:2340ENSG00000169372P78560Death domain-containing protein CRADDgencc
MED23HGNC:2372ENSG00000112282Q9ULK4Mediator of RNA polymerase II transcription subunit 23gencc
RSRC1HGNC:24152ENSG00000174891Q96IZ7Serine/Arginine-related protein 53gencc
ALKBH8HGNC:25189ENSG00000137760Q96BT7tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ALKBH8gencc
MED9HGNC:25487ENSG00000141026Q9NWA0Mediator of RNA polymerase II transcription subunit 9gencc
UFSP2HGNC:25640ENSG00000109775Q9NUQ7Ufm1-specific protease 2gencc
PGAP1HGNC:25712ENSG00000197121Q75T13GPI inositol-deacylasegencc
EDC3HGNC:26114ENSG00000179151Q96F86Enhancer of mRNA-decapping protein 3gencc
METTL23HGNC:26988ENSG00000181038Q86XA0Histone-arginine methyltransferase METTL23gencc
B3GALNT2HGNC:28596ENSG00000162885Q8NCR0UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2gencc
MED25HGNC:28845ENSG00000104973Q71SY5Mediator of RNA polymerase II transcription subunit 25gencc
IQSEC1HGNC:29112ENSG00000144711Q6DN90IQ motif and SEC7 domain-containing protein 1gencc
WASHC4HGNC:29174ENSG00000136051Q2M389WASH complex subunit 4gencc
DCPSHGNC:29812ENSG00000110063Q96C86m7GpppX diphosphatasegencc
CRBNHGNC:30185ENSG00000113851Q96SW2Protein cereblongencc
TUSC3HGNC:30242ENSG00000104723Q13454Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit TUSC3gencc
TNIKHGNC:30765ENSG00000154310Q9UKE5TRAF2 and NCK-interacting protein kinasegencc
LINS1HGNC:30922ENSG00000140471Q8NG48Protein Lines homolog 1gencc
TECRHGNC:4551ENSG00000099797Q9NZ01Very-long-chain enoyl-CoA reductasegencc
GRIK2HGNC:4580ENSG00000164418Q13002Glutamate receptor ionotropic, kainate 2gencc
HNMTHGNC:5028ENSG00000150540P50135Histamine N-methyltransferasegencc
MAN1B1HGNC:6823ENSG00000177239Q9UKM7Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidasegencc
NDST1HGNC:7680ENSG00000070614P52848Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1gencc
PIGCHGNC:8960ENSG00000135845Q92535Phosphatidylinositol N-acetylglucosaminyltransferase subunit Cgencc
PRSS12HGNC:9477ENSG00000164099P56730Neurotrypsingencc
ZFTRAF1HGNC:17806ENSG00000187954P0DTL6Zinc finger TRAF-type-containing protein 1clinvar
LHFPL5HGNC:21253ENSG00000197753Q8TAF8LHFPL tetraspan subfamily member 5 proteinclinvar
EEFSECHGNC:24614ENSG00000132394P57772Selenocysteine-specific elongation factorclinvar
MROH6HGNC:27814ENSG00000204839A6NGR9Maestro heat-like repeat-containing protein family member 6clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
NSUN2RNA cytosine C(5)-methyltransferase NSUN2RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs).
CC2D1ACoiled-coil and C2 domain-containing protein 1ATranscription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells.
TRAPPC9Trafficking protein particle complex subunit 9Functions as an activator of NF-kappa-B through increased phosphorylation of the IKK complex.
CLIP1CAP-Gly domain-containing linker protein 1Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton.
SARS1Serine–tRNA ligase, cytoplasmicCatalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser).
AIMP1Aminoacyl tRNA synthase complex-interacting multifunctional protein 1Non-catalytic component of the multisynthase complex.
ST3GAL3CMP-N-acetylneuraminate-beta-1,4-galactoside alpha-2,3-sialyltransferaseCatalyzes the formation of the NeuAc-alpha-2,3-Gal-beta-1,4-GlcNAc-, NeuAc-alpha-2,3-Gal-beta-1,3-GlcNAc- and NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc- sequences found in terminal carbohydrate groups of glycoproteins and glycolipids.
SLC12A2Solute carrier family 12 member 2Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane.
UBE4AUbiquitin conjugation factor E4 AUbiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases.
EZREzrinProbably involved in connections of major cytoskeletal structures to the plasma membrane.
FBXO5F-box only protein 5Regulator of APC activity during mitotic and meiotic cell cycle.
FRRS1LDOMON domain-containing protein FRRS1LImportant modulator of glutamate signaling pathway.
FMN2Formin-2Actin-binding protein that is involved in actin cytoskeleton assembly and reorganization.
MBOAT7Membrane-bound acylglycerophosphatidylinositol O-acyltransferase MBOAT7Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA to a lysophosphatidylinositol (1-acylglycerophosphatidylinositol or LPI) leading to the production of a phosphatidylinositol (1,2-diacyl-sn-glycero-3-phosphoino…
FBXO31F-box only protein 31Substrate-recognition component of the SCF(FBXO31) protein ligase complex, which specifically mediates the ubiquitination of proteins amidated at their C-terminus in response to oxidative stress, leading to their degradation by the proteas…
NCDNNeurochondrinProbably involved in signal transduction in the nervous system, via increasing cell surface localization of GRM5/mGluR5 and positively regulating its signaling.
SLC45A1Proton-associated sugar transporter AProton-associated glucose transporter in the brain.
KDM5BLysine-specific demethylase 5BHistone demethylase that demethylates ‘Lys-4’ of histone H3, thereby playing a central role in histone code.
LMAN2LVIP36-like proteinMay be involved in the regulation of export from the endoplasmic reticulum of a subset of glycoproteins.
TTC5Tetratricopeptide repeat protein 5Cofactor involved in the regulation of various cellular mechanisms such as actin regulation, autophagy, chromatin regulation and DNA repair.
ZC3H14Zinc finger CCCH domain-containing protein 14RNA-binding protein involved in the biogenesis of circular RNAs (circRNAs), which are produced by back-splicing circularization of pre-mRNAs.
CRADDDeath domain-containing protein CRADDAdapter protein that associates with PIDD1 and the caspase CASP2 to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis.
MED23Mediator of RNA polymerase II transcription subunit 23Required for transcriptional activation subsequent to the assembly of the pre-initiation complex.
RSRC1Serine/Arginine-related protein 53Has a role in alternative splicing and transcription regulation.
ALKBH8tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ALKBH8Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain.
MED9Mediator of RNA polymerase II transcription subunit 9Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
UFSP2Ufm1-specific protease 2Thiol-dependent isopeptidase that specifically cleaves UFM1, a ubiquitin-like modifier protein, from conjugated proteins, such as CD274/PD-L1, CYB5R3, DDRGK1, MRE11, RPL26/uL24, TRIP4 and RPL26/uL24.
PGAP1GPI inositol-deacylaseGPI inositol-deacylase that catalyzes the remove of the acyl chain linked to the 2-OH position of inositol ring from the GPI-anchored protein (GPI-AP) in the endoplasmic reticulum.
EDC3Enhancer of mRNA-decapping protein 3Binds single-stranded RNA.
METTL23Histone-arginine methyltransferase METTL23Histone methyltransferase that dimethylates histone H3 at ‘Arg-17’, forming asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling.
B3GALNT2UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans.
MED25Mediator of RNA polymerase II transcription subunit 25Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
IQSEC1IQ motif and SEC7 domain-containing protein 1Guanine nucleotide exchange factor for ARF1 and ARF6.
WASHC4WASH complex subunit 4Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fi…
DCPSm7GpppX diphosphataseDecapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3’->5’ exosome-mediated mRNA decay pathway.
CRBNProtein cereblonSubstrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2, ILF2 or GLUL.
TUSC3Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit TUSC3Acts as accessory component of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consens…
TNIKTRAF2 and NCK-interacting protein kinaseSerine/threonine kinase that acts as an essential activator of the Wnt signaling pathway.
TECRVery-long-chain enoyl-CoA reductaseInvolved in both the production of very long-chain fatty acids for sphingolipid synthesis and the degradation of the sphingosine moiety in sphingolipids through the sphingosine 1-phosphate metabolic pathway.
GRIK2Glutamate receptor ionotropic, kainate 2Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid.
HNMTHistamine N-methyltransferaseInactivates histamine by N-methylation.
MAN1B1Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidaseInvolved in glycoprotein quality control targeting of misfolded glycoproteins for degradation.
NDST1Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate.
PIGCPhosphatidylinositol N-acetylglucosaminyltransferase subunit CPart of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI bi…
PRSS12NeurotrypsinPlays a role in neuronal plasticity and the proteolytic action may subserve structural reorganizations associated with learning and memory operations.
LHFPL5LHFPL tetraspan subfamily member 5 proteinAuxiliary subunit of the mechanotransducer (MET) non-specific cation channel complex located at the tips of the shorter stereocilia of cochlear hair cells and that mediates sensory transduction in the auditory system.
EEFSECSelenocysteine-specific elongation factorTranslation factor required for the incorporation of the rare amino acid selenocysteine encoded by UGA codons.
EEF1DElongation factor 1-deltaEF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to the ribosome.

Protein-family classification

Druggable: 14 · Difficult: 7 · Unknown: 30 · Druggable fraction: 0.27

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
Enzyme (other)112.6×0.019
Transporter11.5×0.952
Other/Unknown301.1×0.952
Transcription factor61.0×0.952
Protease10.7×0.952
Kinase10.5×0.952
Scaffold/PPI10.3×0.952

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
NSUN2Enzyme (other)yes2.1.1.202MeTrfase_RsmB-F_NOP2_dom, RCMT, RCMT_NCL1
CC2D1AOther/UnknownnoC2_dom, CC2D1A/B_DM14, C2_domain_sf
TRAPPC9Other/UnknownnoTrs120_TRAPPC9, Trs120_TRAPPC9_N, TPR_TRAPPC9_Trs120
CLIP1Transcription factornoCAP-Gly_domain, CLIP1_ZNF, CAP-Gly_dom_sf
SARS1Enzyme (other)yes6.1.1.11aa-tRNA-synt_IIb, Ser-tRNA-ligase_type_1, aa-tRNA-synth_II
AIMP1Other/UnknownnotRNA-bd_dom, NA-bd_OB-fold,
ST3GAL3Enzyme (other)yes2.4.99.2Glyco_trans_29, Sialyl_trans, GT29-like_sf
SLC12A2Other/UnknownnoSLC12A1/SLC12A2, NKCC1, AA-permease/SLC12A_dom
UBE4ATranscription factorno2.3.2.27Ubox_domain, Znf_RING/FYVE/PHD, Ub_conjug_fac_E4_core
EZROther/UnknownnoFERM_domain, Ez/rad/moesin-like, Moesin_tail_sf
FBXO5Other/UnknownnoF-box_dom, ZF_ZBR, FBX5_43
FRRS1LOther/UnknownnoDOMON_domain, FRRS1L
FMN2Other/UnknownnoDEP_dom, FH2_Formin, FH2_Formin_sf
MBOAT7Enzyme (other)yes2.3.1.B46MBOAT_fam, LPLAT_7/PORCN-like
FBXO31Other/UnknownnoF-box_dom, F-box-like_dom_sf, FBXO31/39
NCDNOther/UnknownnoNeurochondrin, ARM-type_fold
SLC45A1TransporteryesMFS, MFS_trans_sf
KDM5BTranscription factorno1.14.11.67ARID_dom, Znf_PHD, JmjC_dom
LMAN2LOther/UnknownnoLectin_leg, ConA-like_dom_sf, Intracellular_Lectin-GPT
TTC5Other/UnknownnoTPR-like_helical_dom_sf, TPR_rpt, TTC5_OB
ZC3H14Transcription factornoZnf_CCCH, Nab2/ZC3H14
CRADDOther/UnknownnoDeath_dom, CARD, DEATH-like_dom_sf
MED23Other/UnknownnoMediator_Med23
RSRC1Transcription factornoSRRP53
ALKBH8Enzyme (other)yes2.1.1.229RRM_dom, Oxoglu/Fe-dep_dioxygenase_dom, Nucleotide-bd_a/b_plait_sf
MED9Other/UnknownnoMed9, Med7/Med21-like, MED9_metazoa
UFSP2Other/UnknownnoUFSP1/2_DUB_cat, UFSP2-like_2nd
PGAP1Other/UnknownnoPGAP1-ab_dom-like, AB_hydrolase_fold, PGAP1/BST1
EDC3Other/UnknownnoYjeF_N_dom, FDF_dom, Lsm14-like_N
METTL23Other/UnknownnoMethyltransf_16, SAM-dependent_MTases_sf
B3GALNT2Enzyme (other)yes2.4.1.313Glyco_trans_31
MED25Other/UnknownnoMed25_PTOV, Mediator_Med25_SD1, Mediator_Med25_VWA
IQSEC1Scaffold/PPInoSec7_dom, PH_domain, PH-like_dom_sf
WASHC4Other/UnknownnoWASH7, WASH-4_N, WASH-7_central
DCPSEnzyme (other)yes3.6.1.59DcpS/DCS2, Scavenger_mRNA_decap_enz_N, Histidine_triad_CS
CRBNOther/UnknownnoLon_prtase_N, Yippee/Mis18/Cereblon, PUA-like_sf
TUSC3Other/UnknownnoMAGT1/OST3/OST6, Thioredoxin-like_sf
TNIKKinaseyesProt_kinase_dom, CNH_dom, Ser/Thr_kinase_AS
LINS1Other/UnknownnoProtein_Lines, Lines_C, LINES_N
TECREnzyme (other)yes1.3.1.933-oxo-5_a-steroid_4-DH_C, Ubiquitin-like_domsf, SRD5A/TECR
GRIK2Other/UnknownnoIontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
HNMTEnzyme (other)yes2.1.1.8HHMT-like, SAM-dependent_MTases_sf
MAN1B1Enzyme (other)yes3.2.1.113Glyco_hydro_47, 6hp_glycosidase-like_sf, Seven-hairpin_glycosidases
NDST1Enzyme (other)yes2.8.2.8Sulfotransferase_dom, Heparan_SO4_deacetylase_dom, P-loop_NTPase
PIGCOther/UnknownnoPlno_GlcNAc_GPI2
PRSS12ProteaseyesKringle, SRCR, Trypsin_dom
ZFTRAF1Transcription factornoZnf_TRAF, Znf_RING, Znf_RING/FYVE/PHD
LHFPL5Other/UnknownnoLHFPL
EEFSECOther/UnknownnoT_Tr_GTP-bd_dom, EFTu-like_2, Transl_B-barrel_sf
MROH6Other/UnknownnoARM-like, ARM-type_fold, Maestro_heat-like_prot

Expression context

Cohort genes with no expression data: 0.

46 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)51
unknown0

Top tissues across cohort

TissueCohort genes
calcaneal tendon9
secondary oocyte5
cerebellar hemisphere5
right hemisphere of cerebellum5
apex of heart5
cortical plate5
male germ line stem cell (sensu Vertebrata) in testis4
left testis4
stromal cell of endometrium4
gastrocnemius3
hindlimb stylopod muscle3
body of pancreas3
Brodmann (1909) area 233
oocyte3
right testis3
heart left ventricle3
right uterine tube2
mucosa of transverse colon2
islet of Langerhans2
tendon2

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
NSUN2260ubiquitousmarkerupper arm skin, right uterine tube, secondary oocyte
CC2D1A134ubiquitousmarkerright hemisphere of cerebellum, mucosa of transverse colon, cerebellar hemisphere
TRAPPC9258ubiquitousmarkerhindlimb stylopod muscle, gastrocnemius, apex of heart
CLIP1299ubiquitousmarkerbiceps brachii, buccal mucosa cell, skeletal muscle tissue of rectus abdominis
SARS1291ubiquitousmarkerislet of Langerhans, body of pancreas, frontal pole
AIMP1295ubiquitousmarkercalcaneal tendon, rectum, tendon
ST3GAL3178ubiquitousmarkerhindlimb stylopod muscle, gastrocnemius, muscle of leg
SLC12A2277ubiquitousmarkerpalpebral conjunctiva, parotid gland, inferior vagus X ganglion
UBE4A298ubiquitousmarkerendothelial cell, Brodmann (1909) area 23, middle temporal gyrus
EZR291ubiquitousmarkerventricular zone, bronchial epithelial cell, epithelium of bronchus
FBXO5225ubiquitousmarkerventricular zone, ganglionic eminence, secondary oocyte
FRRS1L189broadmarkermiddle temporal gyrus, Brodmann (1909) area 23, orbitofrontal cortex
FMN2187broadmarkercortical plate, prefrontal cortex, Brodmann (1909) area 9
MBOAT7141ubiquitousmarkerblood, right adrenal gland, right adrenal gland cortex
FBXO31261ubiquitousmarkercerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
NCDN208ubiquitousmarkermiddle frontal gyrus, Brodmann (1909) area 10, nucleus accumbens
SLC45A1167ubiquitousyesmale germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, prefrontal cortex
KDM5B272ubiquitousmarkersperm, male germ cell, left testis
LMAN2L267ubiquitousmarkerislet of Langerhans, renal medulla, ovary
TTC5227ubiquitousmarkersecondary oocyte, oocyte, primordial germ cell in gonad
ZC3H14298ubiquitousmarkerleft testis, right testis, sperm
CRADD260ubiquitousmarkermale germ line stem cell (sensu Vertebrata) in testis, heart left ventricle, cardiac ventricle
MED23283ubiquitousyesright hemisphere of cerebellum, calcaneal tendon, cerebellar hemisphere
RSRC1264ubiquitousmarkercalcaneal tendon, sural nerve, tendon
ALKBH8226ubiquitousmarkercalcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, cortical plate
MED9195ubiquitousmarkerapex of heart, heart left ventricle, cardiac ventricle
UFSP2290ubiquitousmarkercalcaneal tendon, hindlimb stylopod muscle, triceps brachii
PGAP1271ubiquitousmarkerendothelial cell, ganglionic eminence, upper leg skin
EDC3204ubiquitousmarkerleft testis, right testis, cortical plate
METTL23256ubiquitousmarkerkidney epithelium, epithelial cell of pancreas, left ventricle myocardium

Protein interactions among cohort

Intra-cohort edges: 11.

Hub genes (top 10 by interactor count)

SymbolInteractor count
EZR4,626
AIMP13,917
EEF1D3,866
KDM5B3,722
RSRC13,518
NSUN23,213
TTC52,981
FBXO52,844
EDC32,714
ZC3H142,613

Intra-cohort edges

ABSources
CC2D1ACRBNstring_interaction
CC2D1APRSS12string_interaction
CRBNPRSS12string_interaction
DCPSEDC3string_interaction
EEFSECSARS1string_interaction
EZRSLC12A2intact
EZRTNIKintact
FBXO31FBXO5string_interaction
GRIK2NCDNstring_interaction
MED23MED25biogrid_interaction, string_interaction
PGAP1PIGCstring_interaction

Structural data

PDB: 31 · AlphaFold-only: 20 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CRBNQ96SW290
KDM5BQ9UGL156
SLC12A2P5501114
MED23Q9ULK413
CLIP1P3062211
MED9Q9NWA011
DCPSQ96C8611
TNIKQ9UKE511
MED25Q71SY510
NSUN2Q08J239
SARS1P495919
EZRP153117
HNMTP501357
AIMP1Q129046
EDC3Q96F866
IQSEC1Q6DN906
MAN1B1Q9UKM76
NDST1P528485
TTC5Q8N0Z64
TUSC3Q134544
EEFSECP577724
EEF1DP296924
FBXO5Q9UKT43
CRADDP785603
ALKBH8Q96BT73
FMN2Q9NZ562
FBXO31Q5XUX02
GRIK2Q130022
UBE4AQ141391
MBOAT7Q96N661

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
METTL23Q86XA093.81
UFSP2Q9NUQ791.21
ST3GAL3Q1120390.87
PGAP1Q75T1389.15
LHFPL5Q8TAF889.11
PIGCQ9253588.98
NCDNQ9UBB688.12
B3GALNT2Q8NCR086.81
LMAN2LQ9H0V984.90
WASHC4Q2M38983.82
TRAPPC9Q96Q0582.98
ZFTRAF1P0DTL682.71
FRRS1LQ9P0K980.60
PRSS12P5673077.42
MROH6A6NGR976.21
CC2D1AQ6P1N074.71
LINS1Q8NG4872.44
SLC45A1Q9Y2W366.26
RSRC1Q96IZ758.46
ZC3H14Q6PJT756.87

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 136. Enrichment computed across 51 evidence-associated genes (37 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 37 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Maturation of spike protein321.5×0.027ST3GAL3, TUSC3, MAN1B1
Selenoamino acid metabolism316.0×0.027SARS1, AIMP1, EEFSEC
Respiratory Syncytial Virus Infection Pathway316.0×0.027MED23, MED9, MED25
Metabolism of lipids65.1×0.027ST3GAL3, MBOAT7, MED23, MED9, MED25, TECR
Metabolism103.1×0.027SARS1, AIMP1, ST3GAL3, MBOAT7, MED23, EEFSEC, MED9, MED25 (+2 more)
Maternal to zygotic transition (MZT)238.6×0.027KDM5B, METTL23
RSV-host interactions312.7×0.028MED23, MED9, MED25
Adipogenesis312.7×0.028MED23, MED9, MED25
Defective MAN1B1 causes MRT151308.6×0.034MAN1B1
Cytosolic tRNA aminoacylation223.7×0.034SARS1, AIMP1
Regulation of lipid metabolism by PPARalpha311.4×0.034MED23, MED9, MED25
Transcriptional regulation of white adipocyte differentiation310.5×0.034MED23, MED9, MED25
Asparagine N-linked glycosylation46.5×0.034ST3GAL3, LMAN2L, TUSC3, MAN1B1
Translation of Structural Proteins222.1×0.036ST3GAL3, MAN1B1
Activation of Na-permeable kainate receptors1154.3×0.050GRIK2
tRNA modification in the nucleus and cytosol215.8×0.050NSUN2, ALKBH8
Late SARS-CoV-2 Infection Events215.8×0.050ST3GAL3, MAN1B1
tRNA Aminoacylation215.4×0.050SARS1, AIMP1
PPARA activates gene expression37.7×0.050MED23, MED9, MED25
Viral Infection Pathways54.2×0.050ST3GAL3, MED23, MED9, MED25, MAN1B1
Mitotic Metaphase/Anaphase Transition1102.9×0.063FBXO5
Glycosaminoglycan metabolism211.9×0.076ST3GAL3, NDST1
Sensory processing of sound by outer hair cells of the cochlea211.0×0.083EZR, LHFPL5
TFAP2 (AP-2) family regulates transcription of cell cycle factors161.7×0.088KDM5B
Infectious disease53.4×0.088ST3GAL3, MED23, MED9, MED25, MAN1B1
Metabolism of amino acids and derivatives35.5×0.090SARS1, AIMP1, EEFSEC
DAG1 core M3 glycosylations151.4×0.095B3GALNT2
Cation-coupled Chloride cotransporters144.1×0.095SLC12A2
Signaling by LTK in cancer144.1×0.095CLIP1
COPII-mediated vesicle transport28.8×0.095TRAPPC9, LMAN2L

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 49 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
cognition423.3×0.008METTL23, WASHC4, TUSC3, LINS1
selenocysteine incorporation276.4×0.032SARS1, EEFSEC
DNA damage response66.5×0.032FBXO5, FMN2, FBXO31, TTC5, CRADD, ALKBH8
positive regulation of transcription elongation by RNA polymerase II318.4×0.043MED23, MED9, MED25
RNA polymerase II preinitiation complex assembly316.6×0.043MED23, MED9, MED25
positive regulation of transcription initiation by RNA polymerase II316.6×0.043MED23, MED9, MED25
histamine catabolic process1343.9×0.047HNMT
meiotic cell cycle checkpoint signaling1343.9×0.047NSUN2
protein alpha-1,2-demannosylation1343.9×0.047MAN1B1
positive regulation of cell volume1343.9×0.047SLC12A2
homologous chromosome movement towards spindle pole in meiosis I anaphase1343.9×0.047FMN2
detection of cold stimulus involved in thermoception1343.9×0.047GRIK2
nuclear envelope budding1343.9×0.047WASHC4
endolysosomal toll-like receptor signaling pathway1343.9×0.047WASHC4
apical dendrite arborization1343.9×0.047CC2D1A
negative regulation of vascular endothelial growth factor production1343.9×0.047SARS1
negative regulation of snRNA transcription by RNA polymerase II1343.9×0.047CC2D1A
regulation of estradiol secretion1343.9×0.047KDM5B
positive regulation of mediator complex assembly1343.9×0.047MED25
respiratory gaseous exchange by respiratory system225.5×0.047HNMT, NDST1
tRNA modification224.6×0.047NSUN2, SARS1
tRNA methylation223.7×0.048NSUN2, ALKBH8
actin cytoskeleton organization46.5×0.048EZR, FMN2, IQSEC1, TNIK
viral protein processing222.2×0.050ST3GAL3, MAN1B1
cytoplasmic translational elongation1172.0×0.057EEF1D
seryl-tRNA aminoacylation1172.0×0.057SARS1
negative regulation of DNA endoreduplication1172.0×0.057FBXO5
positive regulation of glucagon secretion1172.0×0.057AIMP1
inorganic anion import across plasma membrane1172.0×0.057SLC12A2
inorganic cation import across plasma membrane1172.0×0.057SLC12A2

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 6 · Phased (≥1): 10 · Undrugged: 41

Druggability breadth: 22 of 51 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.

SymbolExample approved molecule
SLC12A2BUMETANIDE
MED23PALBOCICLIB
CRBNDASABUVIR
TNIKPONATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
TNIK464
CRBN184
KDM5B23
GRIK223
NSUN212
SLC12A214
NCDN12
MED2314
TECR12
EEF1D12

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
BUMETANIDE4SLC12A2
PALBOCICLIB4MED23
DASABUVIR4CRBN
POMALIDOMIDE4CRBN
THALIDOMIDE4CRBN
LENALIDOMIDE4CRBN
PONATINIB4CRBN, TNIK
ASCIMINIB4CRBN
BRIGATINIB4CRBN
CRIZOTINIB4CRBN
LENVATINIB4TNIK
AXITINIB4TNIK
SORAFENIB4TNIK
NERATINIB4TNIK
PACRITINIB4TNIK
VANDETANIB4TNIK
BOSUTINIB4TNIK
PAZOPANIB4TNIK
NINTEDANIB4TNIK
SUNITINIB4TNIK
DASATINIB4TNIK
ERLOTINIB4TNIK
QUIZARTINIB4TNIK
MIDOSTAURIN4TNIK
GEFITINIB4TNIK
CAFFEIC ACID3KDM5B
EBSELEN3KDM5B
IBERDOMIDE3CRBN
URACIL3CRBN
VEPDEGESTRANT3CRBN

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 13.

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

SymbolAssaysType breakdown
CRBN5,948Binding:5779, Functional:154, ADMET:15
TNIK257Binding:257
KDM5B146Binding:146
GRIK292Binding:66, Functional:26
DCPS23Binding:20, ADMET:3
SLC12A213Binding:9, Functional:4
NSUN211Binding:11
MED239Binding:9
HNMT9Binding:7, ADMET:2
EEF1D8Binding:8
NCDN7Binding:7
TECR7Binding:7
EZR4Binding:4
MED253Binding:3
SARS12ADMET:1, Binding:1
AIMP12Binding:2
ST3GAL32Binding:2
UBE4A1Binding:1
MBOAT71Binding:1
WASHC41Binding:1
MAN1B11Binding:1
PRSS121Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
NSUN22.1.1.202, 2.1.1.203multisite-specific tRNA:(cytosine-C5)-methyltransferase, tRNA (cytosine34-C5)-methyltransferase
SARS16.1.1.11serine-tRNA ligase
ST3GAL32.4.99.2, 2.4.99.6beta-D-galactosyl-(1->3)-N-acetyl-beta-D-galactosaminide alpha-2,3-sialyltransferase, N-acetyllactosaminide alpha-2,3-sialyltransferase
UBE4A2.3.2.27, 2.3.2.B12RING-type E3 ubiquitin transferase,
MBOAT72.3.1.B46
KDM5B1.14.11.67[histone H3]-trimethyl-L-lysine4 demethylase
ALKBH82.1.1.229tRNA (carboxymethyluridine34-5-O)-methyltransferase
B3GALNT22.4.1.313protein O-mannose beta-1,3-N-acetylgalactosaminyltransferase
DCPS3.6.1.595’-(N7-methyl 5’-triphosphoguanosine)-[mRNA] diphosphatase
TECR1.3.1.93very-long-chain enoyl-CoA reductase
HNMT2.1.1.8histamine N-methyltransferase
MAN1B13.2.1.113, 3.2.1.209mannosyl-oligosaccharide 1,2-alpha-mannosidase, endoplasmic reticulum Man9GlcNAc2 1,2-alpha-mannosidase
NDST12.8.2.8[heparan sulfate]-glucosamine N-sulfotransferase

Cohort genes with high screening signal

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

SymbolChEMBL assays
KDM5B146
CRBN5,948
TNIK257

Pharmacogenomics

Cohort genes with a PharmGKB record: 51; 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)
BUMETANIDE4SLC12A2
PALBOCICLIB4MED23
DASABUVIR4CRBN
POMALIDOMIDE4CRBN
THALIDOMIDE4CRBN
LENALIDOMIDE4CRBN
PONATINIB4CRBN, TNIK
ASCIMINIB4CRBN
BRIGATINIB4CRBN
CRIZOTINIB4CRBN
LENVATINIB4TNIK
AXITINIB4TNIK
SORAFENIB4TNIK
NERATINIB4TNIK
PACRITINIB4TNIK
VANDETANIB4TNIK
BOSUTINIB4TNIK
PAZOPANIB4TNIK
NINTEDANIB4TNIK
SUNITINIB4TNIK
DASATINIB4TNIK
ERLOTINIB4TNIK
QUIZARTINIB4TNIK
MIDOSTAURIN4TNIK
GEFITINIB4TNIK
CAFFEIC ACID3KDM5B
EBSELEN3KDM5B
IBERDOMIDE3CRBN
URACIL3CRBN
VEPDEGESTRANT3CRBN

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)4SLC12A2, MED23, CRBN, TNIK
BPhased (≥1) drug, not yet approved6NSUN2, NCDN, KDM5B, TECR, GRIK2, EEF1D
CDruggable family + PDB, no drug7SARS1, MBOAT7, ALKBH8, DCPS, HNMT, MAN1B1, NDST1
DDruggable family + AlphaFold only, no drug4ST3GAL3, SLC45A1, B3GALNT2, PRSS12
EDifficult family or no structure, no drug30CC2D1A, TRAPPC9, CLIP1, AIMP1, UBE4A, EZR, FBXO5, FRRS1L, FMN2, FBXO31 (+20 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
CC2D1A0CRBN
MED253MED23
PRSS121CRBN
TRAPPC90—
CLIP10—
SARS12—
AIMP12—
ST3GAL32—
UBE4A1—
EZR4—
FBXO50—
FRRS1L0—
FMN20—
MBOAT71—
FBXO310—
SLC45A10—
LMAN2L0—
TTC50—
ZC3H140—
CRADD0—
RSRC10—
ALKBH80—
MED90—
UFSP20—
PGAP10—
EDC30—
METTL230—
B3GALNT20—
IQSEC10—
WASHC41—

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_interactiondepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot