Syndromic intellectual disability

Summary

Syndromic intellectual disability (MONDO:0000508) is a disease (an umbrella term covering 17 Mondo subtypes) caused by variants in AUTS2, HOXA1, KIF1A, and 4 other genes, with 75 cohort genes. The dominant Reactome pathway is Epigenetic regulation of gene expression (11 cohort genes).

At a glance

• Causal genes: AUTS2 (GenCC Definitive), HOXA1 (GenCC Definitive), KIF1A (GenCC Definitive), TAOK1 (GenCC Definitive) (+3 more)
• Umbrella term: 17 Mondo subtypes
• Cohort genes: 75
• ClinVar variants: 68

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	syndromic intellectual disability
Mondo ID	MONDO:0000508
DOID	DOID:0050888
UMLS	C5680525
MedGen	1842178
Is cancer (heuristic)	no

Also known as: syndrome associated with intellectual disability · syndromic intellectual disability

Data availability: 68 ClinVar variants · 47 GenCC gene-disease records.

Disease family

An umbrella term covering 17 Mondo subtypes.

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

Related subtypes (9): non-syndromic intellectual disability, intellectual developmental disorder and retinitis pigmentosa; IDDRP, PPP2R1A-related intellectual disability, intellectual disability, autosomal dominant, X-linked intellectual disability, intellectual disability, autosomal recessive, NACC1-related neurodevelopmental disorder with epilepsy, cataracts and episodic irritability, SETD2-related neurodevelopmental disorder without or with macrocephaly/overgrowth, intellectual developmental disorder with polymicrogyria and seizures

Subtypes (17): Smith-Magenis syndrome, intellectual disability, Buenos-Aires type, intellectual disability, Wolff type, CK syndrome, AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome, 7p22.1 microduplication syndrome, 9p13 microdeletion syndrome, 3q27.3 microdeletion syndrome, 9q31.1q31.3 microdeletion syndrome, Rubinstein-Taybi syndrome, X-linked syndromic intellectual disability, 9q33.3q34.11 microdeletion syndrome, autosomal recessive syndromic intellectual disability, autosomal dominant syndromic intellectual disability, aplasia cutis-enamel dysplasia syndrome, 2p25.3 microduplication syndrome, dyneinopathy

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

68 retrieved; paginated sample, class counts are floors:

28 uncertain significance, 14 pathogenic, 11 likely pathogenic, 7 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 2 likely benign, 2 not provided, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
424448	NM_030632.3(ASXL3):c.4360C>T (p.Gln1454Ter)	ASXL3	Pathogenic	criteria provided, single submitter
1064658	NC_000019.10:g.41983952_42247520del	ATP1A3	Pathogenic	no assertion criteria provided
521771	NM_003718.5(CDK13):c.2716G>A (p.Glu906Lys)	CDK13	Pathogenic	criteria provided, multiple submitters, no conflicts
1064662	GRCh38/hg38 19q13.2(chr19:42198610-42249880)x1	DEDD2	Pathogenic	no assertion criteria provided
431155	NM_017934.7(PHIP):c.3892C>T (p.Arg1298Ter)	IRAK1BP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162616	NM_006766.5(KAT6A):c.3116_3117del (p.Ile1038_Ser1039insTer)	KAT6A	Pathogenic	criteria provided, single submitter
180678	NM_006766.5(KAT6A):c.3879dup (p.Glu1294fs)	KAT6A	Pathogenic	no assertion criteria provided
208160	NM_001244008.2(KIF1A):c.646C>T (p.Arg216Cys)	KIF1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3236497	NM_170606.3(KMT2C):c.307C>T (p.Gln103Ter)	KMT2C	Pathogenic	criteria provided, single submitter
1064661	GRCh38/hg38 19q13.2(chr19:41987984-42252574)x1	LOC130064549	Pathogenic	no assertion criteria provided
3385328	NM_005481.3(MED16):c.385dup (p.Asp129fs)	MED16	Pathogenic	no assertion criteria provided
3385329	NM_005481.3(MED16):c.932T>C (p.Leu311Pro)	MED16	Pathogenic	no assertion criteria provided
977756	NM_138383.3(MTSS2):c.2011C>T (p.Arg671Trp)	MTSS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1220533	NM_001042424.3(NSD2):c.1363_1364dup (p.Asp455fs)	NSD2	Pathogenic	criteria provided, single submitter
30547	NM_004278.4(PIGL):c.427-1G>A	PIGL	Pathogenic	criteria provided, multiple submitters, no conflicts
977145	NM_005639.3(SYT1):c.1098C>G (p.Asp366Glu)	SYT1	Pathogenic	criteria provided, single submitter
3377102	NM_007118.4(TRIO):c.2046+1G>A	TRIO	Pathogenic	criteria provided, single submitter
1700687	NM_001379291.1(BRD4):c.3666_3672dup (p.Glu1225fs)	BRD4	Likely pathogenic	criteria provided, single submitter
4072313	NM_001379291.1(BRD4):c.3510del (p.Pro1171fs)	BRD4	Likely pathogenic	criteria provided, single submitter
633777	NM_020940.4(FHIP2A):c.115G>T (p.Glu39Ter)	FHIP2A	Likely pathogenic	no assertion criteria provided
4795126	NM_006766.5(KAT6A):c.4521_4522del (p.Ser1507fs)	KAT6A	Likely pathogenic	criteria provided, single submitter
3773800	NM_170675.5(MEIS2):c.170del (p.His57fs)	MEIS2	Likely pathogenic	criteria provided, single submitter
3235269	NM_001042424.3(NSD2):c.1589del (p.Lys530fs)	NSD2	Likely pathogenic	no assertion criteria provided
428590	NM_005048.4(PTH2R):c.473C>T (p.Ser158Phe)	PTH2R	Likely pathogenic	no assertion criteria provided
3068702	NM_030665.4(RAI1):c.600del (p.Leu201fs)	RAI1	Likely pathogenic	criteria provided, single submitter
4759495	NM_007118.4(TRIO):c.7065del (p.Ala2356fs)	TRIO	Likely pathogenic	no assertion criteria provided
3258101	NM_014991.6(WDFY3):c.9361C>T (p.Gln3121Ter)	WDFY3	Likely pathogenic	criteria provided, single submitter
4526437	NM_006885.4(ZFHX3):c.4520del (p.Gly1507fs)	ZFHX3	Likely pathogenic	criteria provided, single submitter
3711243	NM_018263.6(ASXL2):c.4153C>G (p.Gln1385Glu)	ASXL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2780586	NM_015570.4(AUTS2):c.959C>T (p.Pro320Leu)	AUTS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 244 · Orphanet: 87 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
AUTS2	Definitive	Autosomal dominant	syndromic intellectual disability	5
HOXA1	Definitive	Autosomal recessive	syndromic intellectual disability	7
HUWE1	Definitive	X-linked	intellectual disability, X-linked syndromic, Turner type	6
KIF1A	Definitive	Autosomal dominant	syndromic intellectual disability	19
MED13	Definitive	Autosomal dominant	intellectual developmental disorder 61	6
MYT1L	Definitive	Autosomal dominant	intellectual disability, autosomal dominant 39	6
RLIM	Definitive	X-linked	non-syndromic X-linked intellectual disability	7
TAOK1	Definitive	Autosomal dominant	syndromic intellectual disability	6
TCF20	Definitive	Autosomal dominant	developmental delay with variable intellectual impairment and behavioral abnormalities	6
TRIO	Definitive	Autosomal dominant	syndromic intellectual disability	9
TRMT1	Definitive	Autosomal recessive	intellectual developmental disorder, autosomal recessive 68	6
ACTL6B	Strong	Autosomal dominant	intellectual developmental disorder with severe speech and ambulation defects	10
BPTF	Strong	Autosomal dominant	syndromic intellectual disability	5
DDX6	Strong	Autosomal dominant	intellectual developmental disorder with impaired language and dysmorphic facies	4
DOCK3	Strong	Autosomal recessive	neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia	3
JARID2	Strong	Autosomal dominant	developmental delay with variable intellectual disability and dysmorphic facies	4
KDM4B	Strong	Autosomal dominant	intellectual developmental disorder, autosomal dominant 65	5
MED23	Strong	Autosomal recessive	intellectual disability, autosomal recessive 18	6
NBEA	Strong	Autosomal dominant	syndromic intellectual disability	5
PUS7	Strong	Autosomal recessive	intellectual developmental disorder with abnormal behavior, microcephaly, and short stature	5
TANC2	Strong	Autosomal dominant	intellectual developmental disorder with autistic features and language delay, with or without seizures	6
ZMYM3	Strong	X-linked	intellectual developmental disorder, X-linked 112	4
ACTL6A	Moderate	Autosomal dominant	syndromic intellectual disability	4
BCORL1	Supportive	Autosomal dominant	syndromic intellectual disability	8
CCDC32	Supportive	Autosomal dominant	syndromic intellectual disability	3
DPYSL5	Supportive	Autosomal dominant	syndromic intellectual disability	4
ETFA	Supportive	Autosomal dominant	syndromic intellectual disability	8
FBXW11	Supportive	Autosomal dominant	syndromic intellectual disability	6
KMT2E	Supportive	Autosomal dominant	syndromic intellectual disability	6
MADD	Supportive	Autosomal dominant	syndromic intellectual disability	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRIO	Orphanet:476126	Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
AUTS2	Orphanet:352490	Autism spectrum disorder due to AUTS2 deficiency
AUTS2	Orphanet:641372	B-lymphoblastic leukemia/lymphoma with t(7;9)(q11.2;p13.2)
WDFY3	Orphanet:528084	Non-specific syndromic intellectual disability
BPTF	Orphanet:529962	17q24.2 microdeletion syndrome
BPTF	Orphanet:686482	BPTF-related intellectual disability-facial dysmorphism-skeletal anomalies syndrome
MYT1L	Orphanet:647799	MYT1L-related developmental delay-intellectual disability-obesity syndrome
MYT1L	Orphanet:699850	2p25.3 microduplication syndrome
KIF1A	Orphanet:101010	Autosomal spastic paraplegia type 30
KIF1A	Orphanet:662367	NESCAV syndrome
KIF1A	Orphanet:970	Hereditary sensory and autonomic neuropathy type 2
SATB1	Orphanet:684232	Intellectual disability-epilepsy-dental anomalies-facial dysmorphism syndrome
SLC12A2	Orphanet:633021	SLC12A2-related autosomal recessive neonatal-developmental delay-intellectual disability-feeding difficulty-sensorineural deafness syndrome
SLC12A2	Orphanet:633024	SLC12A2-related autosomal dominant infantile-developmental delay-intellectual disability-sensorineural deafness syndrome
TCF20	Orphanet:528084	Non-specific syndromic intellectual disability
TRIP12	Orphanet:528084	Non-specific syndromic intellectual disability
RLIM	Orphanet:528084	Non-specific syndromic intellectual disability
FBXW11	Orphanet:528084	Non-specific syndromic intellectual disability
NTNG2	Orphanet:528084	Non-specific syndromic intellectual disability
ACTL6B	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
ACTL6B	Orphanet:528084	Non-specific syndromic intellectual disability
ZMIZ1	Orphanet:528084	Non-specific syndromic intellectual disability
KMT2E	Orphanet:528084	Non-specific syndromic intellectual disability
SIN3B	Orphanet:500166	SIN3-related intellectual disability syndrome due to a point mutation
TRAPPC4	Orphanet:528084	Non-specific syndromic intellectual disability
DPYSL5	Orphanet:528084	Non-specific syndromic intellectual disability
DPYSL5	Orphanet:7	3C syndrome
MED13	Orphanet:528084	Non-specific syndromic intellectual disability
NTNG1	Orphanet:3095	Atypical Rett syndrome
NTNG1	Orphanet:528084	Non-specific syndromic intellectual disability
MED23	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
MED27	Orphanet:528084	Non-specific syndromic intellectual disability
ACTL6A	Orphanet:528084	Non-specific syndromic intellectual disability
BCORL1	Orphanet:528084	Non-specific syndromic intellectual disability
TRMT1	Orphanet:528084	Non-specific syndromic intellectual disability
PUS7	Orphanet:528084	Non-specific syndromic intellectual disability
DDX6	Orphanet:528084	Non-specific syndromic intellectual disability
CCDC32	Orphanet:528084	Non-specific syndromic intellectual disability
KDM4B	Orphanet:528084	Non-specific syndromic intellectual disability
TNRC6B	Orphanet:528084	Non-specific syndromic intellectual disability
SVBP	Orphanet:528084	Non-specific syndromic intellectual disability
TAOK1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
DOCK3	Orphanet:528084	Non-specific syndromic intellectual disability
TANC2	Orphanet:528084	Non-specific syndromic intellectual disability
HUWE1	Orphanet:528084	Non-specific syndromic intellectual disability
ETFA	Orphanet:394529	Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type
ETFA	Orphanet:394532	Multiple acyl-CoA dehydrogenase deficiency, mild type
HOXA1	Orphanet:69737	Bosley-Salih-Alorainy syndrome
HOXA1	Orphanet:69739	Athabaskan brainstem dysgenesis syndrome
JARID2	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRIO	HGNC:12303	ENSG00000038382	O75962	Triple functional domain protein	gencc,clinvar
AUTS2	HGNC:14262	ENSG00000158321	Q8WXX7	Autism susceptibility gene 2 protein	gencc,clinvar
WDFY3	HGNC:20751	ENSG00000163625	Q8IZQ1	WD repeat and FYVE domain-containing protein 3	gencc,clinvar
BPTF	HGNC:3581	ENSG00000171634	Q12830	Nucleosome-remodeling factor subunit BPTF	gencc,clinvar
MYT1L	HGNC:7623	ENSG00000186487	Q9UL68	Myelin transcription factor 1-like protein	gencc,clinvar
KIF1A	HGNC:888	ENSG00000130294	Q12756	Kinesin-like protein KIF1A	gencc,clinvar
SATB1	HGNC:10541	ENSG00000182568	Q01826	DNA-binding protein SATB1	gencc
SLC12A2	HGNC:10911	ENSG00000064651	P55011	Solute carrier family 12 member 2	gencc
TCF20	HGNC:11631	ENSG00000100207	Q9UGU0	Transcription factor 20	gencc
TRIP12	HGNC:12306	ENSG00000153827	Q14669	E3 ubiquitin-protein ligase TRIP12	gencc
ZMYM3	HGNC:13054	ENSG00000147130	Q14202	Zinc finger MYM-type protein 3	gencc
RLIM	HGNC:13429	ENSG00000131263	Q9NVW2	E3 ubiquitin-protein ligase RLIM	gencc
FBXW11	HGNC:13607	ENSG00000072803	Q9UKB1	F-box/WD repeat-containing protein 11	gencc
NTNG2	HGNC:14288	ENSG00000196358	Q96CW9	Netrin-G2	gencc
ACTL6B	HGNC:160	ENSG00000077080	O94805	Actin-like protein 6B	gencc
ZMIZ1	HGNC:16493	ENSG00000108175	Q9ULJ6	Zinc finger MIZ domain-containing protein 1	gencc
KMT2E	HGNC:18541	ENSG00000005483	Q8IZD2	Inactive histone-lysine N-methyltransferase 2E	gencc
SIN3B	HGNC:19354	ENSG00000127511	O75182	Paired amphipathic helix protein Sin3b	gencc
TRAPPC4	HGNC:19943	ENSG00000196655	Q9Y296	Trafficking protein particle complex subunit 4	gencc
DPYSL5	HGNC:20637	ENSG00000157851	Q9BPU6	Dihydropyrimidinase-related protein 5	gencc
MED13	HGNC:22474	ENSG00000108510	Q9UHV7	Mediator of RNA polymerase II transcription subunit 13	gencc
NTNG1	HGNC:23319	ENSG00000162631	Q9Y2I2	Netrin-G1	gencc
MED23	HGNC:2372	ENSG00000112282	Q9ULK4	Mediator of RNA polymerase II transcription subunit 23	gencc
MED27	HGNC:2377	ENSG00000160563	Q6P2C8	Mediator of RNA polymerase II transcription subunit 27	gencc
ACTL6A	HGNC:24124	ENSG00000136518	O96019	Actin-like protein 6A	gencc
BOD1	HGNC:25114	ENSG00000145919	Q96IK1	Biorientation of chromosomes in cell division protein 1	gencc
BCORL1	HGNC:25657	ENSG00000085185	Q5H9F3	BCL-6 corepressor-like protein 1	gencc
TRMT1	HGNC:25980	ENSG00000104907	Q9NXH9	tRNA (guanine(26)-N(2))-dimethyltransferase	gencc
PUS7	HGNC:26033	ENSG00000091127	Q96PZ0	Pseudouridylate synthase 7 homolog	gencc
DDX6	HGNC:2747	ENSG00000110367	P26196	Probable ATP-dependent RNA helicase DDX6	gencc
CCDC32	HGNC:28295	ENSG00000128891	Q9BV29	Coiled-coil domain-containing protein 32	gencc
KDM4B	HGNC:29136	ENSG00000127663	O94953	Lysine-specific demethylase 4B	gencc
TNRC6B	HGNC:29190	ENSG00000100354	Q9UPQ9	Trinucleotide repeat-containing gene 6B protein	gencc
SVBP	HGNC:29204	ENSG00000177868	Q8N300	Small vasohibin-binding protein	gencc
TAOK1	HGNC:29259	ENSG00000160551	Q7L7X3	Serine/threonine-protein kinase TAO1	gencc
DOCK3	HGNC:2989	ENSG00000088538	Q8IZD9	Dedicator of cytokinesis protein 3	gencc
TANC2	HGNC:30212	ENSG00000170921	Q9HCD6	Protein TANC2	gencc
HUWE1	HGNC:30892	ENSG00000086758	Q7Z6Z7	E3 ubiquitin-protein ligase HUWE1	gencc
ETFA	HGNC:3481	ENSG00000140374	P13804	Electron transfer flavoprotein subunit alpha, mitochondrial	gencc
HOXA1	HGNC:5099	ENSG00000105991	P49639	Homeobox protein Hox-A1	gencc
JARID2	HGNC:6196	ENSG00000008083	Q92833	Protein Jumonji	gencc
MADD	HGNC:6766	ENSG00000110514	Q8WXG6	MAP kinase-activating death domain protein	gencc
NBEA	HGNC:7648	ENSG00000172915	Q8NFP9	Neurobeachin	gencc
PSMD12	HGNC:9557	ENSG00000197170	O00232	26S proteasome non-ATPase regulatory subunit 12	gencc
SYT1	HGNC:11509	ENSG00000067715	P21579	Synaptotagmin-1	clinvar
TAF6	HGNC:11540	ENSG00000106290	P49848	Transcription initiation factor TFIID subunit 6	clinvar
MED12	HGNC:11957	ENSG00000184634	Q93074	Mediator of RNA polymerase II transcription subunit 12	clinvar
NSD2	HGNC:12766	ENSG00000109685	O96028	Histone-lysine N-methyltransferase NSD2	clinvar
KAT6A	HGNC:13013	ENSG00000083168	Q92794	Histone acetyltransferase KAT6A	clinvar
KDM3B	HGNC:1337	ENSG00000120733	Q7LBC6	Lysine-specific demethylase 3B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRIO	Triple functional domain protein	Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases.
AUTS2	Autism susceptibility gene 2 protein	Component 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.
WDFY3	WD repeat and FYVE domain-containing protein 3	Required for selective macroautophagy (aggrephagy).
BPTF	Nucleosome-remodeling factor subunit BPTF	Regulatory subunit of the ATP-dependent NURF-1 and NURF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcrip…
MYT1L	Myelin transcription factor 1-like protein	Transcription factor that plays a key role in neuronal differentiation by specifically repressing expression of non-neuronal genes during neuron differentiation.
KIF1A	Kinesin-like protein KIF1A	Kinesin motor with a plus-end-directed microtubule motor activity.
SATB1	DNA-binding protein SATB1	Crucial silencing factor contributing to the initiation of X inactivation mediated by Xist RNA that occurs during embryogenesis and in lymphoma.
SLC12A2	Solute carrier family 12 member 2	Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane.
TCF20	Transcription factor 20	Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression.
TRIP12	E3 ubiquitin-protein ligase TRIP12	E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair.
ZMYM3	Zinc finger MYM-type protein 3	Plays a role in the regulation of cell morphology and cytoskeletal organization.
RLIM	E3 ubiquitin-protein ligase RLIM	E3 ubiquitin-protein ligase that acts as a negative coregulator for LIM homeodomain transcription factors by mediating the ubiquitination and subsequent degradation of LIM cofactors LDB1 and LDB2 and by mediating the recruitment the SIN3a/…
FBXW11	F-box/WD repeat-containing protein 11	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
NTNG2	Netrin-G2	Involved in controlling patterning and neuronal circuit formation at the laminar, cellular, subcellular and synaptic levels.
ACTL6B	Actin-like protein 6B	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
ZMIZ1	Zinc finger MIZ domain-containing protein 1	Acts as a transcriptional coactivator.
KMT2E	Inactive histone-lysine N-methyltransferase 2E	Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription.
SIN3B	Paired amphipathic helix protein Sin3b	Acts as a transcriptional repressor.
TRAPPC4	Trafficking protein particle complex subunit 4	Core component of the TRAPP complexes which has a function of guanine nucleotide exchange factor activity for Rab1 GTPase.
DPYSL5	Dihydropyrimidinase-related protein 5	Involved in the negative regulation of dendrite outgrowth.
MED13	Mediator of RNA polymerase II transcription subunit 13	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
NTNG1	Netrin-G1	Involved in controlling patterning and neuronal circuit formation at the laminar, cellular, subcellular and synaptic levels.
MED23	Mediator of RNA polymerase II transcription subunit 23	Required for transcriptional activation subsequent to the assembly of the pre-initiation complex.
MED27	Mediator of RNA polymerase II transcription subunit 27	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
ACTL6A	Actin-like protein 6A	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
BOD1	Biorientation of chromosomes in cell division protein 1	Required for proper chromosome biorientation through the detection or correction of syntelic attachments in mitotic spindles.
BCORL1	BCL-6 corepressor-like protein 1	Transcriptional corepressor.
TRMT1	tRNA (guanine(26)-N(2))-dimethyltransferase	Dimethylates a single guanine residue at position 26 of most nuclear- and mitochondrial-encoded tRNAs using S-adenosyl-L-methionine as donor of the methyl groups. tRNA guanine(26)-dimethylation is required for redox homeostasis and ensure…
PUS7	Pseudouridylate synthase 7 homolog	Pseudouridylate synthase that catalyzes pseudouridylation of RNAs.
DDX6	Probable ATP-dependent RNA helicase DDX6	Essential for the formation of P-bodies, cytosolic membrane-less ribonucleoprotein granules involved in RNA metabolism through the coordinated storage of mRNAs encoding regulatory functions.
CCDC32	Coiled-coil domain-containing protein 32	Regulates clathrin-mediated endocytsois of cargos such as transferrin probably through the association and modulation of adaptor protein complex 2 (AP-2).
KDM4B	Lysine-specific demethylase 4B	Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a role in histone code.
TNRC6B	Trinucleotide repeat-containing gene 6B protein	Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs).
SVBP	Small vasohibin-binding protein	Enhances the tyrosine carboxypeptidase activity of VASH1 and VASH2, thereby promoting the removal of the C-terminal tyrosine residue of alpha-tubulin.
TAOK1	Serine/threonine-protein kinase TAO1	Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability.
DOCK3	Dedicator of cytokinesis protein 3	Potential guanine nucleotide exchange factor (GEF).
TANC2	Protein TANC2	Scaffolding protein in the dendritic spines which acts as immobile postsynaptic posts able to recruit KIF1A-driven dense core vesicles to dendritic spines.
HUWE1	E3 ubiquitin-protein ligase HUWE1	E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins.
ETFA	Electron transfer flavoprotein subunit alpha, mitochondrial	Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase.
HOXA1	Homeobox protein Hox-A1	Sequence-specific transcription factor.
JARID2	Protein Jumonji	Regulator of histone methyltransferase complexes that plays an essential role in embryonic development, including heart and liver development, neural tube fusion process and hematopoiesis.
MADD	MAP kinase-activating death domain protein	Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family.
NBEA	Neurobeachin	Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the membrane.
PSMD12	26S proteasome non-ATPase regulatory subunit 12	Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins.
SYT1	Synaptotagmin-1	Calcium sensor that participates in triggering neurotransmitter release at the synapse.
TAF6	Transcription initiation factor TFIID subunit 6	The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription.
MED12	Mediator of RNA polymerase II transcription subunit 12	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
NSD2	Histone-lysine N-methyltransferase NSD2	Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at ‘Lys-36’ (H3K36me2).
KAT6A	Histone acetyltransferase KAT6A	Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro).
KDM3B	Lysine-specific demethylase 3B	Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a central role in histone code.

Protein-family classification

Druggable: 12 · Difficult: 30 · Unknown: 33 · Druggable fraction: 0.16

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	20	2.2×	0.002
Scaffold/PPI	10	2.3×	0.027
Enzyme (other)	9	1.4×	0.285
Kinase	3	1.1×	0.639
Other/Unknown	33	0.8×	0.985

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRIO	Kinase	yes		DH_dom, Prot_kinase_dom, CRAL-TRIO_dom
AUTS2	Other/Unknown	no		AUTS2
WDFY3	Transcription factor	no		Znf_FYVE, BEACH_dom, WD40_rpt
BPTF	Transcription factor	no		Bromodomain, Znf_PHD, Znf_FYVE_PHD
MYT1L	Transcription factor	no		Znf_C2H2C, Myelin_TF, Znf_C2H2C_sf
KIF1A	Scaffold/PPI	no	5.6.1.3	FHA_dom, Kinesin_motor_dom, PH_domain
SATB1	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
SLC12A2	Other/Unknown	no		SLC12A1/SLC12A2, NKCC1, AA-permease/SLC12A_dom
TCF20	Transcription factor	no		Znf_PHD, Znf_RING/FYVE/PHD, EPHD
TRIP12	Enzyme (other)	yes	2.3.2.26	HECT_dom, WWE_dom, ARM-like
ZMYM3	Transcription factor	no		Znf_MYM, TRASH_dom, ZMYM2-like_C
RLIM	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, RING_finger_E3_ligase
FBXW11	Scaffold/PPI	no		WD40_rpt, F-box_dom, WD40/YVTN_repeat-like_dom_sf
NTNG2	Other/Unknown	no		EGF, LE_dom, Laminin_N
ACTL6B	Other/Unknown	no		Actin, Actin_CS, ATPase_NBD
ZMIZ1	Transcription factor	no		Znf_MIZ, Znf_RING/FYVE/PHD, ZMIZ1_N
KMT2E	Transcription factor	no		SET_dom, Znf_PHD, Znf_FYVE_PHD
SIN3B	Other/Unknown	no		PAH, HDAC_interact_dom, Sin3_C
TRAPPC4	Other/Unknown	no		TRAPPC, Longin-like_dom_sf
DPYSL5	Other/Unknown	no		Amidohydro-rel, Metal-dep_hydrolase_composite, Hydantoinase/dihydroPyrase
MED13	Other/Unknown	no		Med13_C, MID_MedPIWI, Mediator_complx_sub13
NTNG1	Other/Unknown	no		EGF, LE_dom, Laminin_N
MED23	Other/Unknown	no		Mediator_Med23
MED27	Other/Unknown	no		Mediator_Med27
ACTL6A	Other/Unknown	no		Actin, Actin_CS, ATPase_NBD
BOD1	Other/Unknown	no		BOD1L1, BOD1/SHG1_dom
BCORL1	Scaffold/PPI	no		Ankyrin_rpt, PUFD, Ankyrin_rpt-contain_sf
TRMT1	Transcription factor	no		Znf_CCCH, Trm1, SAM-dependent_MTases_sf
PUS7	Enzyme (other)	yes	5.4.99.27	PsdUridine_synth_TruD, PsdUridine_synth_TruD_insert, PsdUridine_synth_cat_dom_sf
DDX6	Enzyme (other)	yes	3.6.4.13	RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_dom
CCDC32	Other/Unknown	no		CCDC32
KDM4B	Transcription factor	no	1.14.11.27	Znf_PHD, Tudor, JmjC_dom
TNRC6B	Other/Unknown	no		Nucleotide-bd_a/b_plait_sf, Argonaute_hook_dom, TNRC6_PABC-bd
SVBP	Other/Unknown	no		SVBP
TAOK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
DOCK3	Scaffold/PPI	no		SH3_domain, ARM-type_fold, DOCK
TANC2	Scaffold/PPI	no		Ankyrin_rpt, TPR-like_helical_dom_sf, TPR_rpt
HUWE1	Enzyme (other)	yes	2.3.2.26	HECT_dom, WWE_dom, UBA-like_sf
ETFA	Other/Unknown	no		ETF_a/FixB, Rossmann-like_a/b/a_fold, ETF_a/b_N
HOXA1	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
JARID2	Transcription factor	no		ARID_dom, JmjC_dom, JmjN
MADD	Other/Unknown	no		cDENN_dom, dDENN_dom, uDENN_dom
NBEA	Scaffold/PPI	no		BEACH_dom, WD40_rpt, NBEA-like_DUF1088
PSMD12	Other/Unknown	no		PCI_dom, WH-like_DNA-bd_sf, WH_DNA-bd_sf
SYT1	Other/Unknown	no		C2_dom, Synaptotagmin, C2_domain_sf
TAF6	Other/Unknown	no		TAF_TATA-bd_Histone-like_dom, Histone-fold, TAF6_C
MED12	Other/Unknown	no		Mediator_Med12, Mediator_Med12_catenin-bd, Mediator_Med12_LCEWAV
NSD2	Transcription factor	no	2.1.1.356	PWWP_dom, SET_dom, Znf_RING
KAT6A	Transcription factor	no	2.3.1.48	Znf_PHD, HAT_MYST-type, Histone_H1/H5_H15
KDM3B	Enzyme (other)	yes	1.14.11.65	JmjC_dom, LSDs-like, KDM3A/B_DUF7030

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	17
ganglionic eminence	11
ventricular zone	9
secondary oocyte	9
sural nerve	8
calcaneal tendon	8
buccal mucosa cell	8
oocyte	8
endothelial cell	6
right hemisphere of cerebellum	5
corpus callosum	4
Brodmann (1909) area 23	4
middle temporal gyrus	4
right adrenal gland	3
right adrenal gland cortex	3
adrenal tissue	3
globus pallidus	3
medial globus pallidus	3
leukocyte	3
monocyte	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRIO	279	ubiquitous	marker	sural nerve, cortical plate, stromal cell of endometrium
AUTS2	292	ubiquitous	marker	cortical plate, tibia, ganglionic eminence
WDFY3	293	ubiquitous	marker	sural nerve, calcaneal tendon, corpus callosum
BPTF	290	ubiquitous	marker	sural nerve, ventricular zone, cortical plate
MYT1L	192	tissue_specific	marker	endothelial cell, cortical plate, Brodmann (1909) area 23
KIF1A	198	broad	marker	right frontal lobe, postcentral gyrus, parietal lobe
SATB1	294	ubiquitous	marker	orbitofrontal cortex, frontal pole, thymus
SLC12A2	277	ubiquitous	marker	palpebral conjunctiva, parotid gland, inferior vagus X ganglion
TCF20	134	ubiquitous	yes	cortical plate, ganglionic eminence, tonsil
TRIP12	302	ubiquitous	marker	calcaneal tendon, male germ cell, sperm
ZMYM3	281	ubiquitous	marker	right adrenal gland, right adrenal gland cortex, endothelial cell
RLIM	256	ubiquitous	marker	middle temporal gyrus, cartilage tissue, adrenal tissue
FBXW11	297	ubiquitous	marker	corpus callosum, medial globus pallidus, globus pallidus
NTNG2	173	broad	marker	pancreatic ductal cell, monocyte, leukocyte
ACTL6B	164	broad	marker	cortical plate, right hemisphere of cerebellum, cerebellar hemisphere
ZMIZ1	295	ubiquitous	marker	dorsal motor nucleus of vagus nerve, tibia, seminal vesicle
KMT2E	264	ubiquitous	marker	tendon of biceps brachii, tendon, mucosa of paranasal sinus
SIN3B	261	ubiquitous	marker	body of uterus, right uterine tube, right ovary
TRAPPC4	134	ubiquitous	marker	cortical plate, islet of Langerhans, adenohypophysis
DPYSL5	133	broad	marker	cortical plate, ganglionic eminence, ventricular zone
MED13	295	ubiquitous	marker	endothelial cell, visceral pleura, germinal epithelium of ovary
NTNG1	198	broad	marker	lateral nuclear group of thalamus, buccal mucosa cell, Brodmann (1909) area 23
MED23	283	ubiquitous	yes	right hemisphere of cerebellum, calcaneal tendon, cerebellar hemisphere
MED27	271	ubiquitous	marker	oocyte, endothelial cell, secondary oocyte
ACTL6A	272	ubiquitous	marker	primordial germ cell in gonad, calcaneal tendon, ganglionic eminence
BOD1	259	ubiquitous	marker	oocyte, secondary oocyte, ventricular zone
BCORL1	250	ubiquitous	marker	cervix squamous epithelium, cardia of stomach, vena cava
TRMT1	230	ubiquitous	marker	lower esophagus mucosa, granulocyte, left ovary
PUS7	254	ubiquitous	marker	buccal mucosa cell, secondary oocyte, oocyte
DDX6	271	ubiquitous	marker	ganglionic eminence, calcaneal tendon, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 40.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRD4	7,883
DDX6	5,922
DDB1	5,810
HUWE1	5,793
ACTL6A	5,583
HDAC4	4,771
ACTL6B	4,543
ASXL2	4,417
TRIP12	4,193
MEF2C	4,063

Intra-cohort edges

A	B	Sources
ADARB1	TCF20	biogrid_interaction
ASXL2	ASXL3	string_interaction
ASXL3	BRD4	biogrid_interaction, string_interaction
ASXL3	DDB1	biogrid_interaction
ASXL3	WDFY3	string_interaction
BCORL1	HDAC4	string_interaction
BCORL1	HDAC9	string_interaction
BOD1	SYT1	intact
CCDC82	MED12	intact
DDB1	HUWE1	biogrid_interaction
DDB1	MEIS2	string_interaction
DOCK3	HOXA1	biogrid_interaction, intact
H1-4	NSD2	intact
HDAC4	HDAC9	biogrid_interaction
HDAC4	MEF2C	biogrid_interaction, intact, string_interaction
HDAC9	MEF2C	intact, string_interaction
HDAC9	SIN3B	biogrid_interaction
KAT6A	TNRC6B	biogrid_interaction
KDM3B	KDM4B	string_interaction
KIF1A	MADD	string_interaction
KIF1A	TANC2	string_interaction
KIF21B	NSD2	string_interaction
KMT2C	ZFHX3	string_interaction
KMT2C	ZMYM3	string_interaction
MED12	MED13	biogrid_interaction, string_interaction
MED12	MED16	biogrid_interaction, string_interaction
MED12	MED23	string_interaction
MED12	MED27	biogrid_interaction
MED13	MED16	biogrid_interaction
MED13	MED23	string_interaction
MED13	MED27	biogrid_interaction
MED16	MED23	string_interaction
MED16	MED27	biogrid_interaction, string_interaction
MED16	MYT1L	biogrid_interaction
MED23	MYT1L	biogrid_interaction
MEF2C	MEIS2	string_interaction
NAA15	PSMD12	biogrid_interaction
PUF60	TRMT1	intact
RLIM	SSBP3	string_interaction
SATB1	ZMIZ1	biogrid_interaction

Structural data

PDB: 52 · AlphaFold-only: 23 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRD4	O60885	619
DDB1	Q16531	205
PSMD12	O00232	118
BPTF	Q12830	45
KDM3B	Q7LBC6	36
TAF6	P49848	32
H1-4	P10412	26
ACTL6A	O96019	25
SVBP	Q8N300	24
SYT1	P21579	24
NSD2	O96028	22
KIF1A	Q12756	21
KAT6A	Q92794	21
HUWE1	Q7Z6Z7	19
HDAC4	P56524	19
JARID2	Q92833	16
PUF60	Q9UHX1	16
SLC12A2	P55011	14
MED23	Q9ULK4	13
ADARB1	P78563	13
NAA15	Q9BXJ9	12
MED27	Q6P2C8	11
MED16	Q9Y2X0	10
DDX6	P26196	9
KMT2C	Q8NEZ4	9
SATB1	Q01826	8
KDM4B	O94953	6
TRIP12	Q14669	5
MED13	Q9UHV7	5
ATP1A3	P13637	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACTL6B	O94805	91.52
IRAK1BP1	Q5VVH5	82.40
FHIP2A	Q5W0V3	80.50
TAOK1	Q7L7X3	77.36
BOD1	Q96IK1	77.06
DOCK3	Q8IZD9	75.52
DEDD2	Q8WXF8	72.80
KIF21B	O75037	70.07
CCDC32	Q9BV29	69.74
CCDC82	Q8N4S0	64.94
MADD	Q8WXG6	64.59
ZMYM3	Q14202	63.19
MTSS2	Q765P7	62.75
TANC2	Q9HCD6	59.92
HOXA1	P49639	59.15
MEF2C	Q06413	56.80
MYT1L	Q9UL68	55.73
SSBP3	Q9BWW4	55.71
SETD5	Q9C0A6	47.10
AUTS2	Q8WXX7	41.89
ASXL3	Q9C0F0	39.70
TNRC6B	Q9UPQ9	39.58
TCF20	Q9UGU0	39.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 351. Enrichment computed across 80 evidence-associated genes (61 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 61 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Epigenetic regulation of gene expression	11	12.9×	2e-07	MED12, KMT2C, MED16, SIN3B, MED13, MED23, MED27, ACTL6A (+3 more)
Gene expression (Transcription)	17	5.0×	4e-06	AUTS2, TAF6, MED12, KAT6A, KMT2C, ACTL6B, CDK13, MED16 (+9 more)
Epigenetic regulation by WDR5-containing histone modifying complexes	7	17.7×	1e-05	MED12, KMT2C, MED16, MED13, MED23, MED27, BOD1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	6	21.2×	2e-05	MED12, KMT2C, MED16, MED13, MED23, MED27
RNA Polymerase II Transcription	14	5.2×	2e-05	AUTS2, TAF6, MED12, KAT6A, KMT2C, ACTL6B, CDK13, MED16 (+6 more)
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	6	19.4×	3e-05	MED12, KMT2C, MED16, MED13, MED23, MED27
Regulation of lipid metabolism by PPARalpha	6	13.9×	2e-04	MED12, MED16, SIN3B, MED13, MED23, MED27
Respiratory Syncytial Virus Infection Pathway	5	16.1×	6e-04	MED12, MED16, MED13, MED23, MED27
Generic Transcription Pathway	14	3.5×	0.001	AUTS2, TAF6, MED12, KAT6A, KMT2C, ACTL6B, CDK13, MED16 (+6 more)
RSV-host interactions	5	12.8×	0.001	MED12, MED16, MED13, MED23, MED27
Adipogenesis	5	12.8×	0.001	MED12, MED16, MED13, MED23, MED27
Transcriptional regulation by RUNX1	5	12.0×	0.002	AUTS2, KMT2C, ACTL6B, SIN3B, ACTL6A
Transcriptional regulation of white adipocyte differentiation	5	10.6×	0.002	MED12, MED16, MED13, MED23, MED27
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	6	8.1×	0.002	MED12, KMT2C, MED16, MED13, MED23, MED27
Chromatin organization	6	8.0×	0.002	KAT6A, KDM3B, KMT2C, ACTL6B, ACTL6A, KDM4B
Chromatin modifying enzymes	6	7.1×	0.004	KAT6A, KDM3B, KMT2C, ACTL6B, ACTL6A, KDM4B
PPARA activates gene expression	5	7.7×	0.009	MED12, MED16, MED13, MED23, MED27
Infectious disease	9	3.7×	0.014	SYT1, TAF6, MED12, BRD4, MED16, MED13, MED23, MED27 (+1 more)
Viral Infection Pathways	8	4.0×	0.014	TAF6, MED12, BRD4, MED16, MED13, MED23, MED27, ATP1A3
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	3	14.8×	0.019	AUTS2, ACTL6B, ACTL6A
NOTCH1 Intracellular Domain Regulates Transcription	3	11.7×	0.035	HDAC4, HDAC9, NBEA
DNA Double Strand Break Response	2	15.6×	0.115	KDM4B, BAZ1B
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	2	15.0×	0.117	ACTL6B, ACTL6A
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	3	7.2×	0.117	NSD2, KDM4B, BAZ1B
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	3	7.2×	0.117	SATB1, HDAC4, HDAC9
Notch-HLH transcription pathway	2	13.4×	0.131	HDAC4, HDAC9
C6 deamination of adenosine	1	93.6×	0.134	ADARB1
Formation of editosomes by ADAR proteins	1	93.6×	0.134	ADARB1
UCH proteinases	3	6.1×	0.157	ASXL2, ACTL6A, PSMD12
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	3	5.9×	0.166	KMT2C, SIN3B, TNRC6B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 78 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of transcription initiation by RNA polymerase II	6	20.9×	2e-04	TAF6, MED12, MED16, MED13, MED23, MED27
positive regulation of DNA-templated transcription	14	5.0×	2e-04	TAF6, MED12, KAT6A, BRD4, FBXW11, HDAC4, MED16, KMT2E (+6 more)
chromatin remodeling	9	8.4×	2e-04	BPTF, SATB1, BRD4, HDAC4, ACTL6B, ACTL6A, KDM4B, JARID2 (+1 more)
positive regulation of transcription by RNA polymerase II	18	3.4×	4e-04	AUTS2, BPTF, TCF20, MED12, BRD4, KMT2C, HDAC4, SSBP3 (+10 more)
positive regulation of transcription elongation by RNA polymerase II	5	19.3×	6e-04	BRD4, CDK13, MED16, MED23, MED27
regulation of dendritic spine development	3	64.8×	1e-03	KIF1A, TANC2, MEF2C
negative regulation of transcription by RNA polymerase II	15	3.4×	0.002	BPTF, MYT1L, SATB1, NSD2, RLIM, HDAC4, HDAC9, SIN3B (+7 more)
positive regulation of myoblast differentiation	4	18.8×	0.004	ACTL6B, ACTL6A, MEF2C, ZFHX3
regulation of transcription by RNA polymerase II	18	2.7×	0.005	BPTF, MYT1L, SATB1, TAF6, TCF20, KAT6A, KDM3B, BRD4 (+10 more)
dense core granule cytoskeletal transport	2	108.0×	0.007	KIF1A, TANC2
RNA polymerase II preinitiation complex assembly	4	13.9×	0.009	TAF6, MED16, MED23, MED27
regulation of neuron projection arborization	2	72.0×	0.014	NTNG2, NTNG1
positive regulation of T cell differentiation	3	17.5×	0.026	ACTL6B, ZMIZ1, ACTL6A
embryonic neurocranium morphogenesis	2	48.0×	0.027	MED12, HOXA1
regulation of DNA-templated transcription	9	3.6×	0.027	BPTF, NSD2, KAT6A, KMT2E, MED23, ACTL6A, SETD5, MEF2C (+1 more)
epigenetic regulation of gene expression	3	14.7×	0.036	HDAC4, HDAC9, KMT2E
transcription initiation at RNA polymerase II promoter	3	14.4×	0.036	TAF6, MED23, MED27
sinoatrial valve morphogenesis	1	216.1×	0.065	MEF2C
prechordal plate formation	1	216.1×	0.065	SSBP3
midbrain-hindbrain boundary initiation	1	216.1×	0.065	SSBP3
hypoglossal nerve morphogenesis	1	216.1×	0.065	ADARB1
positive regulation of cell volume	1	216.1×	0.065	SLC12A2
regulation of striated muscle cell differentiation	1	216.1×	0.065	HDAC9
semicircular canal formation	1	216.1×	0.065	HOXA1
synchronous neurotransmitter secretion	1	216.1×	0.065	SYT1
fast, calcium ion-dependent exocytosis of neurotransmitter	1	216.1×	0.065	SYT1
protein localization to pericentric heterochromatin	1	216.1×	0.065	JARID2
regulation of metallopeptidase activity	1	216.1×	0.065	SVBP
regulation of mesoderm development	1	216.1×	0.065	PUS7
intracellular potassium ion homeostasis	2	25.4×	0.065	SLC12A2, ATP1A3

Therapeutics

Drug target analysis

Approved (phase 4): 11 · Phase ≥3: 12 · Phased (≥1): 17 · Undrugged: 58

Druggability breadth: 34 of 80 evidence-associated genes (42%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SLC12A2	BUMETANIDE
MED23	PALBOCICLIB
KDM4B	CICLOPIROX
TAOK1	FEDRATINIB
PSMD12	BORTEZOMIB
NSD2	VENETOCLAX
BRD4	ACETAMINOPHEN
HDAC4	CELECOXIB
HDAC9	CELECOXIB
DDB1	POMALIDOMIDE
ATP1A3	OMEPRAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TAOK1	58	4
BRD4	31	4
HDAC4	31	4
HDAC9	28	4
CDK13	20	3
NSD2	8	4
DDB1	7	4
KDM4B	5	4
ATP1A3	5	4
BPTF	2	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BUMETANIDE	4	SLC12A2
PALBOCICLIB	4	MED23, TAOK1
CICLOPIROX	4	KDM4B
FEDRATINIB	4	BRD4, TAOK1
SORAFENIB	4	TAOK1
RUXOLITINIB	4	TAOK1
ENTRECTINIB	4	TAOK1
PACRITINIB	4	TAOK1
NILOTINIB	4	TAOK1
BOSUTINIB	4	TAOK1
ABEMACICLIB	4	TAOK1
BRIGATINIB	4	TAOK1
PAZOPANIB	4	TAOK1
SUNITINIB	4	TAOK1
DASATINIB	4	TAOK1
CRIZOTINIB	4	TAOK1
IMATINIB	4	TAOK1
BORTEZOMIB	4	PSMD12
CARFILZOMIB	4	PSMD12
VENETOCLAX	4	NSD2
MITOXANTRONE	4	NSD2
ACETAMINOPHEN	4	BRD4
NITROXOLINE	4	BRD4
ROMIDEPSIN	4	BRD4, HDAC4, HDAC9
BELINOSTAT	4	BRD4, HDAC4, HDAC9
PANOBINOSTAT	4	BRD4, HDAC4, HDAC9
ALPRAZOLAM	4	BRD4
LENALIDOMIDE	4	BRD4, DDB1
NORFLOXACIN	4	BRD4
VORINOSTAT	4	BRD4, HDAC4, HDAC9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 14.

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

Symbol	Assays	Type breakdown
BRD4	4,603	Binding:4569, Functional:30, ADMET:4
HDAC4	1,941	Binding:1919, ADMET:13, Functional:6, Toxicity:3
HDAC9	1,625	Binding:1612, ADMET:8, Functional:4, Toxicity:1
NSD2	264	Binding:256, Functional:8
CDK13	257	Binding:250, Functional:7
TAOK1	231	Binding:230, Functional:1
BPTF	125	Binding:123, Functional:2
DDB1	71	Binding:71
KDM4B	61	Binding:60, Functional:1
ATP1A3	45	Binding:45
KAT6A	42	Binding:39, Functional:3
KMT2C	29	Binding:29
PSMD12	27	Binding:27
SLC12A2	13	Binding:9, Functional:4
KDM3B	13	Binding:13
MED23	9	Binding:9
ACTL6A	7	Binding:7
PUF60	7	Binding:7
MED12	6	Binding:6
MED16	6	Binding:6
ADARB1	5	Binding:5
DDX6	4	Binding:4
HUWE1	4	Binding:3, Functional:1
TRIO	2	Binding:2
KIF1A	2	Binding:2
KMT2E	1	Binding:1
TRMT1	1	Binding:1
ETFA	1	Binding:1
TAF6	1	Binding:1
NAA15	1	Binding:1
H1-4	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KIF1A	5.6.1.3	plus-end-directed kinesin ATPase
TRIP12	2.3.2.26	HECT-type E3 ubiquitin transferase
PUS7	5.4.99.27	tRNA pseudouridine13 synthase
DDX6	3.6.4.13	RNA helicase
KDM4B	1.14.11.27, 1.14.11.66, 1.14.11.69	[histone H3]-dimethyl-L-lysine36 demethylase, [histone H3]-trimethyl-L-lysine9 demethylase, [histone H3]-trimethyl-L-lysine36 demethylase
HUWE1	2.3.2.26	HECT-type E3 ubiquitin transferase
NSD2	2.1.1.356, 2.1.1.357, 2.1.1.359	[histone H3]-lysine27 N-trimethyltransferase, [histone H3]-lysine36 N-dimethyltransferase, [histone H3]-lysine36 N-trimethyltransferase
KAT6A	2.3.1.48	histone acetyltransferase
KDM3B	1.14.11.65	[histone H3]-dimethyl-L-lysine9 demethylase
HDAC4	3.5.1.98	histone deacetylase
HDAC9	3.5.1.98	histone deacetylase
CDK13	2.7.11.22, 2.7.11.23	cyclin-dependent kinase, [RNA-polymerase]-subunit kinase
ADARB1	3.5.4.37	double-stranded RNA adenine deaminase
NAA15	2.3.1.255, 2.3.1.258	N-terminal amino-acid Nalpha-acetyltransferase NatA, N-terminal methionine Nalpha-acetyltransferase NatE

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BPTF	125
TAOK1	231
NSD2	264
BRD4	4,603
HDAC4	1,941
HDAC9	1,625
CDK13	257

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.

Compound	Max phase	Cohort target (bioactivity)
BUMETANIDE	4	SLC12A2
PALBOCICLIB	4	MED23, TAOK1
CICLOPIROX	4	KDM4B
FEDRATINIB	4	BRD4, TAOK1
SORAFENIB	4	TAOK1
RUXOLITINIB	4	TAOK1
ENTRECTINIB	4	TAOK1
PACRITINIB	4	TAOK1
NILOTINIB	4	TAOK1
BOSUTINIB	4	TAOK1
ABEMACICLIB	4	TAOK1
BRIGATINIB	4	TAOK1
PAZOPANIB	4	TAOK1
SUNITINIB	4	TAOK1
DASATINIB	4	TAOK1
CRIZOTINIB	4	TAOK1
IMATINIB	4	TAOK1
BORTEZOMIB	4	PSMD12
CARFILZOMIB	4	PSMD12
VENETOCLAX	4	NSD2
MITOXANTRONE	4	NSD2
ACETAMINOPHEN	4	BRD4
NITROXOLINE	4	BRD4
ROMIDEPSIN	4	BRD4, HDAC4, HDAC9
BELINOSTAT	4	BRD4, HDAC4, HDAC9
PANOBINOSTAT	4	BRD4, HDAC4, HDAC9
ALPRAZOLAM	4	BRD4
LENALIDOMIDE	4	BRD4, DDB1
NORFLOXACIN	4	BRD4
VORINOSTAT	4	BRD4, HDAC4, HDAC9

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	11	SLC12A2, MED23, KDM4B, TAOK1, PSMD12, NSD2, BRD4, HDAC4, HDAC9, DDB1 (+1 more)
B	Phased (≥1) drug, not yet approved	6	BPTF, ACTL6A, DDX6, MED12, CDK13, MED16
C	Druggable family + PDB, no drug	7	TRIO, TRIP12, PUS7, HUWE1, KDM3B, ADARB1, NAA15
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	51	AUTS2, WDFY3, MYT1L, KIF1A, SATB1, TCF20, ZMYM3, RLIM, FBXW11, NTNG2 (+41 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MED13	0	MED12
KDM3B	13	KDM4B
ASXL3	0	BRD4
MEF2C	0	HDAC4
TRIO	2	—
AUTS2	0	—
WDFY3	0	—
MYT1L	0	—
KIF1A	2	—
SATB1	0	—
TCF20	0	—
TRIP12	0	—
ZMYM3	0	—
RLIM	0	—
FBXW11	0	—
NTNG2	0	—
ACTL6B	0	—
ZMIZ1	0	—
KMT2E	1	—
SIN3B	0	—
TRAPPC4	0	—
DPYSL5	0	—
NTNG1	0	—
MED27	0	—
BOD1	0	—
BCORL1	0	—
TRMT1	1	—
PUS7	0	—
CCDC32	0	—
TNRC6B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.