Cleft palate

Summary

Cleft palate (MONDO:0016064) is a disease (an umbrella term covering 9 Mondo subtypes) with 52 cohort genes and 80 clinical trials. The dominant Reactome pathway is Formation of the non-canonical BAF (ncBAF) complex (3 cohort genes). Top therapeutic interventions include sodium chloride, bupivacaine, and hydromorphone.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 52
• ClinVar variants: 59
• Clinical trials: 80

Clinical features

Epidemiology

Prevalence records

54 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000		Europe	Validated
Prevalence at birth	1-5 / 10 000	53.6	Europe	Validated
Point prevalence	1-5 / 10 000		Austria	Validated
Point prevalence	1-5 / 10 000		Belgium	Validated
Point prevalence	1-5 / 10 000		Croatia	Validated
Point prevalence	>1 / 1000		Denmark	Validated
Point prevalence	1-5 / 10 000		France	Validated
Point prevalence	1-5 / 10 000		Germany	Validated
Point prevalence	6-9 / 10 000		Hungary	Validated
Point prevalence	1-5 / 10 000		Ireland	Validated
Point prevalence	1-5 / 10 000		Italy	Validated
Point prevalence	6-9 / 10 000		Malta	Validated
Point prevalence	1-5 / 10 000		Netherlands	Validated
Point prevalence	6-9 / 10 000		Norway	Validated
Point prevalence	1-5 / 10 000		Poland	Validated
Point prevalence	1-5 / 10 000		Portugal	Validated
Point prevalence	1-5 / 10 000		Spain	Validated
Point prevalence	1-5 / 10 000		Switzerland	Validated
Point prevalence	6-9 / 10 000		United Kingdom	Validated
Point prevalence	1-5 / 10 000		Ukraine	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	cleft palate
Mondo ID	MONDO:0016064
MeSH	D002972
Orphanet	2014
DOID	DOID:674
ICD-10-CM	Q35
ICD-11	2129534948
NCIT	C87069
SNOMED CT	63567004
UMLS	C2981150
MedGen	756015
MedDRA	10009269
Is cancer (heuristic)	no

Also known as: palatoschisis · uranostaphyloschisis

Data availability: 59 ClinVar variants · 7 cell lines.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › orofacial cleft › cleft palate

Related subtypes (15): cleft lip, orofacial cleft 1, cleft lip/palate-ectodermal dysplasia syndrome, orofacial cleft 2, orofacial cleft 4, orofacial cleft 9, orofacial cleft 12, orofacial cleft 13, familial median cleft of the upper and lower lips, cleft lip and alveolus, cleft lip/palate, orofacial cleft 8, GRHL3-related orofacial clefting, orofacial cleft 7, ARHGAP29-related non-syndromic orofacial cleft

Subtypes (9): isolated cleft palate, cleft soft palate, Rapp-Hodgkin syndrome, bifid uvula, cleft palate with or without ankyloglossia, X-linked, cleft hard palate, submucosal cleft palate, Kuster syndrome, soft and hard cleft palate

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

59 retrieved; paginated sample, class counts are floors:

18 uncertain significance, 14 conflicting classifications of pathogenicity, 9 pathogenic/likely pathogenic, 7 pathogenic, 6 likely benign, 3 likely pathogenic, 1 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
267815	46;X;t(X;5)(p11.23;q35)dn		Pathogenic	criteria provided, single submitter
267851	46;XX;ins(5;6)(p13;p24p25)dn		Pathogenic	criteria provided, single submitter
449190	NM_001101.5(ACTB):c.826G>A (p.Glu276Lys)	ACTB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
817301	NM_152424.4(AMER1):c.1489del (p.Arg497fs)	AMER1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11755	NM_001110556.2(FLNA):c.620C>T (p.Pro207Leu)	FLNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208722	NM_002074.5(GNB1):c.239T>C (p.Ile80Thr)	GNB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
400	NM_019892.6(INPP5E):c.1132C>T (p.Arg378Cys)	INPP5E	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3417	NM_006147.4(IRF6):c.16C>T (p.Arg6Cys)	IRF6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
545640	NM_001128922.2(LRRC32):c.1630C>T (p.Arg544Ter)	LRRC32	Pathogenic/Likely pathogenic	no assertion criteria provided
224962	NM_170675.5(MEIS2):c.992GAA[2] (p.Arg333del)	MEIS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523556	NM_133433.4(NIPBL):c.7459del (p.Glu2487fs)	NIPBL	Pathogenic	criteria provided, single submitter
996741	NM_012233.3(RAB3GAP1):c.151-5T>G	RAB3GAP1	Pathogenic	no assertion criteria provided
2519	NM_001172509.2(SATB2):c.715C>T (p.Arg239Ter)	SATB2	Pathogenic	criteria provided, multiple submitters, no conflicts
523423	NM_001172509.2(SATB2):c.1654_1655del (p.Arg552fs)	SATB2	Pathogenic	criteria provided, multiple submitters, no conflicts
981664	NM_001080517.3(SETD5):c.2168dup (p.Leu723fs)	SETD5	Pathogenic	no assertion criteria provided
212246	NM_003072.5(SMARCA4):c.2936G>A (p.Arg979Gln)	SMARCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523552	NM_001854.4(COL11A1):c.4048_4065del (p.Ser1350_Pro1355del)	COL11A1	Likely pathogenic	criteria provided, single submitter
3383997	NM_170675.5(MEIS2):c.1010_1012del (p.Pro337_Met338delinsLeu)	MEIS2	Likely pathogenic	criteria provided, single submitter
374230	NM_001134673.4(NFIA):c.905del (p.Gly302fs)	NFIA	Likely pathogenic	no assertion criteria provided
4072406	NM_005157.6(ABL1):c.2204C>T (p.Thr735Met)	ABL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1805861	NM_004815.4(ARHGAP29):c.62_63del (p.Ser21fs)	ARHGAP29	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2628931	NM_001273.5(CHD4):c.247G>A (p.Gly83Arg)	CHD4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1409097	NM_017780.4(CHD7):c.8197G>A (p.Ala2733Thr)	CHD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
193897	NM_014714.4(IFT140):c.1336A>G (p.Ile446Val)	IFT140	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
317984	NM_014714.4(IFT140):c.4381G>A (p.Asp1461Asn)	IFT140	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1478945	NM_004977.3(KCNC3):c.781GCGGGCGGC[1] (p.261AGG[1])	KCNC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
932587	NM_019842.4(KCNQ5):c.7C>A (p.Arg3Ser)	LOC129996711	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2047035	NM_001394062.1(MACF1):c.20455G>A (p.Val6819Ile)	MACF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
95900	NM_001378120.1(MBD5):c.2101A>G (p.Met701Val)	MBD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
377301	NM_001346754.2(PIGW):c.617_620del (p.Val206fs)	MYO19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 141 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROR2	Orphanet:1507	Autosomal recessive Robinow syndrome
ROR2	Orphanet:572385	Brachydactyly type B1
SMARCA2	Orphanet:3051	Nicolaides-Baraitser syndrome
SMARCA2	Orphanet:637013	SMARCA2-related blepharophimosis-intellectual disability syndrome
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax
TBX22	Orphanet:324601	X-linked cleft palate and ankyloglossia
TBX22	Orphanet:921	Abruzzo-Erickson syndrome
TSC1	Orphanet:210159	Adult hepatocellular carcinoma
TSC1	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC1	Orphanet:538	Lymphangioleiomyomatosis
TSC1	Orphanet:805	Tuberous sclerosis complex
ACTB	Orphanet:2995	Baraitser-Winter cerebrofrontofacial syndrome
ACTB	Orphanet:64755	Becker nevus syndrome
ACTB	Orphanet:673556	Pseudomyogenic hemangioendothelioma
ACTB	Orphanet:674653	Actinomyopathy-associated syndromic thrombocytopenia
ACTB	Orphanet:79107	Developmental malformations-deafness-dystonia syndrome
MACF1	Orphanet:572013	Posterior-predominant lissencephaly-broad flat pons and medulla-midline crossing defects syndrome
CTCF	Orphanet:363611	CTCF-related neurodevelopmental disorder
IRF2BPL	Orphanet:597623	IRF2BPL-related regressive neurodevelopmental disorder-dystonia-seizures syndrome
NLRP3	Orphanet:1451	CINCA syndrome
NLRP3	Orphanet:47045	Familial cold urticaria
NLRP3	Orphanet:575	Muckle-Wells syndrome
NLRP3	Orphanet:647815	Keratitis fugax hereditaria
RAB3GAP1	Orphanet:1387	Cataract-intellectual disability-hypogonadism syndrome
RAB3GAP1	Orphanet:2510	Micro syndrome
KDM5B	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
KDM5B	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
NEK9	Orphanet:464366	NEK9-related lethal skeletal dysplasia
NEK9	Orphanet:64754	Nevus comedonicus syndrome
PMPCA	Orphanet:1170	Autosomal recessive cerebelloparenchymal disorder type 3
CHD4	Orphanet:653712	CHD4-related neurodevelopmental disorder
MBD5	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
MBD5	Orphanet:228402	2q23.1 microdeletion syndrome
CHD7	Orphanet:138	CHARGE syndrome
CHD7	Orphanet:39041	Omenn syndrome
CHD7	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
CHD7	Orphanet:478	Kallmann syndrome
INPP5E	Orphanet:1454	Joubert syndrome with hepatic defect
INPP5E	Orphanet:220493	Joubert syndrome with ocular defect
INPP5E	Orphanet:475	Isolated Joubert syndrome
INPP5E	Orphanet:75858	MORM syndrome
SATB2	Orphanet:251019	2q32q33 deletion syndrome
SATB2	Orphanet:251028	SATB2-associated syndrome due to a chromosomal rearrangement
SATB2	Orphanet:576283	SATB2-associated syndrome due to a pathogenic variant
COL11A1	Orphanet:2021	Fibrochondrogenesis
COL11A1	Orphanet:440354	Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome
COL11A1	Orphanet:560	Marshall syndrome

Cohort genes → proteins

52 cohort genes, 52 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	52

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ROR2	HGNC:10257	ENSG00000169071	Q01974	Tyrosine-protein kinase transmembrane receptor ROR2	clinvar
SMARCA2	HGNC:11098	ENSG00000080503	P51531	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2	clinvar
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	clinvar
TBX22	HGNC:11600	ENSG00000122145	Q9Y458	T-box transcription factor TBX22	clinvar
TSC1	HGNC:12362	ENSG00000165699	Q92574	Hamartin	clinvar
ACTB	HGNC:132	ENSG00000075624	P60709	Actin, cytoplasmic 1	clinvar
MACF1	HGNC:13664	ENSG00000127603	O94854	Microtubule-actin cross-linking factor 1, isoforms 6/7	clinvar
CTCF	HGNC:13723	ENSG00000102974	P49711	Transcriptional repressor CTCF	clinvar
IRF2BPL	HGNC:14282	ENSG00000119669	Q9H1B7	Probable E3 ubiquitin-protein ligase IRF2BPL	clinvar
NLRP3	HGNC:16400	ENSG00000162711	Q96P20	NACHT, LRR and PYD domains-containing protein 3	clinvar
RAB3GAP1	HGNC:17063	ENSG00000115839	Q15042	Rab3 GTPase-activating protein catalytic subunit	clinvar
KDM5B	HGNC:18039	ENSG00000117139	Q9UGL1	Lysine-specific demethylase 5B	clinvar
NEK9	HGNC:18591	ENSG00000119638	Q8TD19	Serine/threonine-protein kinase Nek9	clinvar
PMPCA	HGNC:18667	ENSG00000165688	Q10713	Mitochondrial-processing peptidase subunit alpha	clinvar
CHD4	HGNC:1919	ENSG00000111642	Q14839	ATP-dependent chromatin remodeler CHD4	clinvar
MBD5	HGNC:20444	ENSG00000204406	Q9P267	Methyl-CpG-binding domain protein 5	clinvar
CHD7	HGNC:20626	ENSG00000171316	Q9P2D1	ATP-dependent chromatin remodeler CHD7	clinvar
INPP5E	HGNC:21474	ENSG00000148384	Q9NRR6	Phosphatidylinositol polyphosphate 5-phosphatase type IV	clinvar
SATB2	HGNC:21637	ENSG00000119042	Q9UPW6	DNA-binding protein SATB2	clinvar
COL11A1	HGNC:2186	ENSG00000060718	P12107	Collagen alpha-1(XI) chain	clinvar
PACS2	HGNC:23794	ENSG00000179364	Q86VP3	Phosphofurin acidic cluster sorting protein 2	clinvar
NDC1	HGNC:25525	ENSG00000058804	Q9BTX1	Nucleoporin NDC1	clinvar
SETD5	HGNC:25566	ENSG00000168137	Q9C0A6	Histone-lysine N-methyltransferase SETD5	clinvar
CPLANE1	HGNC:25801	ENSG00000197603	Q9H799	Ciliogenesis and planar polarity effector 1	clinvar
MYO19	HGNC:26234	ENSG00000278259	Q96H55	Unconventional myosin-XIX	clinvar
PIEZO2	HGNC:26270	ENSG00000154864	Q9H5I5	Piezo-type mechanosensitive ion channel component 2	clinvar
AMER1	HGNC:26837	ENSG00000184675	Q5JTC6	APC membrane recruitment protein 1	clinvar
NIPBL	HGNC:28862	ENSG00000164190	Q6KC79	Nipped-B-like protein	clinvar
SPECC1L	HGNC:29022	ENSG00000100014	Q69YQ0	Cytospin-A	clinvar
IFT140	HGNC:29077	ENSG00000187535	Q96RY7	Intraflagellar transport protein 140 homolog	clinvar
ASXL3	HGNC:29357	ENSG00000141431	Q9C0F0	Putative Polycomb group protein ASXL3	clinvar
TENM4	HGNC:29945	ENSG00000149256	Q6N022	Teneurin-4	clinvar
ARHGAP29	HGNC:30207	ENSG00000137962	Q52LW3	Rho GTPase-activating protein 29	clinvar
EBP	HGNC:3133	ENSG00000147155	Q15125	3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase	clinvar
FANCD2	HGNC:3585	ENSG00000144554	Q9BXW9	Fanconi anemia group D2 protein	clinvar
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	clinvar
LRRC32	HGNC:4161	ENSG00000137507	Q14392	Transforming growth factor beta activator LRRC32	clinvar
GJA1	HGNC:4274	ENSG00000152661	P17302	Gap junction alpha-1 protein	clinvar
GLB1	HGNC:4298	ENSG00000170266	P16278	Beta-galactosidase	clinvar
GNB1	HGNC:4396	ENSG00000078369	P62873	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	clinvar
HAO1	HGNC:4809	ENSG00000101323	Q9UJM8	2-Hydroxyacid oxidase 1	clinvar
IDH2	HGNC:5383	ENSG00000182054	P48735	Isocitrate dehydrogenase [NADP], mitochondrial	clinvar
INPP1	HGNC:6071	ENSG00000151689	P49441	Inositol polyphosphate 1-phosphatase	clinvar
IRAK1	HGNC:6112	ENSG00000184216	P51617	Interleukin-1 receptor-associated kinase 1	clinvar
IRF6	HGNC:6121	ENSG00000117595	O14896	Interferon regulatory factor 6	clinvar
KCNC3	HGNC:6235	ENSG00000131398	Q14003	Voltage-gated potassium channel KCNC3	clinvar
MEIS2	HGNC:7001	ENSG00000134138	O14770	Homeobox protein Meis2	clinvar
SEPTIN9	HGNC:7323	ENSG00000184640	Q9UHD8	Septin-9	clinvar
ABL1	HGNC:76	ENSG00000097007	P00519	Tyrosine-protein kinase ABL1	clinvar
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ROR2	Tyrosine-protein kinase transmembrane receptor ROR2	Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes.
SMARCA2	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
TBX22	T-box transcription factor TBX22	Probable transcriptional regulator involved in developmental processes.
TSC1	Hamartin	Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolec…
ACTB	Actin, cytoplasmic 1	Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells.
CTCF	Transcriptional repressor CTCF	Chromatin binding factor that binds to DNA sequence specific sites and regulates the 3D structure of chromatin.
IRF2BPL	Probable E3 ubiquitin-protein ligase IRF2BPL	Probable E3 ubiquitin protein ligase involved in the proteasome-mediated ubiquitin-dependent degradation of target proteins.
NLRP3	NACHT, LRR and PYD domains-containing protein 3	Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis.
RAB3GAP1	Rab3 GTPase-activating protein catalytic subunit	Catalytic subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of RAB3GAP1 and RAB3GAP2, which accelerates the otherwise slow GTP hydrolysis catalyzed by Rab proteins.
KDM5B	Lysine-specific demethylase 5B	Histone demethylase that demethylates ‘Lys-4’ of histone H3, thereby playing a central role in histone code.
NEK9	Serine/threonine-protein kinase Nek9	Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation.
PMPCA	Mitochondrial-processing peptidase subunit alpha	Substrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins.
CHD4	ATP-dependent chromatin remodeler CHD4	ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA.
MBD5	Methyl-CpG-binding domain protein 5	Non-catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at ‘Lys-120’ (H2AK119ub1).
CHD7	ATP-dependent chromatin remodeler CHD7	ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP.
INPP5E	Phosphatidylinositol polyphosphate 5-phosphatase type IV	Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,5-bispho…
SATB2	DNA-binding protein SATB2	Binds to DNA, at nuclear matrix- or scaffold-associated regions.
COL11A1	Collagen alpha-1(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
PACS2	Phosphofurin acidic cluster sorting protein 2	Multifunctional sorting protein that controls the endoplasmic reticulum (ER)-mitochondria communication, including the apposition of mitochondria with the ER and ER homeostasis.
NDC1	Nucleoporin NDC1	Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope.
SETD5	Histone-lysine N-methyltransferase SETD5	Chromatin regulator required for brain development: acts as a regulator of RNA elongation rate, thereby regulating neural stem cell (NSC) proliferation and synaptic transmission.
CPLANE1	Ciliogenesis and planar polarity effector 1	Involved in ciliogenesis.
MYO19	Unconventional myosin-XIX	Actin-based motor molecule with ATPase activity that localizes to the mitochondrion outer membrane.
PIEZO2	Piezo-type mechanosensitive ion channel component 2	Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain.
AMER1	APC membrane recruitment protein 1	Regulator of the canonical Wnt signaling pathway.
NIPBL	Nipped-B-like protein	Plays an important role in the loading of the cohesin complex on to DNA.
SPECC1L	Cytospin-A	Involved in cytokinesis and spindle organization.
IFT140	Intraflagellar transport protein 140 homolog	Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs).
ASXL3	Putative Polycomb group protein ASXL3	Putative Polycomb group (PcG) protein.
TENM4	Teneurin-4	Involved in neural development, regulating the establishment of proper connectivity within the nervous system.
ARHGAP29	Rho GTPase-activating protein 29	GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.
EBP	3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase	Isomerase that catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers a catalytic step in the postlanosterol biosynthesis of cholesterol.
FANCD2	Fanconi anemia group D2 protein	Required for maintenance of chromosomal stability.
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.
LRRC32	Transforming growth factor beta activator LRRC32	Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space.
GJA1	Gap junction alpha-1 protein	Structural component of the gap junction, a specialized intercellular structure consisting of a cluster of closely packed pairs of transmembrane channels, the connexons, that allow passage of small molecules and electrical signals between…
GLB1	Beta-galactosidase	Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.
GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems.
HAO1	2-Hydroxyacid oxidase 1	Broad substrate specificity (S)-2-hydroxy-acid oxidase that preferentially oxidizes glycolate.
IDH2	Isocitrate dehydrogenase [NADP], mitochondrial	Plays a role in intermediary metabolism and energy production.
INPP1	Inositol polyphosphate 1-phosphatase	Mg(2+)-dependent phosphatase that catalyzes the hydrolysis of the 1-position phosphate from inositol 1,4-bisphosphate and inositol 1,3,4-trisphosphate and participates in inositol phosphate metabolism.
IRAK1	Interleukin-1 receptor-associated kinase 1	Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens.
IRF6	Interferon regulatory factor 6	Probable DNA-binding transcriptional activator.
KCNC3	Voltage-gated potassium channel KCNC3	Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons.
MEIS2	Homeobox protein Meis2	Involved in transcriptional regulation.
SEPTIN9	Septin-9	Filament-forming cytoskeletal GTPase.
ABL1	Tyrosine-protein kinase ABL1	Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autopha…
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.
NFIA	Nuclear factor 1 A-type	Recognizes and binds the palindromic sequence 5’-TTGGCNNNNNGCCAA-3’ present in viral and cellular promoters and in the origin of replication of adenovirus type 2.

Protein-family classification

Druggable: 12 · Difficult: 13 · Unknown: 27 · Druggable fraction: 0.23

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
Kinase	4	2.1×	0.813
Scaffold/PPI	5	1.7×	0.813
Ion channel	1	2.1×	0.836
Phosphatase	1	1.6×	0.836
Transcription factor	8	1.3×	0.836
Other/Unknown	27	0.9×	0.837
Enzyme (other)	4	0.9×	0.837
Protease	1	0.7×	0.837
Antibody/Immunoglobulin	1	0.6×	0.837

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ROR2	Kinase	yes	2.7.10.1	Kringle, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
SMARCA2	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
TBX22	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TSC1	Other/Unknown	no		Hamartin
ACTB	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
MACF1	Scaffold/PPI	no		Spectrin_repeat, EF_hand_dom, GAR_dom
CTCF	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger_PRDM4/PRDM1/PRDM14
IRF2BPL	Transcription factor	no		IRF-2BP1_2-like_Znf, I2BP1/2_C3HC4-RING_sf, Zf-C3HC4_IRF-2BP1_2
NLRP3	Other/Unknown	no		Leu-rich_rpt, DAPIN, NACHT_NTPase
RAB3GAP1	Other/Unknown	no		Rab3GAP1_conserved, Rab3GAP1_C, Rab3GAP1
KDM5B	Transcription factor	no	1.14.11.67	ARID_dom, Znf_PHD, JmjC_dom
NEK9	Kinase	yes		Reg_chr_condens, Prot_kinase_dom, Ser/Thr_kinase_AS
PMPCA	Protease	yes	3.4.24.64	Pept_M16_Zn_BS, Peptidase_M16_C, Metalloenz_LuxS/M16
CHD4	Transcription factor	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
MBD5	Other/Unknown	no		PWWP_dom, Methyl_CpG_DNA-bd, DNA-bd_dom_sf
CHD7	Other/Unknown	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
INPP5E	Enzyme (other)	yes	3.1.3.36	IPPc, Endo/exonu/phosph_ase_sf, INPP5E
SATB2	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
COL11A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
PACS2	Other/Unknown	no		PACS1/2_C, PACS1/2_N
NDC1	Other/Unknown	no		Nucleoporin_prot_Ndc1/Nup
SETD5	Other/Unknown	no		SET_dom, SETD5_SET, SET_dom_sf
CPLANE1	Scaffold/PPI	no		CPLANE1, WD40_repeat_dom_sf
MYO19	Other/Unknown	no		Myosin_head_motor_dom-like, P-loop_NTPase, MYSc_Myo19
PIEZO2	Other/Unknown	no		Piezo, Piezo_cap_dom, Piezo_TM25-28
AMER1	Other/Unknown	no		AMER
NIPBL	Other/Unknown	no		ARM-like, ARM-type_fold, Nipped-B_C
SPECC1L	Other/Unknown	no		CH_dom, CH_dom_sf, F-actin_Monoox_Mical
IFT140	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
ASXL3	Other/Unknown	no		Asxl_HARE-HTH, ASX/ASX-like, ASX-like_PHD
TENM4	Other/Unknown	no		EGF, YD, CarboxyPept-like_regulatory
ARHGAP29	Scaffold/PPI	no		RhoGAP_dom, PKC_DAG/PE, Rho_GTPase_activation_prot
EBP	Enzyme (other)	yes	5.3.3.5	EBP, EXPERA
FANCD2	Other/Unknown	no		FANCD2
FLNA	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
LRRC32	Other/Unknown	no		LRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
GJA1	Other/Unknown	no		Connexin, Connexin43, Connexin_N
GLB1	Other/Unknown	no		Glycoside_Hdrlase_35, Galactose-bd-like_sf, GH_hydrolase_sf
GNB1	Scaffold/PPI	no		WD40_G-protein_beta-like, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
HAO1	Enzyme (other)	yes	1.1.3.15	FMN-dep_DH, FMN_hydac_DH_AS, Alpha-hydoxy_acid_DH_FMN
IDH2	Enzyme (other)	yes	1.1.1.42	Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
INPP1	Phosphatase	yes	3.1.3.57	Inositol_monophosphatase-like, Inositol_monophosphatase_CS, Inositol_monoP_metal-BS
IRAK1	Kinase	yes	2.7.10.2	Death_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
IRF6	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf
KCNC3	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
MEIS2	Transcription factor	no		HD, KN_HD, Homeodomain-like_sf
SEPTIN9	Other/Unknown	no		Septin, P-loop_NTPase, G_SEPTIN_dom
ABL1	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_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)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	52
unknown	0

Top tissues across cohort

Tissue	Cohort genes
secondary oocyte	8
calcaneal tendon	6
colonic epithelium	6
cortical plate	6
ganglionic eminence	6
sural nerve	6
male germ line stem cell (sensu Vertebrata) in testis	5
ventricular zone	4
right uterine tube	4
adrenal tissue	4
hair follicle	3
right lobe of liver	3
cervix squamous epithelium	2
left testis	2
lateral globus pallidus	2
urethra	2
dorsal motor nucleus of vagus nerve	2
right lung	2
monocyte	2
mononuclear cell	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ROR2	188	ubiquitous	marker	muscle layer of sigmoid colon, mucosa of stomach, body of uterus
SMARCA2	301	ubiquitous	marker	calcaneal tendon, colonic epithelium, cortical plate
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
TBX22	44	tissue_specific	yes	left testis, right testis, testis
TSC1	297	ubiquitous	marker	substantia nigra pars compacta, gluteal muscle, lateral globus pallidus
ACTB	295	ubiquitous	marker	urethra, postcentral gyrus, saphenous vein
MACF1	303	ubiquitous	marker	inferior olivary complex, dorsal motor nucleus of vagus nerve, right lung
CTCF	297	ubiquitous	marker	ventricular zone, ganglionic eminence, endometrium epithelium
IRF2BPL	259	ubiquitous	marker	germinal epithelium of ovary, cardiac muscle of right atrium, endothelial cell
NLRP3	172	broad	marker	monocyte, mononuclear cell, leukocyte
RAB3GAP1	300	ubiquitous	marker	hair follicle, Brodmann (1909) area 23, secondary oocyte
KDM5B	272	ubiquitous	marker	sperm, male germ cell, left testis
NEK9	296	ubiquitous	marker	tibia, right uterine tube, left ovary
PMPCA	276	ubiquitous	marker	right lobe of liver, adrenal tissue, apex of heart
CHD4	284	ubiquitous	marker	ventricular zone, ganglionic eminence, colonic epithelium
MBD5	243	ubiquitous	marker	calcaneal tendon, adrenal tissue, sural nerve
CHD7	269	ubiquitous	marker	secondary oocyte, cerebellar vermis, sural nerve
INPP5E	279	ubiquitous	yes	right uterine tube, secondary oocyte, oocyte
SATB2	235	ubiquitous	marker	periodontal ligament, cortical plate, mucosa of sigmoid colon
COL11A1	209	broad	marker	tibia, cartilage tissue, periodontal ligament
PACS2	281	ubiquitous	marker	C1 segment of cervical spinal cord, spinal cord, right hemisphere of cerebellum
NDC1	262	ubiquitous	marker	secondary oocyte, oocyte, primordial germ cell in gonad
SETD5	284	ubiquitous	marker	adrenal tissue, colonic epithelium, sural nerve
CPLANE1	195	ubiquitous	marker	sural nerve, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis
MYO19	244	ubiquitous	yes	skin of leg, skin of abdomen, metanephros cortex
PIEZO2	237	broad	marker	sural nerve, corpus callosum, dorsal root ganglion
AMER1	156	ubiquitous	yes	cortical plate, skeletal muscle tissue of rectus abdominis, myocardium
NIPBL	288	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, colonic epithelium
SPECC1L	274	ubiquitous	marker	calcaneal tendon, tendon, male germ line stem cell (sensu Vertebrata) in testis
IFT140	214	ubiquitous	marker	right uterine tube, right lobe of thyroid gland, left lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 11.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCA4	8,138
ABL1	6,937
CHD4	6,397
CTCF	5,713
NF1	5,540
TSC1	5,445
FLNA	5,321
GJA1	4,942
IDH2	4,912
CHD7	4,819

Intra-cohort edges

A	B	Sources
ARHGAP29	IRF6	string_interaction
ASXL3	MBD5	biogrid_interaction
CHD7	SMARCA4	intact
CPLANE1	NIPBL	string_interaction
CTCF	KDM5B	intact
CTCF	NIPBL	string_interaction
FLNA	SEPTIN9	string_interaction
INPP5E	NF1	biogrid_interaction, intact
IRF6	TBX22	string_interaction
NF1	NFIA	string_interaction
SMARCA2	SMARCA4	string_interaction

Structural data

PDB: 38 · AlphaFold-only: 14 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNB1	P62873	1,262
ACTB	P60709	88
ABL1	P00519	85
KDM5B	Q9UGL1	56
SMARCA2	P51531	32
SMARCA4	P51532	31
FLNA	P21333	26
NF1	P21359	26
NLRP3	Q96P20	24
CTCF	P49711	21
HAO1	Q9UJM8	21
GJA1	P17302	19
FANCD2	Q9BXW9	13
CHD4	Q14839	12
IDH2	P48735	11
GLB1	P16278	8
ROR2	Q01974	6
LRRC32	Q14392	6
TSC1	Q92574	5
NFIA	Q12857	5
IFT140	Q96RY7	4
TENM4	Q6N022	4
EBP	Q15125	4
MEIS2	O14770	4
MACF1	O94854	3
CHD7	Q9P2D1	3
SATB2	Q9UPW6	3
AMER1	Q5JTC6	3
NIPBL	Q6KC79	3
SEPTIN9	Q9UHD8	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PMPCA	Q10713	88.46
INPP1	P49441	87.87
MYO19	Q96H55	76.93
IRF6	O14896	74.19
PACS2	Q86VP3	67.10
SPECC1L	Q69YQ0	67.07
KCNC3	Q14003	66.01
ARHGAP29	Q52LW3	64.41
TBX22	Q9Y458	59.38
COL11A1	P12107	53.06
SETD5	Q9C0A6	47.10
MBD5	Q9P267	43.20
ASXL3	Q9C0F0	39.70
CPLANE1	Q9H799

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 424. Enrichment computed across 52 evidence-associated genes (38 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 38 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the non-canonical BAF (ncBAF) complex	3	53.0×	0.004	SMARCA2, SMARCA4, ACTB
Formation of the canonical BAF (cBAF) complex	3	50.1×	0.004	SMARCA2, SMARCA4, ACTB
Formation of the polybromo-BAF (pBAF) complex	3	50.1×	0.004	SMARCA2, SMARCA4, ACTB
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	3	36.1×	0.008	SMARCA2, SMARCA4, ACTB
Regulation of endogenous retroelements	3	29.1×	0.012	SMARCA2, SMARCA4, ACTB
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	4	12.4×	0.020	SMARCA2, SMARCA4, ACTB, CHD4
Regulation of MITF-M-dependent genes involved in pigmentation	3	21.0×	0.023	SMARCA2, SMARCA4, ACTB
Formation of annular gap junctions	2	54.6×	0.031	ACTB, GJA1
Gap junction degradation	2	50.1×	0.033	ACTB, GJA1
RUNX2 regulates bone development	2	42.9×	0.038	SATB2, ABL1
MITF-M-dependent gene expression	3	14.3×	0.038	SMARCA2, SMARCA4, ACTB
Chromatin organization	4	8.6×	0.038	SMARCA2, SMARCA4, ACTB, KDM5B
Gene expression (Transcription)	8	3.8×	0.038	SMARCA2, SMARCA4, ACTB, KDM5B, SATB2, NDC1, IRAK1, ABL1
Cell-extracellular matrix interactions	2	35.4×	0.043	ACTB, FLNA
Formation of the embryonic stem cell BAF (esBAF) complex	2	31.6×	0.047	SMARCA4, ACTB
Chromatin modifying enzymes	4	7.6×	0.047	SMARCA2, SMARCA4, ACTB, KDM5B
Epigenetic regulation of gene expression	4	7.5×	0.047	SMARCA2, SMARCA4, ACTB, ABL1
Transcriptional regulation by RUNX1	3	11.6×	0.051	SMARCA2, SMARCA4, ABL1
Nuclear Envelope Breakdown	2	24.0×	0.065	NEK9, NDC1
RUNX2 regulates osteoblast differentiation	2	24.0×	0.065	SATB2, ABL1
Deletions in the AMER1 gene destabilize the destruction complex	1	300.5×	0.067	AMER1
Mitotic Prophase	2	19.4×	0.083	NEK9, NDC1
MITF-M-regulated melanocyte development	3	9.0×	0.083	SMARCA2, SMARCA4, ACTB
Signaling by WNT	3	8.8×	0.083	ROR2, SMARCA4, AMER1
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	2	18.8×	0.084	NLRP3, ABL1
Parasite infection	2	18.2×	0.084	ACTB, ABL1
Leishmania phagocytosis	2	18.2×	0.084	ACTB, ABL1
MPS IV - Morquio syndrome B (Keratin metabolism)	1	150.3×	0.088	GLB1
MPS IV - Morquio syndrome B (CS/DS degradation)	1	150.3×	0.088	GLB1
RHO GTPases Activate WASPs and WAVEs	2	16.7×	0.088	ACTB, ABL1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 52 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
chromatin remodeling	9	12.6×	2e-05	SMARCA2, SMARCA4, ACTB, KDM5B, CHD4, CHD7, SATB2, NIPBL (+1 more)
cognition	4	22.0×	0.007	CHD7, SETD5, NIPBL, NF1
positive regulation of transcription by RNA polymerase II	13	3.7×	0.007	SMARCA2, SMARCA4, CTCF, IRF2BPL, NLRP3, CHD7, SATB2, NIPBL (+5 more)
regulation of G0 to G1 transition	3	38.9×	0.010	SMARCA2, SMARCA4, ACTB
regulation of nucleotide-excision repair	3	34.7×	0.012	SMARCA2, SMARCA4, ACTB
uterus morphogenesis	2	108.0×	0.015	KDM5B, NIPBL
regulation of mitotic metaphase/anaphase transition	3	28.6×	0.015	SMARCA2, SMARCA4, ACTB
positive regulation of T cell differentiation	3	26.3×	0.017	SMARCA2, SMARCA4, ACTB
positive regulation of myoblast differentiation	3	21.1×	0.028	SMARCA2, SMARCA4, ACTB
positive regulation of stem cell population maintenance	3	19.8×	0.028	SMARCA2, SMARCA4, ACTB
positive regulation of double-strand break repair	3	19.8×	0.028	SMARCA2, SMARCA4, ACTB
actin cytoskeleton organization	5	7.6×	0.028	SPECC1L, FLNA, SEPTIN9, ABL1, NF1
regulation of cell-matrix adhesion	2	49.9×	0.033	TSC1, NF1
secondary palate development	2	46.3×	0.033	CHD7, LRRC32
chromatin looping	2	46.3×	0.033	CTCF, NIPBL
regulation of G1/S transition of mitotic cell cycle	3	17.7×	0.033	SMARCA2, SMARCA4, ACTB
negative regulation of cell differentiation	3	16.5×	0.033	SMARCA2, SMARCA4, ACTB
positive regulation of cell differentiation	3	15.4×	0.036	SMARCA2, SMARCA4, ACTB
retina development in camera-type eye	3	14.7×	0.039	CHD7, GNB1, NFIA
positive regulation of neuron migration	2	38.1×	0.040	NIPBL, FLNA
regulation of DNA-templated transcription	7	4.2×	0.040	SMARCA2, KDM5B, CHD7, SETD5, IRAK1, ABL1, NFIA
right ventricular compact myocardium morphogenesis	1	324.1×	0.047	CHD7
glycine biosynthetic process	1	324.1×	0.047	HAO1
positive regulation of mast cell apoptotic process	1	324.1×	0.047	NF1
mitochondrion migration along actin filament	1	324.1×	0.047	MYO19
external genitalia morphogenesis	1	324.1×	0.047	NIPBL
neural crest cell delamination	1	324.1×	0.047	SPECC1L
regulation of glial cell differentiation	1	324.1×	0.047	NF1
glycolate catabolic process	1	324.1×	0.047	HAO1
positive regulation of norepinephrine uptake	1	324.1×	0.047	ACTB

Therapeutics

Drugs indicated for this disease

0 approved, 3 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Dexmedetomidine	Phase 3 (in late-stage trials)
Folic Acid	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetaminophen, Ampicillin, Bupivacaine, Levobupivacaine, Sulbactam.

Drug target analysis

Approved (phase 4): 9 · Phase ≥3: 11 · Phased (≥1): 17 · Undrugged: 35

Druggability breadth: 26 of 52 evidence-associated genes (50%) 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
NLRP3	CLOMIPHENE
NEK9	MOMELOTINIB
EBP	TRIFLUPERIDOL
GJA1	KANAMYCIN
GLB1	MIGALASTAT
IDH2	ENASIDENIB
IRAK1	PONATINIB
SEPTIN9	BARICITINIB
ABL1	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABL1	122	4
IRAK1	50	4
NEK9	21	4
EBP	16	4
NLRP3	11	4
IDH2	7	4
SEPTIN9	3	4
SMARCA2	2	2
SMARCA4	2	2
KDM5B	2	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOMIPHENE	4	NLRP3
GLYBURIDE	4	NLRP3
MOMELOTINIB	4	NEK9
FEDRATINIB	4	ABL1, IRAK1, NEK9
DABRAFENIB	4	ABL1, IRAK1, NEK9
PACRITINIB	4	IRAK1, NEK9
FOSTAMATINIB	4	NEK9
CRIZOTINIB	4	ABL1, IRAK1, NEK9
TRIFLUPERIDOL	4	EBP
TRIPARANOL	4	EBP
BUFLOMEDIL	4	EBP
TRIFLUOPERAZINE	4	EBP
HALOPERIDOL	4	EBP
NAFTIFINE	4	EBP
AMIODARONE	4	EBP
RALOXIFENE	4	EBP
TAMOXIFEN	4	EBP
DOXORUBICIN	4	EBP
KANAMYCIN	4	GJA1
MIGALASTAT	4	GLB1
ENASIDENIB	4	IDH2
ENASIDENIB MESYLATE	4	IDH2
IVOSIDENIB	4	IDH2
VORASIDENIB	4	IDH2
OLUTASIDENIB	4	IDH2
PONATINIB	4	ABL1, IRAK1
AFATINIB	4	ABL1, IRAK1
AXITINIB	4	ABL1, IRAK1
SORAFENIB	4	ABL1, IRAK1
RUXOLITINIB	4	ABL1, IRAK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

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

Symbol	Assays	Type breakdown
ABL1	3,282	Binding:3254, ADMET:16, Functional:10, Toxicity:2
NLRP3	534	Binding:527, Functional:6, ADMET:1
IRAK1	363	Binding:361, Functional:1, ADMET:1
SMARCA2	311	Binding:274, Functional:25, ADMET:12
NEK9	254	Binding:254
SMARCA4	230	Binding:207, ADMET:12, Functional:11
KDM5B	146	Binding:146
GLB1	124	Binding:123, ADMET:1
IDH2	84	Binding:84
EBP	57	Binding:34, Functional:23
HAO1	30	Binding:30
ACTB	21	Binding:21
KCNC3	21	Binding:20, Toxicity:1
GNB1	12	Binding:12
CHD4	10	Binding:9, Functional:1
FLNA	7	Binding:7
SATB2	6	Binding:6
SPECC1L	6	Binding:6
ROR2	4	Binding:4
GJA1	4	Binding:4
CTCF	2	Binding:2
FANCD2	2	Binding:2
SEPTIN9	2	Binding:2
PMPCA	1	Binding:1
NDC1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ROR2	2.7.10.1	receptor protein-tyrosine kinase
KDM5B	1.14.11.67	[histone H3]-trimethyl-L-lysine4 demethylase
PMPCA	3.4.24.64	mitochondrial processing peptidase
INPP5E	3.1.3.36	phosphoinositide 5-phosphatase
EBP	5.3.3.5	cholestenol DELTA-isomerase
HAO1	1.1.3.15	(S)-2-hydroxy-acid oxidase
IDH2	1.1.1.42	isocitrate dehydrogenase (NADP+)
INPP1	3.1.3.57	inositol-1,4-bisphosphate 1-phosphatase
IRAK1	2.7.10.2	non-specific protein-tyrosine kinase
ABL1	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SMARCA2	311
SMARCA4	230
NLRP3	534
KDM5B	146
NEK9	254
GLB1	124
IRAK1	363
ABL1	3,282

Pharmacogenomics

Cohort genes with a PharmGKB record: 52; 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)
CLOMIPHENE	4	NLRP3
GLYBURIDE	4	NLRP3
MOMELOTINIB	4	NEK9
FEDRATINIB	4	ABL1, IRAK1, NEK9
DABRAFENIB	4	ABL1, IRAK1, NEK9
PACRITINIB	4	IRAK1, NEK9
FOSTAMATINIB	4	NEK9
CRIZOTINIB	4	ABL1, IRAK1, NEK9
TRIFLUPERIDOL	4	EBP
TRIPARANOL	4	EBP
BUFLOMEDIL	4	EBP
TRIFLUOPERAZINE	4	EBP
HALOPERIDOL	4	EBP
NAFTIFINE	4	EBP
AMIODARONE	4	EBP
RALOXIFENE	4	EBP
TAMOXIFEN	4	EBP
DOXORUBICIN	4	EBP
KANAMYCIN	4	GJA1
MIGALASTAT	4	GLB1
ENASIDENIB	4	IDH2
ENASIDENIB MESYLATE	4	IDH2
IVOSIDENIB	4	IDH2
VORASIDENIB	4	IDH2
OLUTASIDENIB	4	IDH2
PONATINIB	4	ABL1, IRAK1
AFATINIB	4	ABL1, IRAK1
AXITINIB	4	ABL1, IRAK1
SORAFENIB	4	ABL1, IRAK1
RUXOLITINIB	4	ABL1, IRAK1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	9	NLRP3, NEK9, EBP, GJA1, GLB1, IDH2, IRAK1, SEPTIN9, ABL1
B	Phased (≥1) drug, not yet approved	8	SMARCA2, SMARCA4, ACTB, KDM5B, CHD4, SPECC1L, FLNA, GNB1
C	Druggable family + PDB, no drug	3	ROR2, INPP5E, HAO1
D	Druggable family + AlphaFold only, no drug	3	PMPCA, INPP1, KCNC3
E	Difficult family or no structure, no drug	29	TBX22, TSC1, MACF1, CTCF, IRF2BPL, RAB3GAP1, MBD5, CHD7, SATB2, COL11A1 (+19 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ROR2	4	—
TBX22	0	—
TSC1	0	—
MACF1	0	—
CTCF	2	—
IRF2BPL	0	—
RAB3GAP1	0	—
PMPCA	1	—
MBD5	0	—
CHD7	0	—
INPP5E	0	—
SATB2	6	—
COL11A1	0	—
PACS2	0	—
NDC1	1	—
SETD5	0	—
CPLANE1	0	—
MYO19	0	—
PIEZO2	0	—
AMER1	0	—
NIPBL	0	—
IFT140	0	—
ASXL3	0	—
TENM4	0	—
ARHGAP29	0	—
FANCD2	2	—
LRRC32	0	—
HAO1	30	—
INPP1	0	—
IRF6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 80.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	64
PHASE4	5
PHASE2	5
PHASE3	4
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03632044	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of Trigeminal Nerve Blockade
NCT06962306	PHASE4	RECRUITING	Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery
NCT02422056	PHASE4	COMPLETED	Acid Tranexamic Effectiveness in Reducing the Intraoperative Bleeding in Palatoplasty
NCT02915042	PHASE4	WITHDRAWN	Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair
NCT02953145	PHASE4	WITHDRAWN	The Use of Fibrin Sealant to Reduce Post Operative Pain in Cleft Palate Surgery
NCT04928352	PHASE3	RECRUITING	Nebulized Bupivacaine Analgesia for Cleft Palate Repair
NCT00098319	PHASE3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	PHASE3	COMPLETED	Oral Cleft Prevention Program
NCT04928391	PHASE3	COMPLETED	A Single Bolus of Dexmedetomidine Versus Normal Saline in Postoperative Agitation
NCT00004639	PHASE2	COMPLETED	Cleft Palate Surgery and Speech Development
NCT00760006	PHASE2	COMPLETED	Preventing Complications in Cleft Palate Repair With Antibiotics
NCT01616953	PHASE1/PHASE2	COMPLETED	Cell Therapy for Craniofacial Bone Defects
NCT01760330	PHASE2	WITHDRAWN	IV Acetaminophen in Children Undergoing Palatoplasty
NCT02247193	PHASE1/PHASE2	COMPLETED	Botulinum Toxin to Improve Cosmesis of Primary Cleft Lip Repair
NCT02350803	PHASE2	COMPLETED	Does Use of Rigid Fixation After Removing Distraction Osteogenesis Device Reduce the Relapse?
NCT03412474	PHASE2	COMPLETED	Suprazygomatic Block in Cleft Palate Surgery in Children
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT02702869	Not specified	ENROLLING_BY_INVITATION	Allied Cleft & Craniofacial Quality-Improvement and Research Network (ACCQUIREnet)
NCT03537976	Not specified	ACTIVE_NOT_RECRUITING	Targeting Surgeons’ Decision-Making for Cleft Lip Surgery
NCT04342234	Not specified	RECRUITING	Neural Network to Calculate Morphology of the Cleft Palate to Reduce Cleft Lip and Palate Treatment Burden.
NCT05357092	Not specified	NOT_YET_RECRUITING	Effects of AlignBabyCleft (ABaCleft)
NCT06338319	Not specified	ENROLLING_BY_INVITATION	Book Sharing for Toddlers With Clefts
NCT06420336	Not specified	RECRUITING	QL vs LAI for Palatoplasty
NCT06477679	Not specified	NOT_YET_RECRUITING	Velopharyngeal Insufficiency Evaluation Post Cleft Palate Repair. Furlow With Buccinator Myomucosal Flap Versus Two Flap Palatoplasty
NCT06856330	Not specified	RECRUITING	Effect of Furlow Palatoplasty With Buccal Myomucosal Flap on the Speech Development
NCT06889181	Not specified	NOT_YET_RECRUITING	Role of Plasma Rich Growth Factor in Repair Primary Cleft Palate
NCT07219901	Not specified	NOT_YET_RECRUITING	Early Intervention in Infants With Unrepaired Cleft Palate: Language, Palatal Function, and Articulation.
NCT07514091	Not specified	NOT_YET_RECRUITING	MRI Assessment of Velopharyngeal Anatomy After Modified Furlow-Buccinator Flap in Late Primary Palate Repair
NCT00097149	Not specified	COMPLETED	Systematic Pediatric Care for Oral Clefts - South America
NCT00285714	Not specified	UNKNOWN	3D Imaging of Hard and Soft Tissue in Orthognathic Surgery
NCT00340977	Not specified	COMPLETED	Svangerskap, Arv, Og Miljo (Pregnancy, Heredity and Environment)
NCT00423072	Not specified	COMPLETED	Middle Ear Pressure Disregulation in Cleft Palate Patients
NCT00584272	Not specified	COMPLETED	Retrospective Study on the Outcome of Cleft Palate Repair: Comparing US Surgical and Ethicon Suture Materials
NCT00773994	Not specified	COMPLETED	Pilot Study Evaluating Characteristic Closure Patterns of the Normal Velopharyngeal Portal
NCT00779961	Not specified	UNKNOWN	An Investigation for the Optimal Timing of a Cleft Palate Repair
NCT00829101	Not specified	COMPLETED	Articulation and Phonology in Children With Unilateral Cleft Lip and Palate
NCT00993551	Not specified	COMPLETED	Timing of Primary Surgery for Cleft Palate
NCT00993993	Not specified	COMPLETED	Relational Development in Children With Cleft Lips and Palates: Influence of the Waiting Period Prior to the First Surgical Intervention and the Parents’ Psychological Perception of the Abnormality
NCT01046591	Not specified	COMPLETED	Sleep and Behavior in Children With Cleft Palate
NCT01252264	Not specified	COMPLETED	FaceBase Biorepository

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SODIUM CHLORIDE	4	4
BUPIVACAINE	4	1
HYDROMORPHONE	4	1
METHADONE HYDROCHLORIDE	4	1
TRANEXAMIC ACID	4	1
ESMETHADONE	3	1
IXMYELOCEL-T	3	1
SULTAMICILLIN	2	1