Multiple congenital anomalies/dysmorphic syndrome

Summary

Multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042) is a disease (an umbrella term covering 5 Mondo subtypes) caused by variants in PDIA6, UBA2, and WNT7B, with 54 cohort genes.

At a glance

• Causal genes: PDIA6 (GenCC Strong), UBA2 (GenCC Strong), WNT7B (GenCC Strong)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 54
• ClinVar variants: 28

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	multiple congenital anomalies/dysmorphic syndrome
Mondo ID	MONDO:0019042
Orphanet	68341
UMLS	C5681310
MedGen	1843247
GARD	0018876
Is cancer (heuristic)	no

Also known as: MCAHS

Data availability: 28 ClinVar variants · 32 GenCC gene-disease records.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › multiple congenital anomalies/dysmorphic syndrome

Related subtypes (51): disorder of sexual differentiation, hereditary neurocutaneous angioma, nevoid basal cell carcinoma syndrome, angioosteohypertrophic syndrome, Larsen syndrome, schwannomatosis, linear nevus sebaceous syndrome, lethal Larsen-like syndrome, pseudodiastrophic dysplasia, focal dermal hypoplasia, microtia, neurofibromatosis-Noonan syndrome, Becker nevus syndrome, Legius syndrome, bone fragility with contractures, arterial rupture, and deafness, blindness - scoliosis - arachnodactyly syndrome, cutis laxa - Marfanoid syndrome, Maffucci syndrome, hydrops fetalis, ankyloblepharon filiforme-imperforate anus syndrome, developmental anomaly of metabolic origin, progeroid syndrome, facial cleft, Desbuquois dysplasia, cysts and fistulae of the face and oral cavity, macroglossia, middle ear anomaly, cleft palate, cutis laxa, infectious embryofetopathy, toxic or drug-related embryofetopathy, hemihyperplasia-multiple lipomatosis syndrome, phakomatosis pigmentokeratotica, phakomatosis pigmentovascularis, PTEN hamartoma tumor syndrome, marfanoid habitus-inguinal hernia-advanced bone age syndrome, neurofibromatosis type 1, congenital limb malformation, hereditary hemorrhagic telangiectasia, urogenital tract malformation, congenital anomaly of kidney and urinary tract, anotia, central nervous system malformation, Ehlers-Danlos syndrome, X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome, joint laxity, short stature, and myopia, diaphragmatic malformation, abdominal wall malformation, port-wine nevi-mega cisterna magna-hydrocephalus syndrome, conjoined twins, TP63-related ectodermal dysplasia spectrum with limb and orofacial malformations

Subtypes (5): multiple congenital anomalies/dysmorphic syndrome-intellectual disability, multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome, multiple congenital anomalies/dysmorphic syndrome without intellectual disability, multiple congenital anomalies due to 14q32.2 imprinting defect, NR2F2 related multiple congenital anomalies/dysmorphic syndrome

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

28 retrieved; paginated sample, class counts are floors:

11 conflicting classifications of pathogenicity, 11 uncertain significance, 3 pathogenic, 2 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703662	GRCh37/hg19 6q27(chr6:168643852-170919482)	C6orf120	Pathogenic	no assertion criteria provided
2579262	GRCh38/hg38 7q22.1(chr7:98454022-100723798)x1	LAMTOR4	Pathogenic	criteria provided, single submitter
1699017	NM_006663.4(PPP1R13L):c.1068dup (p.Ser357fs)	PPP1R13L	Pathogenic	criteria provided, single submitter
1487825	NM_013275.6(ANKRD11):c.3442G>A (p.Gly1148Ser)	ANKRD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
572694	NM_001018113.3(FANCB):c.2342A>G (p.Glu781Gly)	FANCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
715241	NM_003922.4(HERC1):c.12096C>T (p.Val4032=)	HERC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
287524	NM_005529.7(HSPG2):c.4601C>G (p.Pro1534Arg)	HSPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
447549	NM_005529.7(HSPG2):c.3707C>A (p.Ala1236Glu)	HSPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
625995	NM_181523.3(PIK3R1):c.917-1513G>T	PIK3R1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3664384	NM_002653.5(PITX1):c.613A>C (p.Met205Leu)	PITX1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1981924	NM_006662.3(SRCAP):c.8518A>T (p.Ser2840Cys)	SRCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
837316	NM_001032221.6(STXBP1):c.145G>C (p.Asp49His)	STXBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3806268	NM_178548.4(TFAP2E):c.692C>T (p.Thr231Met)	TFAP2E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
259011	NM_003242.6(TGFBR2):c.1254+8A>G	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4075067	NM_001376.5(DYNC1H1):c.2546A>G (p.Asp849Gly)	DYNC1H1	Uncertain significance	criteria provided, single submitter
4074820	NM_006494.4(ERF):c.1448G>A (p.Arg483His)	ERF	Uncertain significance	criteria provided, single submitter
4074937	NM_003922.4(HERC1):c.7883A>C (p.Gln2628Pro)	HERC1	Uncertain significance	criteria provided, single submitter
4075006	NM_015425.6(POLR1A):c.1840A>G (p.Thr614Ala)	LOC126806264	Uncertain significance	criteria provided, single submitter
4075117	NM_004333.6(BRAF):c.1014A>C (p.Lys338Asn)	LOC126860202	Uncertain significance	criteria provided, single submitter
4075272	NM_019066.5(MAGEL2):c.593C>G (p.Pro198Arg)	MAGEL2	Uncertain significance	criteria provided, single submitter
4070908	Single allele	MCRS1	Uncertain significance	criteria provided, single submitter
4070915	NM_006337.5(MCRS1):c.805+71_805+74del	MCRS1	Uncertain significance	criteria provided, single submitter
4074886	NM_016148.5(SHANK1):c.1918G>A (p.Asp640Asn)	SHANK1	Uncertain significance	criteria provided, single submitter
805480	NM_004172.5(SLC1A3):c.1259A>G (p.Glu420Gly)	SLC1A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
4074812	NM_005445.4(SMC3):c.1444G>A (p.Ala482Thr)	SMC3	Uncertain significance	criteria provided, single submitter
331698	NM_001111067.4(ACVR1):c.141C>G (p.His47Gln)	ACVR1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
3350676	NM_004380.3(CREBBP):c.1624C>T (p.Pro542Ser)	CREBBP	Likely benign	criteria provided, single submitter
4074837	NM_001291415.2(KDM6A):c.3983A>G (p.Asn1328Ser)	KDM6A	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 80 · Orphanet: 57 · 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
ARHGAP35	Strong	Autosomal dominant	congenital hypogonadotropic hypogonadism	7
OTUD5	Strong	X-linked	multiple congenital anomalies-neurodevelopmental syndrome, X-linked	4
PDIA6	Strong	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome
UBA2	Strong	Autosomal dominant	multiple congenital anomalies/dysmorphic syndrome	5
WNT7B	Strong	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome	3
BMP7	Moderate	Autosomal dominant	multiple congenital anomalies/dysmorphic syndrome	5
ISLR2	Moderate	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome
NUDCD2	Moderate	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome
PRDM15	Moderate	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome
SEMA3A	Moderate	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome	7
CLTCL1	Supportive	Autosomal recessive	congenital insensitivity to pain with severe intellectual disability	2
NTN1	Supportive	Autosomal dominant	familial congenital mirror movements	5
AAR2	Limited	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome
BAZ1A	Limited	Autosomal dominant	multiple congenital anomalies/dysmorphic syndrome
BRD4	Limited	Autosomal dominant	multiple congenital anomalies/dysmorphic syndrome	4
C16orf90	Limited	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome
CDH4	Limited	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome
KAT14	Limited	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome
KCTD10	Limited	Autosomal dominant	multiple congenital anomalies/dysmorphic syndrome
KIF26B	Limited	Autosomal dominant	multiple congenital anomalies/dysmorphic syndrome
OSBPL9	Limited	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome	2
RARA	Limited	Autosomal dominant	multiple congenital anomalies/dysmorphic syndrome	3
SLC35F5	Limited	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome
SREBF2	Limited	Autosomal dominant	multiple congenital anomalies/dysmorphic syndrome	3
SYDE2	Limited	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome
TFAP2E	Limited	Autosomal dominant	multiple congenital anomalies/dysmorphic syndrome
THSD1	Limited	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome	8
UBE4A	Limited	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome	5
ZMYM5	Limited	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome
ZNF3	Limited	Autosomal recessive	multiple congenital anomalies/dysmorphic syndrome

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SEMA3A	Orphanet:130	Brugada syndrome
SEMA3A	Orphanet:478	Kallmann syndrome
UBE4A	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
WNT7B	Orphanet:2470	Matthew-Wood syndrome
BRD4	Orphanet:199	Cornelia de Lange syndrome
BRD4	Orphanet:443167	NUT midline carcinoma
THSD1	Orphanet:231160	Familial cerebral saccular aneurysm
THSD1	Orphanet:363999	Non-immune hydrops fetalis
CLTCL1	Orphanet:453510	Congenital insensitivity to pain with severe intellectual disability
OTUD5	Orphanet:528084	Non-specific syndromic intellectual disability
UBA2	Orphanet:1114	Aplasia cutis congenita
NTN1	Orphanet:238722	Familial congenital mirror movements
RARA	Orphanet:520	Acute promyelocytic leukemia
SLC1A3	Orphanet:209967	Episodic ataxia type 6
SLC1A3	Orphanet:2131	Alternating hemiplegia of childhood
STXBP1	Orphanet:495818	9q33.3q34.11 microdeletion syndrome
STXBP1	Orphanet:599373	STXBP1-related encephalopathy
TGFBR2	Orphanet:144	Lynch syndrome
TGFBR2	Orphanet:284973	Marfan syndrome type 2
TGFBR2	Orphanet:60030	Loeys-Dietz syndrome
TGFBR2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
TGFBR2	Orphanet:99977	Squamous cell carcinoma of the esophagus
KDM6A	Orphanet:2322	Kabuki syndrome
SRCAP	Orphanet:2044	Floating-Harbor syndrome
SRCAP	Orphanet:528084	Non-specific syndromic intellectual disability
ACVR1	Orphanet:337	Fibrodysplasia ossificans progressiva
ANKRD11	Orphanet:2332	KBG syndrome
ANKRD11	Orphanet:261250	16q24.3 microdeletion syndrome
CREBBP	Orphanet:353277	Rubinstein-Taybi syndrome due to CREBBP mutations
CREBBP	Orphanet:353281	Rubinstein-Taybi syndrome due to 16p13.3 microdeletion
CREBBP	Orphanet:370026	Acute myeloid leukemia with t(8;16)(p11;p13) translocation
CREBBP	Orphanet:592574	Menke-Hennekam syndrome
SMC3	Orphanet:199	Cornelia de Lange syndrome
DYNC1H1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
DYNC1H1	Orphanet:209341	DYNC1H1-related autosomal dominant childhood-onset proximal spinal muscular atrophy
DYNC1H1	Orphanet:284232	Autosomal dominant Charcot-Marie-Tooth disease type 2O
ERF	Orphanet:207	Crouzon syndrome
ERF	Orphanet:647681	Craniosynostosis-facial dysmorphism-Chiari-1 malformation-developmental and language delay syndrome
FANCB	Orphanet:3412	VACTERL with hydrocephalus
FANCB	Orphanet:84	Fanconi anemia
HERC1	Orphanet:457359	Megalencephaly-severe kyphoscoliosis-overgrowth syndrome
HSPG2	Orphanet:1606	1p36 deletion syndrome
HSPG2	Orphanet:1865	Dyssegmental dysplasia, Silverman-Handmaker type
HSPG2	Orphanet:800	Schwartz-Jampel syndrome
MAGEL2	Orphanet:177901	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1
MAGEL2	Orphanet:177904	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2
MAGEL2	Orphanet:177910	Prader-Willi syndrome due to imprinting mutation
MAGEL2	Orphanet:398069	Schaaf-Yang syndrome
MAGEL2	Orphanet:98754	Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15
MAGEL2	Orphanet:994	Fetal akinesia deformation sequence

Cohort genes → proteins

54 cohort genes, 54 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	54

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TFAP2E	HGNC:30774	ENSG00000116819	Q6VUC0	Transcription factor AP-2-epsilon	gencc,clinvar
SEMA3A	HGNC:10723	ENSG00000075213	Q14563	Semaphorin-3A	gencc
BMP7	HGNC:1074	ENSG00000101144	P18075	Bone morphogenetic protein 7	gencc
SREBF2	HGNC:11290	ENSG00000198911	Q12772	Sterol regulatory element-binding protein 2	gencc
UBE4A	HGNC:12499	ENSG00000110344	Q14139	Ubiquitin conjugation factor E4 A	gencc
WNT7B	HGNC:12787	ENSG00000188064	P56706	Protein Wnt-7b	gencc
ZMYM5	HGNC:13029	ENSG00000132950	Q9UJ78	Zinc finger MYM-type protein 5	gencc
ZNF3	HGNC:13089	ENSG00000166526	P17036	Zinc finger protein 3	gencc
BRD4	HGNC:13575	ENSG00000141867	O60885	Bromodomain-containing protein 4	gencc
PRDM15	HGNC:13999	ENSG00000141956	P57071	PR domain zinc finger protein 15	gencc
AAR2	HGNC:15886	ENSG00000131043	Q9Y312	Protein AAR2 homolog	gencc
KAT14	HGNC:15904	ENSG00000149474	Q9H8E8	Cysteine-rich protein 2-binding protein	gencc
OSBPL9	HGNC:16386	ENSG00000117859	Q96SU4	Oxysterol-binding protein-related protein 9	gencc
CDH4	HGNC:1763	ENSG00000179242	P55283	Cadherin-4	gencc
THSD1	HGNC:17754	ENSG00000136114	Q9NS62	Thrombospondin type-1 domain-containing protein 1	gencc
CLTCL1	HGNC:2093	ENSG00000070371	P53675	Clathrin heavy chain 2	gencc
KCTD10	HGNC:23236	ENSG00000110906	Q9H3F6	BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 3	gencc
SLC35F5	HGNC:23617	ENSG00000115084	Q8WV83	Solute carrier family 35 member F5	gencc
OTUD5	HGNC:25402	ENSG00000068308	Q96G74	OTU domain-containing protein 5	gencc
KIF26B	HGNC:25484	ENSG00000162849	Q2KJY2	Kinesin-like protein KIF26B	gencc
ZYG11B	HGNC:25820	ENSG00000162378	Q9C0D3	Protein zyg-11 homolog B	gencc
SYDE2	HGNC:25841	ENSG00000097096	Q5VT97	Rho GTPase-activating protein SYDE2	gencc
ISLR2	HGNC:29286	ENSG00000167178	Q6UXK2	Immunoglobulin superfamily containing leucine-rich repeat protein 2	gencc
PDIA6	HGNC:30168	ENSG00000143870	Q15084	Protein disulfide-isomerase A6	gencc
NUDCD2	HGNC:30535	ENSG00000170584	Q8WVJ2	NudC domain-containing protein 2	gencc
UBA2	HGNC:30661	ENSG00000126261	Q9UBT2	SUMO-activating enzyme subunit 2	gencc
C16orf90	HGNC:34455	ENSG00000215131	A8MZG2	Uncharacterized protein C16orf90	gencc
ARHGAP35	HGNC:4591	ENSG00000160007	Q9NRY4	Rho GTPase-activating protein 35	gencc
NTN1	HGNC:8029	ENSG00000065320	O95631	Netrin-1	gencc
BAZ1A	HGNC:960	ENSG00000198604	Q9NRL2	Bromodomain adjacent to zinc finger domain protein 1A	gencc
RARA	HGNC:9864	ENSG00000131759	P10276	Retinoic acid receptor alpha	gencc
SLC1A3	HGNC:10941	ENSG00000079215	P43003	Excitatory amino acid transporter 1	clinvar
STXBP1	HGNC:11444	ENSG00000136854	P61764	Syntaxin-binding protein 1	clinvar
TGFBR2	HGNC:11773	ENSG00000163513	P37173	TGF-beta receptor type-2	clinvar
KDM6A	HGNC:12637	ENSG00000147050	O15550	Lysine-specific demethylase 6A	clinvar
SHANK1	HGNC:15474	ENSG00000161681	Q9Y566	SH3 and multiple ankyrin repeat domains protein 1	clinvar
SRCAP	HGNC:16974	ENSG00000080603	Q6ZRS2	Chromatin remodeling protein SRCAP	clinvar
ACVR1	HGNC:171	ENSG00000115170	Q04771	Activin receptor type-1	clinvar
PPP1R13L	HGNC:18838	ENSG00000104881	Q8WUF5	RelA-associated inhibitor	clinvar
C6orf120	HGNC:21247	ENSG00000185127	Q7Z4R8	UPF0669 protein C6orf120	clinvar
ANKRD11	HGNC:21316	ENSG00000167522	Q6UB99	Ankyrin repeat domain-containing protein 11	clinvar
CREBBP	HGNC:2348	ENSG00000005339	Q92793	CREB-binding protein	clinvar
SMC3	HGNC:2468	ENSG00000108055	Q9UQE7	Structural maintenance of chromosomes protein 3	clinvar
DYNC1H1	HGNC:2961	ENSG00000197102	Q14204	Cytoplasmic dynein 1 heavy chain 1	clinvar
LAMTOR4	HGNC:33772	ENSG00000188186	Q0VGL1	Ragulator complex protein LAMTOR4	clinvar
ERF	HGNC:3444	ENSG00000105722	P50548	ETS domain-containing transcription factor ERF	clinvar
ETF1	HGNC:3477	ENSG00000120705	P62495	Eukaryotic peptide chain release factor subunit 1	clinvar
FANCB	HGNC:3583	ENSG00000181544	Q8NB91	Fanconi anemia group B protein	clinvar
HERC1	HGNC:4867	ENSG00000103657	Q15751	Probable E3 ubiquitin-protein ligase HERC1	clinvar
HSPG2	HGNC:5273	ENSG00000142798	P98160	Basement membrane-specific heparan sulfate proteoglycan core protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TFAP2E	Transcription factor AP-2-epsilon	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
SEMA3A	Semaphorin-3A	Involved in the development of the olfactory system and in neuronal control of puberty.
BMP7	Bone morphogenetic protein 7	Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis.
SREBF2	Sterol regulatory element-binding protein 2	Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 2), which is embedded in the endoplasmic reticulum membrane.
UBE4A	Ubiquitin conjugation factor E4 A	Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases.
WNT7B	Protein Wnt-7b	Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway.
ZMYM5	Zinc finger MYM-type protein 5	Functions as a transcriptional regulator.
ZNF3	Zinc finger protein 3	Involved in cell differentiation and/or proliferation.
BRD4	Bromodomain-containing protein 4	Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation.
PRDM15	PR domain zinc finger protein 15	Sequence-specific DNA-binding transcriptional regulator.
AAR2	Protein AAR2 homolog	Component of the U5 snRNP complex that is required for spliceosome assembly and for pre-mRNA splicing.
KAT14	Cysteine-rich protein 2-binding protein	Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4.
OSBPL9	Oxysterol-binding protein-related protein 9	Interacts with OSBPL11 to function as lipid transfer proteins.
CDH4	Cadherin-4	Cadherins are calcium-dependent cell adhesion proteins.
THSD1	Thrombospondin type-1 domain-containing protein 1	Is a positive regulator of nascent focal adhesion assembly, involved in the modulation of endothelial cell attachment to the extracellular matrix.
CLTCL1	Clathrin heavy chain 2	Clathrin is the major protein of the polyhedral coat of coated pits and vesicles.
KCTD10	BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 3	Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex.
SLC35F5	Solute carrier family 35 member F5	Putative solute transporter.
OTUD5	OTU domain-containing protein 5	Deubiquitinating enzyme that functions as a negative regulator of the innate immune system.
KIF26B	Kinesin-like protein KIF26B	Essential for embryonic kidney development.
ZYG11B	Protein zyg-11 homolog B	Serves as substrate adapter subunit in the E3 ubiquitin ligase complex ZYG11B-CUL2-Elongin BC.
SYDE2	Rho GTPase-activating protein SYDE2	GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.
ISLR2	Immunoglobulin superfamily containing leucine-rich repeat protein 2	Required for axon extension during neural development.
PDIA6	Protein disulfide-isomerase A6	May function as a chaperone that inhibits aggregation of misfolded proteins.
NUDCD2	NudC domain-containing protein 2	May regulate the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone.
UBA2	SUMO-activating enzyme subunit 2	The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4.
ARHGAP35	Rho GTPase-activating protein 35	Rho GTPase-activating protein (GAP).
NTN1	Netrin-1	Netrins control guidance of CNS commissural axons and peripheral motor axons.
BAZ1A	Bromodomain adjacent to zinc finger domain protein 1A	Regulatory subunit of the ATP-dependent ACF-1 and ACF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and slide edge- and center-positioned histone octamers away from their original location on the…
RARA	Retinoic acid receptor alpha	Receptor for retinoic acid.
SLC1A3	Excitatory amino acid transporter 1	Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate.
STXBP1	Syntaxin-binding protein 1	Participates in the regulation of synaptic vesicle docking and fusion through interaction with GTP-binding proteins.
TGFBR2	TGF-beta receptor type-2	Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.
KDM6A	Lysine-specific demethylase 6A	Histone demethylase that specifically demethylates ‘Lys-27’ of histone H3, thereby playing a central role in histone code.
SHANK1	SH3 and multiple ankyrin repeat domains protein 1	Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and H…
SRCAP	Chromatin remodeling protein SRCAP	Acts both as a chromatin remodeler and transcription coregulator.
ACVR1	Activin receptor type-1	Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation.
PPP1R13L	RelA-associated inhibitor	Regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins.
C6orf120	UPF0669 protein C6orf120	May be involved in induction of apoptosis in CD4(+) T-cells, but not CD8(+) T-cells or hepatocytes.
ANKRD11	Ankyrin repeat domain-containing protein 11	Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells.
CREBBP	CREB-binding protein	Acetylates histones, giving a specific tag for transcriptional activation.
SMC3	Structural maintenance of chromosomes protein 3	Central component of cohesin, a complex required for chromosome cohesion during the cell cycle.
DYNC1H1	Cytoplasmic dynein 1 heavy chain 1	Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules.
LAMTOR4	Ragulator complex protein LAMTOR4	As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids.
ERF	ETS domain-containing transcription factor ERF	Potent transcriptional repressor that binds to the H1 element of the Ets2 promoter.
ETF1	Eukaryotic peptide chain release factor subunit 1	Component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons.
FANCB	Fanconi anemia group B protein	DNA repair protein required for FANCD2 ubiquitination.
HERC1	Probable E3 ubiquitin-protein ligase HERC1	Involved in membrane trafficking via some guanine nucleotide exchange factor (GEF) activity and its ability to bind clathrin.
HSPG2	Basement membrane-specific heparan sulfate proteoglycan core protein	Integral component of basement membranes.
MAGEL2	MAGE-like protein 2	Probably enhances ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases, possibly through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex.

Protein-family classification

Druggable: 10 · Difficult: 14 · Unknown: 30 · Druggable fraction: 0.19

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
Nuclear receptor	1	7.2×	0.494
Antibody/Immunoglobulin	3	1.6×	0.494
Scaffold/PPI	5	1.6×	0.494
Kinase	3	1.5×	0.494
Transcription factor	9	1.4×	0.494
Other/Unknown	30	1.0×	0.762
Protease	1	0.7×	0.887
Enzyme (other)	2	0.4×	0.947

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TFAP2E	Transcription factor	no		TF_AP2, TF_AP2_C
SEMA3A	Antibody/Immunoglobulin	yes		Semap_dom, Ig_sub, Ig-like_dom
BMP7	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
SREBF2	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf
UBE4A	Transcription factor	no	2.3.2.27	Ubox_domain, Znf_RING/FYVE/PHD, Ub_conjug_fac_E4_core
WNT7B	Other/Unknown	no		Wnt, Wnt7, Wnt_CS
ZMYM5	Transcription factor	no		Znf_MYM, TRASH_dom, ZnF_MYMT-QRICH1
ZNF3	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
BRD4	Other/Unknown	no		Bromodomain, Bromodomain_CS, NET_dom
PRDM15	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
AAR2	Other/Unknown	no		AAR2, Aar2_N, AAR2_C
KAT14	Enzyme (other)	yes	2.3.1.48	GNAT_dom, Acyl_CoA_acyltransferase
OSBPL9	Scaffold/PPI	no		Oxysterol-bd, PH_domain, PH-like_dom_sf
CDH4	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
THSD1	Other/Unknown	no		TSP1_rpt, TSP1_rpt_sf, THSD1
CLTCL1	Other/Unknown	no		Clathrin_H-chain/VPS_repeat, TPR-like_helical_dom_sf, Clathrin_H-chain_linker_core
KCTD10	Other/Unknown	no		BTB/POZ_dom, T1-type_BTB, SKP1/BTB/POZ_sf
SLC35F5	Other/Unknown	no		EmrE-like
OTUD5	Protease	yes		OTU_dom, Papain-like_cys_pep_sf, Peptidase_C85-like
KIF26B	Other/Unknown	no		Kinesin_motor_dom, P-loop_NTPase, Kinesin-like_fam
ZYG11B	Other/Unknown	no		Leu-rich_rpt, ARM-like, ARM-type_fold
SYDE2	Other/Unknown	no		C2_dom, RhoGAP_dom, Rho_GTPase_activation_prot
ISLR2	Antibody/Immunoglobulin	yes		Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
PDIA6	Other/Unknown	no		PDI_thioredoxin-like_dom, Thioredoxin_domain, Thioredoxin_CS
NUDCD2	Other/Unknown	no		CS_dom, HSP20-like_chaperone, NudC_fam
UBA2	Other/Unknown	no		ThiF_NAD_FAD-bd, UBQ-activ_enz_E1_CS, Ub_act_enz_dom_a_sf
C16orf90	Other/Unknown	no		DUF4644
ARHGAP35	Other/Unknown	no		RhoGAP_dom, Small_GTPase, FF_domain
NTN1	Other/Unknown	no		Netrin_domain, LE_dom, Laminin_N
BAZ1A	Transcription factor	no		Bromodomain, Znf_PHD, Znf_FYVE_PHD
RARA	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
SLC1A3	Other/Unknown	no		Na-dicarboxylate_symporter, Na-dicarboxylate_symporter_CS, Na:dicarbo_symporter_sf
STXBP1	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
TGFBR2	Kinase	yes	2.7.10.2	TGFB_receptor, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
KDM6A	Enzyme (other)	yes	1.14.11.68	JmjC_dom, TPR-like_helical_dom_sf, TPR_rpt
SHANK1	Scaffold/PPI	no		SH3_domain, PDZ, SAM
SRCAP	Other/Unknown	no		SNF2_N, Helicase_C-like, Helicase_ATP-bd
ACVR1	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
PPP1R13L	Scaffold/PPI	no		SH3_domain, Ankyrin_rpt, iASPP
C6orf120	Other/Unknown	no		UPF0669
ANKRD11	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, ANKRD11
CREBBP	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
SMC3	Other/Unknown	no		RecF/RecN/SMC_N, SMC_hinge, SMC
DYNC1H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
LAMTOR4	Other/Unknown	no		LAMTOR4
ERF	Other/Unknown	no		Ets_dom, WH-like_DNA-bd_sf, WH_DNA-bd_sf
ETF1	Other/Unknown	no		Peptide_chain-rel_eRF1/aRF1, eRF1_Pelota-like_N, eRF1_2
FANCB	Other/Unknown	no		FANCB
HERC1	Scaffold/PPI	no		Reg_chr_condens, HECT_dom, WD40_rpt
HSPG2	Antibody/Immunoglobulin	yes		Laminin_IV, SEA_dom, EGF

Expression context

Cohort genes with no expression data: 0.

48 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)	54
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	11
ganglionic eminence	7
secondary oocyte	6
cortical plate	5
oocyte	5
sural nerve	5
stromal cell of endometrium	4
Brodmann (1909) area 23	4
middle temporal gyrus	4
buccal mucosa cell	4
tendon of biceps brachii	4
adrenal tissue	4
granulocyte	4
primordial germ cell in gonad	3
calcaneal tendon	3
male germ line stem cell (sensu Vertebrata) in testis	3
pigmented layer of retina	2
endothelial cell	2
right uterine tube	2
lower esophagus muscularis layer	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TFAP2E	170	tissue_specific	yes	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
SEMA3A	194	ubiquitous	marker	stromal cell of endometrium, cortical plate, colonic epithelium
BMP7	243	broad	marker	pigmented layer of retina, ventricular zone, endometrium epithelium
SREBF2	287	ubiquitous	marker	ganglionic eminence, cortical plate, ventricular zone
UBE4A	298	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, middle temporal gyrus
WNT7B	122	broad	marker	vena cava, buccal mucosa cell, parotid gland
ZMYM5	264	ubiquitous	yes	buccal mucosa cell, secondary oocyte, oocyte
ZNF3	264	ubiquitous	marker	right uterine tube, ganglionic eminence, secondary oocyte
BRD4	300	ubiquitous	marker	buccal mucosa cell, sural nerve, tendon of biceps brachii
PRDM15	221	ubiquitous	marker	sural nerve, ileal mucosa, primordial germ cell in gonad
AAR2	262	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, smooth muscle tissue
KAT14	247	ubiquitous	marker	deltoid, kidney epithelium, quadriceps femoris
OSBPL9	288	ubiquitous	marker	calcaneal tendon, right lung, popliteal artery
CDH4	118	broad	yes	ventricular zone, ganglionic eminence, adrenal tissue
THSD1	138	broad	marker	ventricular zone, right lung, apex of heart
CLTCL1	208	ubiquitous	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle
KCTD10	258	ubiquitous	marker	epithelial cell of pancreas, tendon of biceps brachii, secondary oocyte
SLC35F5	271	ubiquitous	marker	adrenal tissue, parietal pleura, jejunal mucosa
OTUD5	259	ubiquitous	marker	upper arm skin, cardiac muscle of right atrium, granulocyte
KIF26B	113	ubiquitous	marker	ventricular zone, ganglionic eminence, stromal cell of endometrium
ZYG11B	262	ubiquitous	marker	deltoid, vastus lateralis, tibialis anterior
SYDE2	166	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, muscle layer of sigmoid colon
ISLR2	154	broad	marker	cortical plate, ganglionic eminence, ventricular zone
PDIA6	295	ubiquitous	marker	corpus epididymis, adrenal tissue, islet of Langerhans
NUDCD2	252	ubiquitous	marker	oocyte, ventricular zone, secondary oocyte
UBA2	204	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
C16orf90	21	tissue_specific	yes	left testis, right testis, testis
ARHGAP35	277	ubiquitous	marker	Brodmann (1909) area 23, endothelial cell, middle temporal gyrus
NTN1	218	broad	marker	mucosa of stomach, right atrium auricular region, lower esophagus muscularis layer
BAZ1A	280	ubiquitous	marker	sperm, oocyte, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 13.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KDM6A	8,825
BRD4	7,883
CREBBP	6,959
TGFBR2	5,777
PIK3R1	5,168
SMC3	5,056
DYNC1H1	4,215
UBA2	3,886
RARA	3,885
SHANK1	3,605

Intra-cohort edges

A	B	Sources
ACVR1	BMP7	string_interaction
ANKRD11	SMC3	string_interaction
C16orf90	SYDE2	string_interaction
C16orf90	ZMYM5	string_interaction
CLTCL1	HERC1	string_interaction
CREBBP	PPP1R13L	biogrid_interaction
CREBBP	RARA	biogrid_interaction
CREBBP	SRCAP	string_interaction
CREBBP	SREBF2	intact
ERF	MCRS1	intact
KCTD10	PDIA6	intact
NTN1	SEMA3A	string_interaction
PIK3R1	TGFBR2	biogrid_interaction

Structural data

PDB: 33 · AlphaFold-only: 21 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRD4	O60885	619
CREBBP	Q92793	144
PIK3R1	P27986	105
DYNC1H1	Q14204	97
ACVR1	Q04771	85
ETF1	P62495	33
LAMTOR4	Q0VGL1	25
TGFBR2	P37173	22
UBA2	Q9UBT2	16
ZYG11B	Q9C0D3	14
RARA	P10276	14
SMC3	Q9UQE7	12
SRCAP	Q6ZRS2	10
SLC1A3	P43003	9
SHANK1	Q9Y566	7
PDIA6	Q15084	6
ARHGAP35	Q9NRY4	6
FANCB	Q8NB91	6
NTN1	O95631	5
KDM6A	O15550	5
PPP1R13L	Q8WUF5	5
BMP7	P18075	4
OTUD5	Q96G74	3
ERF	P50548	2
HERC1	Q15751	2
HSPG2	P98160	2
SREBF2	Q12772	1
UBE4A	Q14139	1
ZMYM5	Q9UJ78	1
AAR2	Q9Y312	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT7B	P56706	90.71
SEMA3A	Q14563	84.50
NUDCD2	Q8WVJ2	83.68
C6orf120	Q7Z4R8	81.00
CDH4	P55283	79.02
CLTCL1	P53675	77.53
OSBPL9	Q96SU4	77.10
MCRS1	Q96EZ8	75.90
SLC35F5	Q8WV83	72.79
TFAP2E	Q6VUC0	68.25
KAT14	Q9H8E8	67.36
ISLR2	Q6UXK2	67.24
ZNF3	P17036	66.67
PITX1	P78337	62.81
THSD1	Q9NS62	59.46
PRDM15	P57071	56.66
C16orf90	A8MZG2	54.52
SYDE2	Q5VT97	51.94
KIF26B	Q2KJY2	45.94
MAGEL2	Q9UJ55	44.28
ANKRD11	Q6UB99	39.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 387. Enrichment computed across 54 evidence-associated genes (39 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 39 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of the TFAP2 (AP-2) family of transcription factors	2	48.8×	0.112	TFAP2E, CREBBP
Maternal to zygotic transition (MZT)	2	36.6×	0.112	KDM6A, CREBBP
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	2	32.5×	0.112	TFAP2E, CREBBP
Formation of WDR5-containing histone-modifying complexes	3	20.4×	0.112	KDM6A, KAT14, MCRS1
SUMOylation	3	12.6×	0.112	CREBBP, SMC3, UBA2
Adipogenesis	3	12.0×	0.112	BMP7, SREBF2, CREBBP
Epigenetic regulation by WDR5-containing histone modifying complexes	3	11.9×	0.112	KDM6A, CREBBP, MCRS1
Defective SLC1A3 causes episodic ataxia 6 (EA6)	1	292.8×	0.136	SLC1A3
Glutamate Neurotransmitter Release Cycle	2	23.4×	0.136	SLC1A3, STXBP1
Activation of HOX genes during differentiation	2	22.5×	0.136	KDM6A, CREBBP
TGFBR2 MSI Frameshift Mutants in Cancer	1	146.4×	0.164	TGFBR2
Loss of Function of TGFBR2 in Cancer	1	97.6×	0.164	TGFBR2
TGFBR2 Kinase Domain Mutants in Cancer	1	97.6×	0.164	TGFBR2
TGFBR1 LBD Mutants in Cancer	1	73.2×	0.164	TGFBR2
SUMO is conjugated to E1 (UBA2:SAE1)	1	58.6×	0.164	UBA2
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	58.6×	0.164	CREBBP
Loss of Function of TGFBR1 in Cancer	1	58.6×	0.164	TGFBR2
DSCAM interactions	1	58.6×	0.164	NTN1
NFE2L2 regulating inflammation associated genes	1	58.6×	0.164	CREBBP
NFE2L2 regulating ER-stress associated genes	1	58.6×	0.164	CREBBP
SLC-mediated transport of amino acids	1	58.6×	0.164	SLC1A3
Astrocytic Glutamate-Glutamine Uptake And Metabolism	1	48.8×	0.164	SLC1A3
Loss of Function of SMAD2/3 in Cancer	1	48.8×	0.164	TGFBR2
Signaling by TGF-beta Receptor Complex in Cancer	1	48.8×	0.164	TGFBR2
SMAD2/3 Phosphorylation Motif Mutants in Cancer	1	48.8×	0.164	TGFBR2
TGFBR1 KD Mutants in Cancer	1	48.8×	0.164	TGFBR2
MET activates PI3K/AKT signaling	1	48.8×	0.164	PIK3R1
Activated NTRK3 signals through PI3K	1	48.8×	0.164	PIK3R1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	2	16.3×	0.164	SREBF2, CREBBP
Protein-protein interactions at synapses	2	13.6×	0.164	STXBP1, SHANK1

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
endocardial cushion fusion	2	129.6×	0.035	TGFBR2, ACVR1
chorio-allantoic fusion	2	81.0×	0.035	BMP7, WNT7B
homeostatic process	2	64.8×	0.035	WNT7B, CREBBP
endocardial cushion formation	2	54.0×	0.035	BMP7, ACVR1
cAMP/PKA signal transduction	2	54.0×	0.035	SRCAP, CREBBP
positive regulation of axon extension	3	29.5×	0.035	CDH4, ISLR2, NTN1
positive regulation of SMAD protein signal transduction	3	22.1×	0.035	BMP7, TGFBR2, ACVR1
regulation of DNA replication	3	21.1×	0.035	SMC3, MCRS1, BAZ1A
neuromuscular process controlling balance	3	19.1×	0.035	SLC1A3, SHANK1, HERC1
positive regulation of transcription by RNA polymerase II	11	3.1×	0.035	TFAP2E, BMP7, SREBF2, BRD4, PRDM15, SRCAP, ACVR1, CREBBP (+3 more)
atrioventricular valve morphogenesis	2	46.3×	0.037	TGFBR2, ACVR1
embryonic camera-type eye development	2	46.3×	0.037	PPP1R13L, RARA
chromatin remodeling	5	7.0×	0.037	KDM6A, BRD4, SRCAP, MCRS1, BAZ1A
positive regulation of tolerance induction to self antigen	1	324.1×	0.046	TGFBR2
positive regulation of B cell tolerance induction	1	324.1×	0.046	TGFBR2
regulation of heterochromatin formation	1	324.1×	0.046	BAZ1A
regulation of cell projection size	1	324.1×	0.046	WNT7B
chemoattraction of dopaminergic neuron axon	1	324.1×	0.046	WNT7B
determination of affect	1	324.1×	0.046	SHANK1
Sertoli cell fate commitment	1	324.1×	0.046	RARA
lobar bronchus development	1	324.1×	0.046	WNT7B
endocardial cushion cell fate commitment	1	324.1×	0.046	ACVR1
negative regulation of mesenchymal cell apoptotic process involved in nephron morphogenesis	1	324.1×	0.046	BMP7
outer medullary collecting duct development	1	324.1×	0.046	WNT7B
obsolete positive regulation of vesicle docking	1	324.1×	0.046	STXBP1
mesenchymal cell apoptotic process involved in nephron morphogenesis	1	324.1×	0.046	BMP7
inferior endocardial cushion morphogenesis	1	324.1×	0.046	TGFBR2
regulation of acrosomal vesicle exocytosis	1	324.1×	0.046	STXBP1
activin receptor signaling pathway	2	34.1×	0.046	TGFBR2, ACVR1
pharyngeal system development	2	30.9×	0.046	BMP7, ACVR1

Therapeutics

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 9 · Phased (≥1): 12 · Undrugged: 42

Druggability breadth: 23 of 54 evidence-associated genes (43%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

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

Symbol	Example approved molecule
BRD4	ACETAMINOPHEN
RARA	BEXAROTENE
TGFBR2	PONATINIB
KDM6A	DEFERIPRONE
ACVR1	MOMELOTINIB
CREBBP	COLCHICINE
PIK3R1	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ACVR1	39	4
BRD4	31	4
PIK3R1	26	4
TGFBR2	22	4
CREBBP	13	4
RARA	11	4
UBA2	3	3
SLC1A3	2	3
KDM6A	1	4
SMC3	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ACETAMINOPHEN	4	BRD4
FEDRATINIB	4	ACVR1, BRD4, TGFBR2
NITROXOLINE	4	BRD4
ROMIDEPSIN	4	BRD4
BELINOSTAT	4	BRD4
PANOBINOSTAT	4	BRD4
ALPRAZOLAM	4	BRD4
LENALIDOMIDE	4	BRD4
NORFLOXACIN	4	BRD4
VORINOSTAT	4	BRD4
BEXAROTENE	4	RARA
ADAPALENE	4	RARA
TAZAROTENE	4	RARA
TAMIBAROTENE	4	RARA
TRIFAROTENE	4	RARA
TRETINOIN	4	RARA
ALITRETINOIN	4	RARA
PONATINIB	4	TGFBR2
VEMURAFENIB	4	TGFBR2
SORAFENIB	4	TGFBR2
DABRAFENIB	4	TGFBR2
TOVORAFENIB	4	TGFBR2
PAZOPANIB	4	TGFBR2
DASATINIB	4	ACVR1, TGFBR2
DEFERIPRONE	4	KDM6A
MOMELOTINIB	4	ACVR1
PACRITINIB	4	ACVR1
VANDETANIB	4	ACVR1
LORLATINIB	4	ACVR1
GILTERITINIB	4	ACVR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
BRD4	4,603	Binding:4569, Functional:30, ADMET:4
CREBBP	687	Binding:644, Functional:43
PIK3R1	493	Binding:470, ADMET:23
RARA	368	Binding:279, Functional:85, ADMET:4
ACVR1	299	Binding:293, Functional:4, ADMET:2
TGFBR2	188	Binding:188
SLC1A3	47	Binding:38, Functional:9
KDM6A	40	Binding:36, Functional:4
UBA2	32	Binding:30, Functional:2
SREBF2	22	Binding:22
PDIA6	13	Binding:12, Functional:1
ZYG11B	12	Binding:12
BAZ1A	10	Binding:10
SMC3	7	Binding:7
DYNC1H1	7	Binding:7
MCRS1	6	Binding:6
HSPG2	2	Binding:2
UBE4A	1	Binding:1
OTUD5	1	Binding:1
ARHGAP35	1	Binding:1
NTN1	1	Binding:1
STXBP1	1	Binding:1
ETF1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UBE4A	2.3.2.27, 2.3.2.B12	RING-type E3 ubiquitin transferase,
KAT14	2.3.1.48	histone acetyltransferase
TGFBR2	2.7.10.2	non-specific protein-tyrosine kinase
KDM6A	1.14.11.68	[histone H3]-trimethyl-L-lysine27 demethylase
ACVR1	2.7.10.2	non-specific protein-tyrosine kinase
CREBBP	2.3.1.48	histone acetyltransferase
PIK3R1	2.7.1.153	phosphatidylinositol-4,5-bisphosphate 3-kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BRD4	4,603
RARA	368
TGFBR2	188
ACVR1	299
CREBBP	687
PIK3R1	493

Pharmacogenomics

Cohort genes with a PharmGKB record: 54; 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)
ACETAMINOPHEN	4	BRD4
FEDRATINIB	4	ACVR1, BRD4, TGFBR2
NITROXOLINE	4	BRD4
ROMIDEPSIN	4	BRD4
BELINOSTAT	4	BRD4
PANOBINOSTAT	4	BRD4
ALPRAZOLAM	4	BRD4
LENALIDOMIDE	4	BRD4
NORFLOXACIN	4	BRD4
VORINOSTAT	4	BRD4
BEXAROTENE	4	RARA
ADAPALENE	4	RARA
TAZAROTENE	4	RARA
TAMIBAROTENE	4	RARA
TRIFAROTENE	4	RARA
TRETINOIN	4	RARA
ALITRETINOIN	4	RARA
PONATINIB	4	TGFBR2
VEMURAFENIB	4	TGFBR2
SORAFENIB	4	TGFBR2
DABRAFENIB	4	TGFBR2
TOVORAFENIB	4	TGFBR2
PAZOPANIB	4	TGFBR2
DASATINIB	4	ACVR1, TGFBR2
DEFERIPRONE	4	KDM6A
MOMELOTINIB	4	ACVR1
PACRITINIB	4	ACVR1
VANDETANIB	4	ACVR1
LORLATINIB	4	ACVR1
GILTERITINIB	4	ACVR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	BRD4, RARA, TGFBR2, KDM6A, ACVR1, CREBBP, PIK3R1
B	Phased (≥1) drug, not yet approved	5	UBA2, SLC1A3, SMC3, DYNC1H1, MCRS1
C	Druggable family + PDB, no drug	2	OTUD5, HSPG2
D	Druggable family + AlphaFold only, no drug	3	SEMA3A, KAT14, ISLR2
E	Difficult family or no structure, no drug	37	TFAP2E, BMP7, SREBF2, UBE4A, WNT7B, ZMYM5, ZNF3, PRDM15, AAR2, OSBPL9 (+27 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BMP7	0	ACVR1
SRCAP	0	CREBBP
TFAP2E	0	—
SEMA3A	0	—
SREBF2	22	—
UBE4A	1	—
WNT7B	0	—
ZMYM5	0	—
ZNF3	0	—
PRDM15	0	—
AAR2	0	—
KAT14	0	—
OSBPL9	0	—
CDH4	0	—
THSD1	0	—
CLTCL1	0	—
KCTD10	0	—
SLC35F5	0	—
OTUD5	1	—
KIF26B	0	—
ZYG11B	12	—
SYDE2	0	—
ISLR2	0	—
PDIA6	13	—
NUDCD2	0	—
C16orf90	0	—
ARHGAP35	1	—
NTN1	1	—
BAZ1A	10	—
STXBP1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.