Orofacial cleft 1

Summary

Orofacial cleft 1 (MONDO:0007335) is a disease with 18 cohort genes.

At a glance

• Cohort genes: 18
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	orofacial cleft 1
Mondo ID	MONDO:0007335
MeSH	C566121
OMIM	119530
DOID	DOID:0080395
NCIT	C124838
UMLS	C1861537
MedGen	349303
GARD	0027776
Is cancer (heuristic)	no

Also known as: OFC1 · orofacial cleft 1 · orofacial cleft-1

Data availability: 17 ClinVar variants · 17 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › orofacial cleft › orofacial cleft 1

Related subtypes (15): cleft lip, 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, cleft palate, orofacial cleft 8, GRHL3-related orofacial clefting, orofacial cleft 7, ARHGAP29-related non-syndromic orofacial cleft

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

17 retrieved; paginated sample, class counts are floors:

6 conflicting classifications of pathogenicity, 6 uncertain significance, 3 likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4294309	NM_006147.4(IRF6):c.947T>C (p.Leu316Pro)	IRF6	Pathogenic	criteria provided, single submitter
4291093	NM_198525.3(KIF7):c.3257C>T (p.Ala1086Val)	KIF7	Pathogenic	criteria provided, single submitter
2575897	NM_004465.2(FGF10):c.355G>A (p.Gly119Arg)	FGF10	Likely pathogenic	criteria provided, single submitter
2575898	NM_005461.5(MAFB):c.11A>G (p.Glu4Gly)	MAFB	Likely pathogenic	criteria provided, single submitter
4278447	NM_002361.4(MAG):c.1231+3G>C	MAG	Likely pathogenic	criteria provided, single submitter
258213	NM_001844.5(COL2A1):c.1649G>T (p.Arg550Leu)	COL2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1300944	NM_023110.3(FGFR1):c.1865G>A (p.Arg622Gln)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904875	NM_025074.7(FRAS1):c.7573C>T (p.Arg2525Cys)	FRAS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3059314	NM_002226.5(JAG2):c.2063G>A (p.Arg688His)	JAG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1950511	NM_133433.4(NIPBL):c.6955-9dup	NIPBL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
130662	NM_001267550.2(TTN):c.15796C>T (p.Arg5266Ter)	TTN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2575899	NM_001040272.6(ADAMTSL1):c.281C>T (p.Ser94Leu)	ADAMTSL1	Uncertain significance	criteria provided, single submitter
2575896	NM_001797.4(CDH11):c.*239dup	CDH11	Uncertain significance	criteria provided, single submitter
2575902	NM_004822.3(NTN1):c.725T>C (p.Val242Ala)	NTN1	Uncertain significance	criteria provided, single submitter
2575900	NM_001024630.4(RUNX2):c.*2263C>T	RUNX2	Uncertain significance	criteria provided, single submitter
2584555	NM_002958.4(RYK):c.355-4703C>G	RYK	Uncertain significance	criteria provided, single submitter
2575901	NM_005680.3(TAF1B):c.197dup (p.Asn66fs)	TAF1B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 78 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RUNX2	Orphanet:1452	Cleidocranial dysplasia
RUNX2	Orphanet:2504	Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome
TTN	Orphanet:140922	Titin-related limb-girdle muscular dystrophy R10
TTN	Orphanet:154	Familial isolated dilated cardiomyopathy
TTN	Orphanet:169186	Autosomal recessive centronuclear myopathy
TTN	Orphanet:178464	Hereditary myopathy with early respiratory failure
TTN	Orphanet:289377	Early-onset myopathy with fatal cardiomyopathy
TTN	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
TTN	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
TTN	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
TTN	Orphanet:324604	Classic multiminicore myopathy
TTN	Orphanet:334	Hereditary atrial fibrillation
TTN	Orphanet:466921	Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome
TTN	Orphanet:609	Tibial muscular dystrophy
TTN	Orphanet:707983	Early-onset autosomal recessive TTN-related distal myopathy
ADAMTSL1	Orphanet:521445	Microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome
CDH11	Orphanet:1299	Branchioskeletogenital syndrome
FRAS1	Orphanet:2052	Fraser syndrome
FRAS1	Orphanet:93100	Renal agenesis, unilateral
COL2A1	Orphanet:137678	Spondyloepiphyseal dysplasia with metatarsal shortening
COL2A1	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL2A1	Orphanet:1856	Spondyloperipheral dysplasia-short ulna syndrome
COL2A1	Orphanet:209867	Autosomal dominant rhegmatogenous retinal detachment
COL2A1	Orphanet:2380	Legg-Calvé-Perthes disease
COL2A1	Orphanet:459051	Spondyloepiphyseal dysplasia, Stanescu type
COL2A1	Orphanet:485	Kniest dysplasia
COL2A1	Orphanet:85166	Platyspondylic dysplasia, Torrance type
COL2A1	Orphanet:85198	Dysspondyloenchondromatosis
COL2A1	Orphanet:86820	Familial avascular necrosis of femoral head
COL2A1	Orphanet:90653	Stickler syndrome type 1
COL2A1	Orphanet:93279	Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis
COL2A1	Orphanet:93296	Achondrogenesis type 2
COL2A1	Orphanet:93297	Hypochondrogenesis
COL2A1	Orphanet:93315	Spondylometaphyseal dysplasia, ‘corner fracture’ type
COL2A1	Orphanet:93316	Spondylometaphyseal dysplasia, Schmidt type
COL2A1	Orphanet:93346	Spondyloepimetaphyseal dysplasia congenita, Strudwick type
COL2A1	Orphanet:94068	Spondyloepiphyseal dysplasia congenita
NIPBL	Orphanet:199	Cornelia de Lange syndrome
NIPBL	Orphanet:329802	5p13 microduplication syndrome
KIF7	Orphanet:166024	Multiple epiphyseal dysplasia-macrocephaly-facial dysmorphism syndrome
KIF7	Orphanet:2189	Hydrolethalus
KIF7	Orphanet:2754	Orofaciodigital syndrome type 6
KIF7	Orphanet:36	Acrocallosal syndrome
ERCC2	Orphanet:1466	COFS syndrome
ERCC2	Orphanet:220295	Xeroderma pigmentosum-Cockayne syndrome complex
ERCC2	Orphanet:33364	Trichothiodystrophy
ERCC2	Orphanet:910	Xeroderma pigmentosum
FGF10	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGF10	Orphanet:86815	Aplasia of lacrimal and salivary glands
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement

Cohort genes → proteins

18 cohort genes, 18 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	18

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RUNX2	HGNC:10472	ENSG00000124813	Q13950	Runt-related transcription factor 2	clinvar
RYK	HGNC:10481	ENSG00000163785	P34925	Tyrosine-protein kinase RYK	clinvar
TAF1B	HGNC:11533	ENSG00000115750	Q53T94	TATA box-binding protein-associated factor RNA polymerase I subunit B	clinvar
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	clinvar
ADAMTSL1	HGNC:14632	ENSG00000178031	Q8N6G6	ADAMTS-like protein 1	clinvar
CDH11	HGNC:1750	ENSG00000140937	P55287	Cadherin-11	clinvar
FRAS1	HGNC:19185	ENSG00000138759	Q86XX4	Extracellular matrix organizing protein FRAS1	clinvar
COL2A1	HGNC:2200	ENSG00000139219	P02458	Collagen alpha-1(II) chain	clinvar
NIPBL	HGNC:28862	ENSG00000164190	Q6KC79	Nipped-B-like protein	clinvar
KIF7	HGNC:30497	ENSG00000166813	Q2M1P5	Kinesin-like protein KIF7	clinvar
ERCC2	HGNC:3434	ENSG00000104884	P18074	General transcription and DNA repair factor IIH helicase subunit XPD	clinvar
FGF10	HGNC:3666	ENSG00000070193	O15520	Fibroblast growth factor 10	clinvar
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	clinvar
IRF6	HGNC:6121	ENSG00000117595	O14896	Interferon regulatory factor 6	clinvar
JAG2	HGNC:6189	ENSG00000184916	Q9Y219	Protein jagged-2	clinvar
MAFB	HGNC:6408	ENSG00000204103	Q9Y5Q3	Transcription factor MafB	clinvar
MAG	HGNC:6783	ENSG00000105695	P20916	Myelin-associated glycoprotein	clinvar
NTN1	HGNC:8029	ENSG00000065320	O95631	Netrin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RUNX2	Runt-related transcription factor 2	Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis.
RYK	Tyrosine-protein kinase RYK	May be a coreceptor along with FZD8 of Wnt proteins, such as WNT1, WNT3, WNT3A and WNT5A.
TAF1B	TATA box-binding protein-associated factor RNA polymerase I subunit B	Component of RNA polymerase I core factor complex that acts as a GTF2B/TFIIB-like factor and plays a key role in multiple steps during transcription initiation such as pre-initiation complex (PIC) assembly and postpolymerase recruitment ev…
TTN	Titin	Key component in the assembly and functioning of vertebrate striated muscles.
CDH11	Cadherin-11	Cadherins are calcium-dependent cell adhesion proteins.
FRAS1	Extracellular matrix organizing protein FRAS1	Involved in extracellular matrix organization.
COL2A1	Collagen alpha-1(II) chain	Type II collagen is specific for cartilaginous tissues.
NIPBL	Nipped-B-like protein	Plays an important role in the loading of the cohesin complex on to DNA.
KIF7	Kinesin-like protein KIF7	Essential for hedgehog signaling regulation: acts both as a negative and positive regulator of sonic hedgehog (Shh) and Indian hedgehog (Ihh) pathways, acting downstream of SMO, through both SUFU-dependent and -independent mechanisms.
ERCC2	General transcription and DNA repair factor IIH helicase subunit XPD	ATP-dependent 5’-3’ DNA helicase.
FGF10	Fibroblast growth factor 10	Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation.
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
IRF6	Interferon regulatory factor 6	Probable DNA-binding transcriptional activator.
JAG2	Protein jagged-2	Putative Notch ligand involved in the mediation of Notch signaling.
MAFB	Transcription factor MafB	Acts as a transcriptional activator or repressor.
MAG	Myelin-associated glycoprotein	Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2.
NTN1	Netrin-1	Netrins control guidance of CNS commissural axons and peripheral motor axons.

Protein-family classification

Druggable: 6 · Difficult: 3 · Unknown: 9 · Druggable fraction: 0.33

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	3	4.6×	0.127
Antibody/Immunoglobulin	2	3.2×	0.313
Transcription factor	3	1.4×	0.625
Other/Unknown	9	0.9×	0.792
Enzyme (other)	1	0.7×	0.792

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RUNX2	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
RYK	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, WIF
TAF1B	Transcription factor	no		TF_Rrn7_Zf, TAF1B/Rrn7, Rrn7_cyclin_C
TTN	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ig_sub2, Ig_sub
ADAMTSL1	Antibody/Immunoglobulin	yes		TSP1_rpt, Ig_sub2, Ig_sub
CDH11	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
FRAS1	Other/Unknown	no		EGF, VWF_dom, Calx_beta
COL2A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
NIPBL	Other/Unknown	no		ARM-like, ARM-type_fold, Nipped-B_C
KIF7	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
ERCC2	Enzyme (other)	yes	3.6.4.12	RAD3/XPD, DNA/RNA_helicase_DEAH_CS, Helicase-like_DEXD_c2
FGF10	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
IRF6	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf
JAG2	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, VWF_dom
MAFB	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf
MAG	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
NTN1	Other/Unknown	no		Netrin_domain, LE_dom, Laminin_N

Expression context

Cohort genes with no expression data: 0.

17 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)	18
unknown	0

Top tissues across cohort

Tissue	Cohort genes
tibia	3
buccal mucosa cell	3
calcaneal tendon	3
stromal cell of endometrium	3
male germ line stem cell (sensu Vertebrata) in testis	2
lower esophagus muscularis layer	2
mucosa of paranasal sinus	1
trabecular bone tissue	1
left ovary	1
adrenal tissue	1
primordial germ cell in gonad	1
biceps brachii	1
gluteal muscle	1
skeletal muscle tissue of biceps brachii	1
lower esophagus	1
sural nerve	1
periodontal ligament	1
germinal epithelium of ovary	1
parietal pleura	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RUNX2	241	ubiquitous	marker	tibia, mucosa of paranasal sinus, trabecular bone tissue
RYK	293	ubiquitous	marker	buccal mucosa cell, calcaneal tendon, left ovary
TAF1B	256	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, adrenal tissue
TTN	223	broad	marker	biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
ADAMTSL1	182	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, sural nerve
CDH11	277	ubiquitous	marker	periodontal ligament, stromal cell of endometrium, tibia
FRAS1	212	ubiquitous	marker	germinal epithelium of ovary, parietal pleura, renal medulla
COL2A1	145	broad	marker	tibia, cartilage tissue, corpus epididymis
NIPBL	288	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, colonic epithelium
KIF7	165	ubiquitous	yes	kidney epithelium, cardiac muscle of right atrium, left ventricle myocardium
ERCC2	184	ubiquitous	marker	stromal cell of endometrium, right adrenal gland, left adrenal gland
FGF10	169	broad	marker	buccal mucosa cell, synovial joint, endocervix
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
IRF6	228	broad	marker	secondary oocyte, upper leg skin, esophagus squamous epithelium
JAG2	281	broad	marker	nipple, apex of heart, pituitary gland
MAFB	277	ubiquitous	marker	renal glomerulus, skin of hip, gingiva
MAG	187	broad	marker	C1 segment of cervical spinal cord, spinal cord, inferior vagus X ganglion
NTN1	218	broad	marker	mucosa of stomach, right atrium auricular region, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR1	5,693
TTN	4,237
FGF10	4,233
RUNX2	4,101
JAG2	3,546
NIPBL	3,278
ERCC2	2,746
MAFB	2,671
FRAS1	2,552
MAG	2,513

Intra-cohort edges

A	B	Sources
COL2A1	MAG	biogrid_interaction
COL2A1	RUNX2	string_interaction
FGF10	FGFR1	string_interaction
IRF6	JAG2	string_interaction
IRF6	MAFB	string_interaction

Structural data

PDB: 11 · AlphaFold-only: 7 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR1	P11362	83
TTN	Q8WZ42	64
ERCC2	P18074	51
COL2A1	P02458	11
KIF7	Q2M1P5	5
NTN1	O95631	5
RUNX2	Q13950	4
NIPBL	Q6KC79	3
JAG2	Q9Y219	3
FGF10	O15520	2
RYK	P34925	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAG	P20916	80.53
TAF1B	Q53T94	79.35
CDH11	P55287	77.65
IRF6	O14896	74.19
ADAMTSL1	Q8N6G6	71.26
MAFB	Q9Y5Q3	63.87
FRAS1	Q86XX4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 169. Enrichment computed across 18 evidence-associated genes (17 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 17 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
FGFR1b ligand binding and activation	2	149.3×	0.013	FGF10, FGFR1
Phospholipase C-mediated cascade: FGFR1	2	79.0×	0.017	FGF10, FGFR1
Downstream signaling of activated FGFR1	2	64.0×	0.017	FGF10, FGFR1
PI-3K cascade:FGFR1	2	61.1×	0.017	FGF10, FGFR1
SHC-mediated cascade:FGFR1	2	58.4×	0.017	FGF10, FGFR1
FRS-mediated FGFR1 signaling	2	53.7×	0.017	FGF10, FGFR1
Negative regulation of FGFR1 signaling	2	43.3×	0.023	FGF10, FGFR1
RNA Polymerase I Transcription Termination	2	38.4×	0.025	TAF1B, ERCC2
PI3K Cascade	2	32.0×	0.033	FGF10, FGFR1
RNA Polymerase I Transcription Initiation	2	26.3×	0.043	TAF1B, ERCC2
Signaling by FGFR1 amplification mutants	1	335.9×	0.046	FGFR1
FGFR1c and Klotho ligand binding and activation	1	167.9×	0.069	FGFR1
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	167.9×	0.069	JAG2
Signaling by plasma membrane FGFR1 fusions	1	167.9×	0.069	FGFR1
p75NTR regulates axonogenesis	1	134.3×	0.069	MAG
DSCAM interactions	1	134.3×	0.069	NTN1
RUNX2 regulates chondrocyte maturation	1	134.3×	0.069	RUNX2
RUNX2 regulates genes involved in differentiation of myeloid cells	1	134.3×	0.069	RUNX2
Constitutive Signaling by Aberrant PI3K in Cancer	2	14.9×	0.069	FGF10, FGFR1
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	96.0×	0.070	JAG2
CDH11 homotypic and heterotypic interactions	1	96.0×	0.070	CDH11
Regulation of gene expression in early pancreatic precursor cells	1	84.0×	0.070	FGF10
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	84.0×	0.070	RUNX2
RUNX2 regulates genes involved in cell migration	1	84.0×	0.070	RUNX2
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	84.0×	0.070	FGFR1
Axonal growth inhibition (RHOA activation)	1	74.6×	0.070	MAG
Signaling by NOTCH1 HD Domain Mutants in Cancer	1	74.6×	0.070	JAG2
Netrin mediated repulsion signals	1	74.6×	0.070	NTN1
Regulation of CDH11 mRNA translation by microRNAs	1	74.6×	0.070	CDH11
RNA Polymerase I Promoter Escape	2	14.3×	0.070	TAF1B, ERCC2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
stem cell proliferation	4	69.3×	6e-05	RUNX2, FGF10, FGFR1, IRF6
inner ear morphogenesis	4	66.9×	6e-05	COL2A1, FGFR1, MAFB, NTN1
metanephros morphogenesis	2	468.1×	6e-04	FRAS1, FGF10
positive regulation of stem cell proliferation	3	87.8×	6e-04	RUNX2, FGF10, FGFR1
regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling	2	374.5×	7e-04	FGF10, FGFR1
skeletal system development	4	27.9×	7e-04	CDH11, COL2A1, FGFR1, JAG2
central nervous system myelin formation	2	267.5×	0.001	ERCC2, MAG
chondrocyte differentiation	3	50.1×	0.001	RUNX2, COL2A1, FGFR1
odontogenesis of dentin-containing tooth	3	50.1×	0.001	RUNX2, FGF10, JAG2
response to sodium phosphate	2	187.2×	0.002	RUNX2, FGFR1
roof of mouth development	3	41.3×	0.002	FRAS1, COL2A1, IRF6
limb bud formation	2	170.2×	0.002	COL2A1, FGF10
organ induction	2	133.8×	0.003	FGF10, FGFR1
in utero embryonic development	4	16.0×	0.003	ERCC2, FGFR1, JAG2, MAFB
embryonic digestive tract morphogenesis	2	104.0×	0.004	NIPBL, FGF10
negative regulation of stem cell proliferation	2	93.6×	0.005	FGF10, IRF6
negative regulation of axon extension	2	81.4×	0.006	MAG, NTN1
rhombomere 6 development	1	936.2×	0.009	MAFB
embryonic genitalia morphogenesis	1	936.2×	0.009	FGF10
regulation of activin receptor signaling pathway	1	936.2×	0.009	FGF10
external genitalia morphogenesis	1	936.2×	0.009	NIPBL
ligamentous ossification	1	936.2×	0.009	RUNX2
urothelial cell proliferation	1	936.2×	0.009	FGF10
positive regulation of urothelial cell proliferation	1	936.2×	0.009	FGF10
bronchiole morphogenesis	1	936.2×	0.009	FGF10
mesenchymal-epithelial cell signaling involved in lung development	1	936.2×	0.009	FGF10
fibroblast growth factor receptor signaling pathway involved in mammary gland specification	1	936.2×	0.009	FGF10
submandibular salivary gland formation	1	936.2×	0.009	FGF10
semicircular canal fusion	1	936.2×	0.009	FGF10
lung proximal/distal axis specification	1	936.2×	0.009	FGF10

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 15

Druggability breadth: 8 of 18 evidence-associated genes (44%) 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
ERCC2	SUNITINIB
FGFR1	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
ERCC2	16	4
TAF1B	1	2
RUNX2	0	0
RYK	0	0
TTN	0	0
ADAMTSL1	0	0
CDH11	0	0
FRAS1	0	0
COL2A1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SUNITINIB	4	ERCC2, FGFR1
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
DASATINIB	4	FGFR1
MIDOSTAURIN	4	FGFR1
DINACICLIB	3	ERCC2
DEFACTINIB	3	ERCC2
ALVOCIDIB	3	ERCC2
LINIFANIB	3	FGFR1
SEMAXANIB	3	FGFR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
MAG	12	Binding:12
TAF1B	6	Binding:6
KIF7	5	Binding:5
ERCC2	3	Binding:3
COL2A1	2	Binding:2
TTN	1	Binding:1
NTN1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RYK	2.7.10.1	receptor protein-tyrosine kinase
TTN	2.7.11.1	non-specific serine/threonine protein kinase
ERCC2	3.6.4.12	DNA helicase
FGFR1	2.7.10.1	receptor 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
FGFR1	1,465

Pharmacogenomics

Cohort genes with a PharmGKB record: 18; 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)
SUNITINIB	4	ERCC2, FGFR1
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
DASATINIB	4	FGFR1
MIDOSTAURIN	4	FGFR1
DINACICLIB	3	ERCC2
DEFACTINIB	3	ERCC2
ALVOCIDIB	3	ERCC2
LINIFANIB	3	FGFR1
SEMAXANIB	3	FGFR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	ERCC2, FGFR1
B	Phased (≥1) drug, not yet approved	1	TAF1B
C	Druggable family + PDB, no drug	2	RYK, TTN
D	Druggable family + AlphaFold only, no drug	2	ADAMTSL1, MAG
E	Difficult family or no structure, no drug	11	RUNX2, CDH11, FRAS1, COL2A1, NIPBL, KIF7, FGF10, IRF6, JAG2, MAFB (+1 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FGF10	0	FGFR1
RUNX2	0	—
RYK	0	—
TTN	1	—
ADAMTSL1	0	—
CDH11	0	—
FRAS1	0	—
COL2A1	2	—
NIPBL	0	—
KIF7	5	—
IRF6	0	—
JAG2	0	—
MAFB	0	—
MAG	12	—
NTN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.