Autosomal dominant prognathism

Summary

Autosomal dominant prognathism (MONDO:0008312) is a disease caused by ERLEC1 (GenCC Strong), with 7 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: ERLEC1 (GenCC Strong)
• Cohort genes: 7
• ClinVar variants: 11
• Phenotypes (HPO): 3

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		55	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

3 HPO clinical features (Orphanet curated; top 3 by frequency):

HPO ID	Term	Frequency
HP:0000303	Mandibular prognathia	Very frequent (80-99%)
HP:0010807	Open bite	Very frequent (80-99%)
HP:0000232	Everted lower lip vermilion	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant prognathism
Mondo ID	MONDO:0008312
MeSH	D008313
OMIM	176700
Orphanet	2964
UMLS	C0399526
MedGen	98316
GARD	0010319
Is cancer (heuristic)	no

Also known as: Habsburg jaw · Hapsburg jaw · prognathism mandibular

Data availability: 11 ClinVar variants · 2 GenCC gene-disease records.

Disease family

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 › multiple congenital anomalies/dysmorphic syndrome without intellectual disability › autosomal dominant prognathism

Related subtypes (167): Treacher-Collins syndrome, branchio-oto-renal syndrome, acrorenal syndrome, Townes-Brocks syndrome, Ascher syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, branchiooculofacial syndrome, Gordon syndrome, cataract-aberrant oral frenula-growth delay syndrome, cherubism, Alagille syndrome, cleft palate-lateral synechia syndrome, blepharocheilodontic syndrome, craniofacial-deafness-hand syndrome, cryptomicrotia-brachydactyly-excess fingertip arch syndrome, Beare-Stevenson cutis gyrata syndrome, Cyprus facial-neuromusculoskeletal syndrome, deafness-craniofacial syndrome, short stature-valvular heart disease-characteristic facies syndrome, 3-M syndrome, external auditory canal atresia-vertical talus-hypertelorism syndrome, femoral-facial syndrome, multinodular goiter-cystic kidney-polydactyly syndrome, hand-foot-genital syndrome, Bencze syndrome, oculoauriculovertebral spectrum with radial defects, Holt-Oram syndrome, mullerian duct anomalies-limb anomalies syndrome, Aase-Smith syndrome, LADD syndrome, Noonan syndrome with multiple lentigines, median nodule of the upper lip, Nager acrofacial dysostosis, Marshall syndrome, Binder syndrome, Schilbach-Rott syndrome, nasopalpebral lipoma-coloboma syndrome, short stature-craniofacial anomalies-genital hypoplasia syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, scalp-ear-nipple syndrome, flat face-microstomia-ear anomaly syndrome, Czeizel-Losonci syndrome, otospondylomegaepiphyseal dysplasia, autosomal dominant, ventricular extrasystoles with syncopal episodes-perodactyly-robin sequence syndrome, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, acrofacial dysostosis, Weyers type, Freeman-Sheldon syndrome, Ackerman syndrome, acro-renal-mandibular syndrome, acrocraniofacial dysostosis, PAGOD syndrome, alar cartilages hypoplasia-coloboma-telecanthus syndrome, microcephaly-albinism-digital anomalies syndrome, fetal akinesia deformation sequence, Cooper-Jabs syndrome, Barber-Say syndrome, Beemer-Ertbruggen syndrome, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, camptodactyly syndrome, Guadalajara type 1, camptodactyly syndrome, Guadalajara type 2, heart defects-limb shortening syndrome, Verloove Vanhorick-Brubakk syndrome, Juberg-Hayward syndrome, heart defect - tongue hamartoma - polysyndactyly syndrome, Fraser syndrome, split hand-foot malformation 1 with sensorineural hearing loss, von Voss-Cherstvoy syndrome, autosomal recessive faciodigitogenital syndrome, gingival fibromatosis-facial dysmorphism syndrome, Fibulo-ulnar hypoplasia-renal anomalies syndrome, frontofacionasal dysplasia, genito-palato-cardiac syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Holzgreve-Wagner-Rehder syndrome, hydrocephaly-tall stature-joint laxity syndrome, McKusick-Kaufman syndrome, acrofrontofacionasal dysostosis 2, Vici syndrome, Donohue syndrome, Dahlberg-Borer-Newcomer syndrome, macrosomia-microphthalmia-cleft palate syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, Nijmegen breakage syndrome, lethal congenital contracture syndrome 1, Richieri Costa-da Silva syndrome, Keipert syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, ichthyosis-oral and digital anomalies syndrome, otoonychoperoneal syndrome, PHAVER syndrome, polysyndactyly-cardiac malformation syndrome, postaxial acrofacial dysostosis, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, renal-genital-middle ear anomalies, Richieri Costa-Pereira syndrome, SHORT syndrome, tetraamelia-multiple malformations syndrome, thymic-renal-anal-lung dysplasia, trigonocephaly-bifid nose-acral anomalies syndrome, white forelock with malformations, syndactyly-telecanthus-anogenital and renal malformations syndrome, Abruzzo-Erickson syndrome, CHILD syndrome, pentalogy of Cantrell, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, short tarsus-absence of lower eyelashes syndrome, PARC syndrome, CODAS syndrome, pectus excavatum-macrocephaly-dysplastic nails syndrome, velo-facial-skeletal syndrome, anophthalmia plus syndrome, van den Ende-Gupta syndrome, absent tibia-polydactyly-arachnoid cyst syndrome, diaphragmatic defect-limb deficiency-skull defect syndrome, cleft lip/palate-intestinal malrotation-cardiopathy syndrome, Matthew-Wood syndrome, microcephaly-cardiac defect-lung malsegmentation syndrome, dislocation of the hip-dysmorphism syndrome, short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome, grange syndrome, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, arhinia, choanal atresia, and microphthalmia, anonychia-microcephaly syndrome, developmental malformations-deafness-dystonia syndrome, lethal congenital contracture syndrome 2, craniolenticulosutural dysplasia, 8q22.1 microdeletion syndrome, Braddock syndrome, choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome, BNAR syndrome, Frias syndrome, lethal congenital contracture syndrome 3, Fontaine progeroid syndrome, microcephaly-facio-cardio-skeletal syndrome, Hadziselimovic type, Nijmegen breakage syndrome-like disorder, Warsaw breakage syndrome, even-plus syndrome, split-foot malformation-mesoaxial polydactyly syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, digitotalar dysmorphism, heart-hand syndrome type 2, night blindness-skeletal anomalies-dysmorphism syndrome, Charlie M syndrome, facial dysmorphism-anorexia-cachexia-eye and skin anomalies syndrome, cleft lip-retinopathy syndrome, Cole-Carpenter syndrome, progressive non-infectious anterior vertebral fusion, dysmorphism-pectus carinatum-joint laxity syndrome, Hirschsprung disease-type D brachydactyly syndrome, mandibuloacral dysplasia, contractures - webbed neck - micrognathia - hypoplastic nipples syndrome, Thomas syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, branchiootic syndrome, auricular abnormalities-cleft lip with or without cleft palate-ocular abnormalities syndrome, Axenfeld-Rieger syndrome, macrostomia-preauricular tags-external ophthalmoplegia syndrome, pelvis syndrome, Fanconi anemia, van der Woude syndrome, hypertrichosis-acromegaloid facial appearance syndrome, 49,XYYYY syndrome, congenital vertebral-cardiac-renal anomalies syndrome, structural heart defects and renal anomalies syndrome, Greig cephalopolysyndactyly-contiguous gene 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

11 retrieved; paginated sample, class counts are floors:

5 likely pathogenic, 4 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
520596	NM_001320.7(CSNK2B):c.94G>A (p.Asp32Asn)	CSNK2B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
267799	46;XY;t(3;17)(p14.3;q24.3)dn		Likely pathogenic	criteria provided, single submitter
830376	NM_015701.5(ERLEC1):c.1237C>T (p.His413Tyr)	ERLEC1	Likely pathogenic	no assertion criteria provided
830377	NM_015701.5(ERLEC1):c.419C>G (p.Thr140Ser)	ERLEC1	Likely pathogenic	no assertion criteria provided
830378	NM_015701.5(ERLEC1):c.419C>T (p.Thr140Ile)	ERLEC1	Likely pathogenic	no assertion criteria provided
830379	NM_015701.5(ERLEC1):c.1448A>G (p.Asn483Ser)	ERLEC1	Likely pathogenic	no assertion criteria provided
373980	NM_021008.4(DEAF1):c.667G>A (p.Gly223Ser)	DEAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
268042	46;XY;t(18;20)(q21.1;p11.23)dn		Uncertain significance	criteria provided, single submitter
559502	GRCh37/hg19 2p23.3(chr2:24807000-25700000)x3	ADCY3	Uncertain significance	no assertion criteria provided
559399	Single allele	C9orf163	Uncertain significance	no assertion criteria provided
2571628	NM_001352702.2(PTK2):c.2563C>T (p.Arg855Ter)	PTK2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 4 · 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
ERLEC1	Strong	Autosomal dominant	autosomal dominant prognathism
ADAMTS1	Limited	Autosomal dominant	autosomal dominant prognathism	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DEAF1	Orphanet:468620	Intellectual disability-epilepsy-extrapyramidal syndrome
DEAF1	Orphanet:714385	Global developmental delay-high pain tolerance-intellectual disability syndrome
CSNK2B	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
CSNK2B	Orphanet:689397	Poirier-Bienvenu neurodevelopmental syndrome

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ERLEC1	HGNC:25222	ENSG00000068912	Q96DZ1	Endoplasmic reticulum lectin 1	gencc,clinvar
ADAMTS1	HGNC:217	ENSG00000154734	Q9UHI8	A disintegrin and metalloproteinase with thrombospondin motifs 1	gencc
DEAF1	HGNC:14677	ENSG00000177030	O75398	Deformed epidermal autoregulatory factor 1 homolog	clinvar
ADCY3	HGNC:234	ENSG00000138031	O60266	Adenylate cyclase type 3	clinvar
CSNK2B	HGNC:2460	ENSG00000204435	P67870	Casein kinase II subunit beta	clinvar
C9orf163	HGNC:26718	ENSG00000196366	Q8N9P6	Uncharacterized protein C9orf163	clinvar
PTK2	HGNC:9611	ENSG00000169398	Q05397	Focal adhesion kinase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ERLEC1	Endoplasmic reticulum lectin 1	Probable lectin that binds selectively to improperly folded lumenal proteins.
ADAMTS1	A disintegrin and metalloproteinase with thrombospondin motifs 1	Metalloprotease which cleaves aggrecan, a cartilage proteoglycan, at the ‘1938-Glu-|-Leu-1939’ site (within the chondroitin sulfate attachment domain), and may be involved in its turnover.
DEAF1	Deformed epidermal autoregulatory factor 1 homolog	Transcription factor that binds to sequence with multiple copies of 5’-TTC[CG]G-3’ present in its own promoter and that of the HNRPA2B1 gene.
ADCY3	Adenylate cyclase type 3	Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.
CSNK2B	Casein kinase II subunit beta	Regulatory subunit of casein kinase II/CK2.
PTK2	Focal adhesion kinase 1	Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle pr…

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.43

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	2	7.9×	0.097
Protease	1	5.2×	0.352
Transcription factor	1	1.2×	0.793
Other/Unknown	3	0.8×	0.858

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ERLEC1	Other/Unknown	no		Man6P_isomerase_rcpt-bd_dom_sf, OS9-like_dom, MRH_dom
ADAMTS1	Protease	yes	3.4.24.B11	TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
DEAF1	Transcription factor	no		SAND_dom, Znf_MYND, SAND-like_dom_sf
ADCY3	Other/Unknown	no		A/G_cyclase, A/G_cyclase_CS, Nucleotide_cyclase
CSNK2B	Kinase	yes		Casein_kinase_II_reg-sub, Casein_kin_II_reg-sub_N, Casein_kinase_II_beta-like
C9orf163	Other/Unknown	no
PTK2	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom

Expression context

Cohort genes with no expression data: 0.

6 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right ovary	2
endothelial cell	1
epithelial cell of pancreas	1
ileal mucosa	1
left uterine tube	1
vena cava	1
Ammon’s horn	1
amygdala	1
temporal lobe	1
sural nerve	1
tibial nerve	1
left testis	1
right testis	1
skin of leg	1
myocardium	1
pituitary gland	1
right uterine tube	1
calcaneal tendon	1
colonic epithelium	1
corpus callosum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ERLEC1	263	ubiquitous	marker	epithelial cell of pancreas, endothelial cell, ileal mucosa
ADAMTS1	283	ubiquitous	marker	right ovary, left uterine tube, vena cava
DEAF1	134	ubiquitous	marker	amygdala, temporal lobe, Ammon’s horn
ADCY3	281	broad	marker	tibial nerve, right ovary, sural nerve
CSNK2B	134	ubiquitous	marker	left testis, right testis, skin of leg
C9orf163	121	tissue_specific	yes	right uterine tube, myocardium, pituitary gland
PTK2	295	ubiquitous	marker	corpus callosum, colonic epithelium, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTK2	4,342
ADCY3	1,965
ADAMTS1	1,835
ERLEC1	1,613
CSNK2B	1,486
DEAF1	784
C9orf163	54

Structural data

PDB: 5 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTK2	Q05397	40
CSNK2B	P67870	10
ERLEC1	Q96DZ1	5
ADAMTS1	Q9UHI8	4
DEAF1	O75398	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADCY3	O60266	76.86
C9orf163	Q8N9P6	33.64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 96. Enrichment computed across 7 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK	1	456.8×	0.038	CSNK2B
WNT mediated activation of DVL	1	285.5×	0.038	CSNK2B
Adenylate cyclase activating pathway	1	228.4×	0.038	ADCY3
Condensation of Prometaphase Chromosomes	1	207.6×	0.038	CSNK2B
Receptor Mediated Mitophagy	1	207.6×	0.038	CSNK2B
Phosphorylation and nuclear translocation of the CRY:PER:kinase complex	1	163.1×	0.038	CSNK2B
Adenylate cyclase inhibitory pathway	1	152.3×	0.038	ADCY3
p130Cas linkage to MAPK signaling for integrins	1	152.3×	0.038	PTK2
Maturation of hRSV A proteins	1	152.3×	0.038	CSNK2B
GRB2:SOS provides linkage to MAPK signaling for Integrins	1	142.8×	0.038	PTK2
DCC mediated attractive signaling	1	142.8×	0.038	PTK2
PKA activation in glucagon signalling	1	134.3×	0.038	ADCY3
Signal regulatory protein family interactions	1	134.3×	0.038	PTK2
PKA activation	1	126.9×	0.038	ADCY3
Activation of GABAB receptors	1	120.2×	0.038	ADCY3
PKA-mediated phosphorylation of CREB	1	114.2×	0.038	ADCY3
GABA B receptor activation	1	108.8×	0.038	ADCY3
Signal transduction by L1	1	103.8×	0.038	CSNK2B
Apoptotic cleavage of cellular proteins	1	95.2×	0.038	PTK2
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1	87.8×	0.038	PTK2
Integrin signaling	1	84.6×	0.038	PTK2
Synthesis of PC	1	81.6×	0.038	CSNK2B
Anti-inflammatory response favouring Leishmania parasite infection	1	78.8×	0.038	ADCY3
Leishmania parasite growth and survival	1	78.8×	0.038	ADCY3
Calmodulin induced events	1	76.1×	0.038	ADCY3
CaM pathway	1	76.1×	0.038	ADCY3
MET activates PTK2 signaling	1	76.1×	0.038	PTK2
Ca-dependent events	1	73.7×	0.038	ADCY3
Aquaporin-mediated transport	1	73.7×	0.038	ADCY3
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	71.4×	0.038	PTK2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
olfactory learning	1	1404.3×	0.015	ADCY3
netrin-activated signaling pathway	1	936.2×	0.015	PTK2
symbiont-mediated disruption of host cell PML body	1	936.2×	0.015	CSNK2B
negative regulation of viral life cycle	1	702.2×	0.015	CSNK2B
vascular endothelial cell response to oscillatory fluid shear stress	1	561.7×	0.015	PTK2
positive regulation of macrophage proliferation	1	561.7×	0.015	PTK2
regulation of substrate adhesion-dependent cell spreading	1	561.7×	0.015	PTK2
regulation of epithelial cell migration	1	468.1×	0.015	PTK2
positive regulation of activin receptor signaling pathway	1	468.1×	0.015	CSNK2B
regulation of mammary gland epithelial cell proliferation	1	468.1×	0.015	DEAF1
detection of muscle stretch	1	401.2×	0.015	PTK2
signal complex assembly	1	351.1×	0.015	PTK2
regulation of endothelial cell migration	1	351.1×	0.015	PTK2
adiponectin-activated signaling pathway	1	351.1×	0.015	CSNK2B
positive regulation of cell-cell adhesion mediated by integrin	1	351.1×	0.015	PTK2
ovulation from ovarian follicle	1	312.1×	0.015	ADAMTS1
endothelial tube morphogenesis	1	312.1×	0.015	CSNK2B
negative regulation of retrograde protein transport, ER to cytosol	1	312.1×	0.015	ERLEC1
integrin-mediated signaling pathway	2	53.5×	0.015	ADAMTS1, PTK2
cAMP biosynthetic process	1	234.1×	0.019	ADCY3
negative regulation of cell adhesion mediated by integrin	1	216.1×	0.019	PTK2
regulation of osteoblast differentiation	1	216.1×	0.019	PTK2
growth hormone receptor signaling pathway	1	200.6×	0.019	PTK2
positive regulation of fibroblast migration	1	187.2×	0.019	PTK2
heart trabecula formation	1	187.2×	0.019	ADAMTS1
cellular response to forskolin	1	187.2×	0.019	ADCY3
negative regulation of cell-cell adhesion	1	165.2×	0.019	PTK2
retrograde protein transport, ER to cytosol	1	165.2×	0.019	ERLEC1
positive regulation of vascular associated smooth muscle cell migration	1	165.2×	0.019	ADAMTS1
acrosome reaction	1	147.8×	0.020	ADCY3

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 4 of 7 evidence-associated genes (57%) 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
CSNK2B	PALBOCICLIB
PTK2	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTK2	56	4
CSNK2B	14	4
ERLEC1	0	0
ADAMTS1	0	0
DEAF1	0	0
ADCY3	0	0
C9orf163	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PALBOCICLIB	4	CSNK2B
MITOXANTRONE	4	CSNK2B
FEDRATINIB	4	PTK2
NERATINIB	4	PTK2
ENTRECTINIB	4	PTK2
FOSTAMATINIB	4	PTK2
CERITINIB	4	PTK2
BOSUTINIB	4	PTK2
LORLATINIB	4	PTK2
BRIGATINIB	4	PTK2
REPOTRECTINIB	4	PTK2
PAZOPANIB	4	PTK2
NINTEDANIB	4	PTK2
SUNITINIB	4	PTK2
ERLOTINIB	4	PTK2
CRIZOTINIB	4	PTK2
QUERCETIN	3	CSNK2B, PTK2
ENTOSPLETINIB	3	CSNK2B
VOLASERTIB	3	PTK2
LINIFANIB	3	PTK2
DEFACTINIB	3	PTK2
ROCILETINIB	3	PTK2
ALISERTIB	3	PTK2
LESTAURTINIB	3	PTK2
SILMITASERTIB	2	CSNK2B
FISETIN	2	CSNK2B
ELLAGIC ACID	2	CSNK2B, PTK2
MOLIBRESIB	2	CSNK2B
CI-1040	2	CSNK2B
LUTEOLIN	2	CSNK2B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
PTK2	990	Binding:989, Functional:1
CSNK2B	421	Binding:419, Functional:2
ADCY3	17	Binding:15, Functional:2
ADAMTS1	8	Binding:7, Toxicity:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADAMTS1	3.4.24.B11, 3.4.24.B12	,
PTK2	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
CSNK2B	421
PTK2	990

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; 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)
PALBOCICLIB	4	CSNK2B
MITOXANTRONE	4	CSNK2B
FEDRATINIB	4	PTK2
NERATINIB	4	PTK2
ENTRECTINIB	4	PTK2
FOSTAMATINIB	4	PTK2
CERITINIB	4	PTK2
BOSUTINIB	4	PTK2
LORLATINIB	4	PTK2
BRIGATINIB	4	PTK2
REPOTRECTINIB	4	PTK2
PAZOPANIB	4	PTK2
NINTEDANIB	4	PTK2
SUNITINIB	4	PTK2
ERLOTINIB	4	PTK2
CRIZOTINIB	4	PTK2
QUERCETIN	3	CSNK2B, PTK2
ENTOSPLETINIB	3	CSNK2B
VOLASERTIB	3	PTK2
LINIFANIB	3	PTK2
DEFACTINIB	3	PTK2
ROCILETINIB	3	PTK2
ALISERTIB	3	PTK2
LESTAURTINIB	3	PTK2
SILMITASERTIB	2	CSNK2B
FISETIN	2	CSNK2B
ELLAGIC ACID	2	CSNK2B, PTK2
MOLIBRESIB	2	CSNK2B
CI-1040	2	CSNK2B
LUTEOLIN	2	CSNK2B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	CSNK2B, PTK2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ADAMTS1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	ERLEC1, DEAF1, ADCY3, C9orf163

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ERLEC1	0	—
ADAMTS1	8	—
DEAF1	0	—
ADCY3	17	—
C9orf163	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.