acrofacial dysostosis, Weyers type

Summary

acrofacial dysostosis, Weyers type (MONDO:0008673) is a disease caused by variants in EVC and EVC2, with 3 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal genes: EVC (GenCC Definitive), EVC2 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 3,294
• Phenotypes (HPO): 19
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0000164	Abnormality of the dentition	Very frequent (80-99%)
HP:0000190	Abnormal oral frenulum morphology	Very frequent (80-99%)
HP:0000668	Hypodontia	Very frequent (80-99%)
HP:0000698	Conical tooth	Very frequent (80-99%)
HP:0001162	Postaxial hand polydactyly	Very frequent (80-99%)
HP:0001231	Abnormal fingernail morphology	Very frequent (80-99%)
HP:0001792	Small nail	Very frequent (80-99%)
HP:0001800	Hypoplastic toenails	Very frequent (80-99%)
HP:0003502	Mild short stature	Very frequent (80-99%)
HP:0006288	Advanced eruption of teeth	Very frequent (80-99%)
HP:0006315	Single median maxillary incisor	Very frequent (80-99%)
HP:0008388	Abnormal toenail morphology	Very frequent (80-99%)
HP:0008404	Nail dystrophy	Very frequent (80-99%)
HP:0100797	Toenail dysplasia	Very frequent (80-99%)
HP:0002006	Facial cleft	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0009738	Abnormality of the antihelix	Frequent (30-79%)
HP:0010557	Overlapping fingers	Frequent (30-79%)
HP:0200055	Small hand	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	acrofacial dysostosis, Weyers type
Mondo ID	MONDO:0008673
MeSH	C536695
OMIM	193530
Orphanet	952
DOID	DOID:0111571
ICD-11	547338814
SNOMED CT	277807007
UMLS	C0457013
MedGen	141594
GARD	0000497
Is cancer (heuristic)	no

Also known as: acrofacial dysostosis of Weyers · curry Hall syndrome · curry-Hall syndrome · wad · Weyers acrodental dysostosis · Weyers acrofacial dysostosis

Data availability: 3,294 ClinVar variants · 7 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 › acrofacial dysostosis, Weyers type

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, autosomal dominant prognathism, 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, 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

600 retrieved; paginated sample, class counts are floors:

401 likely benign, 93 uncertain significance, 67 pathogenic, 15 pathogenic/likely pathogenic, 10 conflicting classifications of pathogenicity, 9 likely pathogenic, 3 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1073308	NC_000004.11:g.(?2200251)(5710240_?)del	ADRA2C	Pathogenic	criteria provided, single submitter
1013604	NM_153717.3(EVC):c.37_38del (p.Arg13fs)	EVC	Pathogenic	criteria provided, multiple submitters, no conflicts
1066868	NM_153717.3(EVC):c.175-2A>G	EVC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068990	NM_153717.3(EVC):c.2561+1dup	EVC	Pathogenic	criteria provided, single submitter
1069685	NC_000004.11:g.(?5798739)(5798969_?)del	EVC	Pathogenic	criteria provided, single submitter
1069686	NC_000004.11:g.(?5809918)(5811348_?)del	EVC	Pathogenic	criteria provided, single submitter
1069687	NC_000004.11:g.(?5754553)(5755670_?)del	EVC	Pathogenic	criteria provided, single submitter
1069725	NM_153717.3(EVC):c.2145_2146insGCCC (p.Gln716fs)	EVC	Pathogenic	criteria provided, single submitter
1069802	NM_153717.3(EVC):c.720dup (p.Lys241Ter)	EVC	Pathogenic	criteria provided, single submitter
1070697	NM_153717.3(EVC):c.539C>A (p.Ser180Ter)	EVC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072443	NM_153717.3(EVC):c.1047_1048del (p.Arg349fs)	EVC	Pathogenic	criteria provided, single submitter
1072476	NM_153717.3(EVC):c.1494del (p.Arg498fs)	EVC	Pathogenic	criteria provided, single submitter
1072936	NM_153717.3(EVC):c.1021C>T (p.Gln341Ter)	EVC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073032	NM_153717.3(EVC):c.1228G>T (p.Glu410Ter)	EVC	Pathogenic	criteria provided, single submitter
1073898	NM_153717.3(EVC):c.2545C>T (p.Gln849Ter)	EVC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074895	NM_153717.3(EVC):c.1290_1291delinsAA (p.Trp430_Gln431delinsTer)	EVC	Pathogenic	criteria provided, single submitter
1074980	NM_153717.3(EVC):c.1746_1747del (p.Phe583fs)	EVC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1210401	NM_153717.3(EVC):c.1750del (p.Gln584fs)	EVC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322838	NM_153717.3(EVC):c.1783_1886+40del	EVC	Pathogenic	criteria provided, multiple submitters, no conflicts
1332830	NM_153717.3(EVC):c.1327C>T (p.Arg443Ter)	EVC	Pathogenic	criteria provided, multiple submitters, no conflicts
1370178	NM_153717.3(EVC):c.788C>G (p.Ser263Ter)	EVC	Pathogenic	criteria provided, single submitter
1371302	NM_153717.3(EVC):c.338dup (p.Ala114fs)	EVC	Pathogenic	criteria provided, single submitter
1374481	NM_153717.3(EVC):c.673del (p.Asp225fs)	EVC	Pathogenic	criteria provided, single submitter
1379233	NM_153717.3(EVC):c.2698C>T (p.Gln900Ter)	EVC	Pathogenic	criteria provided, single submitter
1383767	NM_153717.3(EVC):c.2488G>T (p.Glu830Ter)	EVC	Pathogenic	criteria provided, single submitter
1385574	NM_153717.3(EVC):c.2705del (p.Phe902fs)	EVC	Pathogenic	criteria provided, single submitter
1390075	NM_153717.3(EVC):c.1324C>T (p.Gln442Ter)	EVC	Pathogenic	criteria provided, single submitter
1393169	NM_153717.3(EVC):c.90del (p.Ala31fs)	EVC	Pathogenic	criteria provided, single submitter
1396608	NM_153717.3(EVC):c.583del (p.Arg194_Val195insTer)	EVC	Pathogenic	criteria provided, single submitter
1430455	NC_000004.11:g.(?5803667)(5806578_?)del	EVC	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · 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
EVC	Definitive	Autosomal recessive	acrofacial dysostosis, Weyers type	7
EVC2	Definitive	Autosomal recessive	acrofacial dysostosis, Weyers type	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EVC2	Orphanet:289	Ellis Van Creveld syndrome
EVC2	Orphanet:952	Acrofacial dysostosis, Weyers type
EVC	Orphanet:289	Ellis Van Creveld syndrome
EVC	Orphanet:952	Acrofacial dysostosis, Weyers type

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EVC2	HGNC:19747	ENSG00000173040	Q86UK5	Limbin	gencc,clinvar
EVC	HGNC:3497	ENSG00000072840	P57679	EvC complex member EVC	gencc,clinvar
ADRA2C	HGNC:283	ENSG00000184160	P18825	Alpha-2C adrenergic receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EVC2	Limbin	Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling.
EVC	EvC complex member EVC	Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling.
ADRA2C	Alpha-2C adrenergic receptor	Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate the G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · 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
GPCR	1	8.0×	0.240
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EVC2	Other/Unknown	no		Limbin, Limbin/EVC
EVC	Other/Unknown	no		Limbin/EVC
ADRA2C	GPCR	yes		GPCR_Rhodpsn, ADRA2C_rcpt, ADR_fam

Expression context

Cohort genes with no expression data: 0.

2 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
pancreatic ductal cell	1
primordial germ cell in gonad	1
metanephros cortex	1
stromal cell of endometrium	1
sural nerve	1
decidua	1
descending thoracic aorta	1
endocervix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EVC2	182	ubiquitous	marker	pancreatic ductal cell, calcaneal tendon, primordial germ cell in gonad
EVC	163	ubiquitous	yes	sural nerve, stromal cell of endometrium, metanephros cortex
ADRA2C	236	broad	marker	decidua, endocervix, descending thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADRA2C	1,003
EVC2	913
EVC	759

Intra-cohort edges

A	B	Sources
EVC	EVC2	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADRA2C	P18825	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EVC	P57679	74.49
EVC2	Q86UK5	73.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of SMO	2	423.0×	2e-04	EVC2, EVC
Hedgehog ‘on’ state	2	105.7×	0.001	EVC2, EVC
Adrenaline signalling through Alpha-2 adrenergic receptor	1	1268.9×	0.006	ADRA2C
Adrenoceptors	1	423.0×	0.013	ADRA2C
Platelet Aggregation (Plug Formation)	1	146.4×	0.024	ADRA2C
Adrenaline,noradrenaline inhibits insulin secretion	1	131.3×	0.024	ADRA2C
Surfactant metabolism	1	122.8×	0.024	ADRA2C
Amine ligand-binding receptors	1	115.3×	0.024	ADRA2C
G alpha (z) signalling events	1	77.7×	0.030	ADRA2C
Regulation of insulin secretion	1	73.2×	0.030	ADRA2C
Signaling by Hedgehog	1	61.4×	0.031	EVC2
Integration of energy metabolism	1	58.6×	0.031	ADRA2C
Platelet activation, signaling and aggregation	1	35.2×	0.044	ADRA2C
Signal Transduction	2	6.8×	0.044	EVC2, ADRA2C
Class A/1 (Rhodopsin-like receptors)	1	24.7×	0.059	ADRA2C
GPCR ligand binding	1	21.4×	0.063	ADRA2C
GPCR downstream signalling	1	14.5×	0.087	ADRA2C
Signaling by GPCR	1	13.4×	0.087	ADRA2C
G alpha (i) signalling events	1	13.0×	0.087	ADRA2C
Hemostasis	1	12.0×	0.089	ADRA2C
Metabolism of proteins	1	4.1×	0.234	ADRA2C
Metabolism	1	3.9×	0.237	ADRA2C

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
smoothened signaling pathway	2	120.8×	0.002	EVC2, EVC
negative regulation of epinephrine secretion	1	1123.5×	0.005	ADRA2C
adenylate cyclase-inhibiting adrenergic receptor signaling pathway	1	1123.5×	0.005	ADRA2C
negative regulation of norepinephrine secretion	1	936.2×	0.005	ADRA2C
adrenergic receptor signaling pathway	1	624.1×	0.006	ADRA2C
endochondral bone growth	1	561.7×	0.006	EVC
regulation of smooth muscle contraction	1	401.2×	0.007	ADRA2C
regulation of vasoconstriction	1	267.5×	0.009	ADRA2C
negative regulation of insulin secretion	1	165.2×	0.013	ADRA2C
positive regulation of smoothened signaling pathway	1	140.4×	0.014	EVC
platelet activation	1	89.2×	0.019	ADRA2C
cartilage development	1	83.8×	0.019	EVC
epidermal growth factor receptor signaling pathway	1	82.6×	0.019	ADRA2C
positive regulation of neuron differentiation	1	66.1×	0.022	ADRA2C
muscle organ development	1	55.6×	0.024	EVC
skeletal system development	1	41.9×	0.030	EVC
positive regulation of MAPK cascade	1	26.9×	0.042	ADRA2C
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	26.1×	0.042	ADRA2C
cell-cell signaling	1	23.2×	0.045	ADRA2C
G protein-coupled receptor signaling pathway	1	12.1×	0.081	ADRA2C

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
ADRA2C	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADRA2C	330	4
EVC2	0	0
EVC	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	ADRA2C
CANDESARTAN CILEXETIL	4	ADRA2C
TELMISARTAN	4	ADRA2C
CLOTRIMAZOLE	4	ADRA2C
SIMVASTATIN	4	ADRA2C
METHYSERGIDE	4	ADRA2C
TIZANIDINE	4	ADRA2C
ACETOPHENAZINE	4	ADRA2C
IMIPRAMINE	4	ADRA2C
DROPERIDOL	4	ADRA2C
RIMONABANT	4	ADRA2C
ALOSETRON	4	ADRA2C
ARIPIPRAZOLE	4	ADRA2C
AMOXAPINE	4	ADRA2C
IDARUBICIN	4	ADRA2C
PONATINIB	4	ADRA2C
DESLORATADINE	4	ADRA2C
PRUCALOPRIDE	4	ADRA2C
DULOXETINE	4	ADRA2C
PALONOSETRON	4	ADRA2C
TIOCONAZOLE	4	ADRA2C
NEFAZODONE HYDROCHLORIDE	4	ADRA2C
DESERPIDINE	4	ADRA2C
DIHYDROERGOTAMINE MESYLATE	4	ADRA2C
UNOPROSTONE ISOPROPYL	4	ADRA2C
CINACALCET HYDROCHLORIDE	4	ADRA2C
THIOTHIXENE	4	ADRA2C
BENZTHIAZIDE	4	ADRA2C
CABERGOLINE	4	ADRA2C
BENZTROPINE	4	ADRA2C

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ADRA2C	647	Binding:503, Functional:135, ADMET:7, Unclassified:2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ADRA2C	647

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
ADRA2C	1

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)
BEPRIDIL	4	ADRA2C
CANDESARTAN CILEXETIL	4	ADRA2C
TELMISARTAN	4	ADRA2C
CLOTRIMAZOLE	4	ADRA2C
SIMVASTATIN	4	ADRA2C
METHYSERGIDE	4	ADRA2C
TIZANIDINE	4	ADRA2C
ACETOPHENAZINE	4	ADRA2C
IMIPRAMINE	4	ADRA2C
DROPERIDOL	4	ADRA2C
RIMONABANT	4	ADRA2C
ALOSETRON	4	ADRA2C
ARIPIPRAZOLE	4	ADRA2C
AMOXAPINE	4	ADRA2C
IDARUBICIN	4	ADRA2C
PONATINIB	4	ADRA2C
DESLORATADINE	4	ADRA2C
PRUCALOPRIDE	4	ADRA2C
DULOXETINE	4	ADRA2C
PALONOSETRON	4	ADRA2C
TIOCONAZOLE	4	ADRA2C
NEFAZODONE HYDROCHLORIDE	4	ADRA2C
DESERPIDINE	4	ADRA2C
DIHYDROERGOTAMINE MESYLATE	4	ADRA2C
UNOPROSTONE ISOPROPYL	4	ADRA2C
CINACALCET HYDROCHLORIDE	4	ADRA2C
THIOTHIXENE	4	ADRA2C
BENZTHIAZIDE	4	ADRA2C
CABERGOLINE	4	ADRA2C
BENZTROPINE	4	ADRA2C

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ADRA2C
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	EVC2, EVC

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
EVC2	0	—
EVC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02157038	Not specified	COMPLETED	Neuromuscular Mechanisms Underlying Poor Recovery From Whiplash Injuries