Chromosome 22q11.2 microduplication syndrome

Summary

Chromosome 22q11.2 microduplication syndrome (MONDO:0012020) is a disease with 10 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 10
• ClinVar variants: 30
• Phenotypes (HPO): 40

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		216	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

40 HPO clinical features (Orphanet curated; top 40 by frequency):

HPO ID	Term	Frequency
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0000275	Narrow face	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000348	High forehead	Frequent (30-79%)
HP:0000457	Depressed nasal ridge	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0000600	Abnormality of the pharynx	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001611	Hypernasal speech	Frequent (30-79%)
HP:0002167	Abnormality of speech or vocalization	Frequent (30-79%)
HP:0011800	Midface retrusion	Frequent (30-79%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000319	Smooth philtrum	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000445	Wide nose	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0000722	Compulsive behaviors	Occasional (5-29%)
HP:0000733	Abnormal repetitive mannerisms	Occasional (5-29%)
HP:0000739	Anxiety	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001510	Growth delay	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001636	Tetralogy of Fallot	Occasional (5-29%)
HP:0001669	Transposition of the great arteries	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0004383	Hypoplastic left heart	Occasional (5-29%)
HP:0007018	Attention deficit hyperactivity disorder	Occasional (5-29%)
HP:0008661	Urethral stenosis	Occasional (5-29%)
HP:0009908	Anterior creases of earlobe	Occasional (5-29%)
HP:0010515	Aplasia/Hypoplasia of the thymus	Occasional (5-29%)
HP:0010978	Abnormality of immune system physiology	Occasional (5-29%)
HP:0011611	Interrupted aortic arch	Occasional (5-29%)
HP:0100627	Displacement of the urethral meatus	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 22q11.2 microduplication syndrome
Mondo ID	MONDO:0012020
MeSH	C567224
OMIM	608363
Orphanet	1727
DOID	DOID:0060436
SNOMED CT	699311001
UMLS	C2675369
MedGen	436417
GARD	0010557
Is cancer (heuristic)	no

Also known as: 22q11 duplication syndrome · 22q11.2 duplication · 22q11.2 duplication syndrome · 22q11.2 microduplication syndrome · chromosome 22q11.2 duplication syndrome · chromosome 22q11.2 microduplication syndrome · chromosome 22q11.2 microduplication syndrome, isolated cases · dup(22)(q11) · Duplication 22q11.2 · duplication 22q11.2 · trisomy 22q11.2

Data availability: 30 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › syndrome caused by partial chromosomal duplication › partial duplication of the long arm of chromosome 22 › chromosome 22q11.2 microduplication syndrome

Related subtypes (2): chromosome 22q13 duplication syndrome, distal trisomy 22q

Subtypes (1): distal 22q11.2 microduplication 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

30 retrieved; paginated sample, class counts are floors:

28 pathogenic, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4795128	NC_000022.11:g.(18846911_21222234)dup		Pathogenic	criteria provided, single submitter
1703650	GRCh37/hg19 22q11.1-11.21(chr22:16888899-21915509)	ADA2	Pathogenic	no assertion criteria provided
625807	GRCh37/hg19 22q11.1-11.21(chr22:17289827-20311922)	ADA2	Pathogenic	criteria provided, single submitter
1703645	GRCh37/hg19 22q11.21-11.23(chr22:21798906-25039018)	ADORA2A	Pathogenic	no assertion criteria provided
2580295	GRCh37/hg19 22q11.23(chr22:23658260-25114888)x3	ADORA2A	Pathogenic	criteria provided, single submitter
1703647	GRCh37/hg19 22q11.21(chr22:18917047-21465659)	AIFM3	Pathogenic	no assertion criteria provided
1703649	GRCh37/hg19 22q11.21(chr22:18916827-21804886)	AIFM3	Pathogenic	no assertion criteria provided
2572172	NC_000022.11:g.18948676_21110520dup	AIFM3	Pathogenic	criteria provided, single submitter
4280597	GRCh37/hg19 22q11.21(chr22:18648855-21800471)x3	AIFM3	Pathogenic	criteria provided, single submitter
4820059	NC_000022.11:g.(18870000_18902000)_(21111000_21407000)dup	AIFM3	Pathogenic	criteria provided, single submitter
625582	GRCh37/hg19 22q11.21(chr22:18609712-21408430)	AIFM3	Pathogenic	criteria provided, single submitter
625583	GRCh37/hg19 22q11.21(chr22:18611223-21408430)	AIFM3	Pathogenic	criteria provided, single submitter
625584	GRCh37/hg19 22q11.21(chr22:18650745-21460220)	AIFM3	Pathogenic	criteria provided, single submitter
625585	GRCh37/hg19 22q11.21(chr22:18650803-21460220)	AIFM3	Pathogenic	criteria provided, single submitter
625587	GRCh37/hg19 22q11.21(chr22:18650803-21386010)	AIFM3	Pathogenic	criteria provided, single submitter
625588	GRCh37/hg19 22q11.21(chr22:18892575-21460220)	AIFM3	Pathogenic	criteria provided, single submitter
625681	GRCh37/hg19 22q11.21(chr22:18912514-21431174)	AIFM3	Pathogenic	criteria provided, single submitter
636286	GRCh37/hg19 22q11.21(chr22:18937380-21459713)x3	AIFM3	Pathogenic	no assertion criteria provided
636287	GRCh37/hg19 22q11.21(chr22:18648855-21927646)x3	AIFM3	Pathogenic	no assertion criteria provided
636288	GRCh37/hg19 22q11.21(chr22:19819477-21464764)x3	AIFM3	Pathogenic	no assertion criteria provided
625589	GRCh37/hg19 22q11.21(chr22:18892575-20308800)	ARVCF	Pathogenic	criteria provided, single submitter
625590	GRCh37/hg19 22q11.21(chr22:18900755-21075586)	ARVCF	Pathogenic	criteria provided, single submitter
2574689	GRCh37/hg19 22q11.21(chr22:18916842-20311810)	COMT	Pathogenic	no assertion criteria provided
625622	GRCh37/hg19 22q11.21(chr22:18923898-21431174)	ESS2	Pathogenic	criteria provided, single submitter
1703237	Single allele	LOC130067009	Pathogenic	criteria provided, single submitter
625619	GRCh37/hg19 22q11.21(chr22:18912514-21922035)	MRPL40	Pathogenic	criteria provided, single submitter
981206	GRCh37/hg19 22q11.1-12.1(chr22:16888899-26483608)x3	RTN4R	Pathogenic	no assertion criteria provided
636285	GRCh37/hg19 22q11.21(chr22:18648855-21461017)x3	THAP7	Pathogenic	no assertion criteria provided
1703646	GRCh37/hg19 22q11.21(chr22:20732808-21465659)	AIFM3	Likely pathogenic	no assertion criteria provided
1330164	GRCh37/hg19 22q11.21-11.22(chr22:21905051-22989041)x3	PRAME	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADA2	Orphanet:124	Diamond-Blackfan anemia
ADA2	Orphanet:404553	Deficiency of adenosine deaminase 2
ADA2	Orphanet:820	Sneddon syndrome
COMT	Orphanet:567	22q11.2 deletion syndrome
ADORA2A	Orphanet:363549	Acute encephalopathy with biphasic seizures and late reduced diffusion
ARVCF	Orphanet:567	22q11.2 deletion syndrome

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MRPL40	HGNC:14491	ENSG00000185608	Q9NQ50	Large ribosomal subunit protein mL40	clinvar
ESS2	HGNC:16817	ENSG00000100056	Q96DF8	Splicing factor ESS-2 homolog	clinvar
ADA2	HGNC:1839	ENSG00000093072	Q9NZK5	Adenosine deaminase 2	clinvar
RTN4R	HGNC:18601	ENSG00000040608	Q9BZR6	Reticulon-4 receptor	clinvar
COMT	HGNC:2228	ENSG00000093010	P21964	Catechol O-methyltransferase	clinvar
THAP7	HGNC:23190	ENSG00000184436	Q9BT49	THAP domain-containing protein 7	clinvar
ADORA2A	HGNC:263	ENSG00000128271	P29274	Adenosine receptor A2a	clinvar
AIFM3	HGNC:26398	ENSG00000183773	Q96NN9	Apoptosis-inducing factor 3	clinvar
ARVCF	HGNC:728	ENSG00000099889	O00192	Splicing regulator ARVCF	clinvar
PRAME	HGNC:9336	ENSG00000185686	P78395	Melanoma antigen preferentially expressed in tumors	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ESS2	Splicing factor ESS-2 homolog	May be involved in pre-mRNA splicing.
ADA2	Adenosine deaminase 2	Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses.
RTN4R	Reticulon-4 receptor	Receptor for RTN4, OMG and MAG.
COMT	Catechol O-methyltransferase	Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones.
THAP7	THAP domain-containing protein 7	Chromatin-associated, histone tail-binding protein that represses transcription via recruitment of HDAC3 and nuclear hormone receptor corepressors.
ADORA2A	Adenosine receptor A2a	Receptor for adenosine.
AIFM3	Apoptosis-inducing factor 3	Induces apoptosis through a caspase dependent pathway.
ARVCF	Splicing regulator ARVCF	Contributes to the regulation of alternative splicing of pre-mRNAs.
PRAME	Melanoma antigen preferentially expressed in tumors	Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex, which mediates ubiquitination of target proteins, leading to their degradation.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 6 · Druggable fraction: 0.3

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
Enzyme (other)	2	2.4×	0.695
GPCR	1	2.4×	0.695
Other/Unknown	6	1.1×	0.701
Transcription factor	1	0.8×	0.725

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MRPL40	Other/Unknown	no		Ribosomal_mL40, Ribosomal_mL40_metazoa/plant
ESS2	Other/Unknown	no		Nuclear_protein_DGCR14_ESS-2
ADA2	Enzyme (other)	yes	3.5.4.4	A_deaminase_dom, Ado/ade_deaminase, ADGF
RTN4R	Other/Unknown	no		Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
COMT	Enzyme (other)	yes	2.1.1.6	SAM_O-MeTrfase, Catechol_O-MeTrfase_euk, SAM-dependent_MTases_sf
THAP7	Transcription factor	no		THAP_Znf, THAP7
ADORA2A	GPCR	yes		GPCR_Rhodpsn, Adeno_A2A_rcpt, Adenosn_rcpt
AIFM3	Other/Unknown	no		FAD/NAD-linked_Rdtase_dimer_sf, Rieske_2Fe-2S, FAD/NAD-binding_dom
ARVCF	Other/Unknown	no		Armadillo, ARM-like, ARM-type_fold
PRAME	Other/Unknown	no		PRAME, LRR_dom_sf, LRRC14/PRAME

Expression context

Cohort genes with no expression data: 0.

7 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)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right testis	3
right hemisphere of cerebellum	3
left testis	2
cerebellar cortex	2
cerebellar hemisphere	2
biceps brachii	1
heart right ventricle	1
skeletal muscle tissue of rectus abdominis	1
sperm	1
leukocyte	1
monocyte	1
mononuclear cell	1
right adrenal gland	1
right adrenal gland cortex	1
stromal cell of endometrium	1
adenohypophysis	1
pituitary gland	1
caudate nucleus	1
nucleus accumbens	1
putamen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MRPL40	292	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, heart right ventricle
ESS2	258	ubiquitous	yes	sperm, right testis, left testis
ADA2	254	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
RTN4R	175	broad	yes	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
COMT	296	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, stromal cell of endometrium
THAP7	283	ubiquitous	marker	adenohypophysis, pituitary gland, right testis
ADORA2A	132	broad	marker	putamen, caudate nucleus, nucleus accumbens
AIFM3	180	tissue_specific	marker	mucosa of transverse colon, right frontal lobe, right hemisphere of cerebellum
ARVCF	273	ubiquitous	yes	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
PRAME	117	broad	marker	right testis, left testis, testis

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COMT	3,362
MRPL40	2,393
ADORA2A	2,108
AIFM3	2,051
ADA2	1,808
PRAME	1,804
RTN4R	1,796
THAP7	1,696
ARVCF	1,392
ESS2	1,329

Intra-cohort edges

A	B	Sources
AIFM3	THAP7	string_interaction
ARVCF	COMT	string_interaction

Structural data

PDB: 7 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADORA2A	P29274	188
MRPL40	Q9NQ50	82
COMT	P21964	12
AIFM3	Q96NN9	7
ESS2	Q96DF8	3
ADA2	Q9NZK5	2
RTN4R	Q9BZR6	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRAME	P78395	81.29
THAP7	Q9BT49	70.89
ARVCF	O00192	65.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. Enrichment computed across 10 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
Surfactant metabolism	2	147.3×	0.002	ADA2, ADORA2A
Activation of TRKA receptors	1	2284.0×	0.007	ADORA2A
Enzymatic degradation of Dopamine by monoamine oxidase	1	1142.0×	0.009	COMT
Enzymatic degradation of dopamine by COMT	1	761.3×	0.010	COMT
Adenosine P1 receptors	1	571.0×	0.010	ADORA2A
NGF-independant TRKA activation	1	456.8×	0.010	ADORA2A
p75NTR regulates axonogenesis	1	456.8×	0.010	RTN4R
Nucleotide-like (purinergic) receptors	1	380.7×	0.010	ADORA2A
Axonal growth inhibition (RHOA activation)	1	253.8×	0.014	RTN4R
Metabolism of proteins	3	7.4×	0.015	MRPL40, ADA2, ADORA2A
Methylation	1	163.1×	0.018	COMT
Signaling by NTRK1 (TRKA)	1	39.4×	0.062	ADORA2A
p75 NTR receptor-mediated signalling	1	37.4×	0.062	RTN4R
Signaling by NTRKs	1	36.2×	0.062	ADORA2A
Death Receptor Signaling	1	27.9×	0.067	RTN4R
Mitochondrial translation	1	27.5×	0.067	MRPL40
Mitochondrial translation initiation	1	25.4×	0.067	MRPL40
Mitochondrial translation elongation	1	25.4×	0.067	MRPL40
Mitochondrial ribosome-associated quality control	1	24.6×	0.067	MRPL40
Potential therapeutics for SARS	1	22.8×	0.068	COMT
Mitochondrial translation termination	1	22.0×	0.068	MRPL40
Class A/1 (Rhodopsin-like receptors)	1	14.8×	0.092	ADORA2A
G alpha (s) signalling events	1	14.6×	0.092	ADORA2A
GPCR ligand binding	1	12.8×	0.097	ADORA2A
Translation	1	12.4×	0.097	MRPL40
Signal Transduction	2	4.1×	0.097	RTN4R, ADORA2A
Signaling by Receptor Tyrosine Kinases	1	10.3×	0.110	ADORA2A
GPCR downstream signalling	1	8.7×	0.126	ADORA2A
Signaling by GPCR	1	8.0×	0.131	ADORA2A
Innate Immune System	1	5.1×	0.193	ADA2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
synaptic transmission, dopaminergic	2	421.3×	0.001	COMT, ADORA2A
response to amphetamine	2	99.1×	0.011	COMT, ADORA2A
positive regulation of circadian sleep/wake cycle, sleep	1	1685.2×	0.014	ADORA2A
norepinephrine secretion	1	1685.2×	0.014	COMT
response to dopamine	1	1685.2×	0.014	COMT
catecholamine catabolic process	1	842.6×	0.016	COMT
dopamine secretion	1	561.7×	0.016	COMT
positive regulation of acetylcholine secretion, neurotransmission	1	561.7×	0.016	ADORA2A
regulation of norepinephrine secretion	1	561.7×	0.016	ADORA2A
inosine biosynthetic process	1	561.7×	0.016	ADA2
negative regulation of alpha-beta T cell activation	1	561.7×	0.016	ADORA2A
renal filtration	1	561.7×	0.016	COMT
renin secretion into blood stream	1	421.3×	0.016	COMT
adenosine catabolic process	1	421.3×	0.016	ADA2
cellular response to phosphate starvation	1	421.3×	0.016	COMT
renal sodium excretion	1	421.3×	0.016	COMT
habituation	1	421.3×	0.016	COMT
mastication	1	421.3×	0.016	COMT
renal albumin absorption	1	337.0×	0.019	COMT
cerebellar cortex morphogenesis	1	280.9×	0.021	COMT
G protein-coupled adenosine receptor signaling pathway	1	240.7×	0.021	ADORA2A
positive regulation of glutamate secretion	1	240.7×	0.021	ADORA2A
neuronal signal transduction	1	240.7×	0.021	RTN4R
response to caffeine	1	240.7×	0.021	ADORA2A
response to purine-containing compound	1	210.7×	0.022	ADORA2A
response to salt	1	210.7×	0.022	COMT
response to angiotensin	1	187.2×	0.024	COMT
dopamine catabolic process	1	168.5×	0.025	COMT
inhibitory postsynaptic potential	1	168.5×	0.025	ADORA2A
norepinephrine metabolic process	1	153.2×	0.025	COMT

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 8

Druggability breadth: 2 of 10 evidence-associated genes (20%) 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
COMT	OPICAPONE
ADORA2A	CAFFEINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADORA2A	81	4
COMT	3	4
MRPL40	0	0
ESS2	0	0
ADA2	0	0
RTN4R	0	0
THAP7	0	0
AIFM3	0	0
ARVCF	0	0
PRAME	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OPICAPONE	4	COMT
TOLCAPONE	4	COMT
ENTACAPONE	4	COMT
CAFFEINE	4	ADORA2A
THEOPHYLLINE	4	ADORA2A
ADENOSINE	4	ADORA2A
CLOTRIMAZOLE	4	ADORA2A
THIOTHIXENE	4	ADORA2A
PYRVINIUM	4	ADORA2A
BALSALAZIDE	4	ADORA2A
IMIQUIMOD	4	ADORA2A
FEDRATINIB	4	ADORA2A
NITAZOXANIDE	4	ADORA2A
GLAFENINE	4	ADORA2A
ALLOPURINOL	4	ADORA2A
TRIOXSALEN	4	ADORA2A
PENTOSTATIN	4	ADORA2A
RIFAXIMIN	4	ADORA2A
NISOLDIPINE	4	ADORA2A
CLOFARABINE	4	ADORA2A
DAUNORUBICIN	4	ADORA2A
IBRUTINIB	4	ADORA2A
SILDENAFIL	4	ADORA2A
NIFEDIPINE	4	ADORA2A
IBUDILAST	4	ADORA2A
BITHIONOL	4	ADORA2A
REGADENOSON ANHYDROUS	4	ADORA2A
OSIMERTINIB	4	ADORA2A
RIFAMPIN	4	ADORA2A
AMPHETAMINE	4	ADORA2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
ADORA2A	1,679	Binding:1372, Functional:301, ADMET:6
COMT	55	Binding:47, ADMET:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADA2	3.5.4.4	adenosine deaminase
COMT	2.1.1.6	catechol O-methyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ADORA2A	1,679

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
COMT	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)
OPICAPONE	4	COMT
TOLCAPONE	4	COMT
ENTACAPONE	4	COMT
CAFFEINE	4	ADORA2A
THEOPHYLLINE	4	ADORA2A
ADENOSINE	4	ADORA2A
CLOTRIMAZOLE	4	ADORA2A
THIOTHIXENE	4	ADORA2A
PYRVINIUM	4	ADORA2A
BALSALAZIDE	4	ADORA2A
IMIQUIMOD	4	ADORA2A
FEDRATINIB	4	ADORA2A
NITAZOXANIDE	4	ADORA2A
GLAFENINE	4	ADORA2A
ALLOPURINOL	4	ADORA2A
TRIOXSALEN	4	ADORA2A
PENTOSTATIN	4	ADORA2A
RIFAXIMIN	4	ADORA2A
NISOLDIPINE	4	ADORA2A
CLOFARABINE	4	ADORA2A
DAUNORUBICIN	4	ADORA2A
IBRUTINIB	4	ADORA2A
SILDENAFIL	4	ADORA2A
NIFEDIPINE	4	ADORA2A
IBUDILAST	4	ADORA2A
BITHIONOL	4	ADORA2A
REGADENOSON ANHYDROUS	4	ADORA2A
OSIMERTINIB	4	ADORA2A
RIFAMPIN	4	ADORA2A
AMPHETAMINE	4	ADORA2A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	COMT, ADORA2A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ADA2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	7	MRPL40, ESS2, RTN4R, THAP7, AIFM3, ARVCF, PRAME

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ARVCF	0	COMT
MRPL40	0	—
ESS2	0	—
ADA2	0	—
RTN4R	0	—
THAP7	0	—
AIFM3	0	—
PRAME	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.