Anxiety

Summary

Anxiety (MONDO:0011918) is a disease with 8 cohort genes and 3,279 clinical trials. Top therapeutic interventions include midazolam, hydroxyzine, and buspirone.

At a glance

• Cohort genes: 8
• ClinVar variants: 13
• Clinical trials: 3,279

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	anxiety
Mondo ID	MONDO:0011918
MeSH	D001007
OMIM	607834
ICD-11	2027043655
UMLS	C0003467
MedGen	1613
Is cancer (heuristic)	no

Also known as: anxiety · anxiety-related personality traits

Data availability: 13 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › anxiety disorder › anxiety

Related subtypes (9): separation anxiety disorder, neurocirculatory asthenia, generalized anxiety disorder, phobic disorder, acute stress disorder, neurotic disorder, panic disorder, obsessive-compulsive disorder, mixed anxiety and depressive disorder

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

13 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 5 pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
267833	46;XY;t(6;12)(q14;q24);20p+dn		Pathogenic	criteria provided, single submitter
267861	46;XX;t(2;11)(q11.2;p13)dn		Pathogenic	criteria provided, single submitter
267885	46;XY;t(2;6)(q33;q21)dn		Pathogenic	criteria provided, single submitter
267887	46;XY;t(1;2)(p34.2;q35)dn		Pathogenic	criteria provided, single submitter
983221	NM_022474.4(PALS1):c.1289A>G (p.Glu430Gly)	PALS1	Pathogenic	criteria provided, single submitter
373971	NM_000190.4(HMBS):c.958del (p.Ala320fs)	HMBS	Likely pathogenic	no assertion criteria provided
523565	NM_021728.4(OTX2):c.191_193delinsGG (p.Leu64fs)	OTX2	Likely pathogenic	criteria provided, single submitter
986255	NM_003709.4(KLF7):c.410C>T (p.Thr137Met)	KLF7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
812547	NM_000651.6(CR1):c.6283C>A (p.His2095Asn)	CR1	Uncertain significance	criteria provided, single submitter
1030658	NM_000190.4(HMBS):c.671T>C (p.Val224Ala)	HMBS	Uncertain significance	criteria provided, single submitter
2570695	NM_001039469.3(MARK2):c.1931G>T (p.Arg644Leu)	MARK2	Uncertain significance	criteria provided, single submitter
2570679	NM_032538.3(TTBK1):c.367C>T (p.Arg123Ter)	TTBK1	Uncertain significance	criteria provided, single submitter
2571641	NM_005428.4(VAV1):c.909del (p.Asp303fs)	VAV1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PALS1	Orphanet:528084	Non-specific syndromic intellectual disability
HMBS	Orphanet:79276	Acute intermittent porphyria
OTX2	Orphanet:178364	Syndromic microphthalmia type 5
OTX2	Orphanet:3157	Septo-optic dysplasia spectrum
OTX2	Orphanet:35612	Nanophthalmos
OTX2	Orphanet:95494	Combined pituitary hormone deficiencies, genetic forms
OTX2	Orphanet:98938	Colobomatous microphthalmia
OTX2	Orphanet:990	Agnathia-holoprosencephaly-situs inversus syndrome
OTX2	Orphanet:99001	Butterfly-shaped pigment dystrophy

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
VAV1	HGNC:12657	ENSG00000141968	P15498	Proto-oncogene vav	clinvar
PALS1	HGNC:18669	ENSG00000072415	Q8N3R9	Protein PALS1	clinvar
TTBK1	HGNC:19140	ENSG00000146216	Q5TCY1	Tau-tubulin kinase 1	clinvar
CR1	HGNC:2334	ENSG00000203710	P17927	Complement receptor type 1	clinvar
MARK2	HGNC:3332	ENSG00000072518	Q7KZI7	Serine/threonine-protein kinase MARK2	clinvar
HMBS	HGNC:4982	ENSG00000256269	P08397	Porphobilinogen deaminase	clinvar
KLF7	HGNC:6350	ENSG00000118263	O75840	Krueppel-like factor 7	clinvar
OTX2	HGNC:8522	ENSG00000165588	P32243	Homeobox protein OTX2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VAV1	Proto-oncogene vav	Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.
PALS1	Protein PALS1	Plays a role in tight junction biogenesis and in the establishment of cell polarity in epithelial cells.
TTBK1	Tau-tubulin kinase 1	Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues.
CR1	Complement receptor type 1	Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages.
MARK2	Serine/threonine-protein kinase MARK2	Serine/threonine-protein kinase.
HMBS	Porphobilinogen deaminase	As part of the heme biosynthetic pathway, catalyzes the sequential polymerization of four molecules of porphobilinogen to form hydroxymethylbilane, also known as preuroporphyrinogen.
KLF7	Krueppel-like factor 7	Transcriptional factor.
OTX2	Homeobox protein OTX2	Transcription factor probably involved in the development of the brain and the sense organs.

Protein-family classification

Druggable: 5 · Difficult: 3 · Unknown: 0 · Druggable fraction: 0.62

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	10.4×	0.011
Complement	1	33.5×	0.074
Transcription factor	2	2.1×	0.419
Scaffold/PPI	1	2.2×	0.474
Enzyme (other)	1	1.5×	0.502

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VAV1	Scaffold/PPI	no		DH_dom, SH2, GDS_CDC24_CS
PALS1	Kinase	yes		SH3_domain, PDZ, L27_dom
TTBK1	Kinase	yes	2.7.11.26	Prot_kinase_dom, Kinase-like_dom_sf, Protein_kinase_ATP_BS
CR1	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, SEZ6_CSMD_C4BPB_Regulators
MARK2	Kinase	yes		Prot_kinase_dom, KA1_dom, Ser/Thr_kinase_AS
HMBS	Enzyme (other)	yes	2.5.1.61	HemC, Porphobilin_deaminase_N, Porphobilinogen_deaminase_C
KLF7	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
OTX2	Transcription factor	no		HD, Otx2_TF, Otx_TF

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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	2
monocyte	2
leukocyte	1
germinal epithelium of ovary	1
jejunal mucosa	1
ventricular zone	1
lateral nuclear group of thalamus	1
postcentral gyrus	1
prefrontal cortex	1
blood	1
mononuclear cell	1
esophagus mucosa	1
lower esophagus mucosa	1
bone marrow	1
bone marrow cell	1
trabecular bone tissue	1
buccal mucosa cell	1
cortical plate	1
saphenous vein	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VAV1	188	broad	marker	granulocyte, monocyte, leukocyte
PALS1	272	ubiquitous	marker	jejunal mucosa, ventricular zone, germinal epithelium of ovary
TTBK1	126	broad	yes	lateral nuclear group of thalamus, prefrontal cortex, postcentral gyrus
CR1	184	broad	marker	blood, monocyte, mononuclear cell
MARK2	188	ubiquitous	marker	lower esophagus mucosa, granulocyte, esophagus mucosa
HMBS	271	ubiquitous	marker	trabecular bone tissue, bone marrow, bone marrow cell
KLF7	283	ubiquitous	marker	buccal mucosa cell, cortical plate, saphenous vein
OTX2	62	broad	marker	secondary oocyte, oocyte, pigmented layer of retina

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VAV1	3,042
PALS1	2,825
MARK2	2,461
OTX2	2,368
TTBK1	1,784
CR1	1,218
KLF7	925
HMBS	44

Structural data

PDB: 6 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTBK1	Q5TCY1	16
HMBS	P08397	11
VAV1	P15498	10
PALS1	Q8N3R9	9
CR1	P17927	7
MARK2	Q7KZI7	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OTX2	P32243	60.99
KLF7	O75840	55.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 33. Enrichment computed across 8 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
SARS-CoV-1 targets PDZ proteins in cell-cell junction	1	2284.0×	0.014	PALS1
SARS-CoV-2 targets PDZ proteins in cell-cell junction	1	456.8×	0.027	PALS1
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	228.4×	0.027	CR1
Formation of the posterior neural plate	1	228.4×	0.027	OTX2
Formation of the anterior neural plate	1	207.6×	0.027	OTX2
CD28 dependent Vav1 pathway	1	175.7×	0.027	VAV1
Heme biosynthesis	1	152.3×	0.027	HMBS
Erythropoietin activates RAS	1	152.3×	0.027	VAV1
Regulation of signaling by CBL	1	99.3×	0.031	VAV1
Azathioprine ADME	1	99.3×	0.031	VAV1
VEGFR2 mediated vascular permeability	1	81.6×	0.031	VAV1
Tight junction interactions	1	73.7×	0.031	PALS1
FCERI mediated Ca+2 mobilization	1	71.4×	0.031	VAV1
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	71.4×	0.031	VAV1
FCERI mediated MAPK activation	1	69.2×	0.031	VAV1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1	63.4×	0.031	VAV1
GPVI-mediated activation cascade	1	61.7×	0.031	VAV1
Signaling by SCF-KIT	1	49.6×	0.037	VAV1
Regulation of Complement cascade	1	46.6×	0.037	CR1
FCGR3A-mediated phagocytosis	1	37.4×	0.040	VAV1
NRAGE signals death through JNK	1	36.8×	0.040	VAV1
Regulation of actin dynamics for phagocytic cup formation	1	36.8×	0.040	VAV1
RHOG GTPase cycle	1	29.7×	0.047	VAV1
VEGFA-VEGFR2 Pathway	1	27.9×	0.047	VAV1
G alpha (12/13) signalling events	1	27.5×	0.047	VAV1
Constitutive Signaling by Aberrant PI3K in Cancer	1	25.4×	0.047	VAV1
RAC2 GTPase cycle	1	25.4×	0.047	VAV1
Potential therapeutics for SARS	1	22.8×	0.051	VAV1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	19.4×	0.058	VAV1
RHOA GTPase cycle	1	14.9×	0.072	VAV1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
establishment or maintenance of epithelial cell apical/basal polarity	2	145.3×	0.009	PALS1, MARK2
immune complex clearance by erythrocytes	1	2106.5×	0.010	CR1
protein localization to myelin sheath abaxonal region	1	2106.5×	0.010	PALS1
positive regulation of astrocyte activation	1	2106.5×	0.010	TTBK1
negative regulation of serine-type endopeptidase activity	1	2106.5×	0.010	CR1
organ or tissue specific immune response	1	1053.2×	0.011	CR1
immune complex clearance	1	1053.2×	0.011	CR1
negative regulation of plasma cell differentiation	1	1053.2×	0.011	CR1
positive regulation of activation of membrane attack complex	1	702.2×	0.011	CR1
negative regulation of activation of membrane attack complex	1	702.2×	0.011	CR1
establishment or maintenance of polarity of embryonic epithelium	1	702.2×	0.011	PALS1
negative regulation of complement activation, alternative pathway	1	702.2×	0.011	CR1
positive regulation of serine-type endopeptidase activity	1	702.2×	0.011	CR1
regulation of neurofibrillary tangle assembly	1	702.2×	0.011	MARK2
regulation of epidermal cell differentiation	1	526.6×	0.013	KLF7
establishment or maintenance of cell polarity regulating cell shape	1	526.6×	0.013	MARK2
positive regulation of protein polymerization	1	421.3×	0.013	TTBK1
negative regulation of complement activation	1	421.3×	0.013	CR1
negative regulation of complement-dependent cytotoxicity	1	421.3×	0.013	CR1
regulation of fibroblast growth factor receptor signaling pathway	1	300.9×	0.015	OTX2
negative regulation of complement activation, classical pathway	1	300.9×	0.015	CR1
negative regulation of adipose tissue development	1	300.9×	0.015	KLF7
positive regulation of gastrulation	1	300.9×	0.015	OTX2
axon guidance	2	22.6×	0.015	KLF7, OTX2
negative regulation of immunoglobulin production	1	263.3×	0.015	CR1
positive regulation of microglial cell activation	1	263.3×	0.015	TTBK1
immune response-regulating cell surface receptor signaling pathway	1	234.1×	0.015	VAV1
myelin assembly	1	234.1×	0.015	PALS1
morphogenesis of an epithelial sheet	1	210.7×	0.015	PALS1
obsolete protoporphyrinogen IX biosynthetic process	1	210.7×	0.015	HMBS

Therapeutics

Drugs indicated for this disease

16 approved, 100 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Alprazolam	Approved (phase 4)
Bromazepam	Approved (phase 4)
Buspirone	Approved (phase 4)
Chlordiazepoxide	Approved (phase 4)
Clobazam	Approved (phase 4)
Clotiazepam	Approved (phase 4)
Diazepam	Approved (phase 4)
Halazepam	Approved (phase 4)
Hydroxyzine	Approved (phase 4)
Ketazolam	Approved (phase 4)
Lorazepam	Approved (phase 4)
Mebutamate	Approved (phase 4)
Medazepam	Approved (phase 4)
Meprobamate	Approved (phase 4)
Oxazepam	Approved (phase 4)
Prazepam	Approved (phase 4)
Acamprosate	Phase 3 (in late-stage trials)
Agomelatine	Phase 3 (in late-stage trials)
Amibegron	Phase 3 (in late-stage trials)
Amisulpride	Phase 3 (in late-stage trials)
Amitriptyline	Phase 3 (in late-stage trials)
Aripiprazole	Phase 3 (in late-stage trials)
Benperidol	Phase 3 (in late-stage trials)
Benzodiazepine	Phase 3 (in late-stage trials)
Biperiden	Phase 3 (in late-stage trials)
Bromperidol	Phase 3 (in late-stage trials)
Brotizolam	Phase 3 (in late-stage trials)
Bupropion	Phase 3 (in late-stage trials)
Carbamazepine	Phase 3 (in late-stage trials)
Chloral Hydrate	Phase 3 (in late-stage trials)
Chlorprothixene	Phase 3 (in late-stage trials)
Citalopram	Phase 3 (in late-stage trials)
Clomethiazole	Phase 3 (in late-stage trials)
Clomipramine	Phase 3 (in late-stage trials)
Clonazepam	Phase 3 (in late-stage trials)
Clozapine	Phase 3 (in late-stage trials)
Dexmedetomidine	Phase 3 (in late-stage trials)
Diphenhydramine	Phase 3 (in late-stage trials)
Donepezil	Phase 3 (in late-stage trials)
Doxepin	Phase 3 (in late-stage trials)
Duloxetine	Phase 3 (in late-stage trials)
Escitalopram	Phase 3 (in late-stage trials)
Etifoxine	Phase 3 (in late-stage trials)
Fabomotizole	Phase 3 (in late-stage trials)
Fluoxetine	Phase 3 (in late-stage trials)
Flupentixol	Phase 3 (in late-stage trials)
Fluphenazine Enanthate	Phase 3 (in late-stage trials)
Flurazepam	Phase 3 (in late-stage trials)
Fluspirilene	Phase 3 (in late-stage trials)
Fluvoxamine	Phase 3 (in late-stage trials)
Gabapentin	Phase 3 (in late-stage trials)
Galantamine	Phase 3 (in late-stage trials)
Haloperidol	Phase 3 (in late-stage trials)
Hawthorn Leaf With Flower	Phase 3 (in late-stage trials)
Imagabalin	Phase 3 (in late-stage trials)
Imipramine	Phase 3 (in late-stage trials)
Lacosamide	Phase 3 (in late-stage trials)
Lamotrigine	Phase 3 (in late-stage trials)
Lavender Oil	Phase 3 (in late-stage trials)
Levetiracetam	Phase 3 (in late-stage trials)
Levomepromazine	Phase 3 (in late-stage trials)
Lithium Carbonate	Phase 3 (in late-stage trials)
Lormetazepam	Phase 3 (in late-stage trials)
Loxapine	Phase 3 (in late-stage trials)
Maprotiline	Phase 3 (in late-stage trials)
Melatonin	Phase 3 (in late-stage trials)
Melperone	Phase 3 (in late-stage trials)
Memantine	Phase 3 (in late-stage trials)
Mianserin	Phase 3 (in late-stage trials)
Midazolam	Phase 3 (in late-stage trials)
Mirtazapine	Phase 3 (in late-stage trials)
Moclobemide	Phase 3 (in late-stage trials)
Naluzotan	Phase 3 (in late-stage trials)
Nicergoline	Phase 3 (in late-stage trials)
Nitrazepam	Phase 3 (in late-stage trials)
Nortriptyline	Phase 3 (in late-stage trials)
Olanzapine	Phase 3 (in late-stage trials)
Opipramol	Phase 3 (in late-stage trials)
Oxcarbazepine	Phase 3 (in late-stage trials)
Paliperidone	Phase 3 (in late-stage trials)
Paroxetine	Phase 3 (in late-stage trials)
Perazine	Phase 3 (in late-stage trials)
Perphenazine	Phase 3 (in late-stage trials)
Phenobarbital	Phase 3 (in late-stage trials)
Phenytoin	Phase 3 (in late-stage trials)
Pimozide	Phase 3 (in late-stage trials)
Pipamperone	Phase 3 (in late-stage trials)
Piracetam	Phase 3 (in late-stage trials)
Pregabalin	Phase 3 (in late-stage trials)
Promethazine	Phase 3 (in late-stage trials)
Prothipendyl	Phase 3 (in late-stage trials)
Pyritinol	Phase 3 (in late-stage trials)
Quetiapine	Phase 3 (in late-stage trials)
Reboxetine	Phase 3 (in late-stage trials)
Risperidone	Phase 3 (in late-stage trials)
Rivastigmine	Phase 3 (in late-stage trials)
Saredutant	Phase 3 (in late-stage trials)
Sertindole	Phase 3 (in late-stage trials)
Sertraline	Phase 3 (in late-stage trials)
Sulpiride	Phase 3 (in late-stage trials)
Temazepam	Phase 3 (in late-stage trials)
Thioridazine	Phase 3 (in late-stage trials)
Tiagabine	Phase 3 (in late-stage trials)
Tiapride	Phase 3 (in late-stage trials)
Topiramate	Phase 3 (in late-stage trials)
Tranylcypromine	Phase 3 (in late-stage trials)
Trazodone	Phase 3 (in late-stage trials)
Triazolam	Phase 3 (in late-stage trials)
Trimipramine	Phase 3 (in late-stage trials)
Valerian	Phase 3 (in late-stage trials)
Valproic Acid	Phase 3 (in late-stage trials)
Zaleplon	Phase 3 (in late-stage trials)
Ziprasidone	Phase 3 (in late-stage trials)
Zolpidem	Phase 3 (in late-stage trials)
Zopiclone	Phase 3 (in late-stage trials)
Zuclopenthixol	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetaminophen, Butorphanol, Cannabidiol, Cannabinol, Clonidine, Gemcitabine, Lidocaine, Midomafetamine, Propranolol, Sodium Chloride.

Drug target analysis

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

Druggability breadth: 5 of 8 evidence-associated genes (62%) 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
MARK2	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MARK2	45	4
VAV1	0	0
PALS1	0	0
TTBK1	0	0
CR1	0	0
HMBS	0	0
KLF7	0	0
OTX2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	MARK2
FEDRATINIB	4	MARK2
RUXOLITINIB	4	MARK2
BARICITINIB	4	MARK2
TOFACITINIB	4	MARK2
BRIGATINIB	4	MARK2
NINTEDANIB	4	MARK2
SUNITINIB	4	MARK2
MIDOSTAURIN	4	MARK2
CRENOLANIB	3	MARK2
LINIFANIB	3	MARK2
DEFACTINIB	3	MARK2
RIPASUDIL	3	MARK2
DOVITINIB	3	MARK2
LESTAURTINIB	3	MARK2
RUBOXISTAURIN	3	MARK2
DORAMAPIMOD	2	MARK2
SILMITASERTIB	2	MARK2
SU-014813	2	MARK2
CENISERTIB	2	MARK2
ILORASERTIB	2	MARK2
OSI-632	2	MARK2
DECERNOTINIB	2	MARK2
NARAZACICLIB	2	MARK2
UPROSERTIB	2	MARK2
BMS-690514	2	MARK2
DANUSERTIB	2	MARK2
CERDULATINIB	2	MARK2
R-406	2	MARK2
AT-9283	2	MARK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
MARK2	356	Binding:355, Functional:1
TTBK1	74	Binding:74
HMBS	3	Binding:3
VAV1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TTBK1	2.7.11.26	tau-protein kinase
HMBS	2.5.1.61	hydroxymethylbilane synthase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MARK2	356

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; 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)
MOMELOTINIB	4	MARK2
FEDRATINIB	4	MARK2
RUXOLITINIB	4	MARK2
BARICITINIB	4	MARK2
TOFACITINIB	4	MARK2
BRIGATINIB	4	MARK2
NINTEDANIB	4	MARK2
SUNITINIB	4	MARK2
MIDOSTAURIN	4	MARK2
CRENOLANIB	3	MARK2
LINIFANIB	3	MARK2
DEFACTINIB	3	MARK2
RIPASUDIL	3	MARK2
DOVITINIB	3	MARK2
LESTAURTINIB	3	MARK2
RUBOXISTAURIN	3	MARK2
DORAMAPIMOD	2	MARK2
SILMITASERTIB	2	MARK2
SU-014813	2	MARK2
CENISERTIB	2	MARK2
ILORASERTIB	2	MARK2
OSI-632	2	MARK2
DECERNOTINIB	2	MARK2
NARAZACICLIB	2	MARK2
UPROSERTIB	2	MARK2
BMS-690514	2	MARK2
DANUSERTIB	2	MARK2
CERDULATINIB	2	MARK2
R-406	2	MARK2
AT-9283	2	MARK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MARK2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	4	PALS1, TTBK1, CR1, HMBS
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	VAV1, KLF7, OTX2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
VAV1	1	—
PALS1	0	—
TTBK1	74	—
CR1	0	—
HMBS	3	—
KLF7	0	—
OTX2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3,279.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	804
PHASE2	102
PHASE4	67
PHASE3	38
PHASE1	37
PHASE1/PHASE2	22
EARLY_PHASE1	20
PHASE2/PHASE3	10

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04245436	PHASE4	RECRUITING	Acute and Long-Term Antidepressant Treatment Success in Adolescents With Anxiety (AtLAS-A)
NCT04623099	PHASE4	RECRUITING	Pharmacogenetically-guided Escitalopram Treatment for Pediatric Anxiety: Aiming to Improve Safety and Efficacy (PrEcISE)
NCT04751864	PHASE4	ACTIVE_NOT_RECRUITING	Brain Stimulation & Generalized Anxiety Study
NCT05934669	PHASE4	RECRUITING	IN Midazolam vs IN Dexmedetomidine vs IN Ketamine During Minimal Procedures in Pediatric ED
NCT06787976	PHASE4	NOT_YET_RECRUITING	Effect of Dolutegravir Compared With Darunavir/Cobicistat on the Severity of Neuropsychiatric Effects al 12 Weeks in Antirretroviral Treatment-Naive Adults.
NCT06843044	PHASE4	RECRUITING	Efficacy and Safety of Ranquilon in Patients With Anxiety Disorders Due to Neurasthenia and Adjustment Disorders
NCT07182890	PHASE4	RECRUITING	Efficacy of Clostridium Butyricum in Alleviating Anxiety and Depression in Patients With Functional Dyspepsia
NCT07187492	PHASE4	RECRUITING	Efficacy of Bacillus Coagulans in Alleviating Anxiety and Depression in Patients With Functional Dyspepsia
NCT07432815	PHASE4	RECRUITING	Treatment of Psoriasis With Depression and/or Anxiety With Methotrexate vs Combined Methotrexate and Antidepressant
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07542730	PHASE4	NOT_YET_RECRUITING	Diphenhydramine as an Adjunct to Moderate Sedation for Procedural First Trimester Abortions
NCT00174850	PHASE4	COMPLETED	Switching From an SSRI to Tiagabine(GABITRIL) in Order to Alleviate SSRI Induced Sexual Dysfunction
NCT00302107	PHASE4	COMPLETED	A Placebo-Controlled Study of Mirtazapine for PTSD
NCT00596414	PHASE4	COMPLETED	Sedation and Analgesia for Transjugular Liver Biopsy: A Randomized Double Blind Placebo Controlled Trial
NCT00623454	PHASE4	COMPLETED	Non Cardiac Chest Pain and Benign Palpitations
NCT00676364	PHASE4	COMPLETED	Randomized Control Trial of a Topical Anesthetic to Evaluate Pain and Anxiety During Venipuncture
NCT00762099	PHASE4	UNKNOWN	Perioperative Pregabalin Use, Rehabilitation, Pain Outcomes and Anxiety Following Hip Surgery
NCT00826111	PHASE4	COMPLETED	The Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Anxiety and Insomnia
NCT00928772	PHASE4	TERMINATED	Cranial Electro Therapy Stimulation in Reducing Perioperative Anxiety
NCT00951483	PHASE4	COMPLETED	Cardiovascular Biomarkers and Quetiapine in Depression and Anxiety Patients
NCT01081249	PHASE4	COMPLETED	Effects of Oxytocin on Behavior and Physiology in a Psychotherapy Setting
NCT01148186	PHASE4	TERMINATED	An Intervention Study to Reduce the Use and Impact of Potentially Inappropriate Medications Among Older Adults
NCT01155804	PHASE4	UNKNOWN	Assessment of the Effectiveness of a Program of Preparation to Pregnancy and Delivery
NCT01285284	PHASE4	UNKNOWN	Effect of Music Over the Tolerance to Colonoscopy.
NCT01309074	PHASE4	WITHDRAWN	Does Pregabalin Improve Symptoms of Anxiety in Patients With Epilepsy? A Comparison With Sertraline
NCT01411709	PHASE4	COMPLETED	A Study On The Effect Of Vitano® On Physiological And Psychological Responses To Psychological Stress
NCT01441843	PHASE4	COMPLETED	Resistance Under the Microscope
NCT01486615	PHASE4	COMPLETED	Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone
NCT01502644	PHASE4	COMPLETED	Opioid Treatment for Chronic Low Back Pain and the Impact of Mood Symptoms
NCT01533415	PHASE4	COMPLETED	Use of Alpha-Stim Cranial-electrotherapy Stimulation (CES) in the Treatment of Anxiety
NCT01549691	PHASE4	COMPLETED	Reassessment of Premedication in Surgery
NCT01775605	PHASE4	WITHDRAWN	Study of Use of Synera for Pain During Local Skin Infiltration With Lidocaine Before Epidural Placement
NCT01830881	PHASE4	COMPLETED	Evaluation of Oral Midazolam in First-trimester Surgical Abortions
NCT01866605	PHASE4	COMPLETED	A Study of Methods to Reduce Anxiety in Preoperative Elective Surgical Patients
NCT01993459	PHASE4	COMPLETED	The Effects of Midazolam on the Quality of Postoperative Recovery
NCT02028026	PHASE4	WITHDRAWN	The Effects of Vilazodone on Glutamate in the Anterior Cingulate Cortex in Anxious Unipolar Depressives
NCT02168439	PHASE4	COMPLETED	Intranasal Dexmedetomidine vs Intranasal Midazolam as Anxiolysis Prior to Pediatric Laceration Repair
NCT02177955	PHASE4	COMPLETED	Comparative Study of Hemodynamic Changes Caused by Diazepam and Midazolam During Third Molar Surgery
NCT02213302	PHASE4	COMPLETED	Premedication by Midazolam for Emergency Surgery
NCT02213900	PHASE4	COMPLETED	Preventing Post-Operative Delirium in Patients Undergoing a Pneumonectomy, Esophagectomy or Thoracotomy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MIDAZOLAM	4	25
HYDROXYZINE	4	7
BUSPIRONE	4	6
CITALOPRAM	4	6
ALPRAZOLAM	4	3
DARUNAVIR	4	3
DEXMEDETOMIDINE	4	3
MELATONIN	4	3
MIRTAZAPINE	4	3
ONDANSETRON	4	3
VILAZODONE	4	3
CANNABIDIOL	4	2
CLONIDINE	4	2
DIAZEPAM	4	2
DULOXETINE	4	2
LORAZEPAM	4	2
NIACIN	4	2
NITROUS OXIDE	4	2
OXYGEN	4	2
PRAMIPEXOLE	4	2
ZOPICLONE	4	2
ACAMPROSATE	4	1
BREXPIPRAZOLE	4	1
BUPIVACAINE	4	1
CARVEDILOL	4	1
CLOBAZAM	4	1
CYCLOSERINE	4	1
DEXKETOPROFEN	4	1
DIPHENHYDRAMINE	4	1
DOLUTEGRAVIR	4	1