2q37 microdeletion syndrome

Summary

2q37 microdeletion syndrome (MONDO:0010886) is a disease with 9 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 9
• ClinVar variants: 27
• Phenotypes (HPO): 52
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		115	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

52 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000311	Round face	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0011800	Midface retrusion	Very frequent (80-99%)
HP:0001382	Joint hypermobility	Frequent (30-79%)
HP:0000233	Thin vermilion border	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000430	Underdeveloped nasal alae	Frequent (30-79%)
HP:0000463	Anteverted nares	Frequent (30-79%)
HP:0000490	Deeply set eye	Frequent (30-79%)
HP:0000582	Upslanted palpebral fissure	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000964	Eczematoid dermatitis	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001513	Obesity	Frequent (30-79%)
HP:0001537	Umbilical hernia	Frequent (30-79%)
HP:0001770	Toe syndactyly	Frequent (30-79%)
HP:0001773	Short foot	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002209	Sparse scalp hair	Frequent (30-79%)
HP:0002553	Highly arched eyebrow	Frequent (30-79%)
HP:0002558	Supernumerary nipple	Frequent (30-79%)
HP:0002714	Downturned corners of mouth	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0004279	Short palm	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0005280	Depressed nasal bridge	Frequent (30-79%)
HP:0006101	Finger syndactyly	Frequent (30-79%)
HP:0006610	Wide intermamillary distance	Frequent (30-79%)
HP:0007598	Bilateral single transverse palmar creases	Frequent (30-79%)
HP:0010049	Short metacarpal	Frequent (30-79%)
HP:0010761	Broad columella	Frequent (30-79%)
HP:0030680	Abnormal cardiovascular system morphology	Frequent (30-79%)
HP:0045075	Sparse eyebrow	Frequent (30-79%)
HP:0200055	Small hand	Frequent (30-79%)
HP:0000003	Multicystic kidney dysplasia	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000405	Conductive hearing impairment	Occasional (5-29%)
HP:0000470	Short neck	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:0000776	Congenital diaphragmatic hernia	Occasional (5-29%)
HP:0001601	Laryngomalacia	Occasional (5-29%)
HP:0001679	Abnormal aortic morphology	Occasional (5-29%)
HP:0002021	Pyloric stenosis	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0002667	Nephroblastoma	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	2q37 microdeletion syndrome
Mondo ID	MONDO:0010886
MeSH	C538317
OMIM	600430
Orphanet	1001
DOID	DOID:0111704
NCIT	C129021
SNOMED CT	702357000
UMLS	C2931817
MedGen	419169
GARD	0010202
Is cancer (heuristic)	no

Also known as: 2q37 deletion syndrome · 2q37 microdeletion syndrome · 2q37 monosomy · Albright hereditary osteodystrophy type 3 · Albright hereditary osteodystrophy-like syndrome · BDMR · brachydactyly intellectual disability syndrome · brachydactyly mental retardation syndrome · brachydactyly-intellectual disability syndrome · brachydactyly-mental retardation syndrome · Del(2)(q37) · deletion 2q37 · deletion 2q37-qter · monosomy 2q37-qter

Data availability: 27 ClinVar variants · 1 GenCC gene-disease record · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › syndrome caused by partial chromosomal deletion › partial deletion of chromosome 2 › partial deletion of the long arm of chromosome 2 › 2q37 microdeletion syndrome

Related subtypes (8): chromosome 2q32-q33 deletion syndrome, chromosome 2q31.2 deletion syndrome, 2q24 microdeletion syndrome, 2q23.1 microdeletion syndrome, 2q31.1 microdeletion syndrome, 2q33.1 microdeletion syndrome, Mowat-Wilson syndrome due to monosomy 2q22, 2q13 microdeletion 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

27 retrieved; paginated sample, class counts are floors:

12 pathogenic, 5 uncertain significance, 4 benign/likely benign, 2 likely benign, 1 not provided, 1 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1690379	NC_000002.12:g.(211789273_236710421)dup		Pathogenic	criteria provided, single submitter
4795130	NC_000016.10:g.(14833831_16263578)del		Pathogenic	criteria provided, single submitter
1703651	GRCh37/hg19 2q37.1-37.3(chr2:233227837-242783384)	ACKR3	Pathogenic	no assertion criteria provided
3362876	Single allele	ACKR3	Pathogenic	criteria provided, single submitter
981208	GRCh37/hg19 2q37.1-37.3(chr2:233110452-243028452)x1	ASB1	Pathogenic	no assertion criteria provided
1703652	GRCh37/hg19 2q37.2-37.3(chr2:236472789-242783384)	DTYMK	Pathogenic	no assertion criteria provided
625779	GRCh37/hg19 2q37.2-37.3(chr2:237028693-242708080)	FARP2	Pathogenic	criteria provided, single submitter
424498	NM_001378414.1(HDAC4):c.743C>T (p.Pro248Leu)	HDAC4	Pathogenic	criteria provided, multiple submitters, no conflicts
5069	NM_001378414.1(HDAC4):c.2414dup (p.Gly806fs)	HDAC4	Pathogenic	criteria provided, single submitter
1684635	Single allele	ILKAP	Pathogenic	criteria provided, single submitter
4280594	GRCh37/hg19 2q37.1(chr2:233832301-233833236)x1	NGEF	Pathogenic	criteria provided, single submitter
625781	GRCh37/hg19 2q37.3(chr2:239071623-243048760)	OTOS	Pathogenic	criteria provided, single submitter
625780	GRCh37/hg19 2q37.3(chr2:238795602-242918203)	COPS9	Likely pathogenic	criteria provided, single submitter
518341	NM_001378414.1(HDAC4):c.155G>A (p.Arg52His)	HDAC4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1424429	NM_001378414.1(HDAC4):c.1748C>T (p.Pro583Leu)	HDAC4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2038862	NM_001378414.1(HDAC4):c.200G>A (p.Arg67Gln)	HDAC4	Uncertain significance	criteria provided, single submitter
5070	NM_001378414.1(HDAC4):c.490+56_490+120del	HDAC4	Uncertain significance	no assertion criteria provided
594038	NM_001378414.1(HDAC4):c.1649C>T (p.Pro550Leu)	HDAC4	Uncertain significance	criteria provided, multiple submitters, no conflicts
983139	NM_001378414.1(HDAC4):c.1387C>T (p.Gln463Ter)	HDAC4	Uncertain significance	criteria provided, single submitter
281400	NM_001378414.1(HDAC4):c.1809G>A (p.Glu603=)	HDAC4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
283520	NM_001378414.1(HDAC4):c.2371G>A (p.Ala791Thr)	HDAC4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
284218	NM_001378414.1(HDAC4):c.684G>A (p.Pro228=)	HDAC4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
445663	NM_001378414.1(HDAC4):c.2532+18G>A	HDAC4	Likely benign	criteria provided, multiple submitters, no conflicts
719998	NM_001378414.1(HDAC4):c.1534-9G>A	HDAC4	Likely benign	criteria provided, multiple submitters, no conflicts
774111	NM_001378414.1(HDAC4):c.111G>A (p.Ala37=)	HDAC4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
801915	NM_001378414.1(HDAC4):c.95-98del	HDAC4	Benign	criteria provided, multiple submitters, no conflicts
2581141	NM_001378414.1(HDAC4):c.602A>G (p.Tyr201Cys)	HDAC4	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
HDAC4	Limited	Unknown	2q37 microdeletion syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HDAC4	Orphanet:1001	2q37 microdeletion syndrome

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HDAC4	HGNC:14063	ENSG00000068024	P56524	Histone deacetylase 4	gencc,clinvar
ILKAP	HGNC:15566	ENSG00000132323	Q9H0C8	Integrin-linked kinase-associated serine/threonine phosphatase 2C	clinvar
ASB1	HGNC:16011	ENSG00000065802	Q9Y576	Ankyrin repeat and SOCS box protein 1	clinvar
FARP2	HGNC:16460	ENSG00000006607	O94887	FERM, ARHGEF and pleckstrin domain-containing protein 2	clinvar
COPS9	HGNC:21314	ENSG00000172428	Q8WXC6	COP9 signalosome complex subunit 9	clinvar
OTOS	HGNC:22644	ENSG00000178602	Q8NHW6	Otospiralin	clinvar
ACKR3	HGNC:23692	ENSG00000144476	P25106	Atypical chemokine receptor 3	clinvar
DTYMK	HGNC:3061	ENSG00000168393	P23919	Thymidylate kinase	clinvar
NGEF	HGNC:7807	ENSG00000066248	Q8N5V2	Ephexin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HDAC4	Histone deacetylase 4	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
ILKAP	Integrin-linked kinase-associated serine/threonine phosphatase 2C	Protein phosphatase that may play a role in regulation of cell cycle progression via dephosphorylation of its substrates whose appropriate phosphorylation states might be crucial for cell proliferation.
ASB1	Ankyrin repeat and SOCS box protein 1	Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
FARP2	FERM, ARHGEF and pleckstrin domain-containing protein 2	Functions as a guanine nucleotide exchange factor that activates RAC1.
COPS9	COP9 signalosome complex subunit 9	Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes.
OTOS	Otospiralin	May be essential for the survival of the neurosensory epithelium of the inner ear.
ACKR3	Atypical chemokine receptor 3	Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degrad…
DTYMK	Thymidylate kinase	Catalyzes the phosphorylation of thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), the immediate precursor for the DNA building block dTTP, with ATP as the preferred phosphoryl donor in the presence of Mg(2+).
NGEF	Ephexin-1	Acts as a guanine nucleotide exchange factor (GEF) which differentially activates the GTPases RHOA, RAC1 and CDC42.

Protein-family classification

Druggable: 4 · Difficult: 3 · Unknown: 2 · Druggable fraction: 0.44

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
Scaffold/PPI	3	5.8×	0.075
Phosphatase	1	9.3×	0.307
Kinase	1	3.1×	0.478
GPCR	1	2.7×	0.478
Enzyme (other)	1	1.3×	0.652
Other/Unknown	2	0.4×	0.992

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HDAC4	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
ILKAP	Phosphatase	yes		PP2C_BS, PPM-type_phosphatase-like_dom, PP2C
ASB1	Scaffold/PPI	no		SOCS_box, Ankyrin_rpt, SOCS_box-like_dom_sf
FARP2	Scaffold/PPI	no		DH_dom, FERM_domain, Ez/rad/moesin-like
COPS9	Other/Unknown	no		CSN9_metazoa
OTOS	Other/Unknown	no		Otospiralin
ACKR3	GPCR	yes		GPCR_Rhodpsn, ACKR3, GPCR_Rhodpsn_7TM
DTYMK	Kinase	yes	2.7.4.9	Thymidylate_kinase, Thymidylate_kin_CS, P-loop_NTPase
NGEF	Scaffold/PPI	no		DH_dom, SH3_domain, PH_domain

Expression context

Cohort genes with no expression data: 0.

8 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	2
gastrocnemius	1
gluteal muscle	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
C1 segment of cervical spinal cord	1
apex of heart	1
nucleus accumbens	1
adrenal tissue	1
colonic epithelium	1
Brodmann (1909) area 9	1
amygdala	1
upper arm skin	1
adenohypophysis	1
left lobe of thyroid gland	1
pituitary gland	1
synovial joint	1
tendon of biceps brachii	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HDAC4	277	ubiquitous	marker	sural nerve, gluteal muscle, gastrocnemius
ILKAP	276	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
ASB1	270	ubiquitous	marker	apex of heart, C1 segment of cervical spinal cord, nucleus accumbens
FARP2	267	ubiquitous	marker	colonic epithelium, adrenal tissue, sural nerve
COPS9	256	ubiquitous	marker	upper arm skin, amygdala, Brodmann (1909) area 9
OTOS	73	tissue_specific	yes	pituitary gland, adenohypophysis, left lobe of thyroid gland
ACKR3	278	ubiquitous	marker	synovial joint, vena cava, tendon of biceps brachii
DTYMK	224	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, mucosa of transverse colon
NGEF	213	broad	marker	prefrontal cortex, Brodmann (1909) area 46, parietal lobe

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HDAC4	4,771
DTYMK	2,508
ILKAP	2,218
ASB1	1,510
NGEF	1,418
ACKR3	1,142
FARP2	1,118
COPS9	614
OTOS	323

Intra-cohort edges

A	B	Sources
COPS9	OTOS	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DTYMK	P23919	21
HDAC4	P56524	19
ACKR3	P25106	14
COPS9	Q8WXC6	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ILKAP	Q9H0C8	81.99
OTOS	Q8NHW6	81.86
ASB1	Q9Y576	80.61
FARP2	O94887	76.34
NGEF	Q8N5V2	72.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 35. Enrichment computed across 9 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX2 regulates chondrocyte maturation	1	380.7×	0.061	HDAC4
RUNX3 regulates p14-ARF	1	190.3×	0.061	HDAC4
RAC1 GTPase cycle	2	20.4×	0.061	FARP2, NGEF
SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion	1	126.9×	0.069	FARP2
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	82.8×	0.069	FARP2
Notch-HLH transcription pathway	1	68.0×	0.069	HDAC4
EPHA-mediated growth cone collapse	1	63.4×	0.069	NGEF
Interconversion of nucleotide di- and triphosphates	1	59.5×	0.069	DTYMK
SUMOylation of intracellular receptors	1	56.0×	0.069	HDAC4
Metabolism of nucleotides	1	50.1×	0.069	DTYMK
NOTCH1 Intracellular Domain Regulates Transcription	1	39.6×	0.075	HDAC4
Constitutive Signaling by NOTCH1 PEST Domain Mutants	1	32.8×	0.075	HDAC4
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	1	32.8×	0.075	HDAC4
Chemokine receptors bind chemokines	1	31.2×	0.075	ACKR3
NRAGE signals death through JNK	1	30.7×	0.075	NGEF
SUMOylation of chromatin organization proteins	1	26.4×	0.081	HDAC4
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	24.4×	0.083	HDAC4
G alpha (12/13) signalling events	1	22.9×	0.083	NGEF
RHOA GTPase cycle	1	12.4×	0.126	NGEF
Class A/1 (Rhodopsin-like receptors)	1	12.4×	0.126	ACKR3
Peptide ligand-binding receptors	1	12.4×	0.126	ACKR3
CDC42 GTPase cycle	1	12.1×	0.126	NGEF
Class I MHC mediated antigen processing & presentation	1	11.7×	0.126	ASB1
GPCR ligand binding	1	10.7×	0.131	ACKR3
Neddylation	1	7.9×	0.168	ASB1
GPCR downstream signalling	1	7.2×	0.176	ACKR3
Signaling by GPCR	1	6.7×	0.181	ACKR3
G alpha (i) signalling events	1	6.5×	0.181	ACKR3
Antigen processing: Ubiquitination & Proteasome degradation	1	6.2×	0.182	ASB1
Adaptive Immune System	1	5.0×	0.216	ASB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
dUDP biosynthetic process	1	936.2×	0.013	DTYMK
dTDP biosynthetic process	1	936.2×	0.013	DTYMK
oculomotor nerve development	1	936.2×	0.013	ACKR3
negative regulation of protein neddylation	1	936.2×	0.013	COPS9
regulation of integrin activation	1	624.1×	0.013	FARP2
thymidine biosynthetic process	1	624.1×	0.013	DTYMK
negative regulation of protein refolding	1	624.1×	0.013	HDAC4
negative regulation of protein localization to nucleolus	1	624.1×	0.013	COPS9
positive regulation of mesenchymal stem cell migration	1	468.1×	0.015	ACKR3
dTTP biosynthetic process	1	374.5×	0.016	DTYMK
negative regulation of dendritic spine morphogenesis	1	374.5×	0.016	NGEF
hair cycle process	1	312.1×	0.017	FARP2
response to denervation involved in regulation of muscle adaptation	1	267.5×	0.018	HDAC4
podosome assembly	1	234.1×	0.018	FARP2
regulation of synapse pruning	1	234.1×	0.018	NGEF
obsolete negative regulation of transcription by competitive promoter binding	1	144.0×	0.025	HDAC4
positive regulation of protein sumoylation	1	144.0×	0.025	HDAC4
neuron remodeling	1	133.8×	0.025	FARP2
negative regulation of myotube differentiation	1	124.8×	0.025	HDAC4
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1	124.8×	0.025	ACKR3
cardiac muscle hypertrophy in response to stress	1	117.0×	0.025	HDAC4
negative regulation of glycolytic process	1	117.0×	0.025	HDAC4
male genitalia development	1	98.5×	0.029	ASB1
Rac protein signal transduction	1	62.4×	0.041	FARP2
negative regulation of cytokine production	1	56.7×	0.041	ASB1
regulation of GTPase activity	1	56.7×	0.041	NGEF
response to interleukin-1	1	56.7×	0.041	HDAC4
nervous system development	2	10.2×	0.041	HDAC4, NGEF
B cell activation	1	50.6×	0.044	HDAC4
negative regulation of gene expression, epigenetic	1	44.6×	0.044	HDAC4

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 9 evidence-associated genes (44%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
HDAC4	CELECOXIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HDAC4	31	4
ILKAP	0	0
ASB1	0	0
FARP2	0	0
COPS9	0	0
OTOS	0	0
ACKR3	0	0
DTYMK	0	0
NGEF	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CELECOXIB	4	HDAC4
PHENYLBUTANOIC ACID	4	HDAC4
SODIUM PHENYLBUTYRATE	4	HDAC4
ROMIDEPSIN	4	HDAC4
BELINOSTAT	4	HDAC4
PANOBINOSTAT	4	HDAC4
VORINOSTAT	4	HDAC4
GIVINOSTAT	4	HDAC4
BENDAMUSTINE	4	HDAC4
CURCUMIN	3	HDAC4
CAFFEIC ACID	3	HDAC4
PRACINOSTAT	3	HDAC4
TACEDINALINE	3	HDAC4
ENTINOSTAT	3	HDAC4
TUCIDINOSTAT	3	HDAC4
ABEXINOSTAT	3	HDAC4
TASQUINIMOD	3	HDAC4
NANATINOSTAT	2	HDAC4
AR-42	2	HDAC4
CHLOROGENIC ACID	2	HDAC4
DACINOSTAT	2	HDAC4
FIMEPINOSTAT	2	HDAC4
QUISINOSTAT	2	HDAC4
RICOLINOSTAT	2	HDAC4
TINOSTAMUSTINE	2	HDAC4
PYROXAMIDE	1	HDAC4
CUDC-101	1	HDAC4
R-306465	1	HDAC4
GAMMA-AMINOBUTYRIC ACID	1	HDAC4
TRICHOSTATIN	1	HDAC4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
HDAC4	1,941	Binding:1919, ADMET:13, Functional:6, Toxicity:3
ACKR3	102	Binding:77, Functional:24, ADMET:1
DTYMK	38	Binding:36, ADMET:2
ILKAP	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HDAC4	3.5.1.98	histone deacetylase
DTYMK	2.7.4.9	dTMP kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
HDAC4	1,941
ACKR3	102

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; 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)
CELECOXIB	4	HDAC4
PHENYLBUTANOIC ACID	4	HDAC4
SODIUM PHENYLBUTYRATE	4	HDAC4
ROMIDEPSIN	4	HDAC4
BELINOSTAT	4	HDAC4
PANOBINOSTAT	4	HDAC4
VORINOSTAT	4	HDAC4
GIVINOSTAT	4	HDAC4
BENDAMUSTINE	4	HDAC4
CURCUMIN	3	HDAC4
CAFFEIC ACID	3	HDAC4
PRACINOSTAT	3	HDAC4
TACEDINALINE	3	HDAC4
ENTINOSTAT	3	HDAC4
TUCIDINOSTAT	3	HDAC4
ABEXINOSTAT	3	HDAC4
TASQUINIMOD	3	HDAC4
NANATINOSTAT	2	HDAC4
AR-42	2	HDAC4
CHLOROGENIC ACID	2	HDAC4
DACINOSTAT	2	HDAC4
FIMEPINOSTAT	2	HDAC4
QUISINOSTAT	2	HDAC4
RICOLINOSTAT	2	HDAC4
TINOSTAMUSTINE	2	HDAC4
PYROXAMIDE	1	HDAC4
CUDC-101	1	HDAC4
R-306465	1	HDAC4
GAMMA-AMINOBUTYRIC ACID	1	HDAC4
TRICHOSTATIN	1	HDAC4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HDAC4
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	ACKR3, DTYMK
D	Druggable family + AlphaFold only, no drug	1	ILKAP
E	Difficult family or no structure, no drug	5	ASB1, FARP2, COPS9, OTOS, NGEF

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)
ACKR3	102	—
ILKAP	6	—
ASB1	0	—
FARP2	0	—
COPS9	0	—
OTOS	0	—
DTYMK	38	—
NGEF	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
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight