Intellectual disability, autosomal dominant 1

Summary

Intellectual disability, autosomal dominant 1 (MONDO:0007974) is a disease caused by MBD5 (GenCC Strong), with 9 cohort genes.

At a glance

• Causal gene: MBD5 (GenCC Strong)
• Cohort genes: 9
• ClinVar variants: 1,443

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 1
Mondo ID	MONDO:0007974
MeSH	C566947
OMIM	156200
DOID	DOID:0070031
NCIT	C141424
UMLS	C1969562
MedGen	409857
GARD	0018623
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 1 · autosomal dominant non-syndromic intellectual disability caused by mutation in MBD5 · intellectual disability, autosomal dominant 1 · intellectual disability, autosomal dominant type 1 · MBD5 autosomal dominant non-syndromic intellectual disability · mental retardation, autosomal dominant 1 · mental retardation, autosomal dominant type 1 · MRD1

Data availability: 1,443 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › intellectual disability, autosomal dominant › intellectual disability, autosomal dominant 1

Related subtypes (28): intellectual disability, autosomal dominant 3, intellectual disability, autosomal dominant 4, intellectual disability, autosomal dominant 5, intellectual disability, autosomal dominant 6, intellectual disability, autosomal dominant 2, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, intellectual disability, autosomal dominant 9, intellectual disability, autosomal dominant 10, intellectual disability, autosomal dominant 11, intellectual disability, autosomal dominant 24, intellectual disability, autosomal dominant 38, intellectual disability, autosomal dominant 39, intellectual disability, autosomal dominant 40, intellectual disability, autosomal dominant 42, autosomal dominant non-syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 65, intellectual developmental disorder, autosomal dominant 69, intellectual developmental disorder, autosomal dominant 66, intellectual developmental disorder, autosomal dominant 64, intellectual developmental disorder, autosomal dominant 67, intellectual developmental disorder, autosomal dominant 68, autosomal dominant syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 70, intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, intellectual developmental disorder, autosomal dominant 72, intellectual developmental disorder, autosomal dominant 74, intellectual developmental disorder, autosomal dominant 75, intellectual developmental disorder, autosomal dominant 76

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:

258 uncertain significance, 204 likely benign, 63 conflicting classifications of pathogenicity, 36 pathogenic, 22 benign/likely benign, 9 benign, 7 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
183384	NC_000002.10:g.146798229_150310317del		Pathogenic	no assertion criteria provided
183383	NC_000002.10:g.148447496_149377297del	EPC2	Pathogenic	no assertion criteria provided
183385	NC_000002.10:g.(148432391_148447295)_(148651456_148737275)del	LOC126806366	Pathogenic	no assertion criteria provided
1069933	NM_001378120.1(MBD5):c.469_476del (p.Thr157fs)	MBD5	Pathogenic	criteria provided, single submitter
1072505	NM_001378120.1(MBD5):c.4585C>T (p.Arg1529Ter)	MBD5	Pathogenic	criteria provided, single submitter
1074163	NM_001378120.1(MBD5):c.707C>G (p.Ser236Ter)	MBD5	Pathogenic	criteria provided, single submitter
1075127	NM_001378120.1(MBD5):c.180C>A (p.Cys60Ter)	MBD5	Pathogenic	criteria provided, multiple submitters, no conflicts
1075681	NM_001378120.1(MBD5):c.1449del (p.Ser484fs)	MBD5	Pathogenic	criteria provided, single submitter
1075828	NM_001378120.1(MBD5):c.598C>T (p.Arg200Ter)	MBD5	Pathogenic	criteria provided, multiple submitters, no conflicts
1292054	NM_001378120.1(MBD5):c.3828dup (p.Asn1277fs)	MBD5	Pathogenic	no assertion criteria provided
1413133	NM_001378120.1(MBD5):c.1188del (p.Met396fs)	MBD5	Pathogenic	criteria provided, single submitter
1423243	NM_001378120.1(MBD5):c.3907C>T (p.Gln1303Ter)	MBD5	Pathogenic	criteria provided, single submitter
1425995	NM_001378120.1(MBD5):c.143del (p.Glu48fs)	MBD5	Pathogenic	criteria provided, single submitter
1427792	NM_001378120.1(MBD5):c.2356C>T (p.Gln786Ter)	MBD5	Pathogenic	criteria provided, single submitter
1429634	NM_001378120.1(MBD5):c.3769del (p.Asp1257fs)	MBD5	Pathogenic	criteria provided, single submitter
1437405	NM_001378120.1(MBD5):c.1379C>A (p.Ser460Ter)	MBD5	Pathogenic	criteria provided, single submitter
1439480	NM_001378120.1(MBD5):c.1648del (p.Ser550fs)	MBD5	Pathogenic	criteria provided, single submitter
1450097	NM_001378120.1(MBD5):c.2113del (p.Leu705fs)	MBD5	Pathogenic	criteria provided, single submitter
1451143	NM_001378120.1(MBD5):c.4729del (p.Ser1577fs)	MBD5	Pathogenic	criteria provided, single submitter
1453746	NM_001378120.1(MBD5):c.1499_1500dup (p.Arg501fs)	MBD5	Pathogenic	criteria provided, single submitter
1455491	NM_001378120.1(MBD5):c.3572del (p.Thr1190_Leu1191insTer)	MBD5	Pathogenic	criteria provided, single submitter
1456069	NM_001378120.1(MBD5):c.3790A>T (p.Arg1264Ter)	MBD5	Pathogenic	criteria provided, single submitter
1457775	NM_001378120.1(MBD5):c.710_725del (p.Ile237fs)	MBD5	Pathogenic	criteria provided, single submitter
1459105	NC_000002.11:g.(?149216328)(149228050_?)del	MBD5	Pathogenic	criteria provided, single submitter
1460283	NC_000002.11:g.(?148730288)(149270510_?)del	MBD5	Pathogenic	criteria provided, single submitter
1703242	NM_001378120.1(MBD5):c.4869G>A (p.Trp1623Ter)	MBD5	Pathogenic	criteria provided, multiple submitters, no conflicts
1703533	GRCh37/hg19 2q22.3-23.1(chr2:148698834-148954778)	MBD5	Pathogenic	no assertion criteria provided
1705638	NM_001378120.1(MBD5):c.14_15del (p.Lys5fs)	MBD5	Pathogenic	criteria provided, single submitter
1709796	NM_001378120.1(MBD5):c.74G>A (p.Trp25Ter)	MBD5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1710256	NM_001378120.1(MBD5):c.1023_1024delinsGA (p.Pro342Thr)	MBD5	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 11 · 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
MBD5	Strong	Autosomal dominant	intellectual disability, autosomal dominant 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MBD5	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
MBD5	Orphanet:228402	2q23.1 microdeletion syndrome
CIC	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
ZMYND11	Orphanet:687424	ZMYND11-related developmental delay-speech delay-seizures-behavioral abnormalities-craniofacial dysmorphism syndrome due to 10p15.3 microdeletion
ZMYND11	Orphanet:694308	ZMYND11-related developmental delay-speech delay-seizures-behavioral abnormalities-craniofacial dysmorphism syndrome due to a point mutation
CDH15	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
WDFY3	Orphanet:528084	Non-specific syndromic intellectual disability
TAOK1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
GRIA1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
GRIA1	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
ITSN1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability

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
MBD5	HGNC:20444	ENSG00000204406	Q9P267	Methyl-CpG-binding domain protein 5	gencc,clinvar
CIC	HGNC:14214	ENSG00000079432	Q96RK0	Protein capicua homolog	clinvar
ZMYND11	HGNC:16966	ENSG00000015171	Q15326	Zinc finger MYND domain-containing protein 11	clinvar
CDH15	HGNC:1754	ENSG00000129910	P55291	Cadherin-15	clinvar
WDFY3	HGNC:20751	ENSG00000163625	Q8IZQ1	WD repeat and FYVE domain-containing protein 3	clinvar
EPC2	HGNC:24543	ENSG00000135999	Q52LR7	Enhancer of polycomb homolog 2	clinvar
TAOK1	HGNC:29259	ENSG00000160551	Q7L7X3	Serine/threonine-protein kinase TAO1	clinvar
GRIA1	HGNC:4571	ENSG00000155511	P42261	Glutamate receptor 1	clinvar
ITSN1	HGNC:6183	ENSG00000205726	Q15811	Intersectin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MBD5	Methyl-CpG-binding domain protein 5	Non-catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at ‘Lys-120’ (H2AK119ub1).
CIC	Protein capicua homolog	Transcriptional repressor which plays a role in development of the central nervous system (CNS).
ZMYND11	Zinc finger MYND domain-containing protein 11	Chromatin reader that specifically recognizes and binds histone H3.3 trimethylated at ‘Lys-36’ (H3.3K36me3) and regulates RNA polymerase II elongation.
CDH15	Cadherin-15	Cadherins are calcium-dependent cell adhesion proteins.
WDFY3	WD repeat and FYVE domain-containing protein 3	Required for selective macroautophagy (aggrephagy).
EPC2	Enhancer of polycomb homolog 2	May play a role in transcription or DNA repair.
TAOK1	Serine/threonine-protein kinase TAO1	Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability.
GRIA1	Glutamate receptor 1	Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid.
ITSN1	Intersectin-1	Adapter protein that provides a link between the endocytic membrane traffic and the actin assembly machinery.

Protein-family classification

Druggable: 1 · Difficult: 3 · Unknown: 5 · Druggable fraction: 0.11

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	1	3.1×	0.553
Scaffold/PPI	1	1.9×	0.553
Transcription factor	2	1.8×	0.553
Other/Unknown	5	1.0×	0.641

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MBD5	Other/Unknown	no		PWWP_dom, Methyl_CpG_DNA-bd, DNA-bd_dom_sf
CIC	Other/Unknown	no		HMG_box_dom, Cic_dom, HMG_box_dom_sf
ZMYND11	Transcription factor	no		PWWP_dom, Bromodomain, Znf_PHD
CDH15	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
WDFY3	Transcription factor	no		Znf_FYVE, BEACH_dom, WD40_rpt
EPC2	Other/Unknown	no		Enhancer_polycomb_C, Enhancer_polycomb-like_N, Enhancer_polycomb
TAOK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
GRIA1	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
ITSN1	Scaffold/PPI	no		C2_dom, DH_dom, EH_dom

Expression context

Cohort genes with no expression data: 0.

9 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
calcaneal tendon	3
sural nerve	3
cerebellar cortex	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2
cranial nerve II	2
corpus callosum	2
cortical plate	2
adrenal tissue	1
caput epididymis	1
cauda epididymis	1
ganglionic eminence	1
germinal epithelium of ovary	1
globus pallidus	1
medial globus pallidus	1
CA1 field of hippocampus	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MBD5	243	ubiquitous	marker	calcaneal tendon, adrenal tissue, sural nerve
CIC	274	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
ZMYND11	301	ubiquitous	marker	cranial nerve II, caput epididymis, cauda epididymis
CDH15	139	broad	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
WDFY3	293	ubiquitous	marker	sural nerve, calcaneal tendon, corpus callosum
EPC2	254	ubiquitous	marker	germinal epithelium of ovary, calcaneal tendon, ganglionic eminence
TAOK1	274	ubiquitous	marker	corpus callosum, globus pallidus, medial globus pallidus
GRIA1	194	broad	marker	CA1 field of hippocampus, cortical plate, cranial nerve II
ITSN1	293	ubiquitous	marker	sural nerve, tibia, cortical plate

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GRIA1	3,443
ITSN1	3,188
WDFY3	1,780
CDH15	1,775
CIC	1,720
EPC2	1,683
MBD5	1,640
TAOK1	1,325
ZMYND11	1,264

Intra-cohort edges

A	B	Sources
EPC2	MBD5	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITSN1	Q15811	11
ZMYND11	Q15326	8
CIC	Q96RK0	7
WDFY3	Q8IZQ1	2
GRIA1	P42261	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDH15	P55291	78.70
TAOK1	Q7L7X3	77.36
EPC2	Q52LR7	58.35
MBD5	Q9P267	43.20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 56. Enrichment computed across 9 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
Activation of AMPA receptors	1	571.0×	0.064	GRIA1
Dengue virus modulates apoptosis	1	142.8×	0.064	TAOK1
Trafficking of GluR2-containing AMPA receptors	1	134.3×	0.064	GRIA1
Trafficking of AMPA receptors	1	108.8×	0.064	GRIA1
Unblocking of NMDA receptors, glutamate binding and activation	1	108.8×	0.064	GRIA1
Synaptic adhesion-like molecules	1	108.8×	0.064	GRIA1
Signaling by Rho GTPases	2	13.7×	0.064	TAOK1, ITSN1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	2	13.4×	0.064	TAOK1, ITSN1
Long-term potentiation	1	95.2×	0.065	GRIA1
Myogenesis	1	76.1×	0.073	CDH15
Cargo concentration in the ER	1	67.2×	0.074	GRIA1
EPHB-mediated forward signaling	1	53.1×	0.074	ITSN1
Adherens junctions interactions	1	49.6×	0.074	CDH15
Cell-cell junction organization	1	49.6×	0.074	CDH15
Cell death signalling via NRAGE, NRIF and NADE	1	43.9×	0.074	ITSN1
Amplification of signal from the kinetochores	1	39.4×	0.074	TAOK1
p75 NTR receptor-mediated signalling	1	37.4×	0.074	ITSN1
Cell junction organization	1	37.4×	0.074	CDH15
NRAGE signals death through JNK	1	36.8×	0.074	ITSN1
RHOQ GTPase cycle	1	36.2×	0.074	ITSN1
EPH-Ephrin signaling	1	33.1×	0.074	ITSN1
COPII-mediated vesicle transport	1	32.6×	0.074	GRIA1
Mitotic Spindle Checkpoint	1	31.7×	0.074	TAOK1
RHOG GTPase cycle	1	29.7×	0.074	ITSN1
Death Receptor Signaling	1	27.9×	0.074	ITSN1
Cell-Cell communication	1	27.5×	0.074	CDH15
G alpha (12/13) signalling events	1	27.5×	0.074	ITSN1
Deubiquitination	1	24.8×	0.076	MBD5
UCH proteinases	1	24.8×	0.076	MBD5
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	23.3×	0.076	TAOK1

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
response to lithium ion	1	936.2×	0.024	GRIA1
positive regulation of locomotion involved in locomotory behavior	1	936.2×	0.024	GRIA1
clathrin-dependent synaptic vesicle endocytosis	1	936.2×	0.024	ITSN1
positive regulation of growth hormone receptor signaling pathway	1	624.1×	0.024	MBD5
cellular response to amine stimulus	1	624.1×	0.024	GRIA1
positive regulation of caveolin-mediated endocytosis	1	468.1×	0.024	ITSN1
response to sucrose	1	374.5×	0.024	GRIA1
cellular response to ammonium ion	1	374.5×	0.024	GRIA1
cellular response to dsRNA	1	374.5×	0.024	GRIA1
response to psychosocial stress	1	374.5×	0.024	GRIA1
regulation of receptor recycling	1	312.1×	0.024	GRIA1
positive regulation of membrane potential	1	312.1×	0.024	GRIA1
response to fungicide	1	312.1×	0.024	GRIA1
regulation of modification of postsynaptic actin cytoskeleton	1	267.5×	0.026	ITSN1
positive regulation of growth hormone secretion	1	208.1×	0.027	ITSN1
cellular response to brain-derived neurotrophic factor stimulus	1	208.1×	0.027	GRIA1
aggrephagy	1	187.2×	0.027	WDFY3
cellular response to L-glutamate	1	187.2×	0.027	GRIA1
conditioned place preference	1	187.2×	0.027	GRIA1
regulation of behavior	1	156.0×	0.031	MBD5
response to morphine	1	133.8×	0.033	GRIA1
response to arsenic-containing substance	1	133.8×	0.033	GRIA1
DNA repair	2	14.2×	0.035	EPC2, TAOK1
behavioral response to pain	1	98.5×	0.037	GRIA1
long-term synaptic depression	1	98.5×	0.037	GRIA1
cellular response to peptide hormone stimulus	1	93.6×	0.037	GRIA1
central nervous system neuron development	1	89.2×	0.037	TAOK1
positive regulation of stress-activated MAPK cascade	1	89.2×	0.037	TAOK1
regulation of transcription elongation by RNA polymerase II	1	89.2×	0.037	ZMYND11
positive regulation of dendritic spine development	1	85.1×	0.037	ITSN1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 7

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
TAOK1	FEDRATINIB
GRIA1	PERAMPANEL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TAOK1	58	4
GRIA1	6	4
MBD5	0	0
CIC	0	0
ZMYND11	0	0
CDH15	0	0
WDFY3	0	0
EPC2	0	0
ITSN1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	TAOK1
SORAFENIB	4	TAOK1
RUXOLITINIB	4	TAOK1
PALBOCICLIB	4	TAOK1
ENTRECTINIB	4	TAOK1
PACRITINIB	4	TAOK1
NILOTINIB	4	TAOK1
BOSUTINIB	4	TAOK1
ABEMACICLIB	4	TAOK1
BRIGATINIB	4	TAOK1
PAZOPANIB	4	TAOK1
SUNITINIB	4	TAOK1
DASATINIB	4	TAOK1
CRIZOTINIB	4	TAOK1
IMATINIB	4	TAOK1
PERAMPANEL	4	GRIA1
CYCLOTHIAZIDE	4	GRIA1
DINACICLIB	3	TAOK1
CRENOLANIB	3	TAOK1
LINIFANIB	3	TAOK1
DEFACTINIB	3	TAOK1
ALVOCIDIB	3	TAOK1
CEDIRANIB	3	TAOK1
LESTAURTINIB	3	TAOK1
RUBOXISTAURIN	3	TAOK1
GLUTAMIC ACID	3	GRIA1
SILMITASERTIB	2	TAOK1
FORETINIB	2	TAOK1
SU-014813	2	TAOK1
ZOTIRACICLIB	2	TAOK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TAOK1	231	Binding:230, Functional:1
GRIA1	168	Binding:127, Functional:39, ADMET:2
ITSN1	5	Binding:5
ZMYND11	1	Binding:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TAOK1	231
GRIA1	168

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)
FEDRATINIB	4	TAOK1
SORAFENIB	4	TAOK1
RUXOLITINIB	4	TAOK1
PALBOCICLIB	4	TAOK1
ENTRECTINIB	4	TAOK1
PACRITINIB	4	TAOK1
NILOTINIB	4	TAOK1
BOSUTINIB	4	TAOK1
ABEMACICLIB	4	TAOK1
BRIGATINIB	4	TAOK1
PAZOPANIB	4	TAOK1
SUNITINIB	4	TAOK1
DASATINIB	4	TAOK1
CRIZOTINIB	4	TAOK1
IMATINIB	4	TAOK1
PERAMPANEL	4	GRIA1
CYCLOTHIAZIDE	4	GRIA1
DINACICLIB	3	TAOK1
CRENOLANIB	3	TAOK1
LINIFANIB	3	TAOK1
DEFACTINIB	3	TAOK1
ALVOCIDIB	3	TAOK1
CEDIRANIB	3	TAOK1
LESTAURTINIB	3	TAOK1
RUBOXISTAURIN	3	TAOK1
GLUTAMIC ACID	3	GRIA1
SILMITASERTIB	2	TAOK1
FORETINIB	2	TAOK1
SU-014813	2	TAOK1
ZOTIRACICLIB	2	TAOK1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	TAOK1, GRIA1
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	7	MBD5, CIC, ZMYND11, CDH15, WDFY3, EPC2, ITSN1

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)
MBD5	0	—
CIC	0	—
ZMYND11	1	—
CDH15	0	—
WDFY3	0	—
EPC2	0	—
ITSN1	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.