Isolated cleft palate

Summary

Isolated cleft palate (MONDO:0007336) is a disease with 10 cohort genes.

At a glance

• Cohort genes: 10
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated cleft palate
Mondo ID	MONDO:0007336
OMIM	119540
DOID	DOID:0110213
UMLS	C1837218
MedGen	332392
GARD	0001896
Is cancer (heuristic)	no

Also known as: cleft palate, isolated · CPI · dominant cleft palate · isolated cleft palate · nonsyndromic cleft palate

Data availability: 13 ClinVar variants · 7 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › orofacial cleft › cleft palate › isolated cleft palate

Related subtypes (8): cleft soft palate, Rapp-Hodgkin syndrome, bifid uvula, cleft palate with or without ankyloglossia, X-linked, cleft hard palate, submucosal cleft palate, Kuster syndrome, soft and hard cleft palate

Subtypes (1): orofacial cleft 3

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 pathogenic, 3 conflicting classifications of pathogenicity, 2 uncertain significance, 1 likely pathogenic, 1 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1172586	NM_198173.3(GRHL3):c.1172G>A (p.Arg391His)	GRHL3	Pathogenic	no assertion criteria provided
219244	NM_198173.3(GRHL3):c.840+1G>T	GRHL3	Pathogenic	criteria provided, single submitter
219245	NM_198173.3(GRHL3):c.916dup (p.Arg306fs)	GRHL3	Pathogenic	criteria provided, single submitter
219246	NM_198173.3(GRHL3):c.1285+2del	GRHL3	Pathogenic	criteria provided, single submitter
522269	NM_001172509.2(SATB2):c.1375C>T (p.Arg459Ter)	SATB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1172584	NM_198173.3(GRHL3):c.22A>G (p.Arg8Gly)	GRHL3	Likely pathogenic	no assertion criteria provided
219243	NM_198173.3(GRHL3):c.738C>T (p.Gly246=)	GRHL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
39617	NM_006206.6(PDGFRA):c.1631T>C (p.Val544Ala)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
39618	NM_006206.6(PDGFRA):c.3155C>T (p.Thr1052Met)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1338788	NM_004815.4(ARHGAP29):c.1865C>T (p.Thr622Met)	ARHGAP29	Uncertain significance	criteria provided, single submitter
1172585	NM_198173.3(GRHL3):c.32G>A (p.Arg11Gln)	GRHL3	Uncertain significance	criteria provided, single submitter
697696	NM_198173.3(GRHL3):c.800C>G (p.Ala267Gly)	GRHL3	Benign	criteria provided, multiple submitters, no conflicts
39616	NM_006206.6(PDGFRA):c.1202C>A (p.Ala401Asp)	PDGFRA	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 20 · 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
ACACB	Limited	Unknown	isolated cleft palate
DENND4B	Limited	Unknown	isolated cleft palate
PDGFRA	Limited	Unknown	isolated cleft palate	8
ARID5B	No Known Disease Relationship	Unknown	isolated cleft palate
MIB1	No Known Disease Relationship	Unknown	isolated cleft palate	5
MORN5	No Known Disease Relationship	Unknown	isolated cleft palate
UBB	No Known Disease Relationship	Autosomal dominant	isolated cleft palate

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDGFRA	Orphanet:168940	Chronic eosinophilic leukemia
PDGFRA	Orphanet:168947	Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement
PDGFRA	Orphanet:199306	Cleft lip/palate
PDGFRA	Orphanet:314950	Primary hypereosinophilic syndrome
PDGFRA	Orphanet:44890	Gastrointestinal stromal tumor
PDGFRA	Orphanet:585877	B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality
UBB	Orphanet:101023	Cleft hard palate
UBB	Orphanet:155878	Submucosal cleft palate
UBB	Orphanet:99771	Bifid uvula
UBB	Orphanet:99772	Cleft velum
MIB1	Orphanet:54260	Left ventricular noncompaction
SATB2	Orphanet:251019	2q32q33 deletion syndrome
SATB2	Orphanet:251028	SATB2-associated syndrome due to a chromosomal rearrangement
SATB2	Orphanet:576283	SATB2-associated syndrome due to a pathogenic variant
GRHL3	Orphanet:101023	Cleft hard palate
GRHL3	Orphanet:155878	Submucosal cleft palate
GRHL3	Orphanet:888	Van der Woude syndrome
GRHL3	Orphanet:99771	Bifid uvula
GRHL3	Orphanet:99772	Cleft velum
ARHGAP29	Orphanet:199306	Cleft lip/palate

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
PDGFRA	HGNC:8803	ENSG00000134853	P16234	Platelet-derived growth factor receptor alpha	gencc,clinvar
UBB	HGNC:12463	ENSG00000170315	P0CG47	Polyubiquitin-B	gencc
ARID5B	HGNC:17362	ENSG00000150347	Q14865	AT-rich interactive domain-containing protein 5B	gencc
MORN5	HGNC:17841	ENSG00000185681	Q5VZ52	MORN repeat-containing protein 5	gencc
MIB1	HGNC:21086	ENSG00000101752	Q86YT6	E3 ubiquitin-protein ligase MIB1	gencc
DENND4B	HGNC:29044	ENSG00000198837	O75064	DENN domain-containing protein 4B	gencc
ACACB	HGNC:85	ENSG00000076555	O00763	Acetyl-CoA carboxylase 2	gencc
SATB2	HGNC:21637	ENSG00000119042	Q9UPW6	DNA-binding protein SATB2	clinvar
GRHL3	HGNC:25839	ENSG00000158055	Q8TE85	Grainyhead-like protein 3 homolog	clinvar
ARHGAP29	HGNC:30207	ENSG00000137962	Q52LW3	Rho GTPase-activating protein 29	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDGFRA	Platelet-derived growth factor receptor alpha	Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis.
UBB	Polyubiquitin-B	Exists either covalently attached to another protein, or free (unanchored).
ARID5B	AT-rich interactive domain-containing protein 5B	Transcription coactivator that binds to the 5’-AATA[CT]-3’ core sequence and plays a key role in adipogenesis and liver development.
MIB1	E3 ubiquitin-protein ligase MIB1	E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins.
DENND4B	DENN domain-containing protein 4B	Guanine nucleotide exchange factor (GEF) which may activate RAB10.
ACACB	Acetyl-CoA carboxylase 2	Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism.
SATB2	DNA-binding protein SATB2	Binds to DNA, at nuclear matrix- or scaffold-associated regions.
GRHL3	Grainyhead-like protein 3 homolog	Transcription factor playing important roles in primary neurulation and in the differentiation of stratified epithelia of both ectodermal and endodermal origin.
ARHGAP29	Rho GTPase-activating protein 29	GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.

Protein-family classification

Druggable: 2 · Difficult: 4 · Unknown: 4 · Druggable fraction: 0.2

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
Transcription factor	3	2.5×	0.555
Kinase	1	2.8×	0.727
Scaffold/PPI	1	1.7×	0.727
Enzyme (other)	1	1.2×	0.727
Other/Unknown	4	0.7×	0.907

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PDGFRA	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
UBB	Other/Unknown	no		Ubiquitin-like_dom, Ubiquitin_CS, Ubiquitin_dom
ARID5B	Other/Unknown	no		ARID_dom, ARID5B_ARID/BRIGHT_DNA-bd, ARID_dom_sf
MORN5	Other/Unknown	no		MORN, Morn5
MIB1	Transcription factor	no		Znf_ZZ, Znf_RING, Ankyrin_rpt
DENND4B	Other/Unknown	no		cDENN_dom, PPR_rpt, dDENN_dom
ACACB	Enzyme (other)	yes	6.3.4.14	Biotin_lipoyl, CPAse_ATP-bd, BC-like_N
SATB2	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
GRHL3	Transcription factor	no		CP2, TF_CP2-like, GRHL1/CP2_C
ARHGAP29	Scaffold/PPI	no		RhoGAP_dom, PKC_DAG/PE, Rho_GTPase_activation_prot

Expression context

Cohort genes with no expression data: 0.

10 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
tibia	2
decidua	1
synovial joint	1
adult organism	1
endothelial cell	1
pons	1
pericardium	1
saphenous vein	1
type B pancreatic cell	1
bronchial epithelial cell	1
bronchus	1
right uterine tube	1
corpus epididymis	1
kidney epithelium	1
granulocyte	1
right hemisphere of cerebellum	1
spleen	1
adipose tissue	1
subcutaneous adipose tissue	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDGFRA	289	ubiquitous	marker	tibia, decidua, synovial joint
UBB	305	ubiquitous	marker	pons, adult organism, endothelial cell
ARID5B	299	ubiquitous	marker	type B pancreatic cell, saphenous vein, pericardium
MORN5	159	broad	marker	bronchial epithelial cell, right uterine tube, bronchus
MIB1	262	ubiquitous	marker	corpus epididymis, kidney epithelium, tibia
DENND4B	289	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, spleen
ACACB	288	ubiquitous	marker	tendon of biceps brachii, adipose tissue, subcutaneous adipose tissue
SATB2	235	ubiquitous	marker	periodontal ligament, cortical plate, mucosa of sigmoid colon
GRHL3	164	broad	marker	lower esophagus mucosa, esophagus mucosa, gingival epithelium
ARHGAP29	283	ubiquitous	marker	visceral pleura, parietal pleura, pleura

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDGFRA	5,186
ACACB	2,991
MIB1	2,280
SATB2	2,254
ARID5B	1,778
ARHGAP29	1,278
GRHL3	1,270
UBB	1,252
MORN5	836
DENND4B	629

Intra-cohort edges

A	B	Sources
ARHGAP29	GRHL3	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UBB	P0CG47	287
PDGFRA	P16234	15
ACACB	O00763	11
MIB1	Q86YT6	6
SATB2	Q9UPW6	3
ARID5B	Q14865	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MORN5	Q5VZ52	91.19
DENND4B	O75064	73.32
ARHGAP29	Q52LW3	64.41
GRHL3	Q8TE85	61.27

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 259. Enrichment computed across 10 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Constitutive Signaling by NOTCH1 HD Domain Mutants	2	190.3×	0.012	UBB, MIB1
NOTCH3 Activation and Transmission of Signal to the Nucleus	2	119.0×	0.012	UBB, MIB1
NOTCH2 Activation and Transmission of Signal to the Nucleus	2	109.8×	0.012	UBB, MIB1
Activated NOTCH1 Transmits Signal to the Nucleus	2	89.2×	0.014	UBB, MIB1
Imatinib-resistant PDGFR mutants	1	1427.5×	0.016	PDGFRA
Sunitinib-resistant PDGFR mutants	1	1427.5×	0.016	PDGFRA
Regorafenib-resistant PDGFR mutants	1	1427.5×	0.016	PDGFRA
Sorafenib-resistant PDGFR mutants	1	1427.5×	0.016	PDGFRA
PDGFR mutants bind TKIs	1	1427.5×	0.016	PDGFRA
Constitutive Signaling by NOTCH1 PEST Domain Mutants	2	49.2×	0.016	UBB, MIB1
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	2	49.2×	0.016	UBB, MIB1
Maturation of protein E	1	356.9×	0.049	UBB
Assembly Of The HIV Virion	1	203.9×	0.049	UBB
Modulation by Mtb of host immune system	1	203.9×	0.049	UBB
FLT3 signaling by CBL mutants	1	203.9×	0.049	UBB
ChREBP activates metabolic gene expression	1	158.6×	0.049	ACACB
Signaling by NOTCH1 HD Domain Mutants in Cancer	1	158.6×	0.049	MIB1
Myoclonic epilepsy of Lafora	1	158.6×	0.049	UBB
PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1	1	158.6×	0.049	UBB
InlA-mediated entry of Listeria monocytogenes into host cells	1	158.6×	0.049	UBB
Prevention of phagosomal-lysosomal fusion	1	158.6×	0.049	UBB
Downregulation of ERBB4 signaling	1	142.8×	0.049	UBB
IRAK2 mediated activation of TAK1 complex	1	142.8×	0.049	UBB
Biotin transport and metabolism	1	129.8×	0.049	ACACB
Regulation of PTEN localization	1	129.8×	0.049	UBB
TICAM1,TRAF6-dependent induction of TAK1 complex	1	129.8×	0.049	UBB
Alpha-protein kinase 1 signaling pathway	1	129.8×	0.049	UBB
Regulation of BACH1 activity	1	129.8×	0.049	UBB
Josephin domain DUBs	1	119.0×	0.049	UBB

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
roof of mouth development	3	82.6×	7e-04	PDGFRA, ARID5B, SATB2
fat pad development	2	374.5×	7e-04	UBB, ARID5B
female gonad development	2	178.3×	0.002	UBB, ARID5B
adrenal gland development	2	149.8×	0.002	PDGFRA, ARID5B
platelet-derived growth factor receptor signaling pathway	2	124.8×	0.003	PDGFRA, ARID5B
face morphogenesis	2	110.1×	0.003	PDGFRA, ARID5B
embryonic skeletal system morphogenesis	2	87.1×	0.004	PDGFRA, SATB2
lactic acid secretion	1	1872.4×	0.007	ACACB
intracellular aspartate homeostasis	1	1872.4×	0.007	ACACB
energy homeostasis	2	60.4×	0.007	UBB, ACACB
protein homotetramerization	2	52.7×	0.007	UBB, ACACB
wound healing	2	50.6×	0.007	PDGFRA, GRHL3
hypothalamus gonadotrophin-releasing hormone neuron development	1	936.2×	0.008	UBB
platelet-derived growth factor receptor-alpha signaling pathway	1	936.2×	0.008	PDGFRA
regulation of cardiac muscle hypertrophy in response to stress	1	936.2×	0.008	ACACB
malonyl-CoA biosynthetic process	1	936.2×	0.008	ACACB
regulation of actin cytoskeleton organization	2	35.0×	0.010	PDGFRA, GRHL3
positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	1	624.1×	0.011	PDGFRA
metanephric glomerular capillary formation	1	624.1×	0.011	PDGFRA
negative regulation of fatty acid beta-oxidation	1	468.1×	0.012	ACACB
positive regulation of heart growth	1	468.1×	0.012	ACACB
regulation of mesenchymal stem cell differentiation	1	468.1×	0.012	PDGFRA
positive regulation of protein monoubiquitination	1	374.5×	0.015	UBB
tricarboxylic acid metabolic process	1	312.1×	0.016	ACACB
intracellular glutamate homeostasis	1	312.1×	0.016	ACACB
positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	312.1×	0.016	UBB
acetyl-CoA metabolic process	1	267.5×	0.017	ACACB
regulation of Rab protein signal transduction	1	267.5×	0.017	DENND4B
neural tube formation	1	234.1×	0.018	MIB1
modification-dependent protein catabolic process	1	234.1×	0.018	UBB

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 10 evidence-associated genes (40%) 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
PDGFRA	PONATINIB
ACACB	BEMPEDOIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDGFRA	77	4
ACACB	4	4
UBB	0	0
ARID5B	0	0
MORN5	0	0
MIB1	0	0
DENND4B	0	0
SATB2	0	0
GRHL3	0	0
ARHGAP29	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	PDGFRA
FEDRATINIB	4	PDGFRA
TIVOZANIB	4	PDGFRA
LENVATINIB	4	PDGFRA
AXITINIB	4	PDGFRA
SORAFENIB	4	PDGFRA
IMATINIB MESYLATE	4	PDGFRA
INFIGRATINIB PHOSPHATE	4	PDGFRA
INFIGRATINIB	4	PDGFRA
REGORAFENIB	4	PDGFRA
CERITINIB	4	PDGFRA
VANDETANIB	4	PDGFRA
NILOTINIB	4	PDGFRA
BOSUTINIB	4	PDGFRA
NINTEDANIB ESYLATE	4	PDGFRA
PEXIDARTINIB	4	PDGFRA
AVAPRITINIB	4	PDGFRA
RIPRETINIB	4	PDGFRA
PAZOPANIB	4	PDGFRA
NINTEDANIB	4	PDGFRA
SUNITINIB	4	PDGFRA
DASATINIB	4	PDGFRA
ERLOTINIB	4	PDGFRA
QUIZARTINIB	4	PDGFRA
MIDOSTAURIN	4	PDGFRA
IMATINIB	4	PDGFRA
BEMPEDOIC ACID	4	ACACB
VATALANIB	3	PDGFRA
MASITINIB	3	PDGFRA
CRENOLANIB	3	PDGFRA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
ACACB	81	Binding:81
SATB2	6	Binding:6
UBB	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PDGFRA	2.7.10.1	receptor protein-tyrosine kinase
ACACB	6.3.4.14, 6.4.1.2	biotin carboxylase, acetyl-CoA carboxylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PDGFRA	1,172

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; 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)
PONATINIB	4	PDGFRA
FEDRATINIB	4	PDGFRA
TIVOZANIB	4	PDGFRA
LENVATINIB	4	PDGFRA
AXITINIB	4	PDGFRA
SORAFENIB	4	PDGFRA
IMATINIB MESYLATE	4	PDGFRA
INFIGRATINIB PHOSPHATE	4	PDGFRA
INFIGRATINIB	4	PDGFRA
REGORAFENIB	4	PDGFRA
CERITINIB	4	PDGFRA
VANDETANIB	4	PDGFRA
NILOTINIB	4	PDGFRA
BOSUTINIB	4	PDGFRA
NINTEDANIB ESYLATE	4	PDGFRA
PEXIDARTINIB	4	PDGFRA
AVAPRITINIB	4	PDGFRA
RIPRETINIB	4	PDGFRA
PAZOPANIB	4	PDGFRA
NINTEDANIB	4	PDGFRA
SUNITINIB	4	PDGFRA
DASATINIB	4	PDGFRA
ERLOTINIB	4	PDGFRA
QUIZARTINIB	4	PDGFRA
MIDOSTAURIN	4	PDGFRA
IMATINIB	4	PDGFRA
BEMPEDOIC ACID	4	ACACB
VATALANIB	3	PDGFRA
MASITINIB	3	PDGFRA
CRENOLANIB	3	PDGFRA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	PDGFRA, ACACB
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	8	UBB, ARID5B, MORN5, MIB1, DENND4B, SATB2, GRHL3, ARHGAP29

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)
UBB	1	—
ARID5B	0	—
MORN5	0	—
MIB1	0	—
DENND4B	0	—
SATB2	6	—
GRHL3	0	—
ARHGAP29	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.