Multiple congenital anomalies-hypotonia-seizures syndrome 1

Summary

Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MONDO:0013563) is a disease caused by PIGN (GenCC Definitive), with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PIGN (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 1,183
• Phenotypes (HPO): 86

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		15	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0006829	Severe muscular hypotonia	Very frequent (80-99%)
HP:0011344	Severe global developmental delay	Very frequent (80-99%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000280	Coarse facial features	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0001182	Tapered finger	Frequent (30-79%)
HP:0001265	Hyporeflexia	Frequent (30-79%)
HP:0001337	Tremor	Frequent (30-79%)
HP:0001615	Hoarse cry	Frequent (30-79%)
HP:0001655	Patent foramen ovale	Frequent (30-79%)
HP:0001773	Short foot	Frequent (30-79%)
HP:0002020	Gastroesophageal reflux	Frequent (30-79%)
HP:0004488	Macrocephaly at birth	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0010291	Prominent palatine ridges	Frequent (30-79%)
HP:0011247	Prominent superior crus of antihelix	Frequent (30-79%)
HP:0012448	Delayed myelination	Frequent (30-79%)
HP:0200055	Small hand	Frequent (30-79%)
HP:0000034	Hydrocele testis	Occasional (5-29%)
HP:0000072	Hydroureter	Occasional (5-29%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000154	Wide mouth	Occasional (5-29%)
HP:0000160	Narrow mouth	Occasional (5-29%)
HP:0000212	Gingival overgrowth	Occasional (5-29%)
HP:0000219	Thin upper lip vermilion	Occasional (5-29%)
HP:0000269	Prominent occiput	Occasional (5-29%)
HP:0000286	Epicanthus	Occasional (5-29%)
HP:0000293	Full cheeks	Occasional (5-29%)
HP:0000308	Microretrognathia	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000319	Smooth philtrum	Occasional (5-29%)
HP:0000350	Small forehead	Occasional (5-29%)
HP:0000396	Overfolded helix	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000470	Short neck	Occasional (5-29%)
HP:0000498	Blepharitis	Occasional (5-29%)
HP:0000565	Esotropia	Occasional (5-29%)
HP:0000582	Upslanted palpebral fissure	Occasional (5-29%)
HP:0000646	Amblyopia	Occasional (5-29%)
HP:0000664	Synophrys	Occasional (5-29%)
HP:0000774	Narrow chest	Occasional (5-29%)
HP:0000932	Abnormality of the posterior cranial fossa	Occasional (5-29%)
HP:0001272	Cerebellar atrophy	Occasional (5-29%)
HP:0001347	Hyperreflexia	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	multiple congenital anomalies-hypotonia-seizures syndrome 1
Mondo ID	MONDO:0013563
OMIM	614080
Orphanet	280633
DOID	DOID:0080138
NCIT	C176896
UMLS	C3279775
MedGen	481405
GARD	0012781
Is cancer (heuristic)	no

Also known as: congenital disorder of glycosylation due to PIGN deficiency · inherited GPI anchor-deficiency · MCAHS1 · multiple congenital anomalies - hypotonia - seizures syndrome · multiple congenital anomalies-hypotonia-seizures syndrome 1 · multiple congenital anomalies-hypotonia-seizures syndrome type 1 · multiple congenital anomalies/dysmorphic syndrome-intellectual disability caused by mutation in PIGN · PIGN multiple congenital anomalies/dysmorphic syndrome-intellectual disability · PIGN-CDG · PIGN-related inherited GPI deficiency

Data availability: 1,183 ClinVar variants · 5 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › multiple congenital anomalies-hypotonia-seizures syndrome 1

Related subtypes (56): Neu-Laxova syndrome, inborn mitochondrial metabolism disorder, Ehlers-Danlos syndrome, spondylodysplastic type, MGAT2-congenital disorder of glycosylation, ALDH18A1-related de Barsy syndrome, classic homocystinuria, Larsen-like syndrome, B3GAT3 type, Nijmegen breakage syndrome, Peters plus syndrome, Wiedemann-Rautenstrauch syndrome, 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency, SHORT syndrome, mucosulfatidosis, CHIME syndrome, creatine transporter deficiency, multiple congenital anomalies-hypotonia-seizures syndrome 2, SLC35A2-congenital disorder of glycosylation, SSR4-congenital disorder of glycosylation, Fabry disease, occipital horn syndrome, Ehlers-Danlos syndrome, musculocontractural type, temtamy preaxial brachydactyly syndrome, B4GALT1-congenital disorder of glycosylation, AICA-ribosiduria, COG7-congenital disorder of glycosylation, permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome, Al-Gazali syndrome, COG1-congenital disorder of glycosylation, RFT1-congenital disorder of glycosylation, Nijmegen breakage syndrome-like disorder, multiple congenital anomalies-hypotonia-seizures syndrome 3, autism spectrum disorder - epilepsy - arthrogryposis syndrome, cutis laxa, autosomal dominant 3, SLC39A8-CDG, transketolase deficiency, mucopolysaccharidosis-plus syndrome, Cockayne syndrome, pontocerebellar hypoplasia type 1, mandibuloacral dysplasia, hyperphosphatasia-intellectual disability syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, CADDS, XYLT1-congenital disorder of glycosylation, hypophosphatasia, sterol biosynthesis disorder, mucolipidosis, mucopolysaccharidosis, oligosaccharidosis, encephalopathy due to sulfite oxidase deficiency, Fanconi anemia, autosomal recessive cutis laxa type 2, Zellweger spectrum disorders, pseudohypoparathyroidism, developmental and epileptic encephalopathy, 77, glycosylphosphatidylinositol biosynthesis defect 15, progressive hypotonia-intellectual disability-facial dysmorphism syndrome due to FYVE-defective RBSN

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:

298 likely benign, 202 uncertain significance, 46 pathogenic, 19 likely pathogenic, 15 benign, 9 pathogenic/likely pathogenic, 6 conflicting classifications of pathogenicity, 5 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
101047	NM_176787.5(PIGN):c.808T>C (p.Ser270Pro)	PIGN	Pathogenic	criteria provided, single submitter
101048	NM_176787.5(PIGN):c.963G>A (p.Gln321=)	PIGN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1012441	NM_176787.5(PIGN):c.1837C>T (p.Arg613Ter)	PIGN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1027678	NM_176787.5(PIGN):c.1660G>A (p.Gly554Arg)	PIGN	Pathogenic	criteria provided, single submitter
1071330	NM_176787.5(PIGN):c.2423dup (p.Asn808fs)	PIGN	Pathogenic	criteria provided, single submitter
1073972	NC_000018.9:g.(?59763071)(59763193_?)del	PIGN	Pathogenic	criteria provided, single submitter
1073974	NC_000018.9:g.(?59805466)(59806318_?)del	PIGN	Pathogenic	criteria provided, single submitter
1073975	NC_000018.9:g.(?59768298)(59770145_?)del	PIGN	Pathogenic	criteria provided, single submitter
1345818	NM_176787.5(PIGN):c.1252-2A>G	PIGN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1358099	NM_176787.5(PIGN):c.439A>T (p.Lys147Ter)	PIGN	Pathogenic	criteria provided, single submitter
1361618	NM_176787.5(PIGN):c.347G>A (p.Trp116Ter)	PIGN	Pathogenic	criteria provided, single submitter
1364069	NM_176787.5(PIGN):c.2147C>G (p.Ser716Ter)	PIGN	Pathogenic	criteria provided, single submitter
1376753	NM_176787.5(PIGN):c.804G>T (p.Trp268Cys)	PIGN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1378427	NM_176787.5(PIGN):c.2026_2027del (p.Arg676fs)	PIGN	Pathogenic	criteria provided, single submitter
1439160	NM_176787.5(PIGN):c.1665_1668dup (p.Val557Ter)	PIGN	Pathogenic	criteria provided, single submitter
1452539	NM_176787.5(PIGN):c.221+1dup	PIGN	Pathogenic	criteria provided, single submitter
1453175	NM_176787.5(PIGN):c.2251_2252del (p.Leu751fs)	PIGN	Pathogenic	criteria provided, single submitter
1517769	NM_176787.5(PIGN):c.1675-1G>T	PIGN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686068	NM_176787.5(PIGN):c.1517G>A (p.Trp506Ter)	PIGN	Pathogenic	criteria provided, multiple submitters, no conflicts
1686069	NM_176787.5(PIGN):c.491_492del (p.Glu164fs)	PIGN	Pathogenic	criteria provided, multiple submitters, no conflicts
1802648	NM_176787.5(PIGN):c.2399G>A (p.Gly800Glu)	PIGN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2019913	NM_176787.5(PIGN):c.2482G>T (p.Gly828Ter)	PIGN	Pathogenic	criteria provided, single submitter
2048119	NM_176787.5(PIGN):c.531G>A (p.Trp177Ter)	PIGN	Pathogenic	criteria provided, single submitter
2084420	NM_176787.5(PIGN):c.1767+1del	PIGN	Pathogenic	criteria provided, single submitter
2095415	NM_176787.5(PIGN):c.24del (p.Leu9fs)	PIGN	Pathogenic	criteria provided, single submitter
2201742	NM_176787.5(PIGN):c.817dup (p.Ala273fs)	PIGN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2427546	NC_000018.9:g.(?59713069)(59828606_?)del	PIGN	Pathogenic	criteria provided, single submitter
2427547	NC_000018.9:g.(?59805456)(59806328_?)del	PIGN	Pathogenic	criteria provided, single submitter
264634	NM_176787.5(PIGN):c.755A>T (p.Asp252Val)	PIGN	Pathogenic	no assertion criteria provided
264635	NM_176787.5(PIGN):c.2340T>A (p.Tyr780Ter)	PIGN	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 5 · 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
PIGN	Definitive	Autosomal recessive	multiple congenital anomalies-hypotonia-seizures syndrome 1	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PIGN	Orphanet:2059	Fryns syndrome
PIGN	Orphanet:280633	Multiple congenital anomalies-hypotonia-seizures syndrome
BCL2	Orphanet:480541	High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement
BCL2	Orphanet:545	Follicular lymphoma
BCL2	Orphanet:98839	Intravascular large B-cell lymphoma

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PIGN	HGNC:8967	ENSG00000197563	O95427	GPI ethanolamine phosphate transferase 1	gencc,clinvar
SERPINB2	HGNC:8584	ENSG00000197632	P05120	Plasminogen activator inhibitor 2	clinvar
BCL2	HGNC:990	ENSG00000171791	P10415	Apoptosis regulator Bcl-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PIGN	GPI ethanolamine phosphate transferase 1	Ethanolamine phosphate transferase that catalyzes an ethanolamine phosphate (EtNP) transfer from phosphatidylethanolamine (PE) to the 2-OH position of the first alpha-1,4-linked mannose of a 2-acyl-6-[alpha-D-mannosyl-(1->6)-alpha-D-mannos…
SERPINB2	Plasminogen activator inhibitor 2	Inhibits urokinase-type plasminogen activator.
BCL2	Apoptosis regulator Bcl-2	Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Phosphatase	1	28.0×	0.071
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PIGN	Phosphatase	yes		Phosphodiest/P_Trfase, GPI_EtnP_transferase_1, Alkaline_phosphatase_core_sf
SERPINB2	Other/Unknown	no		Serpin_fam, PAI-2, Serpin_CS
BCL2	Other/Unknown	no		Bcl2-like, Bcl2_BH4, Bcl2/BclX

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
buccal mucosa cell	1
lower esophagus mucosa	1
amniotic fluid	1
pharyngeal mucosa	1
upper leg skin	1
dorsal motor nucleus of vagus nerve	1
superficial temporal artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PIGN	246	ubiquitous	marker	buccal mucosa cell, calcaneal tendon, lower esophagus mucosa
SERPINB2	184	broad	marker	amniotic fluid, pharyngeal mucosa, upper leg skin
BCL2	275	ubiquitous	marker	dorsal motor nucleus of vagus nerve, superficial temporal artery, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BCL2	8,343
SERPINB2	1,970
PIGN	1,028

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCL2	P10415	55
SERPINB2	P05120	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PIGN	O95427	88.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 33. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
The NLRP1 inflammasome	1	1268.9×	0.019	BCL2
BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members	1	423.0×	0.019	BCL2
Inflammasomes	1	380.7×	0.019	BCL2
NFE2L2 regulating tumorigenic genes	1	317.2×	0.019	BCL2
Dissolution of Fibrin Clot	1	271.9×	0.019	SERPINB2
Activation of BAD and translocation to mitochondria	1	253.8×	0.019	BCL2
Synthesis of glycosylphosphatidylinositol (GPI)	1	211.5×	0.019	PIGN
Regulation of MITF-M-dependent genes involved in apoptosis	1	211.5×	0.019	BCL2
Activation of BH3-only proteins	1	165.5×	0.022	BCL2
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1	146.4×	0.022	BCL2
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1	119.0×	0.024	BCL2
Nuclear events mediated by NFE2L2	1	112.0×	0.024	BCL2
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	100.2×	0.024	SERPINB2
Intrinsic Pathway for Apoptosis	1	97.6×	0.024	BCL2
MITF-M-dependent gene expression	1	60.4×	0.034	BCL2
Extra-nuclear estrogen signaling	1	56.8×	0.034	BCL2
Apoptosis	1	56.0×	0.034	BCL2
Programmed Cell Death	1	48.8×	0.036	BCL2
Cellular response to chemical stress	1	47.6×	0.036	BCL2
ESR-mediated signaling	1	42.8×	0.038	BCL2
KEAP1-NFE2L2 pathway	1	40.1×	0.039	BCL2
MITF-M-regulated melanocyte development	1	38.1×	0.039	BCL2
Interleukin-4 and Interleukin-13 signaling	1	34.3×	0.040	BCL2
Signaling by Nuclear Receptors	1	34.0×	0.040	BCL2
Estrogen-dependent gene expression	1	25.2×	0.052	BCL2
Signaling by Interleukins	1	21.4×	0.058	BCL2
Cytokine Signaling in Immune system	1	13.6×	0.088	BCL2
Cellular responses to stress	1	12.3×	0.093	BCL2
Cellular responses to stimuli	1	10.5×	0.105	BCL2
Innate Immune System	1	8.5×	0.124	BCL2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
melanin metabolic process	1	5617.3×	0.006	BCL2
obsolete negative regulation of cellular pH reduction	1	5617.3×	0.006	BCL2
pigment granule organization	1	5617.3×	0.006	BCL2
regulation of nitrogen utilization	1	2808.7×	0.006	BCL2
CD8-positive, alpha-beta T cell lineage commitment	1	2808.7×	0.006	BCL2
negative regulation of retinal cell programmed cell death	1	2808.7×	0.006	BCL2
positive regulation of neuron maturation	1	1872.4×	0.006	BCL2
cochlear nucleus development	1	1872.4×	0.006	BCL2
regulation of viral genome replication	1	1872.4×	0.006	BCL2
retinal cell programmed cell death	1	1872.4×	0.006	BCL2
dendritic cell apoptotic process	1	1872.4×	0.006	BCL2
regulation of glycoprotein biosynthetic process	1	1404.3×	0.007	BCL2
B cell lineage commitment	1	1123.5×	0.007	BCL2
negative regulation of calcium ion transport into cytosol	1	1123.5×	0.007	BCL2
positive regulation of melanocyte differentiation	1	1123.5×	0.007	BCL2
lymphoid progenitor cell differentiation	1	936.2×	0.008	BCL2
mesenchymal cell development	1	802.5×	0.008	BCL2
gland morphogenesis	1	802.5×	0.008	BCL2
stem cell development	1	802.5×	0.008	BCL2
myeloid cell apoptotic process	1	702.2×	0.008	BCL2
positive regulation of skeletal muscle fiber development	1	702.2×	0.008	BCL2
response to UV-B	1	624.1×	0.008	BCL2
smooth muscle cell migration	1	624.1×	0.008	BCL2
negative regulation of myeloid cell apoptotic process	1	624.1×	0.008	BCL2
negative regulation of mitochondrial depolarization	1	624.1×	0.008	BCL2
negative regulation of dendritic cell apoptotic process	1	624.1×	0.008	BCL2
negative regulation of T cell apoptotic process	1	561.7×	0.008	BCL2
negative regulation of B cell apoptotic process	1	510.7×	0.008	BCL2
negative regulation of osteoblast proliferation	1	510.7×	0.008	BCL2
ear development	1	510.7×	0.008	BCL2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
BCL2	IXABEPILONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BCL2	14	4
PIGN	0	0
SERPINB2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IXABEPILONE	4	BCL2
VENETOCLAX	4	BCL2
EPIGALOCATECHIN GALLATE	3	BCL2
OBATOCLAX	3	BCL2
NAVITOCLAX	3	BCL2
GOSSYPOL	3	BCL2
SONROTOCLAX	3	BCL2
CHLORCYCLIZINE	2	BCL2
FORMONONETIN	2	BCL2
LACUTOCLAX	2	BCL2
ABT 737	1	BCL2
VOB-560	1	BCL2
AZD-5991	1	BCL2
TAPOTOCLAX	1	BCL2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
BCL2	446	Binding:418, Functional:23, Toxicity:3, ADMET:2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BCL2	446

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

14 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)
IXABEPILONE	4	BCL2
VENETOCLAX	4	BCL2
EPIGALOCATECHIN GALLATE	3	BCL2
OBATOCLAX	3	BCL2
NAVITOCLAX	3	BCL2
GOSSYPOL	3	BCL2
SONROTOCLAX	3	BCL2
CHLORCYCLIZINE	2	BCL2
FORMONONETIN	2	BCL2
LACUTOCLAX	2	BCL2
ABT 737	1	BCL2
VOB-560	1	BCL2
AZD-5991	1	BCL2
TAPOTOCLAX	1	BCL2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BCL2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	PIGN
E	Difficult family or no structure, no drug	1	SERPINB2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PIGN	0	—
SERPINB2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.