Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
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Also known as megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome type 1megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome caused by mutation in PIK3R2MPPH1PIK3R2 megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
Summary
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MONDO:0011313) is a disease caused by variants in PIK3R2 and AKT3, with 5 cohort genes.
At a glance
- Causal genes: PIK3R2 (GenCC Definitive), AKT3 (GenCC Strong)
- Cohort genes: 5
- ClinVar variants: 46
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 |
| Mondo ID | MONDO:0011313 |
| MeSH | C566381 |
| OMIM | 603387 |
| UMLS | C4012727 |
| MedGen | 861164 |
| GARD | 0018077 |
| Is cancer (heuristic) | no |
Also known as: megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 · megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome type 1 · megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome caused by mutation in PIK3R2 · MPPH1 · PIK3R2 megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
Data availability: 46 ClinVar variants · 6 GenCC gene-disease records · 6 cell lines.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › hydrocephalus › megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome › megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
Related subtypes (2): megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 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
46 retrieved; paginated sample, class counts are floors:
25 uncertain significance, 6 benign, 4 pathogenic, 4 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 likely benign, 1 benign/likely benign, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1338376 | NM_001759.4(CCND2):c.851T>A (p.Val284Glu) | CCND2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 143990 | NM_005027.4(PIK3R2):c.1202T>C (p.Leu401Pro) | PIK3R2 | Pathogenic | no assertion criteria provided |
| 280374 | NM_005027.4(PIK3R2):c.1126A>G (p.Lys376Glu) | PIK3R2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 39808 | NM_005027.4(PIK3R2):c.1117G>A (p.Gly373Arg) | PIK3R2 | Pathogenic | reviewed by expert panel |
| 995384 | NM_005027.4(PIK3R2):c.1153G>A (p.Gly385Arg) | PIK3R2 | Pathogenic | no assertion criteria provided |
| 3362503 | NM_005027.4(PIK3R2):c.598+2T>G | LOC130063979 | Likely pathogenic | criteria provided, single submitter |
| 376165 | NM_005027.4(PIK3R2):c.1681A>G (p.Asn561Asp) | PIK3R2 | Likely pathogenic | criteria provided, single submitter |
| 625283 | NM_005027.4(PIK3R2):c.1056C>G (p.Phe352Leu) | PIK3R2 | Likely pathogenic | criteria provided, single submitter |
| 976716 | NM_005027.4(PIK3R2):c.988T>G (p.Trp330Gly) | PIK3R2 | Likely pathogenic | criteria provided, single submitter |
| 1296705 | NM_005027.4(PIK3R2):c.1243G>A (p.Ala415Thr) | PIK3R2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1319057 | NM_005027.4(PIK3R2):c.1217G>A (p.Arg406His) | PIK3R2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2664174 | NM_014795.4(ZEB2):c.1858A>G (p.Ile620Val) | ZEB2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2425279 | NC_000019.9:g.(?17927663)(19312528_?)dup | ARMC6 | Uncertain significance | criteria provided, single submitter |
| 3046834 | NM_005027.4(PIK3R2):c.668G>A (p.Arg223His) | LOC130063979 | Uncertain significance | criteria provided, single submitter |
| 1032968 | NM_005027.4(PIK3R2):c.29G>A (p.Arg10His) | PIK3R2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1405289 | NM_005027.4(PIK3R2):c.553C>G (p.Leu185Val) | PIK3R2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1486430 | NM_005027.4(PIK3R2):c.2120C>T (p.Ala707Val) | PIK3R2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1705289 | NM_005027.4(PIK3R2):c.2063C>T (p.Ser688Leu) | PIK3R2 | Uncertain significance | criteria provided, single submitter |
| 1709855 | NM_005027.4(PIK3R2):c.496G>C (p.Asp166His) | PIK3R2 | Uncertain significance | criteria provided, single submitter |
| 2434859 | NM_005027.4(PIK3R2):c.1883A>G (p.Asn628Ser) | PIK3R2 | Uncertain significance | criteria provided, single submitter |
| 2434860 | NM_005027.4(PIK3R2):c.338A>C (p.Asp113Ala) | PIK3R2 | Uncertain significance | criteria provided, single submitter |
| 2434861 | NM_005027.4(PIK3R2):c.867G>A (p.Gln289=) | PIK3R2 | Uncertain significance | criteria provided, single submitter |
| 2689753 | NM_005027.4(PIK3R2):c.259_263del (p.Gly87fs) | PIK3R2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3065767 | NM_005027.4(PIK3R2):c.1109+1G>A | PIK3R2 | Uncertain significance | criteria provided, single submitter |
| 3583541 | NM_005027.4(PIK3R2):c.158G>C (p.Ser53Thr) | PIK3R2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3583542 | NM_005027.4(PIK3R2):c.1523G>A (p.Arg508His) | PIK3R2 | Uncertain significance | criteria provided, single submitter |
| 3672581 | NM_005027.4(PIK3R2):c.127G>A (p.Val43Met) | PIK3R2 | Uncertain significance | criteria provided, single submitter |
| 3704055 | NM_005027.4(PIK3R2):c.1192G>A (p.Val398Ile) | PIK3R2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3731548 | NM_005027.4(PIK3R2):c.1360C>T (p.Gln454Ter) | PIK3R2 | Uncertain significance | criteria provided, single submitter |
| 4279773 | NM_005027.4(PIK3R2):c.2043G>C (p.Glu681Asp) | PIK3R2 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 15 · Orphanet: 7 · 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 |
|---|---|---|---|---|
| PIK3R2 | Definitive | Autosomal dominant | megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 | 7 |
| AKT3 | Strong | Autosomal dominant | megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 | 8 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PIK3R2 | Orphanet:83473 | Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome |
| AKT3 | Orphanet:83473 | Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome |
| AKT3 | Orphanet:99802 | Hemimegalencephaly |
| ZEB2 | Orphanet:261537 | Mowat-Wilson syndrome due to monosomy 2q22 |
| ZEB2 | Orphanet:261552 | Mowat-Wilson syndrome due to a ZEB2 point mutation |
| ZEB2 | Orphanet:626 | Large/giant congenital melanocytic nevus |
| CCND2 | Orphanet:83473 | Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome |
Cohort genes → proteins
5 cohort genes, 5 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 5 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| PIK3R2 | HGNC:8980 | ENSG00000105647 | O00459 | Phosphatidylinositol 3-kinase regulatory subunit beta | gencc,clinvar |
| AKT3 | HGNC:393 | ENSG00000117020 | Q9Y243 | RAC-gamma serine/threonine-protein kinase | gencc |
| ZEB2 | HGNC:14881 | ENSG00000169554 | O60315 | Zinc finger E-box-binding homeobox 2 | clinvar |
| CCND2 | HGNC:1583 | ENSG00000118971 | P30279 | G1/S-specific cyclin-D2 | clinvar |
| ARMC6 | HGNC:25049 | ENSG00000105676 | Q6NXE6 | Armadillo repeat-containing protein 6 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| PIK3R2 | Phosphatidylinositol 3-kinase regulatory subunit beta | Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). |
| AKT3 | RAC-gamma serine/threonine-protein kinase | AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. |
| ZEB2 | Zinc finger E-box-binding homeobox 2 | Transcriptional inhibitor that binds to DNA sequence 5’-CACCT-3’ in different promoters. |
| CCND2 | G1/S-specific cyclin-D2 | Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. |
Protein-family classification
Druggable: 2 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.4
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 | 2 | 11.1× | 0.036 |
| Transcription factor | 1 | 1.6× | 0.713 |
| Other/Unknown | 2 | 0.7× | 0.877 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| PIK3R2 | Kinase | yes | 2.7.1.137 | RhoGAP_dom, SH2, SH3_domain |
| AKT3 | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, AGC-kinase_C, PH_domain |
| ZEB2 | Transcription factor | no | HD, Di19_Zn-bd, Homeodomain-like_sf | |
| CCND2 | Other/Unknown | no | Cyclin_C-dom, Cyclin_N, Cyclin-like_dom | |
| ARMC6 | Other/Unknown | no | Armadillo, ARM-like, ARM-type_fold |
Expression context
Cohort genes with no expression data: 0.
5 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) | 5 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| cortical plate | 4 |
| ganglionic eminence | 1 |
| stromal cell of endometrium | 1 |
| calcaneal tendon | 1 |
| embryo | 1 |
| monocyte | 1 |
| sural nerve | 1 |
| adrenal tissue | 1 |
| cauda epididymis | 1 |
| seminal vesicle | 1 |
| primordial germ cell in gonad | 1 |
| right lobe of liver | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PIK3R2 | 138 | ubiquitous | marker | cortical plate, ganglionic eminence, stromal cell of endometrium |
| AKT3 | 231 | ubiquitous | marker | cortical plate, calcaneal tendon, embryo |
| ZEB2 | 290 | ubiquitous | marker | cortical plate, sural nerve, monocyte |
| CCND2 | 293 | ubiquitous | marker | adrenal tissue, seminal vesicle, cauda epididymis |
| ARMC6 | 259 | ubiquitous | marker | right lobe of liver, cortical plate, primordial germ cell in gonad |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| CCND2 | 3,569 |
| AKT3 | 3,392 |
| ZEB2 | 3,193 |
| PIK3R2 | 2,751 |
| ARMC6 | 1,001 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| AKT3 | PIK3R2 | string_interaction |
Structural data
PDB: 4 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| PIK3R2 | O00459 | 8 |
| AKT3 | Q9Y243 | 2 |
| ZEB2 | O60315 | 1 |
| CCND2 | P30279 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ARMC6 | Q6NXE6 | 91.10 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 141. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| CD28 dependent PI3K/Akt signaling | 2 | 196.9× | 0.005 | PIK3R2, AKT3 |
| Mitotic G1 phase and G1/S transition | 2 | 92.1× | 0.009 | CCND2, AKT3 |
| Extra-nuclear estrogen signaling | 2 | 85.2× | 0.009 | PIK3R2, AKT3 |
| VEGFA-VEGFR2 Pathway | 2 | 69.6× | 0.011 | PIK3R2, AKT3 |
| AKT-mediated inactivation of FOXO1A | 1 | 713.8× | 0.023 | AKT3 |
| Inhibition of TSC complex formation by AKT (PKB) | 1 | 571.0× | 0.023 | AKT3 |
| Drug-mediated inhibition of CDK4/CDK6 activity | 1 | 571.0× | 0.023 | CCND2 |
| G-protein beta:gamma signalling | 1 | 475.8× | 0.023 | AKT3 |
| Signaling by LTK in cancer | 1 | 407.9× | 0.023 | PIK3R2 |
| RUNX2 regulates genes involved in cell migration | 1 | 356.9× | 0.023 | AKT3 |
| PI3K/AKT activation | 1 | 317.2× | 0.023 | PIK3R2 |
| AKT phosphorylates targets in the nucleus | 1 | 285.5× | 0.023 | AKT3 |
| Formation of the posterior neural plate | 1 | 285.5× | 0.023 | ZEB2 |
| IRS-mediated signalling | 1 | 259.6× | 0.023 | PIK3R2 |
| Regulation of CDH11 gene transcription | 1 | 259.6× | 0.023 | ZEB2 |
| Formation of the anterior neural plate | 1 | 259.6× | 0.023 | ZEB2 |
| Co-stimulation by ICOS | 1 | 259.6× | 0.023 | PIK3R2 |
| Regulation of localization of FOXO transcription factors | 1 | 237.9× | 0.023 | AKT3 |
| Positive Regulation of CDH1 Gene Transcription | 1 | 237.9× | 0.023 | ZEB2 |
| Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects | 1 | 219.6× | 0.023 | CCND2 |
| Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants | 1 | 219.6× | 0.023 | PIK3R2 |
| Signaling by PDGFRA extracellular domain mutants | 1 | 219.6× | 0.023 | PIK3R2 |
| SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 1 | 219.6× | 0.023 | AKT3 |
| Signaling by LTK | 1 | 219.6× | 0.023 | PIK3R2 |
| Downregulation of ERBB2:ERBB3 signaling | 1 | 203.9× | 0.023 | AKT3 |
| AKT phosphorylates targets in the cytosol | 1 | 203.9× | 0.023 | AKT3 |
| Regulation of TP53 Activity through Association with Co-factors | 1 | 203.9× | 0.023 | AKT3 |
| PIP3 activates AKT signaling | 2 | 33.4× | 0.023 | PIK3R2, AKT3 |
| Cell Cycle, Mitotic | 2 | 24.1× | 0.023 | CCND2, AKT3 |
| Cell Cycle | 2 | 18.0× | 0.023 | CCND2, AKT3 |
GO biological processes 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.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| mammillary axonal complex development | 1 | 3370.4× | 0.006 | ZEB2 |
| positive regulation of myofibroblast contraction | 1 | 3370.4× | 0.006 | ZEB2 |
| regulation of blood-brain barrier permeability | 1 | 3370.4× | 0.006 | ZEB2 |
| insulin receptor signaling pathway | 2 | 88.7× | 0.006 | PIK3R2, AKT3 |
| positive regulation of lens fiber cell differentiation | 1 | 1685.2× | 0.006 | ZEB2 |
| regulation of melanosome organization | 1 | 1685.2× | 0.006 | ZEB2 |
| regulation of myofibroblast cell apoptotic process | 1 | 1685.2× | 0.006 | ZEB2 |
| melanocyte migration | 1 | 1123.5× | 0.008 | ZEB2 |
| myofibroblast differentiation | 1 | 674.1× | 0.010 | ZEB2 |
| positive regulation of melanocyte differentiation | 1 | 674.1× | 0.010 | ZEB2 |
| positive regulation of artery morphogenesis | 1 | 674.1× | 0.010 | AKT3 |
| corpus callosum morphogenesis | 1 | 481.5× | 0.011 | ZEB2 |
| corticospinal tract morphogenesis | 1 | 481.5× | 0.011 | ZEB2 |
| fibroblast activation | 1 | 481.5× | 0.011 | ZEB2 |
| developmental pigmentation | 1 | 421.3× | 0.011 | ZEB2 |
| response to oxygen-glucose deprivation | 1 | 421.3× | 0.011 | ZEB2 |
| cellular response to X-ray | 1 | 337.0× | 0.013 | CCND2 |
| negative regulation of fibroblast migration | 1 | 306.4× | 0.013 | ZEB2 |
| positive regulation of melanin biosynthetic process | 1 | 280.9× | 0.013 | ZEB2 |
| negative regulation of PERK-mediated unfolded protein response | 1 | 280.9× | 0.013 | AKT3 |
| cell proliferation in forebrain | 1 | 259.3× | 0.013 | ZEB2 |
| positive regulation of cell size | 1 | 259.3× | 0.013 | AKT3 |
| collateral sprouting | 1 | 240.7× | 0.014 | ZEB2 |
| astrocyte activation | 1 | 198.3× | 0.015 | ZEB2 |
| regulation of stress fiber assembly | 1 | 198.3× | 0.015 | PIK3R2 |
| regulation of mitochondrion organization | 1 | 168.5× | 0.016 | AKT3 |
| positive regulation of vascular endothelial cell proliferation | 1 | 168.5× | 0.016 | AKT3 |
| stress fiber assembly | 1 | 153.2× | 0.017 | ZEB2 |
| brain morphogenesis | 1 | 146.5× | 0.017 | AKT3 |
| positive regulation of cell migration involved in sprouting angiogenesis | 1 | 146.5× | 0.017 | AKT3 |
Therapeutics
Drug target analysis
Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 2
Druggability breadth: 3 of 5 evidence-associated genes (60%) 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 |
|---|---|
| PIK3R2 | IDELALISIB |
| AKT3 | CAPIVASERTIB |
| CCND2 | PALBOCICLIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| AKT3 | 18 | 4 |
| PIK3R2 | 6 | 4 |
| CCND2 | 3 | 4 |
| ZEB2 | 0 | 0 |
| ARMC6 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| IDELALISIB | 4 | PIK3R2 |
| INAVOLISIB | 4 | PIK3R2 |
| CAPIVASERTIB | 4 | AKT3 |
| MIDOSTAURIN | 4 | AKT3 |
| PALBOCICLIB | 4 | CCND2 |
| TASELISIB | 3 | PIK3R2 |
| IPATASERTIB | 3 | AKT3 |
| AFURESERTIB | 3 | AKT3 |
| ENZASTAURIN | 3 | AKT3 |
| FASUDIL | 3 | AKT3 |
| LESTAURTINIB | 3 | AKT3 |
| RUBOXISTAURIN | 3 | AKT3 |
| ALVOCIDIB | 3 | CCND2 |
| ROGINOLISIB | 2 | PIK3R2 |
| AMDIZALISIB | 2 | PIK3R2 |
| PICTILISIB | 2 | PIK3R2 |
| MIRANSERTIB | 2 | AKT3 |
| MK-2206 | 2 | AKT3 |
| UPROSERTIB | 2 | AKT3 |
| AT-13148 | 1 | AKT3 |
| GSK-690693 | 1 | AKT3 |
| GSK-1070916 | 1 | AKT3 |
| JNJ-26483327 | 1 | AKT3 |
| PF-03758309 | 1 | AKT3 |
| BAY-1125976 | 1 | AKT3 |
| VEVORISERTIB | 1 | AKT3 |
| BMS-387032 | 1 | CCND2 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| AKT3 | 660 | Binding:644, Functional:16 |
| CCND2 | 28 | Binding:28 |
| PIK3R2 | 27 | Binding:27 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| PIK3R2 | 2.7.1.137 | phosphatidylinositol 3-kinase |
| AKT3 | 2.7.11.1 | non-specific serine/threonine protein kinase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| AKT3 | 660 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
27 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) |
|---|---|---|
| IDELALISIB | 4 | PIK3R2 |
| INAVOLISIB | 4 | PIK3R2 |
| CAPIVASERTIB | 4 | AKT3 |
| MIDOSTAURIN | 4 | AKT3 |
| PALBOCICLIB | 4 | CCND2 |
| TASELISIB | 3 | PIK3R2 |
| IPATASERTIB | 3 | AKT3 |
| AFURESERTIB | 3 | AKT3 |
| ENZASTAURIN | 3 | AKT3 |
| FASUDIL | 3 | AKT3 |
| LESTAURTINIB | 3 | AKT3 |
| RUBOXISTAURIN | 3 | AKT3 |
| ALVOCIDIB | 3 | CCND2 |
| ROGINOLISIB | 2 | PIK3R2 |
| AMDIZALISIB | 2 | PIK3R2 |
| PICTILISIB | 2 | PIK3R2 |
| MIRANSERTIB | 2 | AKT3 |
| MK-2206 | 2 | AKT3 |
| UPROSERTIB | 2 | AKT3 |
| AT-13148 | 1 | AKT3 |
| GSK-690693 | 1 | AKT3 |
| GSK-1070916 | 1 | AKT3 |
| JNJ-26483327 | 1 | AKT3 |
| PF-03758309 | 1 | AKT3 |
| BAY-1125976 | 1 | AKT3 |
| VEVORISERTIB | 1 | AKT3 |
| BMS-387032 | 1 | CCND2 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 3 | PIK3R2, AKT3, CCND2 |
| 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 | 2 | ZEB2, ARMC6 |
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) |
|---|---|---|
| ZEB2 | 0 | — |
| ARMC6 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.