Houge-Janssens syndrome 2

Summary

Houge-Janssens syndrome 2 (MONDO:0014605) is a disease caused by PPP2R1A (GenCC Definitive), with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PPP2R1A (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 46
• Phenotypes (HPO): 38

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

38 HPO clinical features (Orphanet curated; top 38 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0000194	Open mouth	Frequent (30-79%)
HP:0000297	Facial hypotonia	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001274	Agenesis of corpus callosum	Frequent (30-79%)
HP:0001344	Absent speech	Frequent (30-79%)
HP:0001357	Plagiocephaly	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0002119	Ventriculomegaly	Frequent (30-79%)
HP:0002465	Poor speech	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0012448	Delayed myelination	Frequent (30-79%)
HP:0100704	Cerebral visual impairment	Frequent (30-79%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000122	Unilateral renal agenesis	Occasional (5-29%)
HP:0000151	Aplasia of the uterus	Occasional (5-29%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000324	Facial asymmetry	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000478	Abnormality of the eye	Occasional (5-29%)
HP:0000609	Optic nerve hypoplasia	Occasional (5-29%)
HP:0000752	Hyperactivity	Occasional (5-29%)
HP:0000767	Pectus excavatum	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)
HP:0001385	Hip dysplasia	Occasional (5-29%)
HP:0003250	Aplasia of the vagina	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0005487	Prominent metopic ridge	Occasional (5-29%)
HP:0006955	Olivopontocerebellar hypoplasia	Occasional (5-29%)
HP:0010055	Broad hallux	Occasional (5-29%)
HP:0010721	Abnormal hair whorl	Occasional (5-29%)
HP:0011471	Gastrostomy tube feeding in infancy	Occasional (5-29%)
HP:0012304	Hypoplastic aortic arch	Occasional (5-29%)
HP:0025607	Upper eyelid entropion	Occasional (5-29%)
HP:0100259	Postaxial polydactyly	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Houge-Janssens syndrome 2
Mondo ID	MONDO:0014605
OMIM	616362
Orphanet	457284
DOID	DOID:0070066
UMLS	C4225352
MedGen	899880
GARD	0017803
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 36 · intellectual disability, autosomal dominant 36 · intellectual disability, autosomal dominant type 36 · mental retardation, autosomal dominant 36 · mental retardation, autosomal dominant type 36 · microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome · MRD36

Data availability: 46 ClinVar variants · 4 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 › Houge-Janssens syndrome 2

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid 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

46 retrieved; paginated sample, class counts are floors:

18 uncertain significance, 8 pathogenic/likely pathogenic, 7 conflicting classifications of pathogenicity, 6 likely pathogenic, 5 pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1204633	NM_014225.6(PPP2R1A):c.538A>G (p.Met180Val)	PPP2R1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1297557	NM_014225.6(PPP2R1A):c.658G>A (p.Val220Met)	PPP2R1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1699184	NM_014225.6(PPP2R1A):c.536C>A (p.Pro179His)	PPP2R1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190312	NM_014225.6(PPP2R1A):c.544C>T (p.Arg182Trp)	PPP2R1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190313	NM_014225.6(PPP2R1A):c.536C>T (p.Pro179Leu)	PPP2R1A	Pathogenic	criteria provided, multiple submitters, no conflicts
217458	NM_014225.6(PPP2R1A):c.773G>A (p.Arg258His)	PPP2R1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2504579	NM_014225.6(PPP2R1A):c.843dup (p.Asp282fs)	PPP2R1A	Pathogenic	criteria provided, single submitter
3649140	NM_014225.6(PPP2R1A):c.545G>A (p.Arg182Gln)	PPP2R1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
376505	NM_014225.6(PPP2R1A):c.547C>T (p.Arg183Trp)	PPP2R1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
376506	NM_014225.6(PPP2R1A):c.548G>A (p.Arg183Gln)	PPP2R1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
521503	NM_014225.6(PPP2R1A):c.656C>T (p.Ser219Leu)	PPP2R1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
684494	NM_014225.6(PPP2R1A):c.539T>C (p.Met180Thr)	PPP2R1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6821	NM_007373.4(SHOC2):c.4A>G (p.Ser2Gly)	SHOC2	Pathogenic	reviewed by expert panel
2430276	NM_014225.6(PPP2R1A):c.532A>G (p.Thr178Ala)	PPP2R1A	Likely pathogenic	criteria provided, single submitter
2498148	NM_014225.6(PPP2R1A):c.96C>G (p.Ile32Met)	PPP2R1A	Likely pathogenic	no assertion criteria provided
2504581	NM_014225.6(PPP2R1A):c.1493G>T (p.Arg498Leu)	PPP2R1A	Likely pathogenic	criteria provided, single submitter
3236825	NM_014225.6(PPP2R1A):c.400C>T (p.Arg134Trp)	PPP2R1A	Likely pathogenic	criteria provided, single submitter
985103	NM_014225.6(PPP2R1A):c.548G>C (p.Arg183Pro)	PPP2R1A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
619004	NM_014231.5(VAMP1):c.129+1G>A	TAPBPL	Likely pathogenic	criteria provided, single submitter
1032611	NM_014225.6(PPP2R1A):c.775G>A (p.Val259Ile)	PPP2R1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1197324	NM_014225.6(PPP2R1A):c.430C>T (p.Arg144Cys)	PPP2R1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
804149	NM_014225.6(PPP2R1A):c.754G>A (p.Ala252Thr)	PPP2R1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
916077	NM_014225.6(PPP2R1A):c.655T>C (p.Ser219Pro)	PPP2R1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
957599	NM_014225.6(PPP2R1A):c.352G>A (p.Glu118Lys)	PPP2R1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
976337	NM_014225.6(PPP2R1A):c.275C>T (p.Pro92Leu)	PPP2R1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
992800	NM_014225.6(PPP2R1A):c.1747C>A (p.Leu583Met)	PPP2R1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029258	NM_014225.6(PPP2R1A):c.15C>G (p.Asp5Glu)	PPP2R1A	Uncertain significance	criteria provided, single submitter
1031809	NM_014225.6(PPP2R1A):c.*136C>T	PPP2R1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031810	NM_014225.6(PPP2R1A):c.1306G>A (p.Val436Met)	PPP2R1A	Uncertain significance	criteria provided, single submitter
1372237	NM_014225.6(PPP2R1A):c.343A>G (p.Ile115Val)	PPP2R1A	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
PPP2R1A	Definitive	Autosomal dominant	Houge-Janssens syndrome 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PPP2R1A	Orphanet:457284	Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome
SHOC2	Orphanet:2701	Noonan syndrome-like disorder with loose anagen hair

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
PPP2R1A	HGNC:9302	ENSG00000105568	P30153	Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform	gencc,clinvar
SHOC2	HGNC:15454	ENSG00000108061	Q9UQ13	Leucine-rich repeat protein SHOC-2	clinvar
TAPBPL	HGNC:30683	ENSG00000139192	Q9BX59	Tapasin-related protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PPP2R1A	Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform	The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit.
SHOC2	Leucine-rich repeat protein SHOC-2	Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates activation of the MAPK pathway.
TAPBPL	Tapasin-related protein	Component of the antigen processing and presentation pathway, which binds to MHC class I coupled with beta2-microglobulin/B2M.

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
Antibody/Immunoglobulin	1	9.7×	0.199
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PPP2R1A	Other/Unknown	no		HEAT, ARM-like, ARM-type_fold
SHOC2	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRR_dom_sf
TAPBPL	Antibody/Immunoglobulin	yes		Ig/MHC_CS, Ig_C1-set, Ig_sub

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
adrenal tissue	1
apex of heart	1
cortical plate	1
bone marrow	1
calcaneal tendon	1
sural nerve	1
granulocyte	1
left lobe of thyroid gland	1
right lobe of thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PPP2R1A	285	ubiquitous	marker	cortical plate, adrenal tissue, apex of heart
SHOC2	299	ubiquitous	marker	calcaneal tendon, sural nerve, bone marrow
TAPBPL	258	ubiquitous	marker	granulocyte, left lobe of thyroid gland, right lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PPP2R1A	4,814
SHOC2	2,149
TAPBPL	451

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PPP2R1A	P30153	41
SHOC2	Q9UQ13	13
TAPBPL	Q9BX59	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 149. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RAF activation	2	335.9×	0.001	PPP2R1A, SHOC2
MAPK1/MAPK3 signaling	2	131.3×	0.004	PPP2R1A, SHOC2
MAPK family signaling cascades	2	102.9×	0.005	PPP2R1A, SHOC2
RAF/MAP kinase cascade	2	61.1×	0.009	PPP2R1A, SHOC2
Diseases of signal transduction by growth factor receptors and second messengers	2	56.8×	0.009	PPP2R1A, SHOC2
Signaling by MRAS-complex mutants	1	1427.5×	0.013	SHOC2
E2F mediated regulation of DNA replication	1	815.7×	0.013	PPP2R1A
PP2A-mediated dephosphorylation of key metabolic factors	1	815.7×	0.013	PPP2R1A
SHOC2 M1731 mutant abolishes MRAS complex function	1	713.8×	0.013	SHOC2
Gain-of-function MRAS complexes activate RAF signaling	1	713.8×	0.013	SHOC2
MASTL Facilitates Mitotic Progression	1	571.0×	0.013	PPP2R1A
Signaling by FGFR3	1	571.0×	0.013	PPP2R1A
Signaling by AXIN mutants	1	519.1×	0.013	PPP2R1A
Signaling by CTNNB1 phospho-site mutants	1	519.1×	0.013	PPP2R1A
Signaling by APC mutants	1	519.1×	0.013	PPP2R1A
Signaling by AMER1 mutants	1	519.1×	0.013	PPP2R1A
Signaling by FGFR4	1	519.1×	0.013	PPP2R1A
Regulation of glycolysis by fructose 2,6-bisphosphate metabolism	1	475.8×	0.013	PPP2R1A
ERKs are inactivated	1	439.2×	0.013	PPP2R1A
Glucose metabolism	1	439.2×	0.013	PPP2R1A
Inhibition of replication initiation of damaged DNA by RB1/E2F1	1	407.9×	0.013	PPP2R1A
APC truncation mutants have impaired AXIN binding	1	407.9×	0.013	PPP2R1A
AXIN missense mutants destabilize the destruction complex	1	407.9×	0.013	PPP2R1A
Truncations of AMER1 destabilize the destruction complex	1	407.9×	0.013	PPP2R1A
Signaling by FGFR1	1	407.9×	0.013	PPP2R1A
Signaling by GSK3beta mutants	1	380.7×	0.013	PPP2R1A
CTNNB1 S33 mutants aren’t phosphorylated	1	380.7×	0.013	PPP2R1A
CTNNB1 S37 mutants aren’t phosphorylated	1	380.7×	0.013	PPP2R1A
CTNNB1 S45 mutants aren’t phosphorylated	1	380.7×	0.013	PPP2R1A
CTNNB1 T41 mutants aren’t phosphorylated	1	380.7×	0.013	PPP2R1A

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
negative regulation of antigen processing and presentation of peptide antigen via MHC class I	1	5617.3×	0.002	TAPBPL
meiotic spindle elongation	1	5617.3×	0.002	PPP2R1A
cellular response to growth hormone stimulus	1	5617.3×	0.002	SHOC2
regulation of meiotic cell cycle process involved in oocyte maturation	1	2808.7×	0.002	PPP2R1A
mitotic sister chromatid separation	1	1123.5×	0.004	PPP2R1A
meiotic sister chromatid cohesion, centromeric	1	1123.5×	0.004	PPP2R1A
peptide antigen assembly with MHC class I protein complex	1	936.2×	0.004	TAPBPL
cyclic-GMP-AMP transmembrane import across plasma membrane	1	702.2×	0.005	SHOC2
female meiotic nuclear division	1	561.7×	0.005	PPP2R1A
negative regulation of neural precursor cell proliferation	1	510.7×	0.005	SHOC2
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	510.7×	0.005	PPP2R1A
intracellular signal transduction	2	25.4×	0.005	PPP2R1A, SHOC2
nerve growth factor signaling pathway	1	432.1×	0.005	SHOC2
regulation of growth	1	312.1×	0.006	PPP2R1A
positive regulation of Ras protein signal transduction	1	295.6×	0.006	SHOC2
RNA polymerase II transcription initiation surveillance	1	295.6×	0.006	PPP2R1A
negative regulation of hippo signaling	1	234.1×	0.007	PPP2R1A
T cell homeostasis	1	151.8×	0.009	PPP2R1A
regulation of MAPK cascade	1	151.8×	0.009	SHOC2
spindle assembly	1	147.8×	0.009	PPP2R1A
regulation of cell differentiation	1	144.0×	0.009	PPP2R1A
fibroblast growth factor receptor signaling pathway	1	95.2×	0.013	SHOC2
negative regulation of neuron differentiation	1	90.6×	0.013	SHOC2
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	87.8×	0.013	PPP2R1A
positive regulation of neuron differentiation	1	66.1×	0.017	SHOC2
chromosome segregation	1	57.9×	0.018	PPP2R1A
positive regulation of neuron projection development	1	45.7×	0.023	SHOC2
protein-containing complex assembly	1	38.0×	0.026	PPP2R1A

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PPP2R1A	0	0
SHOC2	0	0
TAPBPL	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PPP2R1A	7	Binding:7

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	TAPBPL
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	PPP2R1A, SHOC2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PPP2R1A	7	—
SHOC2	0	—
TAPBPL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.