Houge-Janssens syndrome 4

Summary

Houge-Janssens syndrome 4 (MONDO:0978293) is a disease caused by PPP2R5C (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PPP2R5C (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Houge-Janssens syndrome 4
Mondo ID	MONDO:0978293
OMIM	621185
UMLS	C6012718
MedGen	1876484
Is cancer (heuristic)	no

Data availability: 12 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Houge-Janssens syndrome › Houge-Janssens syndrome 4

Related subtypes (3): Houge-Janssens syndrome 1, Houge-Janssens syndrome 2, Houge-Janssens 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

12 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
3899885	F55L	PPP2R5C	Pathogenic	no assertion criteria provided
3899886	E122K	PPP2R5C	Pathogenic	no assertion criteria provided
3899887	A130del	PPP2R5C	Pathogenic	no assertion criteria provided
3899888	H133P	PPP2R5C	Pathogenic	no assertion criteria provided
3899889	H133L	PPP2R5C	Pathogenic	no assertion criteria provided
1076998	NM_001352913.2(PPP2R5C):c.694C>T (p.Arg232Trp)	PPP2R5C	Likely pathogenic	criteria provided, single submitter
4076587	NM_001352913.2(PPP2R5C):c.310T>C (p.Cys104Arg)	PPP2R5C	Likely pathogenic	criteria provided, multiple submitters, no conflicts
666303	NM_001352913.2(PPP2R5C):c.529G>A (p.Glu177Lys)	PPP2R5C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
807171	NM_001352913.2(PPP2R5C):c.1195G>A (p.Glu399Lys)	PPP2R5C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3764198	NM_001352913.2(PPP2R5C):c.329T>C (p.Phe110Ser)	PPP2R5C	Uncertain significance	criteria provided, multiple submitters, no conflicts
4819900	NM_001352913.2(PPP2R5C):c.520G>C (p.Asp174His)	PPP2R5C	Uncertain significance	criteria provided, single submitter
4819555	NM_001352913.2(PPP2R5C):c.20A>G (p.Lys7Arg)	PPP2R5C	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
PPP2R5C	Strong	Autosomal dominant	Houge-Janssens syndrome 4	3

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PPP2R5C	HGNC:9311	ENSG00000078304	Q13362	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PPP2R5C	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform	The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PPP2R5C	Other/Unknown	no		PP2A_B56, ARM-like, ARM-type_fold

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
endothelial cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PPP2R5C	293	ubiquitous	marker	sperm, endothelial cell, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PPP2R5C	1,628

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PPP2R5C	Q13362	22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 62. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by AXIN mutants	1	1038.2×	0.007	PPP2R5C
Signaling by CTNNB1 phospho-site mutants	1	1038.2×	0.007	PPP2R5C
Signaling by APC mutants	1	1038.2×	0.007	PPP2R5C
Signaling by AMER1 mutants	1	1038.2×	0.007	PPP2R5C
APC truncation mutants have impaired AXIN binding	1	815.7×	0.007	PPP2R5C
AXIN missense mutants destabilize the destruction complex	1	815.7×	0.007	PPP2R5C
Truncations of AMER1 destabilize the destruction complex	1	815.7×	0.007	PPP2R5C
Signaling by GSK3beta mutants	1	761.3×	0.007	PPP2R5C
CTNNB1 S33 mutants aren’t phosphorylated	1	761.3×	0.007	PPP2R5C
CTNNB1 S37 mutants aren’t phosphorylated	1	761.3×	0.007	PPP2R5C
CTNNB1 S45 mutants aren’t phosphorylated	1	761.3×	0.007	PPP2R5C
CTNNB1 T41 mutants aren’t phosphorylated	1	761.3×	0.007	PPP2R5C
Beta-catenin phosphorylation cascade	1	671.8×	0.007	PPP2R5C
Platelet sensitization by LDL	1	671.8×	0.007	PPP2R5C
Signaling by WNT in cancer	1	601.0×	0.007	PPP2R5C
Co-inhibition by CTLA4	1	519.1×	0.007	PPP2R5C
Regulation of TP53 Expression and Degradation	1	519.1×	0.007	PPP2R5C
Regulation of T cell activation by CD28 family	1	423.0×	0.008	PPP2R5C
Co-stimulation by CD28	1	380.7×	0.009	PPP2R5C
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	356.9×	0.009	PPP2R5C
RAF activation	1	335.9×	0.009	PPP2R5C
Regulation of TP53 Degradation	1	292.8×	0.009	PPP2R5C
Negative regulation of the PI3K/AKT network	1	278.5×	0.009	PPP2R5C
Platelet homeostasis	1	278.5×	0.009	PPP2R5C
Negative regulation of MAPK pathway	1	265.6×	0.009	PPP2R5C
Amplification of signal from the kinetochores	1	196.9×	0.012	PPP2R5C
Degradation of beta-catenin by the destruction complex	1	173.0×	0.013	PPP2R5C
Mitotic Spindle Checkpoint	1	158.6×	0.014	PPP2R5C
Regulation of TP53 Activity	1	132.8×	0.016	PPP2R5C
MAPK1/MAPK3 signaling	1	131.3×	0.016	PPP2R5C

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
meiotic sister chromatid cohesion	1	2407.4×	0.002	PPP2R5C
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	495.6×	0.006	PPP2R5C
DNA damage response, signal transduction by p53 class mediator	1	358.6×	0.006	PPP2R5C
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.028	PPP2R5C
negative regulation of cell population proliferation	1	42.1×	0.028	PPP2R5C
signal transduction	1	16.1×	0.062	PPP2R5C

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PPP2R5C	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PPP2R5C

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PPP2R5C	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.