Bartsocas-Papas syndrome 2

Summary

Bartsocas-Papas syndrome 2 (MONDO:0859154) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bartsocas-Papas syndrome 2
Mondo ID	MONDO:0859154
OMIM	619339
UMLS	C5543445
MedGen	1778443
GARD	0016444
Is cancer (heuristic)	no

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

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › congenital limb malformation › arthrogryposis syndrome › popliteal pterygium syndrome › Bartsocas-Papas syndrome 2

Related subtypes (2): autosomal dominant popliteal pterygium syndrome, Bartsocas-Papas syndrome 1

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1120043	NM_001278.5(CHUK):c.934-2A>G	CHUK	Pathogenic	no assertion criteria provided

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
CHUK	Moderate	Autosomal recessive	Bartsocas-Papas syndrome 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHUK	Orphanet:465824	Fetal encasement syndrome
CHUK	Orphanet:697403	Combined immunodeficiency-hypogammaglobulinemia-skeletal anomalies syndrome due to IKBKA deficiency

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
CHUK	HGNC:1974	ENSG00000213341	O15111	Inhibitor of nuclear factor kappa-B kinase subunit alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHUK	Inhibitor of nuclear factor kappa-B kinase subunit alpha	Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHUK	Kinase	yes	2.7.11.10	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

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
middle frontal gyrus	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHUK	286	ubiquitous	marker	secondary oocyte, middle frontal gyrus, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHUK	5,037

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHUK	O15111	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. 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
IKBKB deficiency causes SCID	1	3806.7×	0.004	CHUK
IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)	1	3806.7×	0.004	CHUK
SLC15A4:TASL-dependent IRF5 activation	1	1903.3×	0.004	CHUK
IkBA variant leads to EDA-ID	1	1631.4×	0.004	CHUK
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10	1	878.5×	0.004	CHUK
AKT phosphorylates targets in the cytosol	1	815.7×	0.004	CHUK
IRAK1 recruits IKK complex	1	815.7×	0.004	CHUK
IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation	1	815.7×	0.004	CHUK
MAP3K8 (TPL2)-dependent MAPK1/3 activation	1	713.8×	0.004	CHUK
RIP-mediated NFkB activation via ZBP1	1	671.8×	0.004	CHUK
Regulation of NF-kappa B signaling	1	634.4×	0.004	CHUK
TICAM1, RIP1-mediated IKK complex recruitment	1	601.0×	0.004	CHUK
Modulation of host responses by IFN-stimulated genes	1	601.0×	0.004	CHUK
IKK complex recruitment mediated by RIP1	1	496.5×	0.004	CHUK
TRAF6 mediated NF-kB activation	1	456.8×	0.005	CHUK
Constitutive Signaling by AKT1 E17K in Cancer	1	423.0×	0.005	CHUK
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	356.9×	0.005	CHUK
TNFR1-induced NF-kappa-B signaling pathway	1	335.9×	0.005	CHUK
NOD1/2 Signaling Pathway	1	317.2×	0.005	CHUK
TAK1-dependent IKK and NF-kappa-B activation	1	300.5×	0.005	CHUK
NIK–>noncanonical NF-kB signaling	1	228.4×	0.006	CHUK
Regulation of TNFR1 signaling	1	223.9×	0.006	CHUK
Dectin-1 mediated noncanonical NF-kB signaling	1	215.5×	0.006	CHUK
Activation of NF-kappaB in B cells	1	196.9×	0.007	CHUK
FCERI mediated NF-kB activation	1	156.4×	0.008	CHUK
CLEC7A (Dectin-1) signaling	1	142.8×	0.008	CHUK
PKR-mediated signaling	1	141.0×	0.008	CHUK
ER-Phagosome pathway	1	129.8×	0.008	CHUK
Downstream TCR signaling	1	128.3×	0.008	CHUK
Interleukin-1 signaling	1	124.1×	0.008	CHUK

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
response to acetate	1	16852.0×	0.002	CHUK
response to cholecystokinin	1	8426.0×	0.002	CHUK
response to hydroperoxide	1	1685.2×	0.005	CHUK
response to amino acid	1	991.3×	0.005	CHUK
striated muscle cell differentiation	1	991.3×	0.005	CHUK
non-canonical NF-kappaB signal transduction	1	842.6×	0.005	CHUK
positive regulation of interferon-alpha production	1	648.1×	0.006	CHUK
toll-like receptor 4 signaling pathway	1	526.6×	0.006	CHUK
skeletal muscle contraction	1	510.7×	0.006	CHUK
canonical NF-kappaB signal transduction	1	366.4×	0.007	CHUK
obsolete negative regulation of NF-kappaB transcription factor activity	1	358.6×	0.007	CHUK
tumor necrosis factor-mediated signaling pathway	1	330.4×	0.007	CHUK
negative regulation of autophagy	1	259.3×	0.008	CHUK
response to toxic substance	1	210.7×	0.008	CHUK
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.008	CHUK
cellular response to virus	1	200.6×	0.008	CHUK
cellular response to tumor necrosis factor	1	163.6×	0.009	CHUK
integrin-mediated signaling pathway	1	160.5×	0.009	CHUK
response to virus	1	144.0×	0.010	CHUK
anatomical structure morphogenesis	1	139.3×	0.010	CHUK
autophagy	1	110.1×	0.012	CHUK
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.017	CHUK
response to xenobiotic stimulus	1	69.1×	0.017	CHUK
immune response	1	47.1×	0.024	CHUK
inflammatory response	1	37.7×	0.029	CHUK
innate immune response	1	33.6×	0.031	CHUK
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	CHUK

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
CHUK	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHUK	15	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	CHUK
DEXAMETHASONE	4	CHUK
NINTEDANIB	4	CHUK
SUNITINIB	4	CHUK
MIDOSTAURIN	4	CHUK
DOVITINIB	3	CHUK
LESTAURTINIB	3	CHUK
FORETINIB	2	CHUK
SU-014813	2	CHUK
LAUROGUADINE	2	CHUK
R-406	2	CHUK
AS-602868	1	CHUK
KW-2449	1	CHUK
IMD-0354	1	CHUK
AST-487	1	CHUK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CHUK	470	Binding:461, Functional:8, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHUK	2.7.11.10	IkappaB kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CHUK	470

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

15 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)
FEDRATINIB	4	CHUK
DEXAMETHASONE	4	CHUK
NINTEDANIB	4	CHUK
SUNITINIB	4	CHUK
MIDOSTAURIN	4	CHUK
DOVITINIB	3	CHUK
LESTAURTINIB	3	CHUK
FORETINIB	2	CHUK
SU-014813	2	CHUK
LAUROGUADINE	2	CHUK
R-406	2	CHUK
AS-602868	1	CHUK
KW-2449	1	CHUK
IMD-0354	1	CHUK
AST-487	1	CHUK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CHUK
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.