Sick sinus syndrome 4

Summary

Sick sinus syndrome 4 (MONDO:0859173) 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	sick sinus syndrome 4
Mondo ID	MONDO:0859173
OMIM	619464
UMLS	C5561949
MedGen	1794159
GARD	0026663
Is cancer (heuristic)	no

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

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart conduction disease › sinoatrial node disorder › sick sinus syndrome › familial sick sinus syndrome › sick sinus syndrome 4

Related subtypes (3): sick sinus syndrome 2, autosomal dominant, sinus node disease and myopia, sick sinus 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
1185051	NM_005273.4(GNB2):c.155G>T (p.Arg52Leu)	GNB2	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
GNB2	Limited	Unknown	sick sinus syndrome 4	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GNB2	Orphanet:166282	Hereditary sick sinus syndrome
GNB2	Orphanet:528084	Non-specific syndromic intellectual disability

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
GNB2	HGNC:4398	ENSG00000172354	P62879	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNB2	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2	Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GNB2	Scaffold/PPI	no		WD40_G-protein_beta-like, WD40_rpt, WD40/YVTN_repeat-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
adenohypophysis	1
lower esophagus mucosa	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNB2	292	ubiquitous	marker	lower esophagus mucosa, ventricular zone, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNB2	1,200

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNB2	P62879	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. 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
G beta:gamma signalling through BTK	1	634.4×	0.005	GNB2
Prostacyclin signalling through prostacyclin receptor	1	601.0×	0.005	GNB2
G beta:gamma signalling through PLC beta	1	571.0×	0.005	GNB2
G beta:gamma signalling through CDC42	1	571.0×	0.005	GNB2
Presynaptic function of Kainate receptors	1	543.8×	0.005	GNB2
ADP signalling through P2Y purinoceptor 12	1	496.5×	0.005	GNB2
G-protein activation	1	475.8×	0.005	GNB2
Thromboxane signalling through TP receptor	1	475.8×	0.005	GNB2
ADP signalling through P2Y purinoceptor 1	1	456.8×	0.005	GNB2
G beta:gamma signalling through PI3Kgamma	1	439.2×	0.005	GNB2
Activation of G protein gated Potassium channels	1	393.8×	0.005	GNB2
Adrenaline,noradrenaline inhibits insulin secretion	1	393.8×	0.005	GNB2
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	1	393.8×	0.005	GNB2
Thrombin signalling through proteinase activated receptors (PARs)	1	356.9×	0.005	GNB2
Glucagon signaling in metabolic regulation	1	346.1×	0.005	GNB2
Glucagon-type ligand receptors	1	346.1×	0.005	GNB2
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	1	300.5×	0.006	GNB2
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.006	GNB2
Vasopressin regulates renal water homeostasis via Aquaporins	1	265.6×	0.006	GNB2
ADORA2B mediated anti-inflammatory cytokines production	1	253.8×	0.006	GNB2
GPER1 signaling	1	248.3×	0.006	GNB2
G alpha (z) signalling events	1	233.1×	0.006	GNB2
Ca2+ pathway	1	178.4×	0.007	GNB2
Extra-nuclear estrogen signaling	1	170.4×	0.007	GNB2
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	160.8×	0.007	GNB2
G alpha (12/13) signalling events	1	137.6×	0.008	GNB2
G alpha (s) signalling events	1	73.2×	0.015	GNB2
G alpha (q) signalling events	1	57.4×	0.018	GNB2
G alpha (i) signalling events	1	39.0×	0.026	GNB2

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
regulation of potassium ion transmembrane transport	1	624.1×	0.003	GNB2
G protein-coupled receptor signaling pathway	1	36.2×	0.028	GNB2

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
GNB2	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	GNB2

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)
GNB2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.