Jeune syndrome - GRK2-related

Summary

Jeune syndrome - GRK2-related (MONDO:0100583) 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	Jeune syndrome - GRK2-related
Mondo ID	MONDO:0100583
GARD	0027278
Is cancer (heuristic)	no

Also known as: asphyxiating thoracic dystrophy - GRK2-related · GRK2-related Jeune syndrome · short rib polydactyly - GRK2 related · short rib thoracic dystrophy - GRK2 related

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › Jeune syndrome › Jeune syndrome - GRK2-related

Related subtypes (23): asphyxiating thoracic dystrophy 1, Ellis-van Creveld syndrome, short-rib thoracic dysplasia 6 with or without polydactyly, short-rib thoracic dysplasia 9 with or without polydactyly, Beemer-Langer syndrome, asphyxiating thoracic dystrophy 2, asphyxiating thoracic dystrophy 3, asphyxiating thoracic dystrophy 4, short-rib thoracic dysplasia 7 with or without polydactyly, asphyxiating thoracic dystrophy 5, short-rib thoracic dysplasia 8 with or without polydactyly, short-rib thoracic dysplasia 10 with or without polydactyly, short-rib thoracic dysplasia 11 with or without polydactyly, short-rib thoracic dysplasia 13 with or without polydactyly, short-rib thoracic dysplasia 14 with polydactyly, short-rib thoracic dysplasia 15 with polydactyly, short-rib thoracic dysplasia 16 with or without polydactyly, short-rib thoracic dysplasia 21 without polydactyly, short-rib thoracic dysplasia 19 with or without polydactyly, short-rib thoracic dysplasia 18 with polydactyly, short-rib thoracic dysplasia 20 with polydactyly, short-rib thoracic dysplasia 17 with or without polydactyly, short-rib thoracic dysplasia 22 without polydactyly

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
4291888	NM_001619.5(GRK2):c.114-32_114-23del	GRK2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
GRK2	HGNC:289	ENSG00000173020	P25098	Beta-adrenergic receptor kinase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GRK2	Beta-adrenergic receptor kinase 1	Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them.

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)
GRK2	Kinase	yes	2.7.11.15	GPCR_kinase, Prot_kinase_dom, AGC-kinase_C

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
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GRK2	231	ubiquitous	marker	granulocyte, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GRK2	2,613

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GRK2	P25098	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. 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
Activation of SMO	1	634.4×	0.010	GRK2
Calmodulin induced events	1	380.7×	0.010	GRK2
CaM pathway	1	380.7×	0.010	GRK2
Ca-dependent events	1	368.4×	0.010	GRK2
G-protein mediated events	1	326.3×	0.010	GRK2
DAG and IP3 signaling	1	317.2×	0.010	GRK2
Opioid Signalling	1	265.6×	0.010	GRK2
PLC beta mediated events	1	265.6×	0.010	GRK2
Signaling by Hedgehog	1	184.2×	0.013	GRK2
Hedgehog ‘on’ state	1	158.6×	0.013	GRK2
Cargo recognition for clathrin-mediated endocytosis	1	104.8×	0.018	GRK2
Intracellular signaling by second messengers	1	91.4×	0.019	GRK2
Clathrin-mediated endocytosis	1	85.2×	0.019	GRK2
G alpha (s) signalling events	1	73.2×	0.020	GRK2
G alpha (q) signalling events	1	57.4×	0.024	GRK2
GPCR downstream signalling	1	43.4×	0.030	GRK2
Signaling by GPCR	1	40.1×	0.030	GRK2
G alpha (i) signalling events	1	39.0×	0.030	GRK2
Membrane Trafficking	1	37.1×	0.030	GRK2
Vesicle-mediated transport	1	34.8×	0.030	GRK2
Signal Transduction	1	10.2×	0.098	GRK2

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
negative regulation of the force of heart contraction by chemical signal	1	16852.0×	6e-04	GRK2
negative regulation of relaxation of smooth muscle	1	8426.0×	6e-04	GRK2
positive regulation of catecholamine secretion	1	5617.3×	6e-04	GRK2
negative regulation of striated muscle contraction	1	5617.3×	6e-04	GRK2
desensitization of G protein-coupled receptor signaling pathway	1	2808.7×	1e-03	GRK2
tachykinin receptor signaling pathway	1	1872.4×	0.001	GRK2
viral genome replication	1	1123.5×	0.002	GRK2
G protein-coupled acetylcholine receptor signaling pathway	1	1053.2×	0.002	GRK2
regulation of the force of heart contraction	1	991.3×	0.002	GRK2
symbiont entry into host cell	1	401.2×	0.003	GRK2
cardiac muscle contraction	1	401.2×	0.003	GRK2
receptor internalization	1	324.1×	0.004	GRK2
heart development	1	78.8×	0.014	GRK2
G protein-coupled receptor signaling pathway	1	36.2×	0.028	GRK2

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
GRK2	CAPIVASERTIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GRK2	6	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CAPIVASERTIB	4	GRK2
PAROXETINE	4	GRK2
PAROXETINE HYDROCHLORIDE	4	GRK2
RAVOXERTINIB	2	GRK2
PF-03758309	1	GRK2
AT-13148	1	GRK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
GRK2	206	Binding:206

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GRK2	2.7.11.15	beta-adrenergic-receptor kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GRK2	206

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

6 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)
CAPIVASERTIB	4	GRK2
PAROXETINE	4	GRK2
PAROXETINE HYDROCHLORIDE	4	GRK2
RAVOXERTINIB	2	GRK2
PF-03758309	1	GRK2
AT-13148	1	GRK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GRK2
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.