Kashin-Beck disease

Summary

Kashin-Beck disease (MONDO:0005610) is a disease with 1 cohort gene (1 GWAS associations across 3 studies) and 1 clinical trial.

At a glance

• Cohort genes: 1
• GWAS associations: 1
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Kashin-Beck disease
Mondo ID	MONDO:0005610
EFO	EFO:0006511
MeSH	D057767
ICD-11	211396970
SNOMED CT	270505009
UMLS	C2745963
MedGen	412531
Is cancer (heuristic)	no

Data availability: 1 GWAS association (3 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › Kashin-Beck disease

Related subtypes (49): atelosteogenesis, midface dysplasia, achondroplasia, Boomerang dysplasia, campomelic dysplasia, cleidocranial dysplasia 1, Leri-Weill dyschondrosteosis, hypochondroplasia, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, Kniest dysplasia, pseudoachondroplasia, ulna metaphyseal dysplasia syndrome, acheiropody, microcephalic osteodysplastic primordial dwarfism type I, microcephalic osteodysplastic primordial dwarfism type II, bone dysplasia, lethal Holmgren type, cleidocranial dysplasia, recessive form, diastrophic dysplasia, hypertrichotic osteochondrodysplasia Cantu type, lethal Kniest-like dysplasia, metaphyseal chondrodysplasia, Kaitila type, metaphyseal chondrodysplasia, Spahr type, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, pycnodysostosis, pyknoachondrogenesis, Pyle disease, schneckenbecken dysplasia, mesomelia-synostoses syndrome, lethal chondrodysplasia, Seller type, acrocapitofemoral dysplasia, brachyolmia, Desbuquois dysplasia, fibrochondrogenesis, multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia, thanatophoric dysplasia, Blount disease, osteogenesis imperfecta, achondrogenesis, acromesomelic dysplasia, neonatal osteosclerotic dysplasia, Akaba Hayasaka syndrome, Fairbank disease, mesomelic dysplasia, spondyloepimetaphyseal dysplasia, cleidocranial dysplasia 2, arterial tortuosity-bone fragility syndrome, linkeropathy

Genetics & variants

GWAS landscape

1 GWAS associations across 3 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs10842750	1e-11	ITPR2	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST003727	Hao J	2016	90	1,627	A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease.
GCST002634	Zhang F	2014	90	1,627	Genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese.
GCST004091	Hao J	2017	0	0	Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	1

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs10842750	12	26537632	A>C,T	0.05	intron_variant	ITPR2	1e-11	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITPR2	Orphanet:468666	Isolated generalized anhidrosis with normal sweat glands

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ITPR2	HGNC:6181	ENSG00000123104	Q14571	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ITPR2	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2	Inositol 1,4,5-trisphosphate-gated calcium channel that upon inositol 1,4,5-trisphosphate binding transports calcium from the endoplasmic reticulum lumen to cytoplasm.

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITPR2	Ion channel	yes		InsP3_rcpt, RIH_dom, Ion_trans_dom

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
adrenal tissue	1
calcaneal tendon	1
germinal epithelium of ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITPR2	273	ubiquitous	marker	calcaneal tendon, adrenal tissue, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITPR2	1,815

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ITPR2	Q14571

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 49. 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
CLEC7A (Dectin-1) induces NFAT activation	1	1038.2×	0.009	ITPR2
Elevation of cytosolic Ca2+ levels	1	713.8×	0.009	ITPR2
Platelet calcium homeostasis	1	713.8×	0.009	ITPR2
VEGFR2 mediated cell proliferation	1	571.0×	0.009	ITPR2
Effects of PIP2 hydrolysis	1	456.8×	0.009	ITPR2
Role of phospholipids in phagocytosis	1	456.8×	0.009	ITPR2
Anti-inflammatory response favouring Leishmania parasite infection	1	393.8×	0.009	ITPR2
Leishmania parasite growth and survival	1	393.8×	0.009	ITPR2
FCERI mediated Ca+2 mobilization	1	356.9×	0.009	ITPR2
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	356.9×	0.009	ITPR2
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.009	ITPR2
G-protein mediated events	1	326.3×	0.009	ITPR2
DAG and IP3 signaling	1	317.2×	0.009	ITPR2
Beta-catenin independent WNT signaling	1	292.8×	0.009	ITPR2
FCGR3A-mediated IL10 synthesis	1	292.8×	0.009	ITPR2
Fcgamma receptor (FCGR) dependent phagocytosis	1	278.5×	0.009	ITPR2
Platelet homeostasis	1	278.5×	0.009	ITPR2
Fc epsilon receptor (FCERI) signaling	1	271.9×	0.009	ITPR2
Opioid Signalling	1	265.6×	0.009	ITPR2
PLC beta mediated events	1	265.6×	0.009	ITPR2
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.009	ITPR2
C-type lectin receptors (CLRs)	1	237.9×	0.009	ITPR2
Signaling by VEGF	1	219.6×	0.009	ITPR2
Regulation of insulin secretion	1	219.6×	0.009	ITPR2
Ion homeostasis	1	203.9×	0.010	ITPR2
Ca2+ pathway	1	178.4×	0.010	ITPR2
Integration of energy metabolism	1	175.7×	0.010	ITPR2
Leishmania infection	1	163.1×	0.010	ITPR2
Parasitic Infection Pathways	1	163.1×	0.010	ITPR2
CLEC7A (Dectin-1) signaling	1	142.8×	0.011	ITPR2

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
cellular response to ethanol	1	1053.2×	0.005	ITPR2
release of sequestered calcium ion into cytosol	1	343.9×	0.006	ITPR2
cellular response to cAMP	1	290.6×	0.006	ITPR2
response to hypoxia	1	95.8×	0.013	ITPR2
signal transduction	1	16.1×	0.062	ITPR2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ITPR2	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
ITPR2	8	Binding:7, Functional:1

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	1	ITPR2
E	Difficult family or no structure, no drug	0

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)
ITPR2	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00376025	PHASE2	UNKNOWN	Antioxidant Supplementation in Patients With Kashin-Beck Disease