Short-rib thoracic dysplasia 22 without polydactyly

Summary

Short-rib thoracic dysplasia 22 without polydactyly (MONDO:0979242) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	short-rib thoracic dysplasia 22 without polydactyly
Mondo ID	MONDO:0979242
MeSH	C566063
OMIM	187750, 621260
GARD	0028115
Is cancer (heuristic)	no

Also known as: thoracic dysostosis, isolated

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › Jeune syndrome › short-rib thoracic dysplasia 22 without polydactyly

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, Jeune syndrome - GRK2-related

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

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3911900	NM_002007.4(FGF4):c.256C>T (p.Leu86Phe)	FGF4	Pathogenic	no assertion criteria provided
1172547	NM_002007.4(FGF4):c.611C>A (p.Pro204His)	FGF4	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
FGF4	HGNC:3682	ENSG00000075388	P08620	Fibroblast growth factor 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGF4	Fibroblast growth factor 4	Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation.

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)
FGF4	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF

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)	1
broad (>20)	0
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
olfactory bulb	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGF4	16	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGF4	4,019

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGF4	P08620	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. 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 activated point mutants of FGFR1	1	951.7×	0.003	FGF4
Signaling by activated point mutants of FGFR3	1	951.7×	0.003	FGF4
FGFR3c ligand binding and activation	1	878.5×	0.003	FGF4
FGFR2c ligand binding and activation	1	878.5×	0.003	FGF4
Phospholipase C-mediated cascade; FGFR3	1	878.5×	0.003	FGF4
FGFRL1 modulation of FGFR1 signaling	1	878.5×	0.003	FGF4
FGFR4 ligand binding and activation	1	815.7×	0.003	FGF4
FGFR1c ligand binding and activation	1	761.3×	0.003	FGF4
Phospholipase C-mediated cascade; FGFR4	1	761.3×	0.003	FGF4
Activated point mutants of FGFR2	1	671.8×	0.003	FGF4
Phospholipase C-mediated cascade: FGFR1	1	671.8×	0.003	FGF4
Phospholipase C-mediated cascade; FGFR2	1	634.4×	0.003	FGF4
PI-3K cascade:FGFR3	1	634.4×	0.003	FGF4
Specification of the neural plate border	1	634.4×	0.003	FGF4
SHC-mediated cascade:FGFR3	1	601.0×	0.003	FGF4
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	601.0×	0.003	FGF4
PI-3K cascade:FGFR4	1	571.0×	0.003	FGF4
Downstream signaling of activated FGFR1	1	543.8×	0.003	FGF4
FRS-mediated FGFR3 signaling	1	543.8×	0.003	FGF4
SHC-mediated cascade:FGFR4	1	543.8×	0.003	FGF4
PI-3K cascade:FGFR1	1	519.1×	0.003	FGF4
SHC-mediated cascade:FGFR1	1	496.5×	0.003	FGF4
PI-3K cascade:FGFR2	1	496.5×	0.003	FGF4
FRS-mediated FGFR4 signaling	1	496.5×	0.003	FGF4
Signaling by FGFR3 in disease	1	496.5×	0.003	FGF4
SHC-mediated cascade:FGFR2	1	475.8×	0.003	FGF4
FRS-mediated FGFR1 signaling	1	456.8×	0.003	FGF4
FRS-mediated FGFR2 signaling	1	439.2×	0.003	FGF4
Negative regulation of FGFR3 signaling	1	439.2×	0.003	FGF4
Negative regulation of FGFR4 signaling	1	407.9×	0.003	FGF4

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 endothelial cell chemotaxis to fibroblast growth factor	1	5617.3×	0.002	FGF4
chondroblast differentiation	1	3370.4×	0.002	FGF4
cranial suture morphogenesis	1	2808.7×	0.002	FGF4
apoptotic process involved in morphogenesis	1	2808.7×	0.002	FGF4
mesenchymal cell proliferation	1	1123.5×	0.004	FGF4
epithelial cell apoptotic process	1	842.6×	0.005	FGF4
cartilage condensation	1	766.0×	0.005	FGF4
embryonic hindlimb morphogenesis	1	581.1×	0.005	FGF4
positive regulation of stem cell proliferation	1	526.6×	0.005	FGF4
positive regulation of cell division	1	337.0×	0.007	FGF4
stem cell proliferation	1	312.1×	0.007	FGF4
odontogenesis of dentin-containing tooth	1	300.9×	0.007	FGF4
fibroblast growth factor receptor signaling pathway	1	285.6×	0.007	FGF4
somatic stem cell population maintenance	1	247.8×	0.007	FGF4
neurogenesis	1	208.1×	0.008	FGF4
cellular response to leukemia inhibitory factor	1	159.0×	0.009	FGF4
regulation of cell migration	1	157.5×	0.009	FGF4
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.016	FGF4
positive regulation of MAPK cascade	1	80.6×	0.016	FGF4
cell-cell signaling	1	69.6×	0.018	FGF4
positive regulation of gene expression	1	38.7×	0.031	FGF4
negative regulation of apoptotic process	1	34.8×	0.032	FGF4
positive regulation of cell population proliferation	1	33.6×	0.032	FGF4
signal transduction	1	16.1×	0.065	FGF4
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	FGF4

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
FGF4	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
FGF4	1	Binding: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	0
E	Difficult family or no structure, no drug	1	FGF4

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)
FGF4	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.