Autosomal dominant spondylocostal dysostosis

Summary

Autosomal dominant spondylocostal dysostosis (MONDO:0015826) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• Phenotypes (HPO): 22

Clinical features

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0002650	Scoliosis	Very frequent (80-99%)
HP:0003422	Vertebral segmentation defect	Very frequent (80-99%)
HP:0003510	Severe short stature	Very frequent (80-99%)
HP:0000269	Prominent occiput	Frequent (30-79%)
HP:0000431	Wide nasal bridge	Frequent (30-79%)
HP:0000463	Anteverted nares	Frequent (30-79%)
HP:0000470	Short neck	Frequent (30-79%)
HP:0000582	Upslanted palpebral fissure	Frequent (30-79%)
HP:0003307	Hyperlordosis	Frequent (30-79%)
HP:0010306	Short thorax	Frequent (30-79%)
HP:0000008	Abnormal morphology of female internal genitalia	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000772	Abnormal rib morphology	Occasional (5-29%)
HP:0000913	Posterior rib fusion	Occasional (5-29%)
HP:0000921	Missing ribs	Occasional (5-29%)
HP:0002205	Recurrent respiratory infections	Occasional (5-29%)
HP:0003298	Spina bifida occulta	Occasional (5-29%)
HP:0005107	Abnormal sacrum morphology	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant spondylocostal dysostosis
Mondo ID	MONDO:0015826
Orphanet	1797
SNOMED CT	716232002
UMLS	C4274761
MedGen	902919
GARD	0012806
Is cancer (heuristic)	no

Also known as: autosomal dominant spondylocostal dysplasia · spondylocostal dysostosis, autosomal dominant

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › vertebral column disorder › spondylocostal dysostosis › autosomal dominant spondylocostal dysostosis

Related subtypes (3): spondylocostal dysostosis 5, autosomal recessive spondylocostal dysostosis, spondylocostal dysostosis 7, autosomal recessive

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
TBX6	Strong	Autosomal recessive	spondylocostal dysostosis 5	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBX6	Orphanet:1797	Autosomal dominant spondylocostal dysostosis
TBX6	Orphanet:2311	Autosomal recessive spondylocostal dysostosis

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
TBX6	HGNC:11605	ENSG00000149922	O95947	T-box transcription factor TBX6	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBX6	T-box transcription factor TBX6	T-box transcription factor that plays an essential role in the determination of the fate of axial stem cells: neural vs mesodermal.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TBX6	Transcription factor	no		TF_T-box, TF_Brachyury, p53-like_TF_DNA-bd_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
buccal mucosa cell	1
diaphragm	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBX6	166	tissue_specific	marker	lower esophagus mucosa, buccal mucosa cell, diaphragm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBX6	1,426

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBX6	O95947	66.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Formation of the posterior neural plate	1	1142.0×	0.004	TBX6
Formation of paraxial mesoderm	1	407.9×	0.005	TBX6
Gastrulation	1	259.6×	0.005	TBX6
Somitogenesis	1	233.1×	0.005	TBX6
Developmental Biology	1	14.5×	0.069	TBX6

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 neuron maturation	1	8426.0×	0.001	TBX6
mesodermal cell fate specification	1	2106.5×	0.002	TBX6
somite rostral/caudal axis specification	1	1532.0×	0.002	TBX6
signal transduction involved in regulation of gene expression	1	702.2×	0.003	TBX6
cell fate specification	1	526.6×	0.003	TBX6
mesoderm development	1	526.6×	0.003	TBX6
negative regulation of neuron projection development	1	237.3×	0.007	TBX6
anatomical structure morphogenesis	1	139.3×	0.010	TBX6
negative regulation of transcription by RNA polymerase II	1	17.7×	0.069	TBX6
positive regulation of transcription by RNA polymerase II	1	14.9×	0.074	TBX6
regulation of transcription by RNA polymerase II	1	11.7×	0.086	TBX6

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
TBX6	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	TBX6

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)
TBX6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.