Spondylocostal dysostosis 4, autosomal recessive

Summary

Spondylocostal dysostosis 4, autosomal recessive (MONDO:0013366) is a disease caused by HES7 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: HES7 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spondylocostal dysostosis 4, autosomal recessive
Mondo ID	MONDO:0013366
OMIM	613686
DOID	DOID:0112364
UMLS	C3150942
MedGen	462292
GARD	0004976
Is cancer (heuristic)	no

Also known as: autosomal recessive spondylocostal dysostosis caused by mutation in HES7 · autosomal recessive spondylocostal dysostosis caused by mutation in Hes7 · HES7 autosomal recessive spondylocostal dysostosis · Hes7 autosomal recessive spondylocostal dysostosis · SCDO4 · spondylocostal dysostosis 4 · spondylocostal dysostosis 4, autosomal recessive

Data availability: 9 ClinVar variants · 2 GenCC gene-disease records.

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 recessive spondylocostal dysostosis › spondylocostal dysostosis 4, autosomal recessive

Related subtypes (4): spondylocostal dysostosis 2, autosomal recessive, spondylocostal dysostosis 3, autosomal recessive, spondylocostal dysostosis 6, autosomal recessive, spondylocostal dysostosis 1, 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

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 pathogenic, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
30696	NM_001165967.2(HES7):c.73C>T (p.Arg25Trp)	HES7	Pathogenic	no assertion criteria provided
30697	NM_001165967.2(HES7):c.571G>T (p.Asp191Tyr)	HES7	Pathogenic	no assertion criteria provided
30698	NM_001165967.2(HES7):c.172A>G (p.Ile58Val)	HES7	Pathogenic	no assertion criteria provided
3255516	NM_001165967.2(HES7):c.113T>C (p.Leu38Pro)	HES7	Likely pathogenic	criteria provided, single submitter
559880	NM_001165967.2(HES7):c.86A>G (p.Asn29Ser)	HES7	Likely pathogenic	criteria provided, single submitter
91404	NM_001165967.2(HES7):c.400_409dup (p.Arg137fs)	HES7	Likely pathogenic	criteria provided, single submitter
1705721	NM_001165967.2(HES7):c.173T>G (p.Ile58Arg)	HES7	Uncertain significance	criteria provided, multiple submitters, no conflicts
4687974	NM_001165967.2(HES7):c.674del (p.Phe225fs)	HES7	Uncertain significance	criteria provided, single submitter
4846807	NM_001165967.2(HES7):c.686G>A (p.Trp229Ter)	LOC130060203	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
HES7	Strong	Autosomal recessive	spondylocostal dysostosis 4, autosomal recessive	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HES7	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
HES7	HGNC:15977	ENSG00000179111	Q9BYE0	Transcription factor HES-7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HES7	Transcription factor HES-7	Transcriptional repressor.

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)
HES7	Transcription factor	no		Orange_dom, bHLH_dom, HES-7_bHLH-O

Expression context

Cohort genes with no expression data: 0.

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
cortical plate	1
right hemisphere of cerebellum	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HES7	142	broad	yes	cortical plate, right hemisphere of cerebellum, upper arm skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HES7	365

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HES7	Q9BYE0	74.31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Somitogenesis	1	233.1×	0.004	HES7

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
post-anal tail morphogenesis	1	732.7×	0.007	HES7
mesoderm development	1	526.6×	0.007	HES7
regulation of neurogenesis	1	401.2×	0.007	HES7
somitogenesis	1	374.5×	0.007	HES7
rhythmic process	1	251.5×	0.008	HES7
anterior/posterior pattern specification	1	181.2×	0.009	HES7
Notch signaling pathway	1	141.6×	0.010	HES7
skeletal system development	1	125.8×	0.010	HES7
negative regulation of transcription by RNA polymerase II	1	17.7×	0.063	HES7
regulation of transcription by RNA polymerase II	1	11.7×	0.086	HES7

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
HES7	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	HES7

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)
HES7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.