Spondylocostal dysostosis 6, autosomal recessive

Summary

Spondylocostal dysostosis 6, autosomal recessive (MONDO:0014694) is a disease caused by RIPPLY2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RIPPLY2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spondylocostal dysostosis 6, autosomal recessive
Mondo ID	MONDO:0014694
OMIM	616566
DOID	DOID:0112360
UMLS	C4225279
MedGen	899713
GARD	0012807
Is cancer (heuristic)	no

Also known as: autosomal recessive spondylocostal dysostosis caused by mutation in RIPPLY2 · RIPPLY2 autosomal recessive spondylocostal dysostosis · SCDO6 · spondylocostal dysostosis 6 · spondylocostal dysostosis 6, autosomal recessive

Data availability: 4 ClinVar variants · 4 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 6, autosomal recessive

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

4 retrieved; paginated sample, class counts are floors:

2 benign, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
221271	NM_001009994.3(RIPPLY2):c.238A>T (p.Arg80Ter)	RIPPLY2-CYB5R4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
221272	NM_001009994.3(RIPPLY2):c.240-4T>G	RIPPLY2-CYB5R4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1165051	NM_001009994.3(RIPPLY2):c.12G>A (p.Ala4=)	RIPPLY2	Benign	criteria provided, multiple submitters, no conflicts
1166321	NM_001009994.3(RIPPLY2):c.96-4G>A	RIPPLY2-CYB5R4	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
RIPPLY2	Strong	Autosomal recessive	spondylocostal dysostosis 6, autosomal recessive	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RIPPLY2	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
RIPPLY2	HGNC:21390	ENSG00000203877	Q5TAB7	Protein ripply2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RIPPLY2	Protein ripply2	Plays a role in somitogenesis.

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)
RIPPLY2	Other/Unknown	no		Ripply_fam

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RIPPLY2	146	broad	yes	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RIPPLY2	556

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RIPPLY2	Q5TAB7	62.67

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	RIPPLY2

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
somite rostral/caudal axis specification	1	1532.0×	0.004	RIPPLY2
post-anal tail morphogenesis	1	732.7×	0.004	RIPPLY2
bone morphogenesis	1	601.9×	0.004	RIPPLY2
embryonic pattern specification	1	543.6×	0.004	RIPPLY2
somitogenesis	1	374.5×	0.005	RIPPLY2
determination of left/right symmetry	1	255.3×	0.006	RIPPLY2
ossification	1	227.7×	0.006	RIPPLY2
Notch signaling pathway	1	141.6×	0.008	RIPPLY2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	RIPPLY2

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
RIPPLY2	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	RIPPLY2

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)
RIPPLY2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.