Axial spondylometaphyseal dysplasia

Summary

Axial spondylometaphyseal dysplasia (MONDO:0011211) is a disease caused by CFAP410 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CFAP410 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 13
• Phenotypes (HPO): 47

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		13	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

47 HPO clinical features (Orphanet curated; top 47 by frequency):

HPO ID	Term	Frequency
HP:0000510	Rod-cone dystrophy	Very frequent (80-99%)
HP:0000556	Retinal dystrophy	Very frequent (80-99%)
HP:0000773	Short ribs	Very frequent (80-99%)
HP:0000774	Narrow chest	Very frequent (80-99%)
HP:0000886	Deformed rib cage	Very frequent (80-99%)
HP:0000887	Cupped ribs	Very frequent (80-99%)
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0002867	Abnormality of the ilium	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0005257	Thoracic hypoplasia	Very frequent (80-99%)
HP:0006431	Proximal femoral metaphyseal abnormality	Very frequent (80-99%)
HP:0007663	Reduced visual acuity	Very frequent (80-99%)
HP:0008786	Iliac crest serration	Very frequent (80-99%)
HP:0009824	Upper limb undergrowth	Very frequent (80-99%)
HP:0045027	Abnormality of the thoracic cavity	Very frequent (80-99%)
HP:0000926	Platyspondyly	Frequent (30-79%)
HP:0002643	Neonatal respiratory distress	Frequent (30-79%)
HP:0002812	Coxa vara	Frequent (30-79%)
HP:0003411	Proximal femoral metaphyseal irregularity	Frequent (30-79%)
HP:0005916	Abnormal metacarpal morphology	Frequent (30-79%)
HP:0006589	Flaring of lower rib cage	Frequent (30-79%)
HP:0006603	Flared, irregular rib ends	Frequent (30-79%)
HP:0006712	Aplasia/Hypoplasia of the ribs	Frequent (30-79%)
HP:0008515	Aplasia/Hypoplasia of the vertebrae	Frequent (30-79%)
HP:0008812	Flattened femoral head	Frequent (30-79%)
HP:0011947	Respiratory tract infection	Frequent (30-79%)
HP:0012774	Increased upper to lower segment ratio	Frequent (30-79%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000613	Photophobia	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000646	Amblyopia	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000938	Osteopenia	Occasional (5-29%)
HP:0001216	Delayed ossification of carpal bones	Occasional (5-29%)
HP:0001530	Mild postnatal growth retardation	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002866	Hypoplastic iliac wing	Occasional (5-29%)
HP:0002943	Thoracic scoliosis	Occasional (5-29%)
HP:0003086	Acromesomelia	Occasional (5-29%)
HP:0003180	Flat acetabular roof	Occasional (5-29%)
HP:0003375	Narrow greater sciatic notch	Occasional (5-29%)
HP:0003521	Disproportionate short-trunk short stature	Occasional (5-29%)
HP:0007641	Dyschromatopsia	Occasional (5-29%)
HP:0007769	Peripheral retinal degeneration	Occasional (5-29%)
HP:0008444	Posterior wedging of vertebral bodies	Occasional (5-29%)
HP:0100864	Short femoral neck	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	axial spondylometaphyseal dysplasia
Mondo ID	MONDO:0011211
MeSH	C535795
OMIM	602271
Orphanet	168549
DOID	DOID:0112299
ICD-11	834893572
UMLS	C1865695
MedGen	356065
GARD	0008720
Is cancer (heuristic)	no

Also known as: SmD axial · SMDAX · spondylometaphyseal dysplasia axial type

Data availability: 13 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › spondylometaphyseal dysplasia › axial spondylometaphyseal dysplasia

Related subtypes (18): Kniest dysplasia, spondyloepimetaphyseal dysplasia, Strudwick type, spondylometaphyseal dysplasia, Kozlowski type, spondylometaphyseal dysplasia, Schmidt type, spondylometaphyseal dysplasia, ‘corner fracture’ type, spondylometaphyseal dysplasia, Sedaghatian type, spondylometaphyseal dysplasia, Golden type, spondylometaphyseal dysplasia-bowed forearms-facial dysmorphism syndrome, Spondyloenchondrodysplasia with immune dysregulation, spondylometaphyseal dysplasia-cone-rod dystrophy syndrome, spondylometaphyseal dysplasia, A4 type, spondylometaphyseal dysplasia, East African type, autosomal recessive spondylometaphyseal dysplasia, Megarbane type, spondylometaphyseal dysplasia, Czarny-Ratajczak type, regressive spondylometaphyseal dysplasia, spondylometaphyseal dysplasia, pagnamenta type, odontochondrodysplasia, SBDS-related severe neonatal spondylometaphyseal dysplasia

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

13 retrieved; paginated sample, class counts are floors:

9 pathogenic, 3 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1413087	NM_004928.3(CFAP410):c.46G>T (p.Glu16Ter)	CFAP410	Pathogenic	criteria provided, multiple submitters, no conflicts
1683424	NM_004928.3(CFAP410):c.642+2T>C	CFAP410	Pathogenic	criteria provided, multiple submitters, no conflicts
428573	NM_004928.3(CFAP410):c.218G>C (p.Arg73Pro)	CFAP410	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
428574	NM_004928.3(CFAP410):c.671T>C (p.Leu224Pro)	CFAP410	Pathogenic	no assertion criteria provided
428575	NM_004928.3(CFAP410):c.103del (p.Ile35fs)	CFAP410	Pathogenic	no assertion criteria provided
428578	NM_004928.3(CFAP410):c.545+1G>A	CFAP410	Pathogenic	criteria provided, single submitter
428579	NM_004928.3(CFAP410):c.643-23A>T	CFAP410	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
428580	NM_004928.3(CFAP410):c.319T>C (p.Tyr107His)	CFAP410	Pathogenic	criteria provided, single submitter
428581	NM_004928.3(CFAP410):c.347C>T (p.Pro116Leu)	CFAP410	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
428582	NM_004928.3(CFAP410):c.331G>A (p.Val111Met)	CFAP410	Pathogenic	criteria provided, multiple submitters, no conflicts
438159	NM_004928.3(CFAP410):c.33_34insAGCTGCACAGCGTGCA (p.Ala12fs)	CFAP410	Pathogenic	criteria provided, multiple submitters, no conflicts
812234	NM_004928.3(CFAP410):c.643-1G>C	CFAP410	Pathogenic	criteria provided, multiple submitters, no conflicts
3064754	NM_004928.3(CFAP410):c.77+2T>C	CFAP410	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 3 · 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
CFAP410	Definitive	Autosomal recessive	axial spondylometaphyseal dysplasia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFAP410	Orphanet:1872	Cone rod dystrophy
CFAP410	Orphanet:653709	Cone rod dystrophy-short stature syndrome
CFAP410	Orphanet:803	Amyotrophic lateral sclerosis

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
CFAP410	HGNC:1260	ENSG00000160226	O43822	Cilia- and flagella-associated protein 410	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFAP410	Cilia- and flagella-associated protein 410	Plays a role in cilia formation and/or maintenance.

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)
CFAP410	Other/Unknown	no		Leu-rich_rpt, U2A’_phosphoprotein32A_C, LRR_dom_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
adenohypophysis	1
right frontal lobe	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFAP410	190	ubiquitous	marker	right uterine tube, adenohypophysis, right frontal lobe

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFAP410	140

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFAP410	O43822	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
smoothened signaling pathway	1	181.2×	0.014	CFAP410
cytoskeleton organization	1	132.7×	0.014	CFAP410
regulation of cell shape	1	123.0×	0.014	CFAP410
cilium assembly	1	73.6×	0.017	CFAP410
DNA damage response	1	53.5×	0.019	CFAP410

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
CFAP410	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
CFAP410	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	CFAP410

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)
CFAP410	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.