Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome

Summary

Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome (MONDO:0014314) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 6
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome
Mondo ID	MONDO:0014314
OMIM	615709
Orphanet	397927
UMLS	C3810343
MedGen	816673
GARD	0017642
Is cancer (heuristic)	no

Also known as: sacral agenesis with vertebral anomalies · SAVA

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system malformation › neural tube defect › sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome

Related subtypes (11): Chiari malformation type I, lateral meningocele syndrome, diastematomyelia, lipomyelomeningocele, leptomyelolipoma, primary tethered cord syndrome, neurenteric cyst, isolated amyelia, caudal regression sequence, parietal foramina, iniencephaly

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

6 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
126564	NM_001366285.2(TBXT):c.512A>G (p.His171Arg)	TBXT	Pathogenic	no assertion criteria provided
1030636	NM_001366285.2(TBXT):c.466G>T (p.Gly156Cys)	TBXT	Uncertain significance	criteria provided, single submitter
1334511	NM_001366285.2(TBXT):c.640G>T (p.Ala214Ser)	TBXT	Uncertain significance	criteria provided, multiple submitters, no conflicts
2546398	NM_001366285.2(TBXT):c.800G>A (p.Gly267Asp)	TBXT	Uncertain significance	criteria provided, multiple submitters, no conflicts
2690227	NM_001366285.2(TBXT):c.118C>G (p.Arg40Gly)	TBXT	Uncertain significance	criteria provided, single submitter
3324124	NM_001366285.2(TBXT):c.1178C>T (p.Ala393Val)	TBXT	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
TBXT	Supportive	Autosomal recessive	sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBXT	Orphanet:178	Chordoma
TBXT	Orphanet:397927	Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome

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
TBXT	HGNC:11515	ENSG00000164458	O15178	T-box transcription factor T	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBXT	T-box transcription factor T	Involved in the transcriptional regulation of genes required for mesoderm formation and differentiation.

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)
TBXT	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
male germ line stem cell (sensu Vertebrata) in testis	1
pancreatic ductal cell	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBXT	42	tissue_specific	marker	primordial germ cell in gonad, pancreatic ductal cell, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBXT	1,028

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TBXT	O15178	56

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	1427.5×	0.003	TBXT
Formation of axial mesoderm	1	815.7×	0.003	TBXT
Formation of definitive endoderm	1	713.8×	0.003	TBXT
Germ layer formation at gastrulation	1	671.8×	0.003	TBXT
Cardiogenesis	1	423.0×	0.003	TBXT
Formation of paraxial mesoderm	1	407.9×	0.003	TBXT
Gastrulation	1	259.6×	0.004	TBXT
Developmental Biology	1	14.5×	0.069	TBXT

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
anterior/posterior axis specification, embryo	1	2106.5×	0.003	TBXT
cardiac muscle cell myoblast differentiation	1	1404.3×	0.003	TBXT
primitive streak formation	1	1404.3×	0.003	TBXT
cell fate specification	1	526.6×	0.004	TBXT
mesoderm development	1	526.6×	0.004	TBXT
mesoderm formation	1	495.6×	0.004	TBXT
somitogenesis	1	374.5×	0.004	TBXT
heart morphogenesis	1	374.5×	0.004	TBXT
negative regulation of transcription by RNA polymerase II	1	17.7×	0.073	TBXT
signal transduction	1	16.1×	0.073	TBXT
positive regulation of transcription by RNA polymerase II	1	14.9×	0.073	TBXT
regulation of transcription by RNA polymerase II	1	11.7×	0.086	TBXT

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
TBXT	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
TBXT	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	TBXT

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)
TBXT	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04766697	Not specified	COMPLETED	SAVA Syndemic Risk Reduction for African American Couples