Poorly differentiated chordoma

Summary

Poorly differentiated chordoma (MONDO:0958164) is a disease with 1 cohort gene and 3 clinical trials. Molecularly, SMARCB1 Loss confers sensitivity to Tazemetostat in Poorly Differentiated Chordoma (CIViC Level C). Top therapeutic interventions include tazemetostat, fludeoxyglucose f 18, and tiragolumab.

At a glance

• Cohort genes: 1
• Clinical trials: 3
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	poorly differentiated chordoma
Mondo ID	MONDO:0958164
DOID	DOID:0081417
NCIT	C177898
UMLS	C5554730
MedGen	1791171
GARD	0026950
Is cancer (heuristic)	no

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › embryonal neoplasm › notochordal tumor › chordoma › poorly differentiated chordoma

Related subtypes (3): skull base chordoma, spinal chordoma, chondroid chordoma

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: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCB1	Orphanet:1465	Coffin-Siris syndrome
SMARCB1	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCB1	Orphanet:2495	Meningioma
SMARCB1	Orphanet:263662	Familial multiple meningioma
SMARCB1	Orphanet:93921	Full schwannomatosis
SMARCB1	Orphanet:99966	Atypical teratoid rhabdoid tumor

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCB1	HGNC:11103	ENSG00000099956	Q12824	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCB1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	Core component of the BAF (hSWI/SNF) complex.

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)
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd

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
cortical plate	1
embryo	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCB1	214	ubiquitous	marker	embryo, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCB1	5,083

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCB1	Q12824	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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 canonical BAF (cBAF) complex	1	634.4×	0.010	SMARCB1
Formation of the polybromo-BAF (pBAF) complex	1	634.4×	0.010	SMARCB1
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.010	SMARCB1
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.010	SMARCB1
Regulation of endogenous retroelements	1	368.4×	0.010	SMARCB1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.010	SMARCB1
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.010	SMARCB1
MITF-M-dependent gene expression	1	181.3×	0.013	SMARCB1
RMTs methylate histone arginines	1	146.4×	0.013	SMARCB1
Transcriptional regulation by RUNX1	1	146.4×	0.013	SMARCB1
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.014	SMARCB1
MITF-M-regulated melanocyte development	1	114.2×	0.014	SMARCB1
Chromatin organization	1	81.6×	0.018	SMARCB1
Chromatin modifying enzymes	1	72.3×	0.018	SMARCB1
Epigenetic regulation of gene expression	1	71.4×	0.018	SMARCB1
RNA Polymerase II Transcription	1	22.5×	0.053	SMARCB1
Gene expression (Transcription)	1	17.8×	0.063	SMARCB1
Generic Transcription Pathway	1	15.1×	0.069	SMARCB1
Developmental Biology	1	14.5×	0.069	SMARCB1

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
single stranded viral RNA replication via double stranded DNA intermediate	1	16852.0×	0.001	SMARCB1
positive regulation of glucose mediated signaling pathway	1	5617.3×	0.002	SMARCB1
RNA polymerase I preinitiation complex assembly	1	3370.4×	0.002	SMARCB1
DNA integration	1	2106.5×	0.003	SMARCB1
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	1	1532.0×	0.003	SMARCB1
hepatocyte differentiation	1	1203.7×	0.003	SMARCB1
host-mediated activation of viral transcription	1	887.0×	0.004	SMARCB1
nucleosome disassembly	1	802.5×	0.004	SMARCB1
regulation of G0 to G1 transition	1	674.1×	0.004	SMARCB1
regulation of nucleotide-excision repair	1	601.9×	0.004	SMARCB1
blastocyst hatching	1	543.6×	0.004	SMARCB1
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.004	SMARCB1
positive regulation of T cell differentiation	1	455.5×	0.004	SMARCB1
transcription initiation-coupled chromatin remodeling	1	383.0×	0.004	SMARCB1
positive regulation of myoblast differentiation	1	366.4×	0.004	SMARCB1
positive regulation of stem cell population maintenance	1	343.9×	0.004	SMARCB1
positive regulation of double-strand break repair	1	343.9×	0.004	SMARCB1
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.004	SMARCB1
positive regulation of cell differentiation	1	267.5×	0.005	SMARCB1
chromatin remodeling	1	73.0×	0.016	SMARCB1
nervous system development	1	45.9×	0.025	SMARCB1
negative regulation of cell population proliferation	1	42.1×	0.026	SMARCB1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.070	SMARCB1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	SMARCB1

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
SMARCB1	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
SMARCB1	7	Binding:7

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	SMARCB1

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)
SMARCB1	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05286801	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
NCT02601950	PHASE2	COMPLETED	A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma
NCT03874455	Not specified	NO_LONGER_AVAILABLE	Tazemetostat Expanded Access Program for Adults With Solid Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TAZEMETOSTAT	4	2
FLUDEOXYGLUCOSE F 18	4	1
TIRAGOLUMAB	3	1
CHEMBL5398431	0	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 2 curated evidence items; also 4 diagnostic, 1 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
SMARCB1 Loss	Tazemetostat	Sensitivity/Response	CIViC C	EID11178 +1