High grade surface osteosarcoma

Summary

High grade surface osteosarcoma (MONDO:0006246) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	high grade surface osteosarcoma
Mondo ID	MONDO:0006246
EFO	EFO:1000296
NCIT	C53958
UMLS	C1266165
MedGen	220428
GARD	0024346
Is cancer (heuristic)	no

Also known as: high grade surface osteosarcoma · high-grade surface osteosarcoma

Data availability: 1 ClinVar variant.

Disease family

Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › sarcoma › osteosarcoma › bone osteosarcoma › peripheral osteosarcoma › high grade surface osteosarcoma

Related subtypes (2): periosteal osteogenic sarcoma, juxtacortical osteosarcoma

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
6066	NM_004260.4(RECQL4):c.1573del (p.Cys525fs)	RECQL4	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RECQL4	Orphanet:1225	Baller-Gerold syndrome
RECQL4	Orphanet:221016	Rothmund-Thomson syndrome type 2
RECQL4	Orphanet:3021	RAPADILINO 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
RECQL4	HGNC:9949	ENSG00000160957	O94761	ATP-dependent DNA helicase Q4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RECQL4	ATP-dependent DNA helicase Q4	An ATP-dependent DNA helicase which unwinds dsDNA with a 3’-overhang in a 3’-5’ direction.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RECQL4	Enzyme (other)	yes	3.6.4.12	Helicase_C-like, DNA_helicase_ATP-dep_RecQ, DEAD/DEAH_box_helicase_dom

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
lower esophagus mucosa	1
mucosa of transverse colon	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RECQL4	212	ubiquitous	yes	lower esophagus mucosa, ventricular zone, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RECQL4	6,330

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RECQL4	O94761	2

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
telomeric D-loop disassembly	1	1872.4×	0.003	RECQL4
telomere maintenance	1	267.5×	0.008	RECQL4
DNA replication	1	165.2×	0.008	RECQL4
double-strand break repair via homologous recombination	1	156.0×	0.008	RECQL4
DNA repair	1	63.8×	0.016	RECQL4

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
RECQL4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RECQL4	3.6.4.12	DNA helicase

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	1	RECQL4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
RECQL4	0	—

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
NCT05515068	Not specified	NOT_YET_RECRUITING	Registry For Children, Adolescents And Adults With Osteosarcoma And Biologically Related Bone Sarcomas