Exostoses, multiple, type 2

Summary

Exostoses, multiple, type 2 (MONDO:0007586) is a disease caused by EXT2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: EXT2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 887

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	exostoses, multiple, type 2
Mondo ID	MONDO:0007586
OMIM	133701
NCIT	C18252
UMLS	C1851413
MedGen	377018
GARD	0002205
Is cancer (heuristic)	no

Also known as: exostoses (Multiple) 2 Gene · exostoses, multiple caused by mutation in EXT2 · exostoses, multiple, type 2 · EXT2 exostoses, multiple · EXT2 Gene

Data availability: 887 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone remodeling disease › hyperostosis › exostosis › hereditary multiple osteochondromas › exostoses, multiple, type 2

Related subtypes (2): exostoses, multiple, type 1, exostoses, multiple, type III

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

600 retrieved; paginated sample, class counts are floors:

253 uncertain significance, 174 likely benign, 81 pathogenic, 32 conflicting classifications of pathogenicity, 27 benign, 20 likely pathogenic, 13 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069929	NM_207122.2(EXT2):c.282T>A (p.Tyr94Ter)	EXT2	Pathogenic	criteria provided, single submitter
1073638	NM_207122.2(EXT2):c.1234C>T (p.Gln412Ter)	EXT2	Pathogenic	criteria provided, multiple submitters, no conflicts
1073639	NM_207122.2(EXT2):c.1287G>A (p.Trp429Ter)	EXT2	Pathogenic	criteria provided, single submitter
1074447	NM_207122.2(EXT2):c.64_68del (p.His22fs)	EXT2	Pathogenic	criteria provided, single submitter
1076808	NM_207122.2(EXT2):c.1577dup (p.Tyr526Ter)	EXT2	Pathogenic	criteria provided, single submitter
1076816	NM_207122.2(EXT2):c.783_784del (p.His262fs)	EXT2	Pathogenic	criteria provided, single submitter
1211965	NM_207122.2(EXT2):c.536+1G>A	EXT2	Pathogenic	criteria provided, multiple submitters, no conflicts
1224433	NM_207122.2(EXT2):c.540G>A (p.Trp180Ter)	EXT2	Pathogenic	criteria provided, multiple submitters, no conflicts
1251963	NM_207122.2(EXT2):c.728del (p.Pro243fs)	EXT2	Pathogenic	no assertion criteria provided
1351327	NM_207122.2(EXT2):c.516del (p.Ala173fs)	EXT2	Pathogenic	criteria provided, single submitter
1352684	NM_207122.2(EXT2):c.680A>G (p.Asp227Gly)	EXT2	Pathogenic	criteria provided, single submitter
1376872	NM_207122.2(EXT2):c.1080-2A>G	EXT2	Pathogenic	criteria provided, single submitter
1378644	NM_207122.2(EXT2):c.1080-1G>A	EXT2	Pathogenic	criteria provided, single submitter
1382216	NM_207122.2(EXT2):c.729del (p.Glu244fs)	EXT2	Pathogenic	criteria provided, single submitter
1386232	NM_207122.2(EXT2):c.398_402del (p.Leu133fs)	EXT2	Pathogenic	criteria provided, single submitter
1392678	NM_207122.2(EXT2):c.537-4_561del	EXT2	Pathogenic	criteria provided, single submitter
1405824	NM_207122.2(EXT2):c.620_626+158del	EXT2	Pathogenic	criteria provided, single submitter
1407563	NM_207122.2(EXT2):c.705_706del (p.Leu236fs)	EXT2	Pathogenic	criteria provided, single submitter
1409142	NM_207122.2(EXT2):c.779del (p.Gly260fs)	EXT2	Pathogenic	criteria provided, single submitter
1414023	NM_207122.2(EXT2):c.1824T>A (p.Tyr608Ter)	EXT2	Pathogenic	criteria provided, single submitter
1417949	NM_207122.2(EXT2):c.1013del (p.Gly338fs)	EXT2	Pathogenic	criteria provided, single submitter
1427412	NM_207122.2(EXT2):c.750del (p.Gln251fs)	EXT2	Pathogenic	criteria provided, single submitter
1432441	NM_207122.2(EXT2):c.1003_1004insA (p.Leu335fs)	EXT2	Pathogenic	criteria provided, single submitter
1451350	NM_207122.2(EXT2):c.939+1del	EXT2	Pathogenic	criteria provided, single submitter
1454141	NM_207122.2(EXT2):c.89del (p.Phe30fs)	EXT2	Pathogenic	criteria provided, single submitter
1455305	NM_207122.2(EXT2):c.1201del (p.Gln401fs)	EXT2	Pathogenic	criteria provided, single submitter
1456520	NM_207122.2(EXT2):c.1080-1G>T	EXT2	Pathogenic	criteria provided, single submitter
1456787	NM_207122.2(EXT2):c.1080-2del	EXT2	Pathogenic	criteria provided, single submitter
1457792	NM_207122.2(EXT2):c.244dup (p.Asp82fs)	EXT2	Pathogenic	criteria provided, multiple submitters, no conflicts
1457793	NM_207122.2(EXT2):c.1286G>A (p.Trp429Ter)	EXT2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · 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
EXT2	Definitive	Autosomal dominant	exostoses, multiple, type 2	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EXT2	Orphanet:321	Multiple osteochondromas
EXT2	Orphanet:466926	Seizures-scoliosis-macrocephaly syndrome
EXT2	Orphanet:52022	Potocki-Shaffer 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
EXT2	HGNC:3513	ENSG00000151348	Q93063	Exostosin-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EXT2	Exostosin-2	Glycosyltransferase forming with EXT1 the heterodimeric heparan sulfate polymerase which catalyzes the elongation of the heparan sulfate glycan backbone.

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)
EXT2	Enzyme (other)	yes	2.4.1.224	Exostosin, GT64_dom, Nucleotide-diphossugar_trans

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
cartilage tissue	1
smooth muscle tissue	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EXT2	269	ubiquitous	marker	stromal cell of endometrium, cartilage tissue, smooth muscle tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EXT2	1,242

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EXT2	Q93063	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Defective EXT2 causes exostoses 2	1	815.7×	0.002	EXT2
Defective EXT1 causes exostoses 1, TRPS2 and CHDS	1	815.7×	0.002	EXT2
HS-GAG biosynthesis	1	346.1×	0.003	EXT2

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
fluid transport	1	5617.3×	0.002	EXT2
endochondral bone morphogenesis	1	4213.0×	0.002	EXT2
polysaccharide biosynthetic process	1	2407.4×	0.002	EXT2
heparin proteoglycan biosynthetic process	1	1685.2×	0.002	EXT2
multicellular organismal-level water homeostasis	1	1685.2×	0.002	EXT2
sulfation	1	1053.2×	0.003	EXT2
sodium ion homeostasis	1	936.2×	0.003	EXT2
glycosaminoglycan biosynthetic process	1	842.6×	0.003	EXT2
heart contraction	1	766.0×	0.003	EXT2
heparan sulfate proteoglycan biosynthetic process	1	561.7×	0.003	EXT2
cellular response to fibroblast growth factor stimulus	1	543.6×	0.003	EXT2
mesoderm formation	1	495.6×	0.003	EXT2
vasodilation	1	366.4×	0.004	EXT2
chondrocyte differentiation	1	300.9×	0.004	EXT2
protein N-linked glycosylation	1	263.3×	0.005	EXT2
ossification	1	227.7×	0.005	EXT2
regulation of blood pressure	1	221.7×	0.005	EXT2
gene expression	1	79.9×	0.013	EXT2

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
EXT2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EXT2	2.4.1.224, 2.4.1.225	glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase, N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase

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	EXT2
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)
EXT2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.