Osteogenesis imperfecta, type 20

Summary

Osteogenesis imperfecta, type 20 (MONDO:0032846) is a disease caused by MESD (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MESD (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta, type 20
Mondo ID	MONDO:0032846
OMIM	618644
DOID	DOID:0111849
UMLS	C5231439
MedGen	1684751
GARD	0025758
Is cancer (heuristic)	no

Also known as: OI20

Data availability: 5 ClinVar variants · 3 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 development disease › osteochondrodysplasia › osteogenesis imperfecta › osteogenesis imperfecta, type 20

Related subtypes (9): brittle bone disorder, osteogenesis imperfecta type 13, osteogenesis imperfecta-retinopathy-seizures-intellectual disability syndrome, high bone mass osteogenesis imperfecta, osteogenesis imperfecta, IIA 22, osteogenesis imperfecta, type 21, COL1A2-related osteogenesis imperfecta, osteogenesis imperfecta and a reduction of bone mineral density., osteogenesis imperfecta, type 23

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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2443890	NM_015154.3(MESD):c.265del (p.Ala89fs)	MESD	Pathogenic	no assertion criteria provided
692263	NM_015154.3(MESD):c.676C>T (p.Arg226Ter)	MESD	Pathogenic	no assertion criteria provided
692265	NM_015154.3(MESD):c.607_611del (p.Thr203fs)	MESD	Pathogenic	no assertion criteria provided
692262	NM_015154.3(MESD):c.632dup (p.Lys212fs)	MESD	Likely pathogenic	criteria provided, single submitter
692264	NM_015154.3(MESD):c.631_632del (p.Lys211fs)	MESD	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
MESD	Strong	Autosomal recessive	osteogenesis imperfecta, type 20	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MESD	Orphanet:216804	Osteogenesis imperfecta type 2

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
MESD	HGNC:13520	ENSG00000117899	Q14696	LRP chaperone MESD	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MESD	LRP chaperone MESD	Chaperone specifically assisting the folding of beta-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs).

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)
MESD	Other/Unknown	no		MESD

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
epithelial cell of pancreas	1
kidney epithelium	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MESD	260	ubiquitous	marker	epithelial cell of pancreas, pancreatic ductal cell, kidney epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MESD	1,046

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MESD	Q14696	67.50

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
positive regulation of skeletal muscle acetylcholine-gated channel clustering	1	1872.4×	0.005	MESD
mesoderm development	1	526.6×	0.006	MESD
protein localization to cell surface	1	495.6×	0.006	MESD
positive regulation of Wnt signaling pathway	1	383.0×	0.006	MESD
phagocytosis	1	240.7×	0.007	MESD
ossification	1	227.7×	0.007	MESD
protein localization to plasma membrane	1	108.7×	0.010	MESD
protein folding	1	103.4×	0.010	MESD
Wnt signaling pathway	1	99.7×	0.010	MESD

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
MESD	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	MESD

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)
MESD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.