Osteogenesis imperfecta, type 21

disease

On this page

Also known as OI21osteogenesis imperfecta 21osteogenesis imperfecta, TYPE XXI

Summary

Osteogenesis imperfecta, type 21 (MONDO:0030861) is a disease caused by KDELR2 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: KDELR2 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta, type 21
Mondo ID	MONDO:0030861
OMIM	619131
DOID	DOID:0112201
UMLS	C5436875
MedGen	1723598
GARD	0025646
Is cancer (heuristic)	no

Also known as: OI21 · osteogenesis imperfecta 21 · osteogenesis imperfecta, TYPE XXI

Data availability: 7 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 21

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

7 retrieved; paginated sample, class counts are floors:

4 pathogenic, 2 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1119976	NM_006854.4(KDELR2):c.13C>T (p.Arg5Trp)	KDELR2	Pathogenic	no assertion criteria provided
1119977	NM_006854.4(KDELR2):c.485A>G (p.Tyr162Cys)	KDELR2	Pathogenic	no assertion criteria provided
988961	NM_006854.4(KDELR2):c.448dup (p.His150fs)	KDELR2	Pathogenic	no assertion criteria provided
988964	NM_006854.4(KDELR2):c.360G>A (p.Trp120Ter)	KDELR2	Pathogenic	no assertion criteria provided
1683644	NM_006854.4(KDELR2):c.505C>T (p.Arg169Cys)	KDELR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
988962	NM_006854.4(KDELR2):c.34C>G (p.His12Asp)	KDELR2	Conflicting classifications of pathogenicity	no assertion criteria provided
988963	NM_006854.4(KDELR2):c.398C>T (p.Pro133Leu)	KDELR2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
KDELR2	Strong	Autosomal recessive	osteogenesis imperfecta, type 21	4

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
KDELR2	HGNC:6305	ENSG00000136240	P33947	ER lumen protein-retaining receptor 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KDELR2	ER lumen protein-retaining receptor 2	Membrane receptor that binds the K-D-E-L sequence motif in the C-terminal part of endoplasmic reticulum resident proteins and maintains their localization in that compartment by participating to their vesicle-mediated recycling back from t…

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)
KDELR2	Other/Unknown	no		ER_ret_rcpt

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
mucosa of sigmoid colon	1
stromal cell of endometrium	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KDELR2	301	ubiquitous	marker	stromal cell of endometrium, tibia, mucosa of sigmoid colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KDELR2	1,168

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KDELR2	P33947	93.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.009	KDELR2
COPI-mediated anterograde transport	1	109.8×	0.009	KDELR2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
maintenance of protein localization in endoplasmic reticulum	1	3370.4×	8e-04	KDELR2
protein retention in ER lumen	1	2407.4×	8e-04	KDELR2
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	337.0×	0.004	KDELR2
protein transport	1	43.9×	0.023	KDELR2

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
KDELR2	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
KDELR2	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	KDELR2

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)
KDELR2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: KDELR2