Osteogenesis imperfecta type 17

Summary

Osteogenesis imperfecta type 17 (MONDO:0014672) is a disease caused by SPARC (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SPARC (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 17
Mondo ID	MONDO:0014672
OMIM	616507
DOID	DOID:0110338
UMLS	C4225301
MedGen	903845
GARD	0016126
Is cancer (heuristic)	no

Also known as: OI17 · osteogenesis imperfecta caused by mutation in SPARC · osteogenesis imperfecta, type XVII · SPARC osteogenesis imperfecta

Data availability: 12 ClinVar variants · 5 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 and a reduction of bone mineral density. › osteogenesis imperfecta type 17

Related subtypes (32): Cole-Carpenter syndrome 1, calvarial doughnut lesions-bone fragility syndrome, osteogenesis imperfecta type 1, osteogenesis imperfecta type 2, osteogenesis imperfecta type 4, gnathodiaphyseal dysplasia, geroderma osteodysplastica, osteogenesis imperfecta type 3, osteogenesis imperfecta type 9, osteoporosis-pseudoglioma syndrome, Wiedemann-Rautenstrauch syndrome, spondylo-ocular syndrome, Bruck syndrome 2, osteogenesis imperfecta type 7, osteogenesis imperfecta type 8, osteogenesis imperfecta type 5, osteogenesis imperfecta type 11, autosomal recessive cutis laxa type 2B, osteogenesis imperfecta type 10, osteogenesis imperfecta type 12, osteogenesis imperfecta type 6, short stature-optic atrophy-Pelger-Huët anomaly syndrome, osteogenesis imperfecta type 14, osteogenesis imperfecta type 15, osteogenesis imperfecta type 16, Cole-Carpenter syndrome 2, Singleton-Merten syndrome 2, autosomal recessive cutis laxa type 2A, Ehlers-Danlos syndrome, spondylodysplastic type, 1, Singleton-Merten syndrome 1, osteogenesis imperfecta, type 18, osteogenesis imperfecta, type 19

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

12 retrieved; paginated sample, class counts are floors:

5 benign, 3 pathogenic, 2 uncertain significance, 1 likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
372141	NM_003118.4(SPARC):c.787G>A (p.Glu263Lys)	LOC126807556	Pathogenic	no assertion criteria provided
3064133	NM_003118.4(SPARC):c.57+1G>C	SPARC	Pathogenic	criteria provided, single submitter
372140	NM_003118.4(SPARC):c.497G>A (p.Arg166His)	SPARC	Pathogenic	no assertion criteria provided
2958729	NM_003118.4(SPARC):c.57T>C (p.Pro19=)	SPARC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032875	NM_003118.4(SPARC):c.*55C>G	LOC126807556	Uncertain significance	criteria provided, single submitter
1347415	NM_003118.4(SPARC):c.157G>A (p.Gly53Arg)	SPARC	Uncertain significance	criteria provided, multiple submitters, no conflicts
2920766	NM_003118.4(SPARC):c.*114_*115del	LOC126807556	Likely benign	criteria provided, multiple submitters, no conflicts
1278457	NM_003118.4(SPARC):c.208+31C>T	SPARC	Benign	criteria provided, multiple submitters, no conflicts
1287045	NM_003118.4(SPARC):c.66A>G (p.Glu22=)	SPARC	Benign	criteria provided, multiple submitters, no conflicts
1296627	NM_003118.4(SPARC):c.120+42T>C	SPARC	Benign	criteria provided, multiple submitters, no conflicts
1296639	NM_003118.4(SPARC):c.55C>T (p.Pro19Ser)	SPARC	Benign	criteria provided, multiple submitters, no conflicts
712370	NM_003118.4(SPARC):c.120+8G>T	SPARC	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
SPARC	Strong	Autosomal recessive	osteogenesis imperfecta type 17	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPARC	Orphanet:216820	Osteogenesis imperfecta type 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
SPARC	HGNC:11219	ENSG00000113140	P09486	SPARC	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPARC	SPARC	Appears to regulate cell growth through interactions with the extracellular matrix and cytokines.

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)
SPARC	Other/Unknown	no		Osteonectin_CS, Kazal_dom, Fol_N

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
periodontal ligament	1
stromal cell of endometrium	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPARC	306	ubiquitous	marker	tibia, stromal cell of endometrium, periodontal ligament

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPARC	3,105

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPARC	P09486	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Scavenging by Class H Receptors	1	2855.0×	0.005	SPARC
Binding and Uptake of Ligands by Scavenger Receptors	1	543.8×	0.012	SPARC
Nuclear signaling by ERBB4	1	346.1×	0.012	SPARC
Signaling by ERBB4	1	271.9×	0.012	SPARC
Response to elevated platelet cytosolic Ca2+	1	163.1×	0.014	SPARC
ECM proteoglycans	1	150.3×	0.014	SPARC
Platelet activation, signaling and aggregation	1	105.7×	0.018	SPARC
Platelet degranulation	1	87.8×	0.018	SPARC
Extracellular matrix organization	1	63.1×	0.023	SPARC
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.025	SPARC
Hemostasis	1	36.0×	0.031	SPARC
Vesicle-mediated transport	1	34.8×	0.031	SPARC
Signal Transduction	1	10.2×	0.098	SPARC

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
semicircular canal morphogenesis	1	2407.4×	0.002	SPARC
regulation of synapse organization	1	648.1×	0.003	SPARC
regulation of cell morphogenesis	1	624.1×	0.003	SPARC
negative regulation of endothelial cell proliferation	1	543.6×	0.003	SPARC
positive regulation of endothelial cell migration	1	251.5×	0.005	SPARC
negative regulation of angiogenesis	1	168.5×	0.006	SPARC

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
SPARC	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	SPARC

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)
SPARC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.