SPARC

Summary

SPARC (secreted protein acidic and cysteine rich, HGNC:11219) is a protein-coding gene on chromosome 5q33.1, encoding SPARC (P09486). Appears to regulate cell growth through interactions with the extracellular matrix and cytokines.

This gene encodes a cysteine-rich acidic matrix-associated protein. The encoded protein is required for the collagen in bone to become calcified but is also involved in extracellular matrix synthesis and promotion of changes to cell shape. The gene product has been associated with tumor suppression but has also been correlated with metastasis based on changes to cell shape which can promote tumor cell invasion. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6678 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteogenesis imperfecta type 17 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 218 total — 3 pathogenic
• Phenotypes (HPO): 25
• MANE Select transcript: NM_003118

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11219
Approved symbol	SPARC
Name	secreted protein acidic and cysteine rich
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	ONT, BM-40
Ensembl gene	ENSG00000113140
Ensembl biotype	protein_coding
OMIM	182120
Entrez	6678

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 35 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000231061, ENST00000520687, ENST00000521327, ENST00000521569, ENST00000522348, ENST00000524277, ENST00000537849, ENST00000538026, ENST00000539687, ENST00000896427, ENST00000896428, ENST00000896429, ENST00000896430, ENST00000896431, ENST00000896432, ENST00000896433, ENST00000896434, ENST00000896435, ENST00000896436, ENST00000896437, ENST00000896438, ENST00000896439, ENST00000896440, ENST00000896441, ENST00000896442, ENST00000896443, ENST00000896444, ENST00000896445, ENST00000896446, ENST00000931462, ENST00000931463, ENST00000951377, ENST00000951378, ENST00000951379, ENST00000951380, ENST00000951381, ENST00000951382, ENST00000951383, ENST00000951384

RefSeq mRNA: 3 — MANE Select: NM_003118 NM_001309443, NM_001309444, NM_003118

CCDS: CCDS4318

Canonical transcript exons

ENST00000231061 — 10 exons

Exon	Start	End
ENSE00000841271	151667467	151667600
ENSE00001023043	151661096	151663599
ENSE00001218290	151686865	151686915
ENSE00003469243	151664087	151664235
ENSE00003477486	151674612	151674674
ENSE00003501224	151673129	151673216
ENSE00003556877	151676132	151676201
ENSE00003591879	151666361	151666509
ENSE00003643634	151671573	151671694
ENSE00003680747	151669664	151669784

Expression profiles

Bgee: expression breadth ubiquitous, 306 present calls, max score 99.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1135.1529 / max 18062.4323, expressed in 1593 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64432	580.0029	1567
64433	393.0763	1540
64434	155.1480	1458
64415	3.4496	867
64427	1.6998	756
64414	1.5143	669
64431	0.1751	88
64430	0.0413	11
64428	0.0352	12
64424	0.0106	4

Top tissues by expression

310 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.98	gold quality
stromal cell of endometrium	CL:0002255	99.97	gold quality
periodontal ligament	UBERON:0008266	99.95	gold quality
gall bladder	UBERON:0002110	99.94	gold quality
trigeminal ganglion	UBERON:0001675	99.91	gold quality
olfactory bulb	UBERON:0002264	99.90	gold quality
dorsal root ganglion	UBERON:0000044	99.88	gold quality
visceral pleura	UBERON:0002401	99.87	gold quality
smooth muscle tissue	UBERON:0001135	99.86	gold quality
descending thoracic aorta	UBERON:0002345	99.86	gold quality
adrenal tissue	UBERON:0018303	99.86	gold quality
ascending aorta	UBERON:0001496	99.85	gold quality
thoracic aorta	UBERON:0001515	99.85	gold quality
peripheral nervous system	UBERON:0000010	99.84	gold quality
nerve	UBERON:0001021	99.84	gold quality
tibial nerve	UBERON:0001323	99.84	gold quality
right coronary artery	UBERON:0001625	99.84	gold quality
spinal cord	UBERON:0002240	99.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.83	gold quality
tendon of biceps brachii	UBERON:0008188	99.83	gold quality
pleura	UBERON:0000977	99.81	gold quality
globus pallidus	UBERON:0001875	99.81	gold quality
parietal pleura	UBERON:0002400	99.81	gold quality
cartilage tissue	UBERON:0002418	99.81	gold quality
medial globus pallidus	UBERON:0002477	99.81	gold quality
superior vestibular nucleus	UBERON:0007227	99.81	gold quality
ventricular zone	UBERON:0003053	99.78	gold quality
skin of hip	UBERON:0001554	99.77	gold quality
coronary artery	UBERON:0001621	99.77	gold quality
right testis	UBERON:0004534	99.77	gold quality

Single-cell (SCXA)

Detected in 65 experiment(s), a significant marker in 59.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	16662.74
E-HCAD-24	yes	11185.75
E-GEOD-130473	yes	8650.35
E-GEOD-83139	yes	8585.86
E-MTAB-6701	yes	8496.86
E-GEOD-75688	yes	8475.51
E-GEOD-75367	yes	7701.46
E-HCAD-23	yes	7543.48
E-MTAB-5061	yes	6935.60
E-MTAB-8221	yes	6925.07
E-MTAB-8410	yes	6681.94
E-MTAB-6678	yes	6473.68
E-MTAB-9388	yes	5696.65
E-MTAB-10596	yes	5571.83
E-GEOD-75140	yes	5454.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT1, E2F3, ESR1, ETS2, JUN, MAF, MAFA, NFE2L2, NFKB, NKX2-1, RARG, RELA, RORA, SATB1, SMAD4, SMOC1, SOX5, SP1, SP3, TP53, TTF1, VDR, VHL, ZFP42

miRNA regulators (miRDB)

91 targeting SPARC, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963

Literature-anchored findings (GeneRIF, showing 40)

• SPARC is induced by VEGF and plays a dual role in the VEGF functions, tumor angiogenesis, and extravasation of tumors mediated by the increased permeability of endothelial barrier function. (PMID:11554745)
• SPARC modulates cell growth, attachment and migration of U87 glioma cells on brain extracellular matrix proteins. (PMID:11716067)
• Osteonectin/SPARC induction by ectopic beta(3) integrin in human radial growth phase primary melanoma cells. (PMID:11782382)
• osteonectin was present mostly in the nonmineralized predentin. (PMID:11856645)
• MYCL1, FHIT, SPARC, p16(INK4) and TP53 genes associated to lung cancer in idiopathic pulmoary fibrosis (PMID:12169206)
• may have role in remodeling and repair of periodontal tissue by promoting proliferation and matrix metalloproteinase-2 production; may regulate osteoclast formation through osteoprotegerin/osteoclastogenesis inhibitory factor in periodontal ligament cells (PMID:12201246)
• SPARC plays an important role in stimulating motility and the invasive behavior of c-Jun/MCF7 cells and that SPARC promoter activation by c-Jun appears to occur through an indirect mechanism. (PMID:12370830)
• Quantitative analysis of osteonectin mRNA in thyroid carcinomas. Increased expression of osteonectin mRNA was observed in anaplastic carcinoma tissue. (PMID:12402984)
• These studies co-localize SPARC to several sites of renal injury previously shown to be sites of PDGF B-chain expression and/or activity. (PMID:12427131)
• the migration of retinal pigment cells in epiretinal membranes is modulated by TSP1 and SPARC and thus that these two proteins ultimately may represent therapeutic targets in the management of the membranes. (PMID:12658547)
• proteolysis of SPARC by MMP-3 produced peptides that regulate endothelial cell proliferation and influence angiogenesis (PMID:12867428)
• In NSCLC, SPARC is selectively synthesized by the cells of the tumoral stroma. (PMID:14500371)
• High SPARC expression showed a trend toward longer survival in non-small cell lung cancer. (PMID:15014008)
• Increased osteonecrin expression is associated with malignant cell transformation of the lung. (PMID:15246191)
• New insights into matricellular trafficking of SPARC. Intra- and extra-cellular localization patterns may influence development, homeostasis, and differentiation of transitional epithelium. (PMID:15389586)
• SPARC expression increases glioma cell survival under stress initiated by serum withdrawal through a decrease in apoptosis. (PMID:15469933)
• SPARC was measured in discs of subjects aged 0-76 years. SPARC may have an unrecognized role in disc remodeling, aging, and degeneration. (PMID:15480132)
• Overexpression of SPARC gene is associated with human gastric carcinoma (PMID:15558074)
• TGFbeta1 can induce increased expression of both SPARC and type I collagen. Specific inhibition of SPARC led to decreased expression of type I collagen and attenuated the profibrotic effect of TGFbeta1 in cultured normal human fibroblasts. (PMID:15641096)
• SPARC plays a crucial role in tumour development in breast cancer (PMID:15763438)
• gamma linolenic acid is a regulator of SPARC secretion and expression in cancer cells (PMID:15763439)
• expression of SPARC in fibroblasts and endothelial cells derived from young donors and old donors decreased 1.6 to 2.3-fold with age (PMID:15795937)
• it was concluded that secreted protein acid rich in cysteine(SPARC) overexpression is a constant and functionally important feature of invasive ductal carcinomas of the breast (PMID:15838642)
• Results show that SPARC can be a beneficial prognostic marker for the stage II tongue carcinoma, of which clinical outcomes are sometimes difficult to predict. (PMID:16012759)
• Data suggest that the motif of SPARC responsible for anti-spreading activity is dependent on the coordination of calcium by a glutamate residue at the Z position of EF-hand 2. (PMID:16121393)
• We concluded that osteonectin was not a chemotactic factor. However, through its anti-adhesive properties, osteonectin induced undirected breast cancer cell motility, and may have enhanced chemoattraction to vitronectin. (PMID:16173048)
• Data show that SPARC binds to plasmin-cleaved fibrinogen, but not to native fibrinogen. (PMID:16263253)
• SPARC or its combination with glypican-3 is considered a potentially useful tumor marker, especially for melanoma at an early stage. (PMID:16299239)
• Clearance of SPARC from the extracellular space by alternatively activated macrophages regulates tissue remodeling and extracellular matrix synthesis. (PMID:16670288)
• Results suggest a possible role for secreted protein, acidic, cysteine-rich (SPARC) in development of functional and/or structural zonation of the human fetal adrenal (PMID:16735494)
• destruction of the basement membrane and appearance of SPARC+ spindle cells are not coincident during the course of brain invasion by meningiomas (PMID:16972886)
• High levels of SPARC are not required for tumor progression, but are necessary for tumor growth and maintenance. (PMID:17022822)
• data further demonstrate the role of SPARC in glioma tumor progression through the activation of intracellular kinases that may provide novel therapeutic targets for advanced cancers (PMID:17213807)
• The expression of SPARC by peritumoral fibroblasts portends a poorer prognosis for patients with pancreatic cancer (PMID:17235047)
• Results show for the first time that forced-expression of SATB1 in K562 cells triggers SPARC up-regulation by binding to a 17bp DNA sequence in the third intron. (PMID:17343824)
• The results indicate that epigenetic gene silencing of SPARC is frequent in colon cancers, and that inactivation of SPARC is related to rapid progression of colon cancers. (PMID:17397030)
• A negative association is noted for alveolar bone loss and salivary osteonectin in postmenopausal women. (PMID:17435158)
• Accumulation of SPARC protein in most tumors compared to normal tissues (p<0.025), suggests an important role in the carcinogenesis of endometrial tumors. (PMID:17487382)
• Our results suggest that their upregulation and activation may be a consequence of increased SPARC expression. These data provide a provisional mechanism whereby SPARC contributes to brain tumor invasion. (PMID:17490812)
• The motif of SPARC that inhibits the synthesis of urothelial cell DNA is not a nuclear localization signal (PMID:17586526)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sparc	ENSDARG00000019353
mus_musculus	Sparc	ENSMUSG00000018593
rattus_norvegicus	Sparc	ENSRNOG00000012840
drosophila_melanogaster	SPARC	FBGN0026562
caenorhabditis_elegans		WBGENE00003893

Paralogs (1): SPARCL1 (ENSG00000152583)

Protein

Protein identifiers

SPARC — P09486 (reviewed: P09486)

Alternative names: Basement-membrane protein 40, Osteonectin, Secreted protein acidic and rich in cysteine

All UniProt accessions (5): P09486, E5RJA5, E5RK62, F5GY03, F5H4E2

UniProt curated annotations — full annotation on UniProt →

Function. Appears to regulate cell growth through interactions with the extracellular matrix and cytokines. Binds calcium and copper, several types of collagen, albumin, thrombospondin, PDGF and cell membranes. There are two calcium binding sites; an acidic domain that binds 5 to 8 Ca(2+) with a low affinity and an EF-hand loop that binds a Ca(2+) ion with a high affinity.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane.

Disease relevance. Osteogenesis imperfecta 17 (OI17) [MIM:616507] An autosomal recessive form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SPARC family.

RefSeq proteins (3): NP_001296372, NP_001296373, NP_003109* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001999	Osteonectin_CS	Conserved_site
IPR002350	Kazal_dom	Domain
IPR003645	Fol_N	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR015369	Follistatin/Osteonectin_EGF	Domain
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR019577	SPARC/Testican_Ca-bd-dom	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR037641	SPARC_FS	Domain

Pfam: PF00050, PF09289, PF10591

UniProt features (59 total): helix 16, strand 8, disulfide bond 7, mutagenesis site 5, turn 5, binding site 5, sequence variant 4, domain 3, sequence conflict 3, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1SRA	X-RAY DIFFRACTION	2
1NUB	X-RAY DIFFRACTION	2.8
1BMO	X-RAY DIFFRACTION	3.1
2V53	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09486-F1	85.07	0.78

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 274; 276; 278; 280; 285

Disulfide bonds (7): 72–83, 77–93, 95–130, 101–123, 112–149, 155–265, 273–289

Glycosylation sites (1): 116

Mutagenesis-validated functional residues (5):

Position	Phenotype
166	strongly reduced collagen binding.
173	strongly reduced collagen binding.
259	loss of collagen binding.
262	strongly reduced collagen binding.
263	loss of collagen binding.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-1251985	Nuclear signaling by ERBB4
R-HSA-3000178	ECM proteoglycans
R-HSA-3000497	Scavenging by Class H Receptors
R-HSA-109582	Hemostasis
R-HSA-1236394	Signaling by ERBB4
R-HSA-1474244	Extracellular matrix organization
R-HSA-162582	Signal Transduction
R-HSA-2173782	Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-5653656	Vesicle-mediated transport
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 470 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOCC_CELL_SURFACE, MODULE_128, GGGTGGRR_PAX4_03, LIEN_BREAST_CARCINOMA_METAPLASTIC

GO Biological Process (6): negative regulation of endothelial cell proliferation (GO:0001937), positive regulation of endothelial cell migration (GO:0010595), negative regulation of angiogenesis (GO:0016525), regulation of cell morphogenesis (GO:0022604), semicircular canal morphogenesis (GO:0048752), regulation of synapse organization (GO:0050807)

GO Molecular Function (6): calcium ion binding (GO:0005509), collagen binding (GO:0005518), extracellular matrix binding (GO:0050840), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (12): extracellular region (GO:0005576), basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), nuclear matrix (GO:0016363), extracellular matrix (GO:0031012), platelet alpha granule (GO:0031091), platelet alpha granule membrane (GO:0031092), platelet alpha granule lumen (GO:0031093), endocytic vesicle lumen (GO:0071682)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Signaling by ERBB4	1
Extracellular matrix organization	1
Binding and Uptake of Ligands by Scavenger Receptors	1
Signaling by Receptor Tyrosine Kinases	1
Vesicle-mediated transport	1
Hemostasis	1
Platelet activation, signaling and aggregation	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	2
extracellular matrix	2
platelet alpha granule	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
cell morphogenesis	1
regulation of anatomical structure morphogenesis	1
tube morphogenesis	1
inner ear morphogenesis	1
embryonic morphogenesis	1
semicircular canal development	1
regulation of synapse structure or activity	1
synapse organization	1
regulation of cellular component organization	1
metal ion binding	1
protein-containing complex binding	1
structural molecule activity	1
cation binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
nuclear lumen	1
external encapsulating structure	1
secretory granule	1
secretory granule membrane	1
secretory granule lumen	1
endocytic vesicle	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

3008 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPARC	ALB	P02768	991
SPARC	BGLAP	P02818	991
SPARC	SPP1	P10451	984
SPARC	VCAM1	P19320	961
SPARC	FN1	P02751	954
SPARC	IBSP	P21815	930
SPARC	VTN	P01141	920
SPARC	SPOCK1	Q08629	851
SPARC	THBS1	P07996	831
SPARC	SMOC1	Q9H4F8	820
SPARC	PTN	P21246	783
SPARC	CCN1	O00622	764
SPARC	NID1	P14543	764
SPARC	CCN3	P48745	758
SPARC	RUNX2	Q13950	757

IntAct

41 interactions, top by confidence:

A	B	Type	Score
SPARC	faf	psi-mi:“MI:0407”(direct interaction)	0.600
faf	SPARC	psi-mi:“MI:0407”(direct interaction)	0.600
SPARC	COL3A1	psi-mi:“MI:0407”(direct interaction)	0.560
SPARC	MYOC	psi-mi:“MI:0915”(physical association)	0.530
SPARC	MYOC	psi-mi:“MI:0407”(direct interaction)	0.530
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
APP	SPARC	psi-mi:“MI:0407”(direct interaction)	0.440
PHOSPHO2	SPARC	psi-mi:“MI:0915”(physical association)	0.400
TBC1D14	SPARC	psi-mi:“MI:0915”(physical association)	0.400
ILF3	SPARC	psi-mi:“MI:0915”(physical association)	0.400
LSG1	SPARC	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
PCNA	SPARC	psi-mi:“MI:0915”(physical association)	0.370
SPARC	XRCC6	psi-mi:“MI:0915”(physical association)	0.370
SPARC	ZNF579	psi-mi:“MI:0915”(physical association)	0.370
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	SNAP23	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350
BFRF1A	SHTN1	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): SPARC (Affinity Capture-MS), SPARC (Two-hybrid), VEGFA (Reconstituted Complex), SPARC (Co-fractionation), SPARC (Co-fractionation), SPARC (Co-fractionation), SPARC (Co-fractionation), SPARC (Co-fractionation), SPARC (Co-fractionation), SPARC (Co-fractionation), ACAA2 (Co-fractionation), AGMAT (Co-fractionation), ATF6 (Co-fractionation), BCAT1 (Co-fractionation), EPHX2 (Co-fractionation)

ESM2 similar proteins: A0A6I8RMG7, A0AVX7, A2VEI2, A4IG32, A5D7A0, B5X186, B5X4E0, I6L9G5, J3S9D9, O35783, O35887, O93390, O93434, P07214, P09486, P13213, P16975, P20112, P22676, P36377, P36378, P41044, P49257, P61022, P61023, P79881, Q05186, Q14257, Q15293, Q28BT4, Q2KJ39, Q3T0K1, Q4U471, Q5R767, Q5R7F0, Q5ZM44, Q62703, Q62902, Q6IP82, Q6IQP3

Diamond homologs: A2ASQ1, A5YT95, G4V4G1, O00468, O35679, O60575, O62650, O93390, O95633, P07214, P09486, P0DKM8, P0DKT1, P10184, P10669, P13213, P16895, P16975, P19883, P20112, P21674, P23499, P25304, P31514, P31515, P31696, P36233, P36377, P36378, P37109, P47931, P50291, Q12841, Q14515, Q1LZB9, Q58D84, Q5R767, Q5R9Y1, Q62356, Q62632

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SATB1	“up-regulates quantity by expression”	SPARC	“transcriptional regulation”
VHL	“up-regulates quantity by expression”	SPARC	“transcriptional regulation”
SMOC1	“up-regulates quantity by expression”	SPARC	“transcriptional regulation”
ETS2	“up-regulates quantity by expression”	SPARC	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

218 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	72
Likely benign	106
Benign	20

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3064133	NM_003118.4(SPARC):c.57+1G>C	Pathogenic
3447805	NM_003118.4(SPARC):c.373_383del (p.Phe125fs)	Pathogenic
372140	NM_003118.4(SPARC):c.497G>A (p.Arg166His)	Pathogenic

SpliceAI

977 predictions. Top by Δscore:

Variant	Effect	Δscore
5:151663600:C:CC	acceptor_gain	1.0000
5:151664079:ACAC:A	donor_loss	1.0000
5:151664080:CACT:C	donor_loss	1.0000
5:151664081:ACTC:A	donor_loss	1.0000
5:151664082:C:CG	donor_loss	1.0000
5:151664083:TCA:T	donor_loss	1.0000
5:151664084:CACTC:C	donor_loss	1.0000
5:151664085:A:AC	donor_gain	1.0000
5:151664085:A:C	donor_loss	1.0000
5:151664085:ACT:A	donor_gain	1.0000
5:151664086:C:CA	donor_gain	1.0000
5:151664086:CT:C	donor_gain	1.0000
5:151664086:CTC:C	donor_gain	1.0000
5:151664086:CTCT:C	donor_gain	1.0000
5:151664086:CTCTG:C	donor_gain	1.0000
5:151664231:GGTAC:G	acceptor_gain	1.0000
5:151664233:TAC:T	acceptor_gain	1.0000
5:151664234:AC:A	acceptor_gain	1.0000
5:151664235:CC:C	acceptor_gain	1.0000
5:151664237:T:C	acceptor_loss	1.0000
5:151666356:CTTA:C	donor_loss	1.0000
5:151666357:TTA:T	donor_loss	1.0000
5:151666358:TAC:T	donor_loss	1.0000
5:151666359:A:AC	donor_gain	1.0000
5:151666359:AC:A	donor_gain	1.0000
5:151666360:C:CC	donor_gain	1.0000
5:151666360:C:CG	donor_loss	1.0000
5:151666360:CC:C	donor_gain	1.0000
5:151666360:CCCGT:C	donor_gain	1.0000
5:151666507:CAC:C	acceptor_gain	1.0000

AlphaMissense

2026 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:151664112:C:A	W286C	1.000
5:151664112:C:G	W286C	1.000
5:151664114:A:G	W286R	1.000
5:151664114:A:T	W286R	1.000
5:151664151:A:C	C273W	1.000
5:151664152:C:T	C273Y	1.000
5:151664175:G:C	C265W	1.000
5:151664176:C:A	C265F	1.000
5:151664176:C:G	C265S	1.000
5:151664176:C:T	C265Y	1.000
5:151664177:A:G	C265R	1.000
5:151664177:A:T	C265S	1.000
5:151664194:A:G	L259P	1.000
5:151664215:A:G	L252P	1.000
5:151664230:A:G	L247P	1.000
5:151664230:A:T	L247H	1.000
5:151666382:A:G	L238P	1.000
5:151666396:C:A	W233C	1.000
5:151666396:C:G	W233C	1.000
5:151666398:A:G	W233R	1.000
5:151666398:A:T	W233R	1.000
5:151667540:A:G	L171P	1.000
5:151667542:C:A	W170C	1.000
5:151667542:C:G	W170C	1.000
5:151667544:A:G	W170R	1.000
5:151667544:A:T	W170R	1.000
5:151667549:C:G	R168P	1.000
5:151667564:A:C	F163C	1.000
5:151667587:G:C	C155W	1.000
5:151669668:G:C	C149W	1.000

dbSNP variants (sampled 300 via entrez): RS1000117864 (5:151670719 G>A,C), RS1000334524 (5:151670621 G>A,T), RS1000434093 (5:151676393 C>G,T), RS1000673656 (5:151676803 C>T), RS1000737970 (5:151682129 C>A,T), RS1000824201 (5:151663771 G>A,T), RS1000897134 (5:151681272 C>T), RS1001253251 (5:151665550 T>C), RS1001278819 (5:151675524 C>T), RS1001322121 (5:151687513 A>G), RS1001384211 (5:151685608 T>A,C), RS1001450939 (5:151681538 T>C), RS1001461088 (5:151662587 A>G), RS1001595242 (5:151662284 G>A,T), RS1001619403 (5:151669186 G>A)

Disease associations

OMIM: gene MIM:182120 | disease phenotypes: MIM:616507, MIM:166200

GenCC curated gene-disease

Disease	Classification	Inheritance
osteogenesis imperfecta type 17	Strong	Autosomal recessive
osteogenesis imperfecta type 4	Supportive	Autosomal dominant

Mondo (3): osteogenesis imperfecta type 17 (MONDO:0014672), osteogenesis imperfecta (MONDO:0019019), osteogenesis imperfecta type 4 (MONDO:0008148)

Orphanet (1): Osteogenesis imperfecta (Orphanet:666)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000364	Hearing abnormality
HP:0000703	Dentinogenesis imperfecta
HP:0000750	Delayed speech and language development
HP:0000926	Platyspondyly
HP:0000939	Osteoporosis
HP:0000977	Soft skin
HP:0001252	Hypotonia
HP:0001324	Muscle weakness
HP:0001382	Joint hypermobility
HP:0002194	Delayed gross motor development
HP:0002751	Kyphoscoliosis
HP:0002757	Recurrent fractures
HP:0002827	Hip dislocation
HP:0002953	Vertebral compression fracture
HP:0003199	Decreased muscle mass
HP:0003396	Syringomyelia
HP:0003593	Infantile onset
HP:0003865	Bowed humerus
HP:0004322	Short stature
HP:0004349	Reduced bone mineral density
HP:0006086	Thin metacarpal cortices
HP:0006470	Thin long bone diaphyses
HP:0011463	Childhood onset
HP:0030746	Intraventricular hemorrhage

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011176_4	Stroke	6.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1059829	SPARC		0.00	0
rs10065756	SPARC		0.00	0
rs17718347	SPARC		0.00	0
rs2347128	SPARC		0.00	0
rs12153644	SPARC		0.00	0
rs1978707	SPARC		0.00	0
rs3210714	SPARC		0.00	0
rs4958487	SPARC		0.00	0
rs967527	SPARC		0.00	0

CTD chemical–gene interactions

93 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression	6
sodium arsenite	affects acetylation, affects methylation, decreases expression, increases expression	4
Cadmium	decreases expression, increases abundance	4
Tetrachlorodibenzodioxin	affects expression, decreases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	4
monomethylarsonous acid	decreases expression, increases expression, affects acetylation, affects methylation	3
Decitabine	affects binding, decreases reaction, increases expression, affects expression, affects methylation (+1 more)	3
Air Pollutants	decreases expression, increases abundance	3
Cadmium Chloride	decreases expression, increases abundance	3
Particulate Matter	decreases expression, increases abundance	3
arsenite	decreases expression, increases methylation	2
perfluorooctane sulfonic acid	affects expression, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Doxorubicin	decreases expression, increases expression	2
Fluorouracil	affects methylation, affects response to substance, increases response to substance	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Paclitaxel	affects cotreatment, decreases expression, increases expression	2
tert-Butylhydroperoxide	increases expression, decreases expression	2
abemaciclib	increases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
cobaltiprotoporphyrin	decreases expression, decreases reaction	1
ascorbate-2-phosphate	decreases expression	1
beta-glycerophosphoric acid	affects cotreatment, increases expression	1
triacsin C	decreases expression	1
avobenzone	increases expression	1

Cellosaurus cell lines

8 cell lines: 4 cancer cell line, 4 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C7DP	Abcam A-549 SPARC KO	Cancer cell line	Male
CVCL_C7ED	Abcam HCT 116 SPARC KO	Cancer cell line	Male
CVCL_LM65	UROtsa Cd#1-SPARC	Transformed cell line	Female
CVCL_LM66	UROtsa Cd#4-SPARC	Transformed cell line	Female
CVCL_LM67	UROtsa As#3-SPARC	Transformed cell line	Female
CVCL_LM68	UROtsa As#6-SPARC	Transformed cell line	Female
CVCL_TQ13	HAP1 SPARC (-) 1	Cancer cell line	Male
CVCL_XT70	HAP1 SPARC (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

78 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00131469	PHASE4	COMPLETED	Study of Teriparatide (FORTEO) to Treat Adults With Osteogenesis Imperfecta
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT01713231	PHASE4	COMPLETED	Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
NCT02303873	PHASE4	COMPLETED	Efficacy and Safety of Alendronate in Chinese Children or Adolescents With Osteogenesis Imperfecta
NCT03735537	PHASE4	COMPLETED	Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid
NCT04152551	PHASE4	RECRUITING	Effects of Bisphosphonates on OI-Related Hearing Loss
NCT00001305	PHASE3	COMPLETED	Growth Hormone Therapy in Osteogenesis Imperfecta
NCT00005901	PHASE3	COMPLETED	Pamidronate to Treat Osteogenesis Imperfecta in Children
NCT00106028	PHASE3	COMPLETED	Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
NCT00982124	PHASE3	COMPLETED	An Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta
NCT02352753	PHASE3	TERMINATED	Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI
NCT03638128	PHASE3	TERMINATED	Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta
NCT05768854	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta
NCT05972551	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
NCT06636071	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta
NCT07366086	PHASE3	RECRUITING	Pediatric Safety Follow-up Study of Prior Treatment With Romosozumab for Osteogenesis Imperfecta
NCT03118570	PHASE2	COMPLETED	A Study in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With BPS804
NCT00063479	PHASE2	COMPLETED	Bisphosphonate Treatment of Osteogenesis Imperfecta
NCT00131118	PHASE2	COMPLETED	Zoledronic Acid in Children (1 -17 Years) With Severe Osteogenesis Imperfecta
NCT01417091	PHASE2	COMPLETED	Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
NCT01679080	PHASE2	TERMINATED	The Effect of Treatment With Teriparatide and Zoledronic Acid in Patients With Osteogenesis Imperfecta
NCT01799798	PHASE2	COMPLETED	Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab
NCT03208582	PHASE2	COMPLETED	Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
NCT03216486	PHASE2	WITHDRAWN	An Exploratory Study of BPS804 Treatment in Adult Patients With Type I, III or IV Osteogenesis Imperfecta
NCT05312697	PHASE2	TERMINATED	Long-term Extension Study of Setrusumab in Adults With Type I, III, or IV Osteogenesis Imperfecta
NCT07062588	PHASE2	RECRUITING	Osteogenesis Imperfecta Trial of AGA2115 for ADUlts With COL1A1 and/or COL1A2 GeNetic Variations (IDUN)
NCT07557446	PHASE2	NOT_YET_RECRUITING	A Dose REgimen-Finding Study of AGA2115 in Chinese Patients With Osteogenesis ImpeRfecta (EIR)
NCT00705120	PHASE1	COMPLETED	Treatment of Severe Osteogenesis Imperfecta by Allogeneic Bone Marrow Transplantation
NCT02172885	PHASE1	COMPLETED	Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta
NCT03064074	PHASE1	COMPLETED	Safety of Fresolimumab in the Treatment of Osteogenesis Imperfecta
NCT04545554	PHASE1	COMPLETED	Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
NCT05231668	PHASE1	TERMINATED	Single Ascending Dose Study of SAR439459 in Adults With Osteogenesis Imperfecta (OI)
NCT06086613	PHASE1	COMPLETED	A First-in-Human Study Evaluating AGA2115 in Adult Healthy Volunteers
NCT05125809	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Placebo for Osteogenesis Imperfecta
NCT03706482	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Boost Brittle Bones Before Birth
NCT04623606	PHASE1/PHASE2	UNKNOWN	Boost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones
NCT05559801	PHASE1/PHASE2	NOT_YET_RECRUITING	Mesenchymal Cell Therapy in Osteogenesis Imperfecta (OI)
NCT00001594	Not specified	COMPLETED	Evaluation and Intervention for the Effects of Osteogenesis Imperfecta
NCT00076830	Not specified	COMPLETED	Evaluation and Treatment of Patients With Connective Tissue Disease
NCT00187018	Not specified	COMPLETED	Marrow Mesenchymal Cell Therapy for Osteogenesis Imperfecta: A Pilot Study