SPARC

secreted protein acidic and cysteine rich, the group of SPARC family

Basic information

Region (hg38): 5:151661096-151686975

Previous symbols: [ "ON" ]

Links

ENSG00000113140 ∙ NCBI:6678 ∙ OMIM:182120 ∙ HGNC:11219 ∙ Uniprot:P09486 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteogenesis imperfecta type 17 (Limited), mode of inheritance: AR
• osteogenesis imperfecta type 17 (Strong), mode of inheritance: AR
• osteogenesis imperfecta type 17 (Moderate), mode of inheritance: AR
• osteogenesis imperfecta type 4 (Supportive), mode of inheritance: AD
• osteogenesis imperfecta type 17 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Keratoconus; Osteogenesis imperfecta, type XVII	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Ophthalmologic	21976959; 26027498
Evidence for pathogenicity of the described variants is unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPARC gene.

• Osteogenesis imperfecta type 17 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPARC gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	52	1	54
missense			56	2	1	59
nonsense						0
start loss			1			1
frameshift						0
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1		1			2
splice region			4	11	1	16
non coding			1	39	18	58
Total	1	0	63	93	20

Variants in SPARC

This is a list of pathogenic ClinVar variants found in the SPARC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-151662989-C-G		Osteogenesis imperfecta	Benign (May 21, 2022)
5-151663423-A-T			Likely benign (May 06, 2019)
5-151663455-CTA-C		Osteogenesis imperfecta type 17	Likely benign (Apr 01, 2024)
5-151663516-G-C		Osteogenesis imperfecta type 17	Uncertain significance (Jun 28, 2018)
5-151663524-G-A		SPARC-related disorder	Likely benign (Apr 05, 2022)
5-151663542-G-C			Benign (Aug 25, 2018)
5-151663582-G-C			Uncertain significance (May 18, 2022)
5-151663584-T-A			Uncertain significance (May 11, 2023)
5-151663592-G-A			Likely benign (Nov 13, 2023)
5-151663652-G-A			Benign (Aug 25, 2018)
5-151663739-C-T			Likely benign (Sep 15, 2019)
5-151663981-C-G			Likely benign (Aug 30, 2018)
5-151664078-G-C			Likely benign (Sep 23, 2022)
5-151664080-C-T			Likely benign (Mar 21, 2023)
5-151664097-G-A		SPARC-related disorder	Likely benign (Apr 05, 2022)
5-151664100-G-A			Likely benign (Aug 04, 2023)
5-151664109-G-A		Osteogenesis imperfecta • SPARC-related disorder	Benign/Likely benign (Jan 25, 2024)
5-151664126-C-T			Uncertain significance (Jul 21, 2022)
5-151664127-G-A			Likely benign (Dec 06, 2022)
5-151664133-C-T			Likely benign (Feb 03, 2023)
5-151664144-C-T			Uncertain significance (Sep 19, 2021)
5-151664148-G-C		Inborn genetic diseases	Uncertain significance (Feb 26, 2024)
5-151664154-G-T		SPARC-related disorder	Likely benign (Sep 21, 2023)
5-151664159-C-T			Uncertain significance (Jul 05, 2022)
5-151664160-G-A			Benign/Likely benign (Jan 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPARC	protein_coding	protein_coding	ENST00000231061	9	26070

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.891	0.108	125740	0	6	125746	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	139	181	0.770	0.0000103	2017
Missense in Polyphen		60	80.758	0.74296		865
Synonymous	0.0379	74	74.4	0.994	0.00000470	551
Loss of Function	3.24	2	16.0	0.125	6.78e-7	192

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: Osteogenesis imperfecta 17 (OI17) [MIM:616507]: An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder 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. {ECO:0000269|PubMed:26027498}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in muscle cell - TarBase;miR-509-3p alteration of YAP1-ECM axis;EMT transition in Colorectal Cancer;Senescence and Autophagy in Cancer;Vesicle-mediated transport;Extracellular matrix organization;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;TGF_beta_Receptor;Hemostasis;ECM proteoglycans;Scavenging by Class H Receptors;Binding and Uptake of Ligands by Scavenger Receptors (Consensus)

Recessive Scores

• pRec: 0.765

Intolerance Scores

• loftool: 0.256
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.38

Haploinsufficiency Scores

• pHI: 0.983
• hipred: Y
• hipred_score: 0.825
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.855

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sparc
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); pigmentation phenotype; neoplasm; limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: sparc
• Affected structure: blood cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: ossification;negative regulation of endothelial cell proliferation;platelet degranulation;receptor-mediated endocytosis;heart development;response to gravity;response to lead ion;positive regulation of endothelial cell migration;negative regulation of angiogenesis;regulation of cell morphogenesis;extracellular matrix organization;lung development;response to lipopolysaccharide;response to L-ascorbic acid;response to cytokine;wound healing;response to peptide hormone;pigmentation;response to ethanol;response to cadmium ion;inner ear development;regulation of synapse organization;response to glucocorticoid;response to cAMP;response to calcium ion;bone development;cellular response to growth factor stimulus
• Cellular component: extracellular region;basement membrane;extracellular space;cytoplasm;mitochondrion;plasma membrane;cell surface;nuclear matrix;platelet alpha granule;platelet alpha granule membrane;platelet alpha granule lumen;collagen-containing extracellular matrix;endocytic vesicle lumen;glutamatergic synapse
• Molecular function: extracellular matrix structural constituent;calcium ion binding;protein binding;collagen binding;extracellular matrix binding