SPARC

Chr 5AR

secreted protein acidic and cysteine rich

Also known as: BM-40, OI17, ON, ONT

NCBI Gene: 6678ENSG00000113140UniProt: P09486

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. [provided by RefSeq, Jun 2015]

Primary Disease Associations & Inheritance

Osteogenesis imperfecta, type XVIIMIM #616507
AR
270
ClinVar variants
15
Pathogenic / LP
0.89
pLI score
2
Active trials
Clinical Summary— SPARC
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 91 VUS of 270 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.39LOEUF
pLI 0.891
Z-score 3.24
OE 0.12 (0.05–0.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.10Z-score
OE missense 0.77 (0.67–0.89)
139 obs / 180.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.05–0.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.67–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 2 / 16.0Missense obs/exp: 139 / 180.5Syn Z: 0.04

ClinVar Variant Classifications

270 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
VUS91
Likely Benign137
Benign22
Conflicting5
15
Pathogenic
91
VUS
137
Likely Benign
22
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
11
0
15
Likely Pathogenic
0
0
0
0
0
VUS
1
80
9
1
91
Likely Benign
1
2
67
67
137
Benign
0
1
18
3
22
Conflicting
—5
Total48510571270

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SPARC · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SPARC-related osteogenesis imperfecta

strong
ARUndeterminedAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Osteogenesis imperfecta, type XVII

MIM #616507

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
nab-Paclitaxel mechanisms of action and delivery.
Yardley DA·J Control Release
2013Review
Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation.
Ren Y et al.·Front Endocrinol (Lausanne)
2022Review
Senolytic treatment for low back pain.
Mannarino M et al.·Sci Adv
2025
The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging.
Ryu S et al.·Immunity
2022
SPARC Stabilizes ApoE to Induce Cholesterol-Dependent Invasion and Sorafenib Resistance in Hepatocellular Carcinoma.
Wan S et al.·Cancer Res
2024
Gut microbial metabolism of 5-ASA diminishes its clinical efficacy in inflammatory bowel disease.
Mehta RS et al.·Nat Med
2023
Exercise training mode effects on myokine expression in healthy adults: A systematic review with meta-analysis.
Bettariga F et al.·J Sport Health Sci
2024Meta-analysis
Tumor-secreted LCN2 impairs gastric cancer progression via autocrine inhibition of the 24p3R/JNK/c-Jun/SPARC axis.
Huang Z et al.·Cell Death Dis
2024
Reduction of SPARC protects mice against NLRP3 inflammasome activation and obesity.
Ryu S et al.·J Clin Invest
2023
Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages.
Wang Z et al.·Cell Rep Med
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Cancer

Onco Move - Improvement of Psychophysical Fitness in Adult Cancer Survivors

NOT YET RECRUITING
NCT07087652Phase NAGdansk University of Physical Education and SportStarted 2025-09-01
Onco Move multicomponent face-to-face training program
Cancer

Sildenafil to Prevent and Reduce Cancer Related Cognitive Impairment

NOT YET RECRUITING
NCT06800092Phase PHASE2, PHASE3The University of Texas Medical Branch, GalvestonStarted 2026-03-15
Sildenafil

External Resources

Links to major genomics databases and tools