SPP1
protein-codingsecreted phosphoprotein 1, the group of Receptor ligands|SIBLING family
Gene summary
The protein encoded by this gene is involved in the attachment of osteoclasts to the mineralized bone matrix. The encoded protein is secreted and binds hydroxyapatite with high affinity. The osteoclast vitronectin receptor is found in the cell membrane and may be involved in the binding to this protein. This protein is also a cytokine that upregulates expression of interferon-gamma and interleukin-12. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
- BNSP
- OPN
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007915
Submitter: Orphanet
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SPP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001040058.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 1 | 5 | |||
| missense | 43 | 9 | 1 | 53 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 0 | 54 | 13 | 2 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001035147.1 | 6 | MANE Select | |
| Ensembl | ENSP00000378517.3 | 6 | MANE Select | |
| RefSeq | NP_000573.1 | 5 | Standard | |
| RefSeq | NP_001035149.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| spp1 | Danio rerio | Structure: dermal bone Quality: decreased process quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- ECM-receptor interaction - Homo sapiens (human)
- Focal adhesion - Homo sapiens (human)
- Toll-like receptor signaling pathway - Homo sapiens (human)
- Apelin signaling pathway - Homo sapiens (human)
Biological Process
- osteoblast differentiation
- androgen catabolic process
- inflammatory response
- cell adhesion
- embryo implantation
Molecular Function
- cytokine activity
- protein binding
- extracellular matrix binding
Cellular Component
- extracellular region
- extracellular space
- endoplasmic reticulum lumen
- Golgi apparatus
- cell projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000395080
- Coding exons
- 6
- Length
- 7744
- Individuals with no LoFs
- 125536
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 212
- Defined
- 125748
- p
- 0.000843
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.281 | 166 | 177 | 0.940 | 0.00000934 | 2138 |
| Missense (PolyPhen) | 54 | 72.979 | 0.73994 | 939 | ||
| Synonymous | 0.255 | 65 | 67.7 | 0.961 | 0.00000395 | 544 |
| Loss of Function | 0.201 | 9 | 9.68 | 0.930 | 4.98e-7 | 100 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00044 | 0.00043 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00051 | 0.00051 | rare |
| European (Non-Finnish) | 0.0016 | 0.0015 | notable |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction.;
Recessive Scores
- pRec
- 0.856
Intolerance Scores
- LoFtool
- 0.981
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 50.34
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0491
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |