IBSP
protein-codingintegrin binding sialoprotein, the group of SIBLING family
Gene summary
The protein encoded by this gene is a major structural protein of the bone matrix. It constitutes approximately 12% of the noncollagenous proteins in human bone and is synthesized by skeletal-associated cell types, including hypertrophic chondrocytes, osteoblasts, osteocytes, and osteoclasts. The only extraskeletal site of its synthesis is the trophoblast. This protein binds to calcium and hydroxyapatite via its acidic amino acid clusters, and mediates cell attachment through an RGD sequence that recognizes the vitronectin receptor. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IBSP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004967.4. 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 | 0 | |||||
| missense | 45 | 3 | 48 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 45 | 3 | 0 | 48 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004958.2 | 6 | MANE Select | |
| Ensembl | ENSP00000226284.5 | 6 | MANE Select | |
| Ensembl | ENSP00000553306.1 | 6 | Standard | |
| Ensembl | ENSP00000801888.1 | 6 | Standard |
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)
- Human papillomavirus infection - Homo sapiens (human)
- Interleukin-11 Signaling Pathway
Biological Process
- osteoblast differentiation
- cell adhesion
- extracellular matrix organization
- bone mineralization
- positive regulation of cell adhesion
Molecular Function
- molecular_function
- integrin binding
Cellular Component
- extracellular region
- extracellular space
- membrane
- vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000226284
- Coding exons
- 6
- Length
- 12342
- Individuals with no LoFs
- 125650
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 92
- Defined
- 125742
- p
- 0.000366
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.464 | 156 | 173 | 0.901 | 0.00000937 | 2072 |
| Missense (PolyPhen) | 59 | 63.805 | 0.92469 | 809 | ||
| Synonymous | 0.684 | 60 | 67.1 | 0.894 | 0.00000440 | 553 |
| Loss of Function | 0.103 | 17 | 17.5 | 0.973 | 0.00000106 | 209 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00039 | 0.00037 | rare |
| Latino/Admixed American | 0.0013 | 0.0011 | notable |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00028 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00031 | 0.00030 | rare |
| South Asian | 0.00030 | 0.00026 | rare |
| Other | 0.00017 | 0.00016 | 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. Promotes Arg-Gly-Asp-dependent cell attachment.;
Recessive Scores
- pRec
- 0.356
Intolerance Scores
- LoFtool
- 0.877
- RVIS EVS
- 1.35
- RVIS percentile EVS
- 94.35
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0774
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |