SP7
protein-codingSp7 transcription factor, the group of Zinc fingers C2H2-type|Sp transcription factors
Gene summary
This gene encodes a member of the Sp subfamily of Sp/XKLF transcription factors. Sp family proteins are sequence-specific DNA-binding proteins characterized by an amino-terminal trans-activation domain and three carboxy-terminal zinc finger motifs. This protein is a bone specific transcription factor and is required for osteoblast differentiation and bone formation.[provided by RefSeq, Jul 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013460
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013460
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0008148
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013460
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Dental; Musculoskeletal
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SP7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001173467.3. 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 | 2 | 65 | 1 | 68 | ||
| missense | 105 | 4 | 109 | |||
| nonsense | 1 | 4 | 5 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | 4 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 2 | 113 | 69 | 1 | 186 |
Highest pathogenic variant AF is 0.000019829566
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001166938.1 | 2 | MANE Select | |
| Ensembl | ENSP00000443827.2 | 2 | MANE Select | |
| RefSeq | NP_001287766.1 | 1 | Standard | |
| RefSeq | NP_690599.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sp7 | Danio rerio | Structure: osteoblast Quality: composition abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Role of Osx and miRNAs in tooth development
- RUNX2 regulates osteoblast differentiation
- RUNX2 regulates bone development
- Transcriptional regulation by RUNX2
- Gene expression (Transcription)
Biological Process
- osteoblast differentiation
- regulation of transcription by RNA polymerase II
- positive regulation of transcription by RNA polymerase II
- hematopoietic stem cell differentiation
- positive regulation of stem cell differentiation
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA binding
- DEAD/H-box RNA helicase binding
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000536324
- Coding exons
- 2
- Length
- 18738
- Individuals with no LoFs
- 125225
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 34
- Defined
- 125259
- p
- 0.000136
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.501 | 231 | 253 | 0.911 | 0.0000142 | 2739 |
| Missense (PolyPhen) | 59 | 76.361 | 0.77264 | 796 | ||
| Synonymous | 0.352 | 97 | 102 | 0.956 | 0.00000551 | 952 |
| Loss of Function | 2.56 | 2 | 11.3 | 0.177 | 5.34e-7 | 133 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00080 | 0.00079 | rare |
| East Asian | 0.000056 | 0.000055 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00019 | 0.00019 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional activator essential for osteoblast differentiation (PubMed:23457570). Binds to SP1 and EKLF consensus sequences and to other G/C-rich sequences (By similarity). {ECO:0000250|UniProtKB:Q8VI67, ECO:0000269|PubMed:23457570}.;
- Disease
- DISEASE: Osteogenesis imperfecta 12 (OI12) [MIM:613849]: A 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. OI12 is an autosomal recessive form characterized by recurrent fractures, mild bone deformations, generalized osteoporosis, delayed teeth eruption, no dentinogenesis imperfecta, normal hearing, and white sclerae. {ECO:0000269|PubMed:20579626}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.310
Intolerance Scores
- LoFtool
- 0.433
- RVIS EVS
- -0.8
- RVIS percentile EVS
- 12.24
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.235
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |