SPIB
protein-codingSpi-B transcription factor, the group of ETS transcription factor family
Gene summary
The protein encoded by this gene is a transcriptional activator that binds to the PU-box (5'-GAGGAA-3') and acts as a lymphoid-specific enhancer. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.4 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 SPIB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003121.5. 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 | 3 | 3 | ||||
| missense | 34 | 4 | 38 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 35 | 7 | 0 | 42 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003112.2 | 6 | MANE Select | |
| Ensembl | ENSP00000471921.1 | 6 | MANE Select | |
| RefSeq | NP_001230927.1 | 3 | Standard | |
| RefSeq | NP_001230928.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of transcription by RNA polymerase II
- cell differentiation
- positive regulation of transcription by RNA polymerase II
Molecular Function
- RNA polymerase II distal enhancer sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000595883
- Coding exons
- 6
- Length
- 12376
- Individuals with no LoFs
- 112437
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 112438
- p
- 0.00000445
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.26 | 110 | 154 | 0.714 | 0.00000937 | 1633 |
| Missense (PolyPhen) | 36 | 66.967 | 0.53758 | 725 | ||
| Synonymous | 0.675 | 67 | 74.4 | 0.901 | 0.00000517 | 534 |
| Loss of Function | 2.98 | 1 | 12.2 | 0.0818 | 5.22e-7 | 146 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000072 | 0.000072 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Sequence specific transcriptional activator which binds to the PU-box, a purine-rich DNA sequence (5'-GAGGAA-3') that can act as a lymphoid-specific enhancer. Promotes development of plasmacytoid dendritic cells (pDCs), also known as type 2 DC precursors (pre-DC2) or natural interferon (IFN)-producing cells. These cells have the capacity to produce large amounts of interferon and block viral replication. May be required for B-cell receptor (BCR) signaling, which is necessary for normal B-cell development and antigenic stimulation. {ECO:0000269|PubMed:10196196, ECO:0000269|PubMed:12393575, ECO:0000269|PubMed:1406622, ECO:0000269|PubMed:15583020}.;
Recessive Scores
- pRec
- 0.186
Intolerance Scores
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.814
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |