SPI1
Spi-1 proto-oncogene, the group of ETS transcription factor family
Basic information
Region (hg38): 11:47354860-47409369
Links
Phenotypes
GenCC
Source:
- agammaglobulinemia 10, autosomal dominant (Strong), mode of inheritance: AD
- agammaglobulinemia 10, autosomal dominant (Definitive), mode of inheritance: AD
- agammaglobulinemia 10, autosomal dominant (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Agammaglobulinemia 10, autosomal dominan | AD | Allergy/Immunology/Infectious | The condition may include early-onset, recurrent infections, and early diagnoses may enable management (eg, with IVIG and an altered vaccination regimen), and early and aggressive treatment of infections; HSCT has been described | Allergy/Immunology/Infectious | 33951726 |
ClinVar
This is a list of variants' phenotypes submitted to
- Agammaglobulinemia (130 variants)
- not_specified (29 variants)
- not_provided (11 variants)
- Agammaglobulinemia_10,_autosomal_dominant (9 variants)
- PU.1-mutated_agammaglobulinemia (6 variants)
- SPI1-related_condition (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPI1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003120.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 1 | 3 | ||
| missense | 6 | 3 | 31 | 94 | 134 | |
| nonsense | 6 | 1 | 1 | 8 | ||
| start loss | 0 | |||||
| frameshift | 8 | 2 | 10 | |||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 21 | 4 | 35 | 1 | 95 |
Highest pathogenic variant AF is 0.0000029024418
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SPI1 | protein_coding | protein_coding | ENST00000227163 | 5 | 23717 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.35 | 75 | 158 | 0.474 | 0.00000882 | 1782 |
| Missense in Polyphen | 16 | 61.851 | 0.25868 | 678 | ||
| Synonymous | -0.219 | 75 | 72.6 | 1.03 | 0.00000474 | 496 |
| Loss of Function | 3.24 | 0 | 12.3 | 0.00 | 5.24e-7 | 145 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Binds to the PU-box, a purine-rich DNA sequence (5'- GAGGAA-3') that can act as a lymphoid-specific enhancer. This protein is a transcriptional activator that may be specifically involved in the differentiation or activation of macrophages or B- cells. Also binds RNA and may modulate pre-mRNA splicing (By similarity). {ECO:0000250}.;
- Pathway
- Acute myeloid leukemia - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Hematopoietic Stem Cell Differentiation;Development of pulmonary dendritic cells and macrophage subsets;ApoE and miR-146 in inflammation and atherosclerosis;Prion disease pathway;Transcriptional regulation by RUNX1;Type II interferon signaling (IFNG);Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;FGF;Glucocorticoid receptor regulatory network;C-MYB transcription factor network;IL4;RUNX1 regulates transcription of genes involved in differentiation of HSCs;RANKL;Transcriptional regulation by RUNX1;Validated targets of C-MYC transcriptional repression;IL4-mediated signaling events;Regulation of retinoblastoma protein
(Consensus)
Recessive Scores
- pRec
- 0.668
Intolerance Scores
- loftool
- 0.464
- rvis_EVS
- -0.16
- rvis_percentile_EVS
- 41.25
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Zebrafish Information Network
- Gene name
- spi1b
- Affected structure
- neutrophil
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;lymphoid progenitor cell differentiation;regulation of transcription by RNA polymerase II;lymphocyte differentiation;cell differentiation;erythrocyte differentiation;macrophage differentiation;granulocyte differentiation;somatic stem cell population maintenance;myeloid dendritic cell differentiation;histone H3 acetylation;hypermethylation of CpG island;negative regulation of MHC class II biosynthetic process;regulation of erythrocyte differentiation;negative regulation of gene expression, epigenetic;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;anatomical structure regression;pri-miRNA transcription by RNA polymerase II;cellular response to ethanol;negative regulation of histone H4 acetylation;apoptotic process involved in blood vessel morphogenesis;positive regulation of pri-miRNA transcription by RNA polymerase II
- Cellular component
- nuclear chromatin;nucleus;nucleoplasm
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II transcription factor binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;RNA binding;protein binding;NFAT protein binding