SPI1

Spi-1 proto-oncogene, the group of ETS transcription factor family

Basic information

Region (hg38): 11:47354860-47409369

Links

ENSG00000066336 ∙ NCBI:6688 ∙ OMIM:165170 ∙ HGNC:11241 ∙ Uniprot:P17947 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• agammaglobulinemia 10, autosomal dominant (Strong), mode of inheritance: AD
• agammaglobulinemia 10, autosomal dominant (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the SPI1 gene.

• Agammaglobulinemia 10, autosomal dominant (2 variants)
• not provided (1 variants)
• PU.1-mutated agammaglobulinemia (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense		2	13		1	16
nonsense	2	1				3
start loss						0
frameshift			1		1	2
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region				1		1
non coding					3	3
Total	3	3	14	1	5

Variants in SPI1

This is a list of pathogenic ClinVar variants found in the SPI1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-47355237-G-T		not specified	Uncertain significance (Nov 25, 2024)
11-47355238-G-A		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355238-G-T		SPI1-related condition	Uncertain significance (May 03, 2024)
11-47355239-G-T		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355240-T-G		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355244-G-A		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355246-C-G		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355246-C-T		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355258-C-T		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355277-C-T		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355280-C-T		not specified • Agammaglobulinemia	Uncertain significance (Jun 11, 2021)
11-47355298-GCTT-G		Agammaglobulinemia	Pathogenic (Aug 28, 2024)
11-47355318-A-C		PU.1-mutated agammaglobulinemia • Agammaglobulinemia 10, autosomal dominant • Agammaglobulinemia	Likely pathogenic (Jun 22, 2022)
11-47355338-GT-G		Agammaglobulinemia	Pathogenic (Aug 28, 2024)
11-47355344-CA-C			Uncertain significance (Jun 06, 2022)
11-47355345-AGC-A		PU.1-mutated agammaglobulinemia • Agammaglobulinemia 10, autosomal dominant • Agammaglobulinemia	Pathogenic (Aug 28, 2024)
11-47355351-C-G		Agammaglobulinemia 10, autosomal dominant	Conflicting classifications of pathogenicity (Mar 06, 2024)
11-47355364-G-A		Agammaglobulinemia	Pathogenic (Aug 28, 2024)
11-47355376-T-G		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355401-C-T		Agammaglobulinemia	Pathogenic (Aug 28, 2024)
11-47355408-T-G		PU.1-mutated agammaglobulinemia • Agammaglobulinemia 10, autosomal dominant • Agammaglobulinemia	Likely pathogenic (Jun 22, 2022)
11-47355425-G-C		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355447-G-C		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355457-C-T		Agammaglobulinemia	Benign (Aug 28, 2024)
11-47355467-C-T		Agammaglobulinemia 10, autosomal dominant	Likely pathogenic (Feb 14, 2023)

GnomAD

Source: gnomAD

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
0.982	0.0179	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: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.318
• hipred: Y
• hipred_score: 0.833
• ghis: 0.638

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

Mouse Genome Informatics

• Gene name: Spi1
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; vision/eye phenotype; craniofacial phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; hematopoietic system phenotype; neoplasm; liver/biliary system phenotype; immune system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

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