SPI1

Spi-1 proto-oncogene

2 disorders 1 causative 1 no genetic record 11p11.2 gene with protein product

HGNC:11241 Monarch NCBI Gene 6688 ENSG00000066336 UniProt P17947 OMIM 165170

Aliases: PU.1, SPI-A, OF, SFPI1, SPI-1.

Normal function · from ai-gene-review (P17947, commit 79fe13b38970) · AI-generated, not KB evidence

SPI1 encodes PU.1, an ETS-family pioneer transcription factor expressed mainly in hematopoietic and immune lineages. PU.1 localizes to nucleus, nucleoplasm, chromatin, and transcription-regulator complexes, where its ETS domain binds purine-rich PU-box/cis-regulatory DNA motifs and works with other transcription factors and chromatin cofactors to activate or repress RNA polymerase II transcription. By opening or selecting regulatory chromatin and coordinating lineage-specific transcriptional programs, PU.1 controls myeloid, macrophage/microglial, dendritic-cell, B-cell, and broader hematopoietic differentiation and immune-cell functional states.

ETS-domain cis-regulatory DNA binding and RNA polymerase II transcription-factor activity at PU-box/ETS motifs in hematopoietic regulatory elements.

molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific · directly involved in: regulation of transcription by RNA polymerase II; positive regulation of transcription by RNA polymerase II; negative regulation of transcription by RNA polymerase II · locations: nucleus; nucleoplasm; chromatin

Pioneer/chromatin-regulatory activity that opens or selects hematopoietic regulatory chromatin and permits cooperative transcription-factor access.

molecular function: chromatin binding · directly involved in: transcription initiation-coupled chromatin remodeling; cell differentiation · locations: chromatin; nucleus

Hematopoietic lineage specification and differentiation, especially B-cell, myeloid/macrophage, dendritic-cell, and microglia-related macrophage programs, through PU.1-dependent transcriptional control.

molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific · directly involved in: myeloid leukocyte differentiation; positive regulation of B cell differentiation; regulation of myeloid progenitor cell differentiation · locations: nucleus; chromatin

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Autosomal Agammaglobulinemia	causative germline	mechanism: Reduced PU.1 Dosage or Activity subtype: AGM10 scoped to subtype: AGM10
Mixed Phenotype Acute Leukemia	no genetic record	mechanism: Failure of Lineage Commitment

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
agammaglobulinemia 10, autosomal dominant MONDO:0030529	AD	Definitive 2024-12-12	Autosomal Agammaglobulinemia causative

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.