HAX1

The protein encoded by this gene is known to associate with hematopoietic cell-specific Lyn substrate 1, a substrate of Src family tyrosine kinases. It also interacts with the product of the polycystic kidney disease 2 gene, mutations in which are associated with autosomal-dominant polycystic kidney disease, and with the F-actin-binding protein, cortactin. It was earlier thought that this gene product is mainly localized in the mitochondria, however, recent studies indicate it to be localized in the cell body. Mutations in this gene result in autosomal recessive severe congenital neutropenia, also known as Kostmann disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HCLS1 Associated Protein X-1

Recruits the Arp2/3 complex to the cell cortex and regulates reorganization of the cortical actin cytoskeleton via its interaction with KCNC3 and the Arp2/3 complex (PubMed:26997484).

Slows down the rate of inactivation of KCNC3 channels (PubMed:26997484).

Promotes GNA13-mediated cell migration. Involved in the clathrin-mediated endocytosis pathway. May be involved in internalization of ABC transporters such as ABCB11. May inhibit CASP9 and CASP3. Promotes cell survival. May regulate intracellular calcium pools.

Cellular response to cytokine stimulus Source: BHF-UCL
Negative regulation of apoptotic process Source: UniProtKB
Positive regulation of actin cytoskeleton reorganization Source: BHF-UCL
Positive regulation of granulocyte differentiation Source: BHF-UCL
Positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
Positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
Positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
Positive regulation of protein kinase B signaling Source: BHF-UCL
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Regulation of actin filament polymerization Source: BHF-UCL
Regulation of apoptotic process Source: ParkinsonsUK-UCL
Regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
Regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL

Mitochondrion; Cell membrane; Endoplasmic reticulum; Nucleus membrane; Cytoplasmic vesicle; Cell cortex; Sarcoplasmic reticulum; P-body
Isoform 1: Cytoplasm; Nucleus. Predominantly cytoplasmic. Also detected in the nucleus when nuclear export is inhibited, and in response to cellular stress caused by arsenite (in vitro).
Isoform 3: Cytoplasm; Nucleus. Predominantly cytoplasmic. Also detected in the nucleus when nuclear export is inhibited (in vitro).
Isoform 4: Cytoplasm; Nucleus. Shuttles between nucleus and cytoplasm.
Isoform 5: Cytoplasm. Predominantly cytoplasmic.

Neutropenia, severe congenital 3, autosomal recessive (SCN3):
The disease is caused by variants affecting the gene represented in this entry. The clinical phenotype due to HAX1 deficiency appears to depend on the localization of the mutations and their influence on the transcript variants. Mutations affecting exclusively isoform 1 are associated with isolated congenital neutropenia, whereas mutations affecting both isoform 1 and isoform 5 are associated with additional neurologic symptoms (PubMed:18337561). A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. Some patients affected by severe congenital neutropenia type 3 have neurological manifestations such as psychomotor retardation and seizures.

Proteolytically cleaved by caspase-3 during apoptosis.