HAX1

Chr 1

HCLS1 associated protein X-1

Also known as: HCLSBP1, HS1BP1, SCN3

NCBI Gene: 10456 ENSG00000143575 UniProt: O00165

The HAX1 protein recruits the Arp2/3 complex to regulate cortical actin cytoskeleton reorganization and is involved in clathrin-mediated endocytosis. Mutations cause autosomal recessive severe congenital neutropenia (Kostmann disease), a primary immunodeficiency affecting neutrophil production and function. The gene shows extremely low tolerance to loss-of-function variants (pLI near 1), indicating it is highly constrained and essential for normal cellular function.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeutropenia, severe congenital 3, autosomal recessive

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

1.38

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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