HAX1: HCLS1 Associated Protein X-1
A multifunctional protein involved in apoptosis, cell migration, and severe congenital neutropenia.
Gene Information Card
| Symbol | HAX1 |
|---|---|
| Full Name | HCLS1 Associated Protein X-1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 10456 ncbi.nlm.nih.gov/gene/10456 |
| Ensembl ID | ENSG00000143569 |
| UniProt ID | O00165 |
| OMIM ID | 605998 |
| HGNC ID | 16915 |
| Aliases | HS1BP1, HAX-1, SCN3 |
Description
HAX1 (HCLS1 Associated Protein X-1) encodes a multifunctional protein involved in the regulation of apoptosis, cell migration, and cytoskeletal organization. It interacts with HCLS1 (HS1) and other signaling molecules. Mutations in HAX1 are a primary cause of autosomal recessive severe congenital neutropenia type 3 (Kostmann disease). The protein is localized to mitochondria and the endoplasmic reticulum, where it modulates calcium homeostasis and caspase activation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Severe congenital neutropenia 3 (SCN3) | Loss-of-function mutations in HAX1 impair mitochondrial membrane potential and increase apoptosis of myeloid progenitor cells, leading to neutropenia. | OMIM #610738; ClinVar |
| Kostmann disease | Same mechanism as SCN3; historically described as autosomal recessive severe congenital neutropenia with maturation arrest at the promyelocyte stage. | OMIM #610738; NCBI Gene |
| Acute myeloid leukemia (AML) | Somatic mutations or altered HAX1 expression may contribute to leukemogenesis, though evidence is limited. | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Lymph node | 8.9 | Medium |
| Liver | 6.3 | Low |
| Heart | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression |
| HL-60 (promyeloblast) | 14.1 | High expression |
| HeLa (cervical) | 9.8 | Medium expression |
| HEK293 (embryonic kidney) | 7.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.130_131insA (p.Trp44X) | Frameshift / Nonsense | Found in SCN3 patients | Loss of function; premature truncation |
| c.550C>T (p.Arg184X) | Nonsense | Found in SCN3 patients | Loss of function; premature truncation |
| c.602G>A (p.Trp201*) | Nonsense | Rare | Loss of function |
| c.1A>G (p.Met1?) | Start loss | Reported in SCN3 | Loss of function; no protein synthesis |
Mutation functional classification
Loss of Function (LOF)
Most HAX1 mutations in severe congenital neutropenia are loss-of-function, leading to truncated or absent protein, increased apoptosis of neutrophils.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in HAX1.
Dominant Negative (DN)
Not described; all known pathogenic mutations are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Apoptosis - modulation of mitochondrial membrane potential
• HS1 signaling in hematopoietic cells
• Cytoskeletal regulation by Rho GTPases
Protein Summary
HAX1 is a 279-amino acid protein (UniProt O00165) localized to mitochondria and endoplasmic reticulum. It contains a Bcl-2 homology domain-like region and interacts with HS1, cortactin, and other proteins. HAX1 protects cells from apoptosis by stabilizing mitochondrial membrane potential and inhibiting caspase-9 activation. Loss of HAX1 function leads to excessive apoptosis of neutrophil precursors, causing severe congenital neutropenia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HAX1 Knockout HEK293 Cell Line | EDJ-KQ2558 | Human | 10456 | Details Get a Quote |
| HAX1 Knockout A-549 Cell Line | EDJ-KQ23213 | Human | 10456 | Details Get a Quote |
| HAX1 Knockout HCT 116 Cell Line | EDJ-KQ23214 | Human | 10456 | Details Get a Quote |
| HAX1 Knockout HeLa Cell Line | EDJ-KQ23215 | Human | 10456 | Details Get a Quote |
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