NCKAP1L
NCK Associated Protein 1 Like
Gene Information Card
| Symbol | NCKAP1L |
|---|---|
| Full Name | NCK Associated Protein 1 Like |
| Gene Type | protein-coding |
| Chromosomal Location | 12q13.13 |
| NCBI Gene ID | 3071 ncbi.nlm.nih.gov/gene/3071 |
| Ensembl ID | ENSG00000111247 |
| UniProt ID | O14598 |
| OMIM ID | 608971 |
| HGNC ID | 7666 |
| Aliases | HEM1, HEM-1, NAP1L, NAP1L1 |
Description
NCKAP1L (NCK Associated Protein 1 Like) encodes a hematopoietic-specific protein that is a component of the WAVE regulatory complex (WRC). This complex regulates actin cytoskeleton reorganization downstream of Rac1 and is essential for immune cell migration, adhesion, and phagocytosis. Mutations in NCKAP1L cause a primary immunodeficiency syndrome characterized by recurrent infections, autoinflammation, and defective neutrophil chemotaxis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 111 (IMD111) | Loss-of-function mutations disrupt WRC assembly, impairing actin polymerization and immune cell motility. | OMIM #618982; ClinVar pathogenic variants |
| Severe combined immunodeficiency (SCID)-like phenotype | Biallelic truncating variants lead to absent protein expression and defective T-cell and NK-cell function. | Case reports in PubMed (PMID: 31564433) |
| Autoinflammatory syndrome | Dysregulated actin dynamics cause aberrant cytokine production and neutrophil extracellular trap formation. | Functional studies in patient-derived cells |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | High |
| Lymph node | 10.8 | High |
| Bone marrow | 9.2 | High |
| Whole blood | 6.7 | Medium |
| Lung | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression |
| HL-60 (promyeloblast) | 12.1 | High expression |
| THP-1 (monocyte) | 9.8 | Medium expression |
| Jurkat (T-cell) | 8.5 | Medium expression |
| HeLa (cervical) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.166C>T (p.Arg56*) | Nonsense | <0.01% | Loss of function; premature truncation |
| c.502_503del (p.Leu168Glufs*12) | Frameshift | <0.01% | Loss of function; absent protein |
| c.1054G>A (p.Gly352Arg) | Missense | <0.01% | Impaired WRC interaction; reduced actin polymerization |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site variants that abolish protein expression or disrupt WRC binding are classified as loss-of-function. These cause autosomal recessive immunodeficiency 111.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NCKAP1L.
Dominant Negative (DN)
No dominant-negative mutations have been described; all known pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Rac1-PAK-WAVE pathway (Reactome R-HSA-5663213)
• Regulation of actin dynamics for phagocytic cup formation (Reactome R-HSA-2029482)
• WAVE regulatory complex assembly (Reactome R-HSA-5663220)
Protein Summary
NCKAP1L encodes the hematopoietic-specific protein HEM-1 (also known as NAP1L), a core component of the WAVE regulatory complex (WRC). The WRC integrates signals from Rac1 to activate the Arp2/3 complex, driving actin polymerization at the leading edge of migrating cells. HEM-1 is essential for proper immune cell chemotaxis, adhesion, and phagocytosis. Loss of HEM-1 leads to severe immunodeficiency with recurrent infections, autoinflammation, and defective neutrophil function. The protein is predominantly expressed in hematopoietic tissues and cell lines.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NCKAP1L Knockout HEK293 Cell Line | EDJ-KQ4856 | Human | 3071 | Details Get a Quote |
| NCKAP1L Knockout HeLa Cell Line | EDJ-KQ53509 | Human | 3071 | Details Get a Quote |
| NCKAP1L Knockout A-549 Cell Line | EDJ-KQ61978 | Human | 3071 | Details Get a Quote |
| NCKAP1L Knockout HCT 116 Cell Line | EDJ-KQ70460 | Human | 3071 | Details Get a Quote |
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