Alt. symbols: HEM1

Approved name: NCK associated protein 1 like
Alt. names: hematopoietic protein 1

Location: 12q13.13: 54497752 - 54548243 (+)
Gene type: protein_coding, 8 transcripts.

Scores: LoFtool: 0.664000 | pLI: 0.99043966 | LOEUF: 0.325

HGNC: 4862

NCBI: 3071, RefSeq: .0

Ensembl: ENSG00000123338.13

LRG_ | Status: none

OMIM: 141180

Expression | ProteinAtlas

NCKAP1L encodes HEM1, an essential hematopoietic-specific regulator of the actin cytoskeleton with roles in lymphocyte development, activation, proliferation and homeostasis; erythrocyte membrane stability; and immune cell phagocytosis and migration (PMID: 16417406, 17696648, 32647003). In T cells, HEM1 is required for mTORC2-dependent AKT phosphorylation, cell proliferation and cytokine secretion (PMID: 32647003). As a subunit of the WAVE2 complex, which signals downstream of RAC to stimulate F-actin polymerization, it restrains T cells from excessive degranulation (PMID: 32647003). However, it also exerts WAVE-independent functions in neutrophil chemotaxis (PMID: 17696648).

Biallelic LOF mutations in NCKAP1L lead to an early onset immune dysregulatory syndrome with features of immunodeficiency, atopy and hyper-inflammation [OMIM: 618982] (PMID: 32766723, 32647003). Affected individuals develop severe bacterial and viral infections, hepatosplenomegaly, lymphoproliferation and HLH-like flares. Labs show dysgammaglobulinemia, increased B cells, irregular T-cell activation and cytokine responses, impaired immune synapse formation, and defective cellular migration. At t he cellular level, these defects are related to abnormal F-actin polymerization and altered intracellular signaling through impaired interactions with ARF1, a critical activator of the WAVE regulatory complex, and Abl interactor 2, another regulator of actin cytoskeleton dynamics. [Load More]