Alt. symbols: TACE | cSVP | CD156B

Approved name: ADAM metallopeptidase domain 17
Alt. names: tumor necrosis factor, alpha, converting enzyme | cartilage snake venom-like protease, TNF-alpha convertase enzyme, a disintegrin and metalloproteinase 17

Location: 2p25.1: 9488486 - 9556732 (-)
Gene type: protein_coding, 28 transcripts.

Scores: LoFtool: 0.287000 | pLI: 0.99736765 | LOEUF: 0.280

HGNC: 195

NCBI: 6868, RefSeq: NG_029873.1

Ensembl: ENSG00000151694.15

LRG_1203 | Status: public

OMIM: 603639

Expression | ProteinAtlas

This gene encodes TACE (TNF-alpha-converting enzyme), a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins implicated in a variety of biologic processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded pre-proprotein is proteolytically processed to generate the mature protease, which functions in the ectodomain shedding of tumor necrosis factor (TNF)-alpha, to release soluble TNF-alpha from its membrane-bound precursor. This protease also functions in the processing of numerous other substrates, including cell adhesion proteins, cytokine and growth factor receptors and epidermal growth factor (EGF) receptor ligands, and plays a prominent role in the activation of the Notch signaling pathway. Elevated expression of this gene has been observed in specific cell types derived from psoriasis, rheumatoid arthritis, multiple sclerosis and Crohn's disease patients, suggesting that the encoded protein may play a role in autoimmune disease. Additionally, this protease may play a role in viral infection through its cleavage of ACE2, the cellular receptor for SARS-CoV and SARS-CoV-2.

Biallelic LOF mutations in ADAM17 are associated with AR neonatal inflammatory skin and bowel disease [OMIM: 614328]. Blaydon et al. (2011) identified a homozygous 4-bp deletion in an affected brother and sister from a consanguineous family of Lebanese origin (PMID: 22010916). Though the girl died at 12 years of age from parvovirus B19–associated myocarditis, her brother had mild cardiomyopathy and led a relatively normal life despite repeated skin infections. Peripheral-blood mononuclear cells (PBMCs) obtained from the brother at 17 years of age showed high levels of lipopolysaccharide (LPS)-induced IL-1β and IL-6 production but impaired release of TNF-α. Kosukcu et al. (2021) identified a homozygous missense variant (c.851T>C; p.Ile284Thr) in one additional patient with severe pustular skin lesions consistent with neutrophilic dermatosis on biopsy and nail abnormalities (PMID: 32447396). Most recently, Imoto et al. (2021) identified compound heterozygosity for variants (c.1699T>C, p.Cys567Arg) and (c.1799G>A, p.Cys600Tyr) in two siblings presenting with exudative whole body erythroderma, recurrent skin infections, sepsis and prolonged diarrhea. In a cell-based assay using Adam10/17 double-knockout mouse embryonic fibroblasts (Adam10/17-/- mEFs) exogenously expressing each of these mutants, PMA-stimulated shedding was strongly reduced in mutant vs wild-type ADAM17. Additional phenotypes reportedly associated with heterozygous ADAM17 LOF have included late-onset Alzheimer disease (PMID: 29988083) and Tetralogy of Fallot (PMID: 30610007). [Load More]