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Using a detailed three\u2010dimensional model of the gp39 extracellular region, we have analyzed 20 mutations in gp39 that were, with one exception, isolated from patients with X\u2010linked hyper IgM (XHIM) syndrome. On the basis of this analysis, the mutations were classified according to their predicted locations and effects. Twelve mutations are thought to compromise the gp39 structure by affecting interactions in hydrophobic core regions or at monomer interfaces, whereas seven others map closely to gp39 residues important for interaction with CD40. The latter mutations may thus, directly or indirectly, interfere with CD40 binding. One naturally occurring mutant whose carrier displays normal immune responses maps to a solvent\u2010exposed position in a loop region of the molecule.<\/jats:p>","DOI":"10.1002\/pro.5560050316","type":"journal-article","created":{"date-parts":[[2010,7,12]],"date-time":"2010-07-12T08:10:49Z","timestamp":1278922249000},"page":"531-534","source":"Crossref","is-referenced-by-count":30,"title":["Classification of mutations in the human CD40 ligand, gp39, that are associated with X\u2010linked hyper IgM syndrome"],"prefix":"10.1002","volume":"5","author":[{"given":"J\u00fcrgen","family":"Bajorath","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuniaki","family":"Seyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeaki","family":"Nonoyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans 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