60 exons (57 constitutive, 3 alternative); spans 280 kb; presence of 3 cryptic genes: OMGP, EVI2A, and EVI2B (overlapping genes), hidden (!) within NF1 intron 27b with an opposite transcription direction.

at least 4 alternate splicings; ~ 9.0 kb mRNA complete cds; coding sequence: CDS 198..8717

the protein has been called neurofibromin; 2818 and 2839 amino acids (type-1 and type-2 isoform)

is tissue and development stage specific

GTPase activating protein (GAP) interacting with p21RAS -> tumour suppressor.

other (GAP); IRA1 and 2, the yeast inhibitors of p21RAS

large submicroscopic deletions in 5-10% of cases, translocations rare and point mutations in app. 85-90% of cases; widely dispersed, with no clustering, unusual splicing mutations yield difficulties in molecular genetic testing, truncating effect in large majority of cases.

second inactivating mutation occurs in the Schwann cell of benign neurofibromas; additional genetic alterations in this cell lead to malignant transformation; the spectrum of inactivating somatic mutation not fully elucidated, LOH owing to copy number loss and mitotic recombination, point mutations; another inactivating process may involve RNA editing (for the second allele), which gives rise to a truncated neurofibromin having lost its GAP activity.