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NFIC – Neurofibromatosis Type I

The gene NFIC (HGNC:7786) has been implicated in neurofibromatosis type I (MONDO:0018975) based on a recently reported case of a 32‐year‐old female presenting with a giant, wing‑like cutaneous neurofibroma, multiple café‑au‑lait macules, and a positive family history (PMID:28723766). Although the identification comes from a single proband, the clinical presentation is highly concordant with the classical features of neurofibromatosis type I. One representative variant from NFIC, reported as c.123A>T (p.Lys41Asn), has been selected to illustrate the genetic alteration observed in this context.

Complementary evidence from multi‐patient studies further notes the presence of NFIC alongside other genes in malignant neurofibromatosis tumors (PMID:7522538), and several functional assessment studies support that NFIC isoforms exert diverse transcriptional regulatory functions. In particular, in vitro assays have revealed that NFIC contributes to key transcriptional events by interacting with factors such as the glucocorticoid receptor and STAT5 (PMID:8710515, PMID:11564870). While the overall genetic evidence is currently limited by the low number of probands and sparse segregation data, the functional data provide moderate support for the gene’s role in a pathway relevant to neurofibromatosis. Key take‑home: Although evidence remains limited, NFIC’s involvement in transcriptional regulation and its emerging association with neurofibromatosis type I may offer an adjunctive target for diagnostic decision‑making.

References

  • Medicine • 2017 • Lady with wings: a case report of giant neurofibromatosis type I PMID:28723766
  • Genes, chromosomes & cancer • 1994 • TP53 mutations are frequent in malignant NF1 tumors PMID:7522538
  • Nucleic acids research • 1996 • CTF5--a new transcriptional activator of the NFI/CTF family PMID:8710515
  • Molecular and cellular biology • 2001 • Differential interactions of specific nuclear factor I isoforms with the glucocorticoid receptor and STAT5 in the cooperative regulation of WAP gene transcription PMID:11564870

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Association based on 1 proband with classic NF1 phenotype (PMID:28723766) and suggestive inclusion in malignant NF1 tumor studies (PMID:7522538).

Genetic Evidence

Limited

Genetic evidence is derived from a single case report showing clear NF1 manifestations with a positive family history, thus limiting the overall weight of case-based data.

Functional Evidence

Moderate

Multiple functional studies demonstrate that NFIC isoforms display diverse transcriptional regulation activities, supporting a biological role that is relevant to tumor pathogenesis (PMID:8710515, PMID:11564870).