HNF4A

HNF4AまたはHNF4α（hepatocyte nuclear factor 4 alpha）、NR2A1（nuclear receptor subfamily 2, group A, member 1）は、ヒトではHNF4A遺伝子にコードされる核内受容体である。 HNF4αはホモ二量体としてDNAに結合する転写因子であり、肝臓遺伝子の発現を調節する転写因子であるHNF1αなど、いくつかの遺伝子の発現を制御する。HNF4αは肝臓、腎臓、腸の発生に関与している。HNF4A遺伝子からは選択的スプライシングにより、複数の転写バリアントが生じる。 HNF4AはPXRとCAR（英語版）を介したCYP3A4の転写活性化に必要である。HNF4A遺伝子の変異は、CYP2D6などHNF4αの下流のタンパク質の活性に影響を与える。 アルカロイドの1種であるベルベリンは、HNF4Aの発現をアップレギュレーションする。 HNF4A遺伝子の変異は、若年発症成人型糖尿病（英語版）（MODY）、特にMODY 1（英語版）と関係している。少なくとも56種類の疾患原因変異がこの遺伝子には発見されている。 大腸がんではHNF4αの増幅が観察される。 HNF4A遺伝子のミスセンス変異は、ファンコーニ症候群の表現型の出現とも関係している。 HNF4αは次に挙げる因子と相互作用することが示されている。 β-カテニン CREB結合タンパク質（英語版） MED1（英語版） MED14（英語版） SHP（英語版） TR4（英語版） ^ a b c GRCh38: Ensembl release 89: ENSG00000101076 - Ensembl, May 2017 ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000017950 - Ensembl, May 2017 ^ Human PubMed Reference: ^ Mouse PubMed Reference: ^ “Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver”. 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Proceedings of the National Academy of Sciences of the United States of America 94 (24): 13209–14. (Nov 1997). Bibcode: 1997PNAS...9413209S. doi:10.1073/pnas.94.24.13209. PMC 24288. PMID 9371825. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC24288/.  HNF-4（英語版） 肝細胞核因子（英語版） FactorBook HNF4A