MARCHF1

Chr 4

membrane associated ring-CH-type finger 1

Also known as: MARCH-I, MARCH1, RNF171

NCBI Gene: 55016 ENSG00000145416 UniProt: Q8TCQ1 OMIM: 613331

MARCH1 encodes a membrane-bound E3 ubiquitin ligase that ubiquitinates and downregulates surface expression of MHC class II molecules, transferrin receptor, and insulin receptor by directing them to lysosomes. The gene shows low constraint to loss-of-function variation (pLI 0.009, LOEUF 0.771), and no definitive human disease associations have been established. While knockout studies in mice suggest potential roles in immune function and insulin sensitivity, pathogenic variants in humans have not been clearly documented in the literature.

OMIM ResearchSummary from RefSeq, UniProt

MARCH1 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH proteins add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH1 downregulates the surface expression of major histocompatibility complex (MHC) class II molecules (see MIM 142880) and other glycoproteins by directing them to the late endosomal/lysosomal compartment (Bartee et al., 2004 [PubMed 14722266]; Thibodeau et al., 2008 [PubMed 18389477]; De Gassart et al., 2008 [PubMed 18305173]).[supplied by OMIM, Mar 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.77

LOEUF

Multiple*

Mechanism· predicted