LMBRD1 (LMBR1 domain containing 1)

6q13

Mutations in the LMBRD1 gene is responsible for methylmalonic aciduria and homocystinuria type cblF (autosomal recessive disorder). It is a disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin and methylcobalamin due to accumulation of free cobalamin in lysosomes, thus preventing its conversion to cofactors.
Clinical features include poor feeding, failure to thrive, developmental delay, stomatitis, glossitis, seizures, macrocytic anemia, neutropenia, thrombocytopenia and methylmalonic aciduria responsive to vitamin B12.

The LMBRD1 gene contains 15 exons, spanning 115 kb. Three transcripts (splice variants) are known, two being protein coding.

The protein has 540 amino acids (61.4 kDa) and localizes to the lysosome membrane. It contains nine transmembrane helices and six putative glycosylation sites with an N terminus in the lysosomal interior and a cytoplasmatic C terminus. It is a probable lysosomal cobalamin transporter, being required to export cobalamin from lysosomes, which in turn allows its conversion to cofactors. It also appears to play a key role in mediating and regulating the endocytosis of the insulin receptor. Isoform 3 coding the nuclear export signal interacting protein (NESI) may play a role in the assembly of hepatitis delta virus.

CHD6 (chromodomain helicase DNA binding protein 6)

20q12

The CHD6 gene, located 403 kb centromeric to STS marker D20S108 is constantly deleted in MDS and MPD associated with del(20q) or ider(20q).

The CHD6 gene contains 37 exons of which 36 are coding, spanning 216 kb. Nine transcripts are known.

The gene encodes a member of the SNF2/RAD54 helicase protein family. The protein has 2715 amino acids (305 kDa) and localizes to the nucleus. It contains two chromodomains, a helicase domain, and an ATPase domain. The protein is thought to be a core member of one or more of chromatin remodelling complexes. It may function as a transcriptional repressor. It is involved in the cellular repression of influenza virus replication and in transcriptional repression of papillomavirus.