Alternative titles; symbols
HGNC Approved Gene Symbol: NDUFB9
Cytogenetic location: 8q24.13 Genomic coordinates (GRCh38): 8:124,539,123-124,549,979 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 8q24.13 | ?Mitochondrial complex I deficiency, nuclear type 24 | 618245 | Autosomal recessive | 3 |
To identify candidate genes for branchiootorenal (BOR) syndrome (113650), Gu et al. (1996) used a set of cosmids that map to 8q13.3, the region involved in that syndrome. Cosmids were used as genomic clones to isolate corresponding cDNAs. One cDNA clone was found to have 89% sequence similarity to the B22 subunit of bovine NADH-ubiquinone oxidoreductase (GenBank X64836), a mitochondrial protein in the respiratory electron transport chain. The human cDNA encodes a 179-amino acid polypeptide sharing 90.5% similarity with the bovine sequence.
Lin et al. (1999) described the genomic structure of the NDUFB9 gene, including the nucleotide sequence, organization, and boundaries of the 4 coding exons.
Smeitink and van den Heuvel (1999) reviewed the available molecular data regarding the human nuclear-encoding complex I subunits.
By radiation hybrid analysis, Emahazion et al. (1998) mapped the NDUFB9 gene to chromosome 8q24.21.
In 2 brothers with mitochondrial complex I deficiency nuclear type 24 (MC1DN24; 618245), Haack et al. (2012) identified a homozygous mutation in the NDUFB9 gene, (L64P; 601445.0001). The mutation, which was found by sequencing of 75 candidate genes in 152 patients with complex I deficiency, segregated with the disorder in the family and was not found in the dbSNP or 1000 Genomes Project databases or in 200 control chromosomes. Patient fibroblasts showed 39% residual complex I activity, which was restored upon transfection with wildtype NDUFB9. Western blot analysis showed decreased levels of NDUFB9 and complex I subunits, consistent with reduced assembly of the overall complex. The proband had onset in infancy of progressive hypotonia associated with increased serum lactate.
Exclusion Studies
Lin et al. (1999) found no mutations in the NDUFB9 gene in 9 BOR syndrome families that did not show mutations in the EYA1 gene (601653).
In 2 brothers with mitochondrial complex I deficiency nuclear type 24 (MC1DN24; 618245), Haack et al. (2012) identified a homozygous c.191T-C transition in the NDUFB9 gene, resulting in a leu64-to-pro (L64P) substitution at a highly conserved residue. The mutation, which was found by sequencing of 75 candidate genes in 152 patients with complex I deficiency, segregated with the disorder in the family and was not found in the dbSNP or 1000 Genomes Project databases or in 200 control chromosomes. Patient fibroblasts showed 39% residual complex I activity, which was restored upon transfection with wildtype NDUFB9. Western blot analysis showed decreased levels of NDUFB9 and complex I subunits, consistent with reduced assembly of the overall complex. The proband had onset in infancy of progressive hypotonia associated with increased serum lactate.
Emahazion, T., Beskow, A., Gyllensten, U., Brookes, A. J. Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain. Cytogenet. Cell Genet. 82: 115-119, 1998. [PubMed: 9763677] [Full Text: https://doi.org/10.1159/000015082]
Gu, J. Z., Lin, X., Wells, D. E. The human B22 subunit of the NADH-ubiquinone oxidoreductase maps to the region of chromosome 8 involved in branchio-oto-renal syndrome. Genomics 35: 6-10, 1996. [PubMed: 8661098] [Full Text: https://doi.org/10.1006/geno.1996.0316]
Haack, T. B., Madignier, F., Herzer, M., Lamantea, E., Danhauser, K., Invernizzi, F., Koch, J., Freitag, M., Drost, R., Hillier, I., Haberberger, B., Mayr, J. A., and 14 others. Mutation screening of 75 candidate genes in 152 complex I deficiency cases identifies pathogenic variants in 16 genes including NDUFB9. J. Med. Genet. 49: 83-89, 2012. [PubMed: 22200994] [Full Text: https://doi.org/10.1136/jmedgenet-2011-100577]
Lin, X., Wells, D. E., Kimberling, W. J., Kumar, S. Human NDUFB9 gene: genomic organization and a possible candidate gene associated with deafness disorder mapped to chromosome 8q13. Hum. Hered. 49: 75-80, 1999. [PubMed: 10077726] [Full Text: https://doi.org/10.1159/000022848]
Smeitink, J., van den Heuvel, L. Human mitochondrial complex I in health and disease. Am. J. Hum. Genet. 64: 1505-1510, 1999. [PubMed: 10330338] [Full Text: https://doi.org/10.1086/302432]