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AliasesBCS1L, BCS, BCS1, BJS, FLNMS, GRACILE, Hs.6719, MC3DN1, PTD, h-BCS, h-BCS1, BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone
External IDsOMIM: 603647 MGI: 1914071 HomoloGene: 3193 GeneCards: BCS1L
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for BCS1L
Genomic location for BCS1L
Band2q35Start218,658,764 bp[1]
End218,663,443 bp[1]
RNA expression pattern
PBB GE BCS1L 207618 s at fs.png
More reference expression data
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC)Chr 2: 218.66 – 218.66 MbChr 1: 74.59 – 74.59 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse
BCS1 N-terminal domain

Mitochondrial chaperone BCS1 (BCS1L), also known as BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone (h-BCS1), is a protein that in humans is encoded by the BCS1L gene. BCS1L is a chaperone protein involved in the assembly of Ubiquinol Cytochrome c Reductase (complex III), which is located in the inner mitochondrial membrane and is part of the electron transport chain. Mutations in this gene are associated with mitochondrial complex III deficiency (nuclear, 1), GRACILE syndrome, and Bjoernstad syndrome.[5][6][7]


BCS1L is located on the q arm of chromosome 2 in position 35 and has 10 exons.[5] The BCS1L gene produces a 47.5 kDa protein composed of 419 amino acids.[8][9] The protein encoded by BCS1L belongs to the AAA ATPase family, BCS1 subfamily. BCS1L is a phosphoprotein and chaperone for Ubiquinol Cytochrome c Reductase assembly. It contains a nucleotide binding site for ATP-binding.[6][7] BCS1L does not contain a mitochondrial targeting sequence but experimental studies confirm that it is imported into mitochondria. A conserved domain at the N-terminus of BCS1L is responsible for the import and intramitochondrial sorting.[10] Associating to the inner mitochondrial membrane, BCS1L has a transmembrane domain in between two topological domains, passing through the inner mitochondrial membrane once. The majority of the protein is in the mitochondrial matrix.[6][7] Several alternatively spliced transcripts encoding two different isoforms have been described.[11]


BCS1L encodes a protein that is located in the inner mitochondrial membrane and involved in the assembly of Ubiquinol Cytochrome c Reductase (complex III). Complex III plays an important role in the mitochondrial respiratory chain by transferring electrons from the Rieske iron-sulfur protein to cytochrome c. BCS1L is essential for this process through its role in the maintenance of mitochondrial tubular networks, respiratory chain assembly, and formation of the LETM1 complex.[12][6][7]

Clinical Significance[edit]

Variants of BCS1L have been associated with mitochondrial complex III deficiency, nuclear 1, GRACILE syndrome, and Bjoernstad syndrome. Mitochondrial complex III deficiency, nuclear 1 is a disorder of the mitochondrial respiratory chain resulting in reduced complex III activity and highly variable clinical features usually resulting in multi-system organ failure. Clinical features may include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness, exercise intolerance, lactic acidosis, hypotonia, seizures, and optic atrophy. Pathogenic mutations have included R45C, R56X,[13][14][15] T50A,[16] R73C,[17] P99L, R155P, V353M,[18] G129R,[19][20] R183C, F368I,[17] and S277N. These mutations tend to affect the ATP-binding residues of BCS1L.[21][7][6]

Growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death (GRACILE) is a recessively inherited lethal disease that results in mutli-system organ failure. GRACILE is characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism. Pathogenic mutations have included S78G, R144Q, and V327A.[22][7][6]

Bjoernstad syndrome ia an autosomal recessive disease primarily affecting hearing. This disease is characterized by congenital hearing loss and twisted hairs, a condition known as pili torti, in which hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair extremely brittle. Pathogenic mutations have included Y301N,[23] R184C,[17] G35R, R114W, R183H, Q302E, and R306H. These mutations tend to affect the protein-protein interactions of BCS1L.[21][7][6]


BCS1L has 11 protein-protein interactions with 8 of them being co-complex interactions. BCS1L has been found to interact with LETM1, DNAJA1, and DDX24.[24]

See also[edit]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000074582 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026172 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "BCS1L BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-08-03. This article incorporates text from this source, which is in the public domain.
  6. ^ a b c d e f g "BCS1L - Mitochondrial chaperone BCS1 - Homo sapiens (Human) - BCS1L gene & protein". www.uniprot.org. Retrieved 2018-08-03. This article incorporates text available under the CC BY 4.0 license.
  7. ^ a b c d e f g "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  8. ^ Yao D. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-08-02.
  9. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  10. ^ Stan T, Brix J, Schneider-Mergener J, Pfanner N, Neupert W, Rapaport D (April 2003). "Mitochondrial protein import: recognition of internal import signals of BCS1 by the TOM complex". Molecular and Cellular Biology. 23 (7): 2239–50. doi:10.1128/MCB.23.7.2239-2250.2003. PMC 150725. PMID 12640110.
  11. ^ "Entrez Gene: BCS1L BCS1-like (yeast)".
  12. ^ Tamai S, Iida H, Yokota S, Sayano T, Kiguchiya S, Ishihara N, Hayashi J, Mihara K, Oka T (August 2008). "Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L". Journal of Cell Science. 121 (Pt 15): 2588–600. doi:10.1242/jcs.026625. PMID 18628306.
  13. ^ De Meirleir L, Seneca S, Damis E, Sepulchre B, Hoorens A, Gerlo E, et al. (August 2003). "Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene". American Journal of Medical Genetics. Part A. 121A (2): 126–31. doi:10.1002/ajmg.a.20171. PMID 12910490.
  14. ^ Ramos-Arroyo MA, Hualde J, Ayechu A, De Meirleir L, Seneca S, Nadal N, Briones P (June 2009). "Clinical and biochemical spectrum of mitochondrial complex III deficiency caused by mutations in the BCS1L gene". Clinical Genetics. 75 (6): 585–7. doi:10.1111/j.1399-0004.2009.01160.x. PMID 19508421.
  15. ^ Gil-Borlado MC, González-Hoyuela M, Blázquez A, García-Silva MT, Gabaldón T, Manzanares J, Vara J, Martín MA, Seneca S, Arenas J, Ugalde C (September 2009). "Pathogenic mutations in the 5' untranslated region of BCS1L mRNA in mitochondrial complex III deficiency". Mitochondrion. 9 (5): 299–305. doi:10.1016/j.mito.2009.04.001. PMID 19389488.
  16. ^ Blázquez A, Gil-Borlado MC, Morán M, Verdú A, Cazorla-Calleja MR, Martín MA, Arenas J, Ugalde C (February 2009). "Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient". Neuromuscular Disorders. 19 (2): 143–6. doi:10.1016/j.nmd.2008.11.016. PMID 19162478.
  17. ^ a b c Fernandez-Vizarra E, Bugiani M, Goffrini P, Carrara F, Farina L, Procopio E, Donati A, Uziel G, Ferrero I, Zeviani M (May 2007). "Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy". Human Molecular Genetics. 16 (10): 1241–52. doi:10.1093/hmg/ddm072. PMID 17403714.
  18. ^ de Lonlay P, Valnot I, Barrientos A, Gorbatyuk M, Tzagoloff A, Taanman JW, Benayoun E, Chrétien D, Kadhom N, Lombès A, de Baulny HO, Niaudet P, Munnich A, Rustin P, Rötig A (September 2001). "A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure". Nature Genetics. 29 (1): 57–60. doi:10.1038/ng706. PMID 11528392.
  19. ^ Al-Owain M, Colak D, Albakheet A, Al-Younes B, Al-Humaidi Z, Al-Sayed M, et al. (September 2013). "Clinical and biochemical features associated with BCS1L mutation". Journal of Inherited Metabolic Disease. 36 (5): 813–20. doi:10.1007/s10545-012-9536-4. PMID 22991165.
  20. ^ Tuppen HA, Fehmi J, Czermin B, Goffrini P, Meloni F, Ferrero I, He L, Blakely EL, McFarland R, Horvath R, Turnbull DM, Taylor RW (August 2010). "Long-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation". Molecular Genetics and Metabolism. 100 (4): 345–8. doi:10.1016/j.ymgme.2010.04.010. PMID 20472482.
  21. ^ a b Hinson JT, Fantin VR, Schönberger J, Breivik N, Siem G, McDonough B, et al. (February 2007). "Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome". The New England Journal of Medicine. 356 (8): 809–19. doi:10.1056/NEJMoa055262. PMID 17314340.
  22. ^ Visapää I, Fellman V, Vesa J, Dasvarma A, Hutton JL, Kumar V, Payne GS, Makarow M, Van Coster R, Taylor RW, Turnbull DM, Suomalainen A, Peltonen L (October 2002). "GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L". American Journal of Human Genetics. 71 (4): 863–76. doi:10.1086/342773. PMC 378542. PMID 12215968.
  23. ^ Siddiqi S, Siddiq S, Mansoor A, Oostrik J, Ahmad N, Kazmi SA, Kremer H, Qamar R, Schraders M (December 2013). "Novel mutation in AAA domain of BCS1L causing Bjornstad syndrome". Journal of Human Genetics. 58 (12): 819–21. doi:10.1038/jhg.2013.101. PMID 24172246.
  24. ^ "14 binary interactions found for search term BCS1L". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-25.

External links[edit]

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.