Reviewed February 2012
What is the official name of the BSCL2 gene?
The official name of this gene is “Berardinelli-Seip congenital lipodystrophy 2 (seipin).”
BSCL2 is the gene's official symbol. The BSCL2 gene is also known by other names, listed below.
What is the normal function of the BSCL2 gene?
The BSCL2 gene provides instructions for making a protein called seipin, whose function is unknown. Within cells, seipin is found in the membrane of a tube-like structure called the endoplasmic reticulum. The endoplasmic reticulum modifies newly produced proteins and also helps transport proteins, fats, and other molecules to specific sites either inside or outside the cell. The BSCL2 gene is active in cells throughout the body, particularly in nerve cells that control muscle movement (motor neurons) and in brain cells. The gene is also active in fat-storing cells called adipocytes, and studies suggest that seipin may play a critical role in the early development of these cells.
How are changes in the BSCL2 gene related to health conditions?
- Berardinelli-Seip congenital lipodystrophy - caused by mutations in the BSCL2 gene
At least 18 mutations in the BSCL2 gene have been identified in people with Berardinelli-Seip congenital lipodystrophy type 2, a condition that affects many organs in the body. Most of the genetic changes that cause this condition lead to the production of a nonfunctional version of the seipin protein. A loss of functional seipin disrupts the normal development and function of adipocytes, which prevents the normal storage of fats in the body. An almost total absence of body fat underlies most of the severe medical problems in people with Berardinelli-Seip congenital lipodystrophy.
About 80 percent of people with Berardinelli-Seip congenital lipodystrophy type 2 also have mild to moderate intellectual disability. A loss of the seipin protein in the brain may help explain why cognitive impairment occurs with this condition.
- Charcot-Marie-Tooth disease - caused by mutations in the BSCL2 gene
A BSCL2 gene mutation has been reported in a small number of people with Charcot-Marie-Tooth disease type 2, a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound.
The BSCL2 gene mutation identified in some individuals with Charcot-Marie-Tooth disease changes one of the protein building blocks (amino acids) used to make seipin. Specifically, the amino acid asparagine is replaced with the amino acid serine at protein position 88 (written as Asn88Ser or N88S). It is unclear how this mutation causes this disorder. The mutation probably alters the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum. This accumulation likely damages and kills motor neurons, which leads to muscle weakness in the arms and legs, a characteristic feature of Charcot-Marie-Tooth disease.
- distal hereditary motor neuropathy, type V - caused by mutations in the BSCL2 gene
At least two BSCL2 gene mutations have been identified in people with distal hereditary motor neuropathy, type V. These mutations change single amino acids used to make seipin. In one mutation, the amino acid serine is replaced with the amino leucine at position 90 (written as Ser90Leu or S90L). The other is the N88S mutation.
It is unclear how BSCL2 gene mutations cause distal hereditary motor neuropathy, type V. These mutations probably alter the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum. This accumulation likely damages and kills motor neurons, which leads to muscle weakness.
- Silver syndrome - caused by mutations in the BSCL2 gene
At least two mutations in the BSCL2 gene, including the N88S and S90L mutations, have been reported to cause Silver syndrome. This condition is characterized by muscle weakness and wasting in the hands and abnormal muscle stiffness (spasticity) in the legs. These mutations likely result in misfolded seipin proteins that accumulate within neurons, leading to cell damage and cell death. Neuronal cell death causes muscle weakness and spasticity in people with Silver syndrome. It is unclear how the same mutations can cause either Silver syndrome; Charcot-Marie-Tooth syndrome; or distal hereditary motor neuropathy, type V in different people. People with Silver syndrome sometimes have family members with the same BSCL2 gene mutation who have one of these other conditions.
Where is the BSCL2 gene located?
Cytogenetic Location: 11q13
Molecular Location on chromosome 11: base pairs 62,690,261 to 62,709,618
The BSCL2 gene is located on the long (q) arm of chromosome 11 at position 13.
More precisely, the BSCL2 gene is located from base pair 62,690,261 to base pair 62,709,618 on chromosome 11.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about BSCL2?
You and your healthcare professional may find the following resources about BSCL2 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28BSCL2%5BTIAB%5D%29%20OR%20%28%28seipin%5BTIAB%5D%29%20OR%20%28SPG17%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201440%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/606158)
Research Resources - Tools for researchers
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=26580)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=15832)
- Inherited Peripheral Neuropathies Mutation Database (http://www.molgen.ua.ac.be/CMTMutations/Mutations/Mutations.cfm?Context=31)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/26580)
What other names do people use for the BSCL2 gene or gene products?
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding BSCL2?
adipose tissue ;
amino acid ;
endoplasmic reticulum ;
peripheral nerves ;
sensory cells ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Agarwal AK, Barnes RI, Garg A. Genetic basis of congenital generalized lipodystrophy. Int J Obes Relat Metab Disord. 2004 Feb;28(2):336-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14557833?dopt=Abstract)
- Agarwal AK, Garg A. Seipin: a mysterious protein. Trends Mol Med. 2004 Sep;10(9):440-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15350896?dopt=Abstract)
- Agarwal AK, Simha V, Oral EA, Moran SA, Gorden P, O'Rahilly S, Zaidi Z, Gurakan F, Arslanian SA, Klar A, Ricker A, White NH, Bindl L, Herbst K, Kennel K, Patel SB, Al-Gazali L, Garg A. Phenotypic and genetic heterogeneity in congenital generalized lipodystrophy. J Clin Endocrinol Metab. 2003 Oct;88(10):4840-7. (http://www.ncbi.nlm.nih.gov/pubmed/14557463?dopt=Abstract)
- Auer-Grumbach M, Schlotter-Weigel B, Lochmüller H, Strobl-Wildemann G, Auer-Grumbach P, Fischer R, Offenbacher H, Zwick EB, Robl T, Hartl G, Hartung HP, Wagner K, Windpassinger C; Austrian Peripheral Neuropathy Study Group. Phenotypes of the N88S Berardinelli-Seip congenital lipodystrophy 2 mutation. Ann Neurol. 2005 Mar;57(3):415-24. (http://www.ncbi.nlm.nih.gov/pubmed/15732094?dopt=Abstract)
- Bienfait HM, Baas F, Koelman JH, de Haan RJ, van Engelen BG, Gabreëls-Festen AA, Ongerboer de Visser BW, Meggouh F, Weterman MA, De Jonghe P, Timmerman V, de Visser M. Phenotype of Charcot-Marie-Tooth disease Type 2. Neurology. 2007 May 15;68(20):1658-67. (http://www.ncbi.nlm.nih.gov/pubmed/17502546?dopt=Abstract)
- Cafforio G, Calabrese R, Morelli N, Mancuso M, Piazza S, Martinuzzi A, Bassi MT, Crippa F, Siciliano G. The first Italian family with evidence of pyramidal impairment as phenotypic manifestation of Silver syndrome BSCL2 gene mutation. Neurol Sci. 2008 Jun;29(3):189-91. doi: 10.1007/s10072-008-0937-y. Epub 2008 Jul 9. (http://www.ncbi.nlm.nih.gov/pubmed/18612770?dopt=Abstract)
- Gene Review: BSCL2-Related Neurologic Disorders/Seipinopathy (http://www.ncbi.nlm.nih.gov/books/NBK1307)
- Gene Review: Charcot-Marie-Tooth Neuropathy Type 2 (http://www.ncbi.nlm.nih.gov/books/NBK1285)
- Ito D, Suzuki N. Molecular pathogenesis of seipin/BSCL2-related motor neuron diseases. Ann Neurol. 2007 Mar;61(3):237-50. (http://www.ncbi.nlm.nih.gov/pubmed/17387721?dopt=Abstract)
- Ito D, Suzuki N. Seipinopathy: a novel endoplasmic reticulum stress-associated disease. Brain. 2009 Jan;132(Pt 1):8-15. doi: 10.1093/brain/awn216. Epub 2008 Sep 12. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18790819?dopt=Abstract)
- Magré J, Delépine M, Khallouf E, Gedde-Dahl T Jr, Van Maldergem L, Sobel E, Papp J, Meier M, Mégarbané A, Bachy A, Verloes A, d'Abronzo FH, Seemanova E, Assan R, Baudic N, Bourut C, Czernichow P, Huet F, Grigorescu F, de Kerdanet M, Lacombe D, Labrune P, Lanza M, Loret H, Matsuda F, Navarro J, Nivelon-Chevalier A, Polak M, Robert JJ, Tric P, Tubiana-Rufi N, Vigouroux C, Weissenbach J, Savasta S, Maassen JA, Trygstad O, Bogalho P, Freitas P, Medina JL, Bonnicci F, Joffe BI, Loyson G, Panz VR, Raal FJ, O'Rahilly S, Stephenson T, Kahn CR, Lathrop M, Capeau J; BSCL Working Group. Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nat Genet. 2001 Aug;28(4):365-70. (http://www.ncbi.nlm.nih.gov/pubmed/11479539?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/26580)
- Rohkamm B, Reilly MM, Lochmüller H, Schlotter-Weigel B, Barisic N, Schöls L, Nicholson G, Pareyson D, Laurà M, Janecke AR, Miltenberger-Miltenyi G, John E, Fischer C, Grill F, Wakeling W, Davis M, Pieber TR, Auer-Grumbach M. Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome. J Neurol Sci. 2007 Dec 15;263(1-2):100-6. Epub 2007 Jul 30. (http://www.ncbi.nlm.nih.gov/pubmed/17663003?dopt=Abstract)
- Szymanski KM, Binns D, Bartz R, Grishin NV, Li WP, Agarwal AK, Garg A, Anderson RG, Goodman JM. The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20890-5. Epub 2007 Dec 18. (http://www.ncbi.nlm.nih.gov/pubmed/18093937?dopt=Abstract)
- van de Warrenburg BP, Scheffer H, van Eijk JJ, Versteeg MH, Kremer H, Zwarts MJ, Schelhaas HJ, van Engelen BG. BSCL2 mutations in two Dutch families with overlapping Silver syndrome-distal hereditary motor neuropathy. Neuromuscul Disord. 2006 Feb;16(2):122-5. Epub 2006 Jan 19. (http://www.ncbi.nlm.nih.gov/pubmed/16427281?dopt=Abstract)
- Windpassinger C, Auer-Grumbach M, Irobi J, Patel H, Petek E, Hörl G, Malli R, Reed JA, Dierick I, Verpoorten N, Warner TT, Proukakis C, Van den Bergh P, Verellen C, Van Maldergem L, Merlini L, De Jonghe P, Timmerman V, Crosby AH, Wagner K. Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. Nat Genet. 2004 Mar;36(3):271-6. Epub 2004 Feb 22. (http://www.ncbi.nlm.nih.gov/pubmed/14981520?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.