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Genetics Home Reference: your guide to understanding genetic conditions
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BSCL2

Reviewed January 2016

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 located in the membrane of a 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 and tissues throughout the body, particularly in nerve cells that control muscle movement (motor neurons) and in the brain. The gene is also active in fat-storing cells called adipocytes, which are the major component of fatty (adipose) tissue. Studies suggest that seipin plays a critical role in the development and function of adipocytes. In particular, seipin is involved in the development of lipid droplets, which are structures within these cells that store fat molecules.

How are changes in the BSCL2 gene related to health conditions?

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) in the seipin protein. 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 the 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 build up 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.

congenital generalized lipodystrophy - caused by mutations in the BSCL2 gene

At least 24 mutations in the BSCL2 gene have been identified in people with congenital generalized lipodystrophy (also called Berardinelli-Seip congenital lipodystrophy) type 2. This rare condition is characterized by an almost total absence of adipose tissue and a very muscular appearance. A shortage of adipose tissue leads to multiple health problems, including high levels of fats called triglycerides circulating in the bloodstream (hypertriglyceridemia) and diabetes mellitus. In some cases, this form of the condition is also associated with intellectual disability, which is usually mild to moderate.

Most of the BSCL2 gene mutations that cause congenital generalized lipodystrophy type 2 lead to the production of a nonfunctional version of the seipin protein or prevent cells from making any of this protein. A loss of functional seipin disrupts the normal development and function of adipocytes, including lipid droplets, which prevents fats from being stored normally in adipose tissue. The resulting lack of body fat underlies most of the signs and symptoms of congenital generalized lipodystrophy type 2. A loss of seipin function in the brain may help explain why intellectual disability can occur with this form of the condition.

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, a progressive disorder that affects motor neurons in the spinal cord. It results in muscle weakness and affects movement of the hands and feet. The mutations that can cause this disorder each change a single amino acid in the seipin protein. 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, described above.

It is unclear how BSCL2 gene mutations cause distal hereditary motor neuropathy, type V. These genetic changes probably alter the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins build up 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, the N88S and S90L mutations described above, 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. The mutations likely result in misfolded seipin proteins that accumulate within neurons, leading to cell damage and cell death. The loss of neurons causes muscle weakness and spasticity in people with Silver syndrome.

It is unclear how the same mutations in the BSCL2 gene can cause 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 62,690,262 to 62,709,619

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/26580))

The BSCL2 gene is located on the long (q) arm of chromosome 11 at position 13.

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 62,690,262 to base pair 62,709,619 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.

What other names do people use for the BSCL2 gene or gene products?

  • BSCL2_HUMAN
  • GNG3LG
  • seipin
  • SPG17

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?

acids ; adipocytes ; adipose tissue ; amino acid ; asparagine ; cell ; congenital ; diabetes ; diabetes mellitus ; disability ; distal ; endoplasmic reticulum ; gene ; hereditary ; hypertriglyceridemia ; leucine ; lipid ; lipid droplet ; lipodystrophy ; motor ; mutation ; neuropathy ; peripheral ; peripheral nerves ; protein ; sensory cells ; serine ; spasticity ; syndrome ; tissue ; triglycerides ; wasting

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References

  • 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)
  • Cartwright BR, Binns DD, Hilton CL, Han S, Gao Q, Goodman JM. Seipin performs dissectible functions in promoting lipid droplet biogenesis and regulating droplet morphology. Mol Biol Cell. 2015 Feb 15;26(4):726-39. doi: 10.1091/mbc.E14-08-1303. Epub 2014 Dec 24. (http://www.ncbi.nlm.nih.gov/pubmed/25540432?dopt=Abstract)
  • Cartwright BR, Goodman JM. Seipin: from human disease to molecular mechanism. J Lipid Res. 2012 Jun;53(6):1042-55. doi: 10.1194/jlr.R023754. Epub 2012 Apr 2. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22474068?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. 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)
  • Wee K, Yang W, Sugii S, Han W. Towards a mechanistic understanding of lipodystrophy and seipin functions. Biosci Rep. 2014 Oct 2;34(5). pii: e00141. doi: 10.1042/BSR20140114. Review. (http://www.ncbi.nlm.nih.gov/pubmed/25195639?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 healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2016
Published: February 8, 2016