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SIL1

MIM.608005 5q31

Tuesday 28 February 2006

SIL1 encodes a nucleotide exchange factor for the heat-shock protein 70 (HSP70) chaperone HSPA5.

- SIL1 (also called BAP) acts as a nucleotide exchange factor for the Hsp70 chaperone BiP (also called GRP78), which is a key regulator of the main functions of the endoplasmic reticulum.

- SIL1 is a resident endoplasmic reticulum (ER) glycoprotein that interacts with the ATPase domain of BIP (HSPA5) (MIM.138120) and enhances nucleotide exchange.

Pathology

- germline mutations of the SIL1 gene in Marinesco-Sjogren syndrome

  • Marinesco-Sjogren syndrome associates cerebellar ataxia, congenital cataracts, and retarded somatic and mental maturation.
  • loss-of-function mutations in SIL1 (#16282978#)
  • disturbed SIL1-HSPA5 interaction and protein folding is the primary pathology in Marinesco-Sjogren syndrome.

References

- Anttonen AK, Mahjneh I, Hamalainen RH, Lagier-Tourenne C, Kopra O, Waris L, Anttonen M, Joensuu T, Kalimo H, Paetau A, Tranebjaerg L, Chaigne D, Koenig M, Eeg-Olofsson O, Udd B, Somer M, Somer H, Lehesjoki AE. The gene disrupted in Marinesco-Sjogren syndrome encodes SIL1, an HSPA5 cochaperone. Nat Genet. 2005 Dec;37(12):1309-11. PMID: #16282978#

- Senderek J, Krieger M, Stendel C, Bergmann C, Moser M, Breitbach-Faller N, Rudnik-Schoneborn S, Blaschek A, Wolf NI, Harting I, North K, Smith J, Muntoni F, Brockington M, Quijano-Roy S, Renault F, Herrmann R, Hendershot LM, Schroder JM, Lochmuller H, Topaloglu H, Voit T, Weis J, Ebinger F, Zerres K. Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy. Nat Genet. 2005 Dec;37(12):1312-4. PMID: #16282977#