Immunoglobulin superfamily, member 1[5] is a plasma membrane glycoprotein encoded by the IGSF1gene,[6][7][8] which maps to the X chromosome in humans and other mammalian species.
IGSF1's function in normal cells is unresolved. The protein is a member of the immunoglobulin (Ig) superfamily. It was predicted to contain 12 Ig loops, a transmembrane domain, and a short cytoplasmic tail. However, during translation of the protein, it is cleaved into amino- and carboxy-terminal domains (NTD and CTD, respectively).[9] Only the CTD is trafficked to the plasma membrane. The NTD is trapped within the endoplasmic reticulum (ER). Pathogenic mutations in the IGSF1 gene block the transport of the CTD to the plasma membrane.
Clinical relevanceedit
Mutations in IGSF1 cause a condition called IGSF1 deficiency syndrome[10] or central hypothyroidism/testicular enlargement (CHTE[11]). The condition, which affects an estimated 1:100,000 people,[12] is more common in males than females. Most affected males are discovered through neonatal screening for hypothyroidism. The extent of hypothyroidism is variable, but most male cases require treatment with thyroid hormone replacement. Males with IGSF1 deficiency exhibit enlarged testicles (also known as macroorchidism) and a delay in the development of secondary sexual characteristics. Post-pubertally, there is no evidence of impaired fertility in these men.
The IGSF1 gene is also active in the brain and in the developing liver. It can also become reactivated in liver cancer (hepatocellular carcinoma).[13]
Animal modeledit
Mice lacking a functional Igsf1 gene similarly exhibit hypothyroidism of central origin.[10] The IGSF1 gene is particularly active in the pituitary gland. The pituitary synthesizes and secretes thyroid-stimulating hormone (TSH). TSH, in turn, stimulates production of the thyroid hormones, thyroxine and triiodothyronine, by the thyroid gland. TSH secretion is controlled by thyrotropin-releasing hormone (TRH), which is released by neurons in the hypothalamus of the brain. In Igsf1 deficient mice, the receptor for TRH is downregulated in the pituitary.[10] This decrease could explain, at least in part, the central hypothyroidism observed in both humans and mice with IGSF1 deficiency. How the loss of IGSF1 causes a decrease in TRH receptors is presently unknown.
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000147255 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000031111 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Entry 300137: Immunoglobulin superfamily, member 1; IGSF1".
^Mazzarella R, Pengue G, Jones J, Jones C, Schlessinger D (Mar 1998). "Cloning and expression of an immunoglobulin superfamily gene (IGSF1) in Xq25". Genomics. 48 (2): 157–62. doi:10.1006/geno.1997.5156. PMID 9521868.
^Frattini A, Faranda S, Redolfi E, Allavena P, Vezzoni P (Jul 1998). "Identification and genomic organization of a gene coding for a new member of the cell adhesion molecule family mapping to Xq25". Gene. 214 (1–2): 1–6. doi:10.1016/S0378-1119(98)00253-4. PMID 9729118.
^"Entrez Gene: IGSF1 immunoglobulin superfamily, member 1".
^Robakis T, Bak B, Lin SH, Bernard DJ, Scheiffele P (Dec 2008). "An internal signal sequence directs intramembrane proteolysis of a cellular immunoglobulin domain protein". The Journal of Biological Chemistry. 283 (52): 36369–76. doi:10.1074/jbc.M807527200. PMC2662301. PMID 18981173.
^ abcSun Y, Bak B, Schoenmakers N, van Trotsenburg AS, Oostdijk W, Voshol P, Cambridge E, White JK, le Tissier P, Gharavy SN, Martinez-Barbera JP, Stokvis-Brantsma WH, Vulsma T, Kempers MJ, Persani L, Campi I, Bonomi M, Beck-Peccoz P, Zhu H, Davis TM, Hokken-Koelega AC, Del Blanco DG, Rangasami JJ, Ruivenkamp CA, Laros JF, Kriek M, Kant SG, Bosch CA, Biermasz NR, Appelman-Dijkstra NM, Corssmit EP, Hovens GC, Pereira AM, den Dunnen JT, Wade MG, Breuning MH, Hennekam RC, Chatterjee K, Dattani MT, Wit JM, Bernard DJ (Dec 2012). "Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement". Nature Genetics. 44 (12): 1375–81. doi:10.1038/ng.2453. PMC3511587. PMID 23143598.
^"Entry 300888: Hypothyroidism, central, and testicular enlargement; CHTE".
^Joustra SD, van Trotsenburg AS, Sun Y, Losekoot M, Bernard DJ, Biermasz NR, Oostdijk W, Wit JM (May 2013). "IGSF1 deficiency syndrome: A newly uncovered endocrinopathy". Rare Diseases. 1 (1): e24883. doi:10.4161/rdis.24883. PMC3915563. PMID 25002994.
^Patil MA, Chua MS, Pan KH, Lin R, Lih CJ, Cheung ST, Ho C, Li R, Fan ST, Cohen SN, Chen X, So S (May 2005). "An integrated data analysis approach to characterize genes highly expressed in hepatocellular carcinoma". Oncogene. 24 (23): 3737–47. doi:10.1038/sj.onc.1208479. PMID 15735714. S2CID 23148568.
Further readingedit
Chapman SC, Woodruff TK (Apr 2001). "Modulation of activin signal transduction by inhibin B and inhibin-binding protein (INhBP)". Molecular Endocrinology. 15 (4): 668–79. doi:10.1210/mend.15.4.0616. PMID 11266516.
Tanaka S, Tatsumi K, Okubo K, Itoh K, Kawamoto S, Matsubara K, Amino N (Feb 2002). "Expression profile of active genes in the human pituitary gland". Journal of Molecular Endocrinology. 28 (1): 33–44. doi:10.1677/jme.0.0280033. PMID 11854097.
Bernard DJ, Burns KH, Haupt B, Matzuk MM, Woodruff TK (Jul 2003). "Normal reproductive function in InhBP/p120-deficient mice". Molecular and Cellular Biology. 23 (14): 4882–91. doi:10.1128/mcb.23.14.4882-4891.2003. PMC162213. PMID 12832474.
Tajima T, Nakamura A, Ishizu K (2013). "A novel mutation of IGSF1 in a Japanese patient of congenital central hypothyroidism without macroorchidism". Endocrine Journal. 60 (2): 245–9. doi:10.1507/endocrj.ej13-0009. PMID 23363888.
Tajima T, Nakamura A, Ishizu K (2013). "A novel mutation of IGSF1 in a Japanese patient of congenital central hypothyroidism without macroorchidism". Endocrine Journal. 60 (2): E1682–91. doi:10.1210/jc.2013-1224. hdl:2115/57864. PMID 23363888.
Joustra SD, Schoenmakers N, Persani L, Campi I, Bonomi M, Radetti G, Beck-Peccoz P, Zhu H, Davis TM, Sun Y, Corssmit EP, Appelman-Dijkstra NM, Heinen CA, Pereira AM, Varewijck AJ, Janssen JA, Endert E, Hennekam RC, Lombardi MP, Mannens MM, Bak B, Bernard DJ, Breuning MH, Chatterjee K, Dattani MT, Oostdijk W, Biermasz NR, Wit JM, van Trotsenburg AS (Dec 2013). "The IGSF1 deficiency syndrome: characteristics of male and female patients". The Journal of Clinical Endocrinology and Metabolism. 98 (12): 4942–52. doi:10.1210/jc.2013-2743. PMID 24108313.
Tajima T, Nakamura A, Morikawa S, Ishizu K (Sep 2014). "Neonatal screening and a new cause of congenital central hypothyroidism". Annals of Pediatric Endocrinology & Metabolism. 19 (3): 117–21. doi:10.6065/apem.2014.19.3.117. PMC4208260. PMID 25346914.
Reynaert N, Braat E, de Zegher F (2015). "Congenital nystagmus and central hypothyroidism". International Journal of Pediatric Endocrinology. 2015 (1): 7. doi:10.1186/s13633-015-0003-5. PMC4360929. PMID 25780367.
This article on a gene on the human X chromosome and/or its associated protein is a stub. You can help Wikipedia by expanding it.
igsf1, immunoglobulin, superfamily, member, plasma, membrane, glycoprotein, encoded, gene, which, maps, chromosome, humans, other, mammalian, species, identifiersaliases, chte, igcd1, igdc1, inhbp, pgsf2, p120, immunoglobulin, superfamily, member, 1external, i. Immunoglobulin superfamily member 1 5 is a plasma membrane glycoprotein encoded by the IGSF1 gene 6 7 8 which maps to the X chromosome in humans and other mammalian species IGSF1IdentifiersAliasesIGSF1 CHTE IGCD1 IGDC1 INHBP PGSF2 p120 immunoglobulin superfamily member 1External IDsOMIM 300137 MGI 2147913 HomoloGene 1195 GeneCards IGSF1Gene location Human Chr X chromosome human 1 BandXq26 1Start131 273 506 bp 1 End131 578 899 bp 1 Gene location Mouse Chr X chromosome mouse 2 BandX X A5Start48 871 413 bp 2 End48 886 626 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inpituitary glandanterior pituitaryhypothalamustibial nervenucleus accumbenssubstantia nigracaudate nucleusislet of Langerhansputamenleft lobe of thyroid glandTop expressed inarcuate nucleusmedian eminencedorsomedial hypothalamic nucleusventromedial nucleussuprachiasmatic nucleusdorsal tegmental nucleusmammillary bodylateral hypothalamusventral tegmental areaparaventricular nucleus of hypothalamusMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functioninhibin binding protein binding coreceptor activity activin receptor antagonist activityCellular componentintegral component of membrane extracellular region membraneBiological processregulation of transcription DNA templated signal transduction negative regulation of activin receptor signaling pathwaySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez3547209268EnsemblENSG00000147255ENSMUSG00000031111UniProtQ8N6C5Q7TQA1RefSeq mRNA NM 001170961NM 001170962NM 001170963NM 001555NM 205833NM 177591NM 177915NM 183335NM 183336RefSeq protein NP 001164432NP 001164433NP 001164434NP 001546NP 991402NP 808259NP 808583NP 899178NP 899179Location UCSC Chr X 131 27 131 58 MbChr X 48 87 48 89 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical relevance 3 Animal model 4 References 5 Further readingFunction editIGSF1 s function in normal cells is unresolved The protein is a member of the immunoglobulin Ig superfamily It was predicted to contain 12 Ig loops a transmembrane domain and a short cytoplasmic tail However during translation of the protein it is cleaved into amino and carboxy terminal domains NTD and CTD respectively 9 Only the CTD is trafficked to the plasma membrane The NTD is trapped within the endoplasmic reticulum ER Pathogenic mutations in the IGSF1 gene block the transport of the CTD to the plasma membrane Clinical relevance editMutations in IGSF1 cause a condition called IGSF1 deficiency syndrome 10 or central hypothyroidism testicular enlargement CHTE 11 The condition which affects an estimated 1 100 000 people 12 is more common in males than females Most affected males are discovered through neonatal screening for hypothyroidism The extent of hypothyroidism is variable but most male cases require treatment with thyroid hormone replacement Males with IGSF1 deficiency exhibit enlarged testicles also known as macroorchidism and a delay in the development of secondary sexual characteristics Post pubertally there is no evidence of impaired fertility in these men The IGSF1 gene is also active in the brain and in the developing liver It can also become reactivated in liver cancer hepatocellular carcinoma 13 Animal model editMice lacking a functional Igsf1 gene similarly exhibit hypothyroidism of central origin 10 The IGSF1 gene is particularly active in the pituitary gland The pituitary synthesizes and secretes thyroid stimulating hormone TSH TSH in turn stimulates production of the thyroid hormones thyroxine and triiodothyronine by the thyroid gland TSH secretion is controlled by thyrotropin releasing hormone TRH which is released by neurons in the hypothalamus of the brain In Igsf1 deficient mice the receptor for TRH is downregulated in the pituitary 10 This decrease could explain at least in part the central hypothyroidism observed in both humans and mice with IGSF1 deficiency How the loss of IGSF1 causes a decrease in TRH receptors is presently unknown References edit a b c GRCh38 Ensembl release 89 ENSG00000147255 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000031111 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Entry 300137 Immunoglobulin superfamily member 1 IGSF1 Mazzarella R Pengue G Jones J Jones C Schlessinger D Mar 1998 Cloning and expression of an immunoglobulin superfamily gene IGSF1 in Xq25 Genomics 48 2 157 62 doi 10 1006 geno 1997 5156 PMID 9521868 Frattini A Faranda S Redolfi E Allavena P Vezzoni P Jul 1998 Identification and genomic organization of a gene coding for a new member of the cell adhesion molecule family mapping to Xq25 Gene 214 1 2 1 6 doi 10 1016 S0378 1119 98 00253 4 PMID 9729118 Entrez Gene IGSF1 immunoglobulin superfamily member 1 Robakis T Bak B Lin SH Bernard DJ Scheiffele P Dec 2008 An internal signal sequence directs intramembrane proteolysis of a cellular immunoglobulin domain protein The Journal of Biological Chemistry 283 52 36369 76 doi 10 1074 jbc M807527200 PMC 2662301 PMID 18981173 a b c Sun Y Bak B Schoenmakers N van Trotsenburg AS Oostdijk W Voshol P Cambridge E White JK le Tissier P Gharavy SN Martinez Barbera JP Stokvis Brantsma WH Vulsma T Kempers MJ Persani L Campi I Bonomi M Beck Peccoz P Zhu H Davis TM Hokken Koelega AC Del Blanco DG Rangasami JJ Ruivenkamp CA Laros JF Kriek M Kant SG Bosch CA Biermasz NR Appelman Dijkstra NM Corssmit EP Hovens GC Pereira AM den Dunnen JT Wade MG Breuning MH Hennekam RC Chatterjee K Dattani MT Wit JM Bernard DJ Dec 2012 Loss of function mutations in IGSF1 cause an X linked syndrome of central hypothyroidism and testicular enlargement Nature Genetics 44 12 1375 81 doi 10 1038 ng 2453 PMC 3511587 PMID 23143598 Entry 300888 Hypothyroidism central and testicular enlargement CHTE Joustra SD van Trotsenburg AS Sun Y Losekoot M Bernard DJ Biermasz NR Oostdijk W Wit JM May 2013 IGSF1 deficiency syndrome A newly uncovered endocrinopathy Rare Diseases 1 1 e24883 doi 10 4161 rdis 24883 PMC 3915563 PMID 25002994 Patil MA Chua MS Pan KH Lin R Lih CJ Cheung ST Ho C Li R Fan ST Cohen SN Chen X So S May 2005 An integrated data analysis approach to characterize genes highly expressed in hepatocellular carcinoma Oncogene 24 23 3737 47 doi 10 1038 sj onc 1208479 PMID 15735714 S2CID 23148568 Further reading editChapman SC Woodruff TK Apr 2001 Modulation of activin signal transduction by inhibin B and inhibin binding protein INhBP Molecular Endocrinology 15 4 668 79 doi 10 1210 mend 15 4 0616 PMID 11266516 Tanaka S Tatsumi K Okubo K Itoh K Kawamoto S Matsubara K Amino N Feb 2002 Expression profile of active genes in the human pituitary gland Journal of Molecular Endocrinology 28 1 33 44 doi 10 1677 jme 0 0280033 PMID 11854097 Bernard DJ Burns KH Haupt B Matzuk MM Woodruff TK Jul 2003 Normal reproductive function in InhBP p120 deficient mice Molecular and Cellular Biology 23 14 4882 91 doi 10 1128 mcb 23 14 4882 4891 2003 PMC 162213 PMID 12832474 Tajima T Nakamura A Ishizu K 2013 A novel mutation of IGSF1 in a Japanese patient of congenital central hypothyroidism without macroorchidism Endocrine Journal 60 2 245 9 doi 10 1507 endocrj ej13 0009 PMID 23363888 Tajima T Nakamura A Ishizu K 2013 A novel mutation of IGSF1 in a Japanese patient of congenital central hypothyroidism without macroorchidism Endocrine Journal 60 2 E1682 91 doi 10 1210 jc 2013 1224 hdl 2115 57864 PMID 23363888 Joustra SD Schoenmakers N Persani L Campi I Bonomi M Radetti G Beck Peccoz P Zhu H Davis TM Sun Y Corssmit EP Appelman Dijkstra NM Heinen CA Pereira AM Varewijck AJ Janssen JA Endert E Hennekam RC Lombardi MP Mannens MM Bak B Bernard DJ Breuning MH Chatterjee K Dattani MT Oostdijk W Biermasz NR Wit JM van Trotsenburg AS Dec 2013 The IGSF1 deficiency syndrome characteristics of male and female patients The Journal of Clinical Endocrinology and Metabolism 98 12 4942 52 doi 10 1210 jc 2013 2743 PMID 24108313 Tajima T Nakamura A Morikawa S Ishizu K Sep 2014 Neonatal screening and a new cause of congenital central hypothyroidism Annals of Pediatric Endocrinology amp Metabolism 19 3 117 21 doi 10 6065 apem 2014 19 3 117 PMC 4208260 PMID 25346914 Reynaert N Braat E de Zegher F 2015 Congenital nystagmus and central hypothyroidism International Journal of Pediatric Endocrinology 2015 1 7 doi 10 1186 s13633 015 0003 5 PMC 4360929 PMID 25780367 nbsp This article on a gene on the human X chromosome and or its associated protein is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title IGSF1 amp oldid 1193519090, wikipedia, wiki, book, books, library,
