EFHC2

EFHC2 is located on the negative strand (sense strand) of the X chromosome at p11.3. EFHC2 is one of a few, select number of genes with in vitro evidence suggesting it escapes X inactivation.{{cite journal | vauthors = Castagné R, Zeller T, Rotival M, Szymczak S, Truong V, Schillert A, Trégouët DA, Münzel T, Ziegler A, Cambien F, Blankenberg S, Tiret L | title = Influence of sex and genetic variability on expression of X-linked genes in human monocytes | journal = Genomics | volume = 98 | issue = 5 | pages = 320–6 | date = Nov 2011 | pmid = 21763416 | doi = 10.1016/j.ygeno.2011.06.009 | doi-access = free }} EFHC2 spans 195,796 base pairs and is neighbored by NDP, the gene encoding for Norrie disease protein. Preliminary evidence based on genome wide association studies have linked a SNP in the intron between exons 13 and 14 of EFHC2 with harm avoidance.{{cite journal | vauthors = Blaya C, Moorjani P, Salum GA, Gonçalves L, Weiss LA, Leistner-Segal S, Manfro GG, Smoller JW | title = Preliminary evidence of association between EFHC2, a gene implicated in fear recognition, and harm avoidance | journal = Neuroscience Letters | volume = 452 | issue = 1 | pages = 84–6 | date = Mar 2009 | pmid = 19429002 | doi = 10.1016/j.neulet.2009.01.036 | s2cid = 39604977 }}

The mRNA transcript encoding the EFHC2 protein is 3,269 base pairs. The first ninety base pairs compose the five prime untranslated region and the last 1913 base pairs compose the three prime untranslated region.

Image:EFHC2 protein schematic.tif

The EFHC2 gene encodes a 749-amino acid protein which contains three DM10 domains ({{InterPro|IPR006602}}) and three calcium-binding EF-hand motifs.

The isoelectric point of EFHC2 is estimated to be 7.13 in humans.{{cite book | vauthors = Wilkins MR, Gasteiger E, Bairoch A, Sanchez JC, Williams KL, Appel RD, Hochstrasser DF | title = 2-D Proteome Analysis Protocols | chapter = Protein identification and analysis tools in the ExPASy server | series = Methods in Molecular Biology | volume = 112 | pages = 531–52 | year = 1999 | pmid = 10027275 | doi = 10.1385/1-59259-584-7:531 | isbn = 1-59259-584-7 }} Relative to other proteins expressed in humans, EFHC2 has fewer alanine residues and a greater number of tyrosine residues and is predicted to reside in the cytoplasm.{{cite journal | vauthors = Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S | title = Methods and algorithms for statistical analysis of protein sequences | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 6 | pages = 2002–6 | date = Mar 1992 | pmid = 1549558 | pmc = 48584 | doi = 10.1073/pnas.89.6.2002 | bibcode = 1992PNAS...89.2002B | doi-access = free }}{{cite journal | vauthors = Horton P, Nakai K | title = Better prediction of protein cellular localization sites with the k nearest neighbors classifier | journal = Proceedings. International Conference on Intelligent Systems for Molecular Biology | volume = 5 | pages = 147–52 | year = 1997 | pmid = 9322029 }}

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EFHC2 is widely expressed in the central nervous system as well as peripheral tissues.{{cite journal | vauthors = Weiss LA, Purcell S, Waggoner S, Lawrence K, Spektor D, Daly MJ, Sklar P, Skuse D | title = Identification of EFHC2 as a quantitative trait locus for fear recognition in Turner syndrome | journal = Human Molecular Genetics | volume = 16 | issue = 1 | pages = 107–13 | date = Jan 2007 | pmid = 17164267 | doi = 10.1093/hmg/ddl445 | doi-access = free }}

A related protein, EFHC1 is encoded by a gene on chromosome 6. It has been suggested that both proteins are involved in the development of epilepsy{{cite journal | vauthors = Gu W, Sander T, Heils A, Lenzen KP, Steinlein OK | title = A new EF-hand containing gene EFHC2 on Xp11.4: tentative evidence for association with juvenile myoclonic epilepsy | journal = Epilepsy Research | volume = 66 | issue = 1–3 | pages = 91–8 | year = 2005 | pmid = 16112844 | doi = 10.1016/j.eplepsyres.2005.07.003 | s2cid = 25572315 }}{{cite journal | vauthors = Suzuki T, Delgado-Escueta AV, Aguan K, Alonso ME, Shi J, Hara Y, Nishida M, Numata T, Medina MT, Takeuchi T, Morita R, Bai D, Ganesh S, Sugimoto Y, Inazawa J, Bailey JN, Ochoa A, Jara-Prado A, Rasmussen A, Ramos-Peek J, Cordova S, Rubio-Donnadieu F, Inoue Y, Osawa M, Kaneko S, Oguni H, Mori Y, Yamakawa K | title = Mutations in EFHC1 cause juvenile myoclonic epilepsy | journal = Nature Genetics | volume = 36 | issue = 8 | pages = 842–9 | date = Aug 2004 | pmid = 15258581 | doi = 10.1038/ng1393 | s2cid = 32916803 }} and that this gene may be associated with fear recognition in individuals with Turner syndrome.

A mutation in EFHC2 which results in a serine to a tyrosine substitution at amino acid position 430 (S430Y) has been associated with juvenile myoclonic epilepsy in a male, German population. Additionally, a single nucleotide polymorphism in EFHC2 correlates to a reduced ability of Turner syndrome patients to recognize fear in facial expressions;{{cite journal | vauthors = Rodriguez-Revenga L, Madrigal I, Alkhalidi LS, Armengol L, González E, Badenas C, Estivill X, Milà M | title = Contiguous deletion of the NDP, MAOA, MAOB, and EFHC2 genes in a patient with Norrie disease, severe psychomotor retardation and myoclonic epilepsy | journal = American Journal of Medical Genetics Part A | volume = 143A | issue = 9 | pages = 916–20 | date = May 2007 | pmid = 17431911 | doi = 10.1002/ajmg.a.31521 | s2cid = 36917690 }} however, these findings remain controversial.{{cite journal | vauthors = Zinn AR, Kushner H, Ross JL | title = EFHC2 SNP rs7055196 is not associated with fear recognition in 45,X Turner syndrome | journal = American Journal of Medical Genetics Part B | volume = 147B | issue = 4 | pages = 507–9 | date = Jun 2008 | pmid = 17948898 | doi = 10.1002/ajmg.b.30625 | s2cid = 36643937 }}

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