CHD7

Chromodomain helicase DNA binding protein 7
PDB rendering based on 2ckc.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2CKC​, 2V0E​, 2V0F​
Identifiers
Symbols	CHD7 ; CRG; HH5; IS3; KAL5
External IDs	OMIM: 608892 MGI: 2444748 HomoloGene: 19067 GeneCards: CHD7 Gene
EC number	3.6.4.12
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • chromatin binding • helicase activity • protein binding • ATP binding Cellular component • nucleus • nucleoplasm • nucleolus Biological process • skeletal system development • in utero embryonic development • heart morphogenesis • transcription, DNA-templated • regulation of transcription, DNA-templated • rRNA processing • central nervous system development • adult heart development • sensory perception of sound • adult walking behavior • blood circulation • chromatin modification • cranial nerve development • olfactory nerve development • olfactory bulb development • T cell differentiation • female genitalia development • embryonic hindlimb morphogenesis • positive regulation of multicellular organism growth • olfactory behavior • inner ear morphogenesis • nose development • semicircular canal morphogenesis • genitalia development • artery morphogenesis • regulation of neurogenesis • cognition • palate development • retina development in camera-type eye • regulation of growth hormone secretion • limb development • face development • epithelium development Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	55636	320790
Ensembl	ENSG00000171316	ENSMUSG00000041235
UniProt	Q9P2D1	A2AJK6
RefSeq (mRNA)	NM_017780	NM_001033395
RefSeq (protein)	NP_060250	NP_001264078
Location (UCSC)	Chr 8: 60.68 – 60.87 Mb	Chr 4: 8.69 – 8.87 Mb
PubMed search

Chromodomain-helicase-DNA-binding protein 7 also known as ATP-dependent helicase CHD7 is an enzyme that in humans is encoded by the CHD7 gene.^[1][2]

CHD7 is an ATP-dependent chromatin remodeler homologous to the Drosophila trithorax-group protein Kismet.^[3] Mutations in CHD7 are associated with CHARGE syndrome.^[4]

Model organisms

Chd7 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Abnormal[5]
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal[6]
Body temperature	Normal
Eye morphology	Abnormal[7]
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Abnormal
Salmonella infection	Normal[8]
Citrobacter infection	Normal[9]
All tests and analysis from[10][11]

Model organisms have been used in the study of CHD7 function. A conditional knockout mouse line, called Chd7^{tm2a(EUCOMM)Wtsi[12][13]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[14][15][16]

Bergmeister's papilla, histological section.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[10][17] Twenty four tests were carried out on mutant mice and five significant abnormalities were observed.^[10] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice. Male heterozygotes displayed abnormal pelvic elevation in a modified SHIRPA test and have a high incidence of Bergmeister's papilla in both eyes. When the brains of heterozygous animals were studied, an absence of corpus callosum was observed.^[10]

References

1. Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (Feb 2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Research 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
2. "Entrez Gene: chromodomain helicase DNA binding protein 7".
3. Bajpai R, Chen DA, Rada-Iglesias A, Zhang J, Xiong Y, Helms J, Chang CP, Zhao Y, Swigut T, Wysocka J (Feb 2010). "CHD7 cooperates with PBAF to control multipotent neural crest formation". Nature 463 (7283): 958–62. doi:10.1038/nature08733. PMC 2890258. PMID 20130577.
4. Vissers LE, van Ravenswaaij CM, Admiraal R, Hurst JA, de Vries BB, Janssen IM, van der Vliet WA, Huys EH, de Jong PJ, Hamel BC, Schoenmakers EF, Brunner HG, Veltman JA, van Kessel AG (Sep 2004). "Mutations in a new member of the chromodomain gene family cause CHARGE syndrome". Nature Genetics 36 (9): 955–7. doi:10.1038/ng1407. PMID 15300250.
5. "Neurological assessment data for Chd7". Wellcome Trust Sanger Institute.
6. "Radiography data for Chd7". Wellcome Trust Sanger Institute.
7. "Eye morphology data for Chd7". Wellcome Trust Sanger Institute.
8. "Salmonella infection data for Chd7". Wellcome Trust Sanger Institute.
9. "Citrobacter infection data for Chd7". Wellcome Trust Sanger Institute.
10. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
11. Mouse Resources Portal, Wellcome Trust Sanger Institute.
12. "International Knockout Mouse Consortium".
13. "Mouse Genome Informatics".
14. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
15. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
16. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
17. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Delahaye A, Sznajer Y, Lyonnet S, Elmaleh-Bergès M, Delpierre I, Audollent S, Wiener-Vacher S, Mansbach AL, Amiel J, Baumann C, Bremond-Gignac D, Attié-Bitach T, Verloes A, Sanlaville D (Aug 2007). "Familial CHARGE syndrome because of CHD7 mutation: clinical intra- and interfamilial variability". Clinical Genetics 72 (2): 112–21. doi:10.1111/j.1399-0004.2007.00821.x. PMID 17661815.
• Van de Laar I, Dooijes D, Hoefsloot L, Simon M, Hoogeboom J, Devriendt K (Nov 2007). "Limb anomalies in patients with CHARGE syndrome: an expansion of the phenotype". American Journal of Medical Genetics. Part A 143A (22): 2712–5. doi:10.1002/ajmg.a.32008. PMID 17937444.
• Holak HM, Kohlhase J, Holak SA, Holak NH (Jun 2008). "New recognized ophthalmic morphologic anomalies in CHARGE syndrome caused by the R2319C mutation in the CHD7 gene". Ophthalmic Genetics 29 (2): 79–84. doi:10.1080/13816810801918391. PMID 18484313.
• Sanlaville D, Verloes A (Apr 2007). "CHARGE syndrome: an update". European Journal of Human Genetics 15 (4): 389–99. doi:10.1038/sj.ejhg.5201778. PMID 17299439.
• Kim HG, Kurth I, Lan F, Meliciani I, Wenzel W, Eom SH, Kang GB, Rosenberger G, Tekin M, Ozata M, Bick DP, Sherins RJ, Walker SL, Shi Y, Gusella JF, Layman LC (Oct 2008). "Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome". American Journal of Human Genetics 83 (4): 511–9. doi:10.1016/j.ajhg.2008.09.005. PMC 2561938. PMID 18834967.
• Dagle JM, Lepp NT, Cooper ME, Schaa KL, Kelsey KJ, Orr KL, Caprau D, Zimmerman CR, Steffen KM, Johnson KJ, Marazita ML, Murray JC (Apr 2009). "Determination of genetic predisposition to patent ductus arteriosus in preterm infants". Pediatrics 123 (4): 1116–23. doi:10.1542/peds.2008-0313. PMC 2734952. PMID 19336370.
• Wincent J, Schulze A, Schoumans J (2009). "Detection of CHD7 deletions by MLPA in CHARGE syndrome patients with a less typical phenotype". European Journal of Medical Genetics 52 (4): 271–2. doi:10.1016/j.ejmg.2009.02.005. PMID 19248844.
• Wincent J, Holmberg E, Strömland K, Soller M, Mirzaei L, Djureinovic T, Robinson K, Anderlid B, Schoumans J (Jul 2008). "CHD7 mutation spectrum in 28 Swedish patients diagnosed with CHARGE syndrome". Clinical Genetics 74 (1): 31–8. doi:10.1111/j.1399-0004.2008.01014.x. PMID 18445044.
• Gennery AR, Slatter MA, Rice J, Hoefsloot LH, Barge D, McLean-Tooke A, Montgomery T, Goodship JA, Burt AD, Flood TJ, Abinun M, Cant AJ, Johnson D (Jul 2008). "Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome". Clinical and Experimental Immunology 153 (1): 75–80. doi:10.1111/j.1365-2249.2008.03681.x. PMC 2432100. PMID 18505430.
• Tellier AL, Cormier-Daire V, Abadie V, Amiel J, Sigaudy S, Bonnet D, de Lonlay-Debeney P, Morrisseau-Durand MP, Hubert P, Michel JL, Jan D, Dollfus H, Baumann C, Labrune P, Lacombe D, Philip N, LeMerrer M, Briard ML, Munnich A, Lyonnet S (Apr 1998). "CHARGE syndrome: report of 47 cases and review". American Journal of Medical Genetics 76 (5): 402–9. doi:10.1002/(SICI)1096-8628(19980413)76:5<402::AID-AJMG7>3.0.CO;2-O. PMID 9556299.
• Jongmans MC, van Ravenswaaij-Arts CM, Pitteloud N, Ogata T, Sato N, Claahsen-van der Grinten HL, van der Donk K, Seminara S, Bergman JE, Brunner HG, Crowley WF, Hoefsloot LH (Jan 2009). "CHD7 mutations in patients initially diagnosed with Kallmann syndrome--the clinical overlap with CHARGE syndrome". Clinical Genetics 75 (1): 65–71. doi:10.1111/j.1399-0004.2008.01107.x. PMC 2854009. PMID 19021638.
• Jongmans MC, Hoefsloot LH, van der Donk KP, Admiraal RJ, Magee A, van de Laar I, Hendriks Y, Verheij JB, Walpole I, Brunner HG, van Ravenswaaij CM (Jan 2008). "Familial CHARGE syndrome and the CHD7 gene: a recurrent missense mutation, intrafamilial recurrence and variability". American Journal of Medical Genetics. Part A 146A (1): 43–50. doi:10.1002/ajmg.a.31921. PMID 18074359.
• Vuorela PE, Penttinen MT, Hietala MH, Laine JO, Huoponen KA, Kääriäinen HA (Oct 2008). "A familial CHARGE syndrome with a CHD7 nonsense mutation and new clinical features". Clinical Dysmorphology 17 (4): 249–53. doi:10.1097/MCD.0b013e328306a704. PMID 18978652.
• Bergman JE, de Wijs I, Jongmans MC, Admiraal RJ, Hoefsloot LH, van Ravenswaaij-Arts CM (2008). "Exon copy number alterations of the CHD7 gene are not a major cause of CHARGE and CHARGE-like syndrome". European Journal of Medical Genetics 51 (5): 417–25. doi:10.1016/j.ejmg.2008.03.003. PMID 18472328.
• Lee YW, Kim SC, Shin YL, Kim JW, Hong HS, Lee YK, Ki CS (Mar 2009). "Clinical and genetic analysis of the CHD7 gene in Korean patients with CHARGE syndrome". Clinical Genetics 75 (3): 290–3. doi:10.1111/j.1399-0004.2008.01127.x. PMID 19159393.
• Qi Q, Yi L, Yang C, Chen H, Shen L, Mo X, Hu Y, Wang Y (Dec 2008). "[Mutation analysis of the CHD7 gene in patients with congenital heart disease]". Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics 25 (6): 637–41. PMID 19065520.
• Writzl K, Cale CM, Pierce CM, Wilson LC, Hennekam RC (2007). "Immunological abnormalities in CHARGE syndrome". European Journal of Medical Genetics 50 (5): 338–45. doi:10.1016/j.ejmg.2007.05.002. PMID 17684005.
• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (Jun 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
• Vuorela P, Ala-Mello S, Saloranta C, Penttinen M, Pöyhönen M, Huoponen K, Borozdin W, Bausch B, Botzenhart EM, Wilhelm C, Kääriäinen H, Kohlhase J (Oct 2007). "Molecular analysis of the CHD7 gene in CHARGE syndrome: identification of 22 novel mutations and evidence for a low contribution of large CHD7 deletions". Genetics in Medicine 9 (10): 690–4. doi:10.1097/GIM.0b013e318156e68e. PMID 18073582.
• Layman WS, McEwen DP, Beyer LA, Lalani SR, Fernbach SD, Oh E, Swaroop A, Hegg CC, Raphael Y, Martens JR, Martin DM (Jun 2009). "Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome". Human Molecular Genetics 18 (11): 1909–23. doi:10.1093/hmg/ddp112. PMC 2678924. PMID 19279158.
• Buck, Cassandra; Balasubramanian, Ravikumar; Crowley, Jr, William F (2013-07-18). Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency. NBK1334. In Pagon RA, Bird TD, Dolan CR, ed. (1993). GeneReviews™ [Internet]. Seattle WA: University of Washington, Seattle.
• Lalani SR, Hefner MA, Belmont JW, Davenport SL (2012-02-02). CHARGE Syndrome. NBK1117. In GeneReviews
• Bardakjian T, Weiss A, Schneider AS (2006-05-26). Anophthalmia/Microphthalmia Overview. NBK1378. In GeneReviews

External links

• CHD7 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)