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CHD6 (chromodomain helicase DNA binding protein 6)

Written2014-08Melissa Lathrop, C Harker Rhodes, Steve Fiering
Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA

Abstract CHD6 is a chromatin remodeling protein characterized to play a role in transcriptional repression of genes and viruses. It occurs in a nuclear location as a component of a larger complex which associates with RNA Pol II. Mutations in CHD6 are associated with motor coordination defects, and development of cancers following substitutions and translocations.

Keywords Chromodomain Helicase DNA Binding protein 6 - CHD6

(Note : for Links provided by Atlas : click)


Alias (NCBI)CHD-6
HGNC (Hugo) CHD6
HGNC Alias symbKIAA1335
LocusID (NCBI) 84181
Atlas_Id 43211
Location 20q12  [Link to chromosome band 20q12]
Location_base_pair Starts at 41402083 and ends at 41618377 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping CHD6.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CHD6 (20q12)::ABHD12 (20p11.21)CHD6 (20q12)::CHD6 (20q12)CHD6 (20q12)::CNBD2 (20q11.23)
CHD6 (20q12)::EFCAB11 (14q32.11)CHD6 (20q12)::FAT3 (11q14.3)CHD6 (20q12)::MAML2 (11q21)
CHD6 (20q12)::MCUR1 (6p23)CHD6 (20q12)::TFIP11 (22q12.1)CHD6 (20q12)::WFDC11 (20q13.12)
DNAH6 (2p11.2)::CHD6 (20q12)LRP5 (11q13.2)::CHD6 (20q12)STK35 (20p13)::CHD6 (20q12)
TANC2 (17q23.2)::CHD6 (20q12)TCF7L2 (10q25.2)::CHD6 (20q12)


  CHD6 is a located on chromosome 20q12 in humans. The transcript contains 38 exons. Exons are indicated relative to size in red, 5' and 3' untranslated regions are indicated in blue. Exon number is indicated below graphic. Position of the gene on the chromosome and the location of the centromere and q terminus are indicated (adapted from the NCBI graphics viewer).
Description The CHD6 gene is encoded by 38 exons spanning 216394 bp. In addition to the full length transcript there are 5 predicted but not specifically reported splice variants of human CHD6. The CHD6 cDNA sequence spans 10826 bp, with a 5' untranslated region of 179 bp, an open reading frame of 8148 bp, and a 3' untranslated region of 2492 bp (NCBI: NM_032221.4) (Schuster and Stöger, 2002).
Transcription CHD6 mRNA is found in all tissues examined, with the greatest levels found on reproductive tissues, digestive tissues, brain, bone marrow, muscle, lymph node, and spleen (EMBL-EBI: E-MTAB-1733).
Pseudogene CHD6 in humans has no identified pseudogene.


  CHD6 protein functional domains. Chromodomains are highlighted in purple, the highly conserved SNF2-like ATPase region is indicated in light blue, and the DNA binding domain (green oval) contains BRK binding sights, indicated by the red diamonds.
Description CHD6 is a member of the very homologous SNF2 superfamily of chromatin remodeling enzymes (SWI2/SNF2, ISWI, and CHD enzyme families). These enzymes all contain a highly conserved HELICc DEAD-like helicase/ATPase with seven conserved catalytic regions (Brown et al., 2007; Marfella and Imbalzano, 2007). The nine CHD family members all contain n-terminal chromodomains and the HELICc ATPase/helicase region, and are split into three subfamilies, distinguished by the additional functional domains in each (Marfella and Imbalzano, 2007; Stanley et al., 2013). CHD6 contains a DNA binding region in its c-terminal region with conserved BRK domains (Schuster and Stöger, 2002). CHD6 is localized to the nucleus and is found in large multi-protein chromatin remodeling complexes, including the Nrf2 transcription factor (Nioi et al., 2005). Additionally, CHD6 is a DNA dependent ATPase. CHD6 protein is expected to function as a transcriptional repressor and it has been shown to be interact with RNA Pol II proteins (Lutz et al., 2006) and to be involved in the cellular repression of viral replication (Fertey et al., 2010; Alfonso et al., 2011; Alfonso et al., 2013). Size: 2715 amino acids; 305412 Da.
Expression CHD6 protein is expressed in all tissues assayed including, monocytes, lymphocytes, kidney, liver, lung, colon, bone, brain, ovary, prostate, cervix, and breast (Data sourced from MOPED, PaxDb, and MaxQB, by Version: 3.12.142 28 July 2014). Low dose radiation induces CHD6 expression in the lymphoblastoid cell line AHH-1, and both A549 and HeLa cell lines (Wang et al., 2006).
Localisation Nuclear.
Function Chromatin remodeling, transcription co-factor binding, suppression of gene expression.
Homology CHD6 has homologues in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.


Note There have been no reports of naturally occurring homozygous inactivation of CHD6. Mutations have been identified in several types of cancer, however, no nonsense or frameshift mutations exclusive to CHD6 have been associated with cancer to date (Cosmic database). Haploinsufficiency in CHD6 has been reported in miscarriage and mental retardation (Yamada et al., 2010) and mutation of the ATPase region in mice resulted in an ataxia phenotype (Lathrop et al., 2010).

Implicated in

Entity Acute myeloid leukemia (AML)
Note The presence of a fusion gene between LMBRD1 and CHD6 was identified in a case report of AML. Development of AML from an acute MDS/MPD diagnosis occurred over two years. FISH mapping of increasingly specific bacterial artificial chromosomes was used to identify the breakpoints of this AML between exons 1 and 2 of CHD6 (Douet-Guilbert et al., 2014).
Hybrid/Mutated Gene Fusion gene between LMBRD1-CHD6 .
Note Chromosome 20q12 is a common breakpoint associated with the development of MPD/MDS, however with the increased specificity of chromosome mapping techniques the frequency of the CHD6 gene specifically mutated in this disease is still being more precisely determined (Huh et al., 2010; Padhi et al., 2013).
Entity Colorectal cancer
Note CHD6 has been implicated in two studies using genome wide analysis of colorectal cancer cell lines. A comparison between tumor cell lines and primary tumors found that cell lines accurately reflect the diversity of mutations associated with primary tumor samples (Mouradov et al., 2014). Additionally this study determined that mutations in chromatin state regulators (including CHD6) are commonly found in colorectal cancer. Further research examined the copy number variation (CNV) found between colorectal cancer and normal tissue samples (Ali Hassan et al., 2014). Significant alterations in CNV were observed on chromosomes 8, 13, and 20. The gain of copies on chromosome 20q12 was the most significant finding, occurring in 45% of tumor tissues examined, specifically over a 2445 kbp region containing eight genes that include PTPRT, TOP1, and CHD6 (Ali Hassan et al., 2014).
Entity Bladder transitional cell carcinoma (TCC)
Note Analysis of multiple TCC tissues identified a group of chromatin remodeling enzyme genes with mutations occurring in 59% of patients. CHD6 was found mutated in multiple lines examined, however, only in one line was the mutation exclusive to CHD6. Linked mutation of CHD6 and two other genes, ANK2 or LRP2 was found to correlate with the development of TCC (Gui et al., 2011).
Entity Various cancers (malignant melanoma, glioma, cervical cancer, lung, urinary tract, large intestine, and others)
Note Whole genome analysis of tumor tissues and culture cell lines have identified point mutations within CHD6. These mutations and copy number variations occur at low frequencies and are often not likely pathologically associated with the development of the cancers. The alterations have been found in the following tissues: malignant melanoma (5 substitution mutations: NCBI ClinVar Database, last update 04-24-2014), multiple tumor tissue sources identifying 283 mutations in haematopoietic and lymphoid (0.23% of tested samples), central nervous system (0.74%), cervix (14.3%), endometrium (8.5%), prostate, urinary tract (14.3%), ovary, breast, lung (7.0%), stomach (6.4%), skin, kidney, large intestine (10.6%), liver, oesophagus, and pancreas. The bulk of mutations are composed of nonsense substitution: 7.42%, missense substitution: 68.90%, synonymous substitution: 27.92%, deletion frameshift: 2.12% (COSMIC Database, v69). This database further identified copynumber variants in the following tissues; haematopoietic and lymphoid, central nervous system, breast, lung, endometrium, kidney, large intestine, lung, ovary, and pancreas tumor tissues, with gain of copy number, more common than loss of copy number (COSMIC Database, v69).
Entity Influenza/human papillomavirus
Note CHD6 has been identified as playing a role in the repression of influenza A infections. It associates with viral ribonuclear proteins in infected cells (Alfonso et al., 2011). Loss of CHD6 by siRNA silencing results in an increased viral replication, while in lungs of infected mice, CHD6 is degraded upon infection and exposure to the three subunits of the viral polymerase (Alfonso et al., 2013). Recent reports also indicate that CHD6 interacts with human papillomavirus proteins, binding and repressing the expression of oncogenes (Fertey et al., 2010). This suggests that CHD6 plays a role in gene suppression and is important in the response to viral infection.
Entity Ataxia
Note Mutations in CHD6 that affect functional subunits are linked to the development of an ataxic phenotype. The deletion of the ATPase region of CHD6 in a mouse model resulted in deficiencies in coordinated movement, which did not progress over time (Lathrop et al., 2010). Additionally, a recent study utilizing genome wide analysis of genes associate with coordination defects in ADHD identified CHD6 as one of the most relevant target genes (Fliers et al., 2012).


CHD6 chromatin remodeler is a negative modulator of influenza virus replication that relocates to inactive chromatin upon infection.
Alfonso R, Lutz T, Rodriguez A, Chavez JP, Rodriguez P, Gutierrez S, Nieto A.
Cell Microbiol. 2011 Dec;13(12):1894-906. doi: 10.1111/j.1462-5822.2011.01679.x. Epub 2011 Sep 30.
PMID 21899694
CHD6, a cellular repressor of influenza virus replication, is degraded in human alveolar epithelial cells and mice lungs during infection.
Alfonso R, Rodriguez A, Rodriguez P, Lutz T, Nieto A.
J Virol. 2013 Apr;87(8):4534-44. doi: 10.1128/JVI.00554-12. Epub 2013 Feb 13.
PMID 23408615
Integrated analysis of copy number variation and genome-wide expression profiling in colorectal cancer tissues.
Ali Hassan NZ, Mokhtar NM, Kok Sin T, Mohamed Rose I, Sagap I, Harun R, Jamal R.
PLoS One. 2014 Apr 2;9(4):e92553. doi: 10.1371/journal.pone.0092553. eCollection 2014.
PMID 24694993
How many remodelers does it take to make a brain? Diverse and cooperative roles of ATP-dependent chromatin-remodeling complexes in development.
Brown E, Malakar S, Krebs JE.
Biochem Cell Biol. 2007 Aug;85(4):444-62. (REVIEW)
PMID 17713580
A novel translocation (6;20)(q13;q12) in acute myeloid leukemia likely results in LMBRD1-CHD6 fusion.
Douet-Guilbert N, De Braekeleer E, Tous C, Gueganic N, Basinko A, Le Bris MJ, Morel F, De Braekeleer M.
Leuk Lymphoma. 2014 Jul 15:1-2. [Epub ahead of print]
PMID 24844365
Interaction of the papillomavirus E8--E2C protein with the cellular CHD6 protein contributes to transcriptional repression.
Fertey J, Ammermann I, Winkler M, Stoger R, Iftner T, Stubenrauch F.
J Virol. 2010 Sep;84(18):9505-15. doi: 10.1128/JVI.00678-10. Epub 2010 Jul 14.
PMID 20631145
Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function.
Fliers EA, Vasquez AA, Poelmans G, Rommelse N, Altink M, Buschgens C, Asherson P, Banaschewski T, Ebstein R, Gill M, Miranda A, Mulas F, Oades RD, Roeyers H, Rothenberger A, Sergeant J, Sonuga-Barke E, Steinhausen HC, Faraone SV, Buitelaar JK, Franke B.
World J Biol Psychiatry. 2012 Mar;13(3):211-22. doi: 10.3109/15622975.2011.560279. Epub 2011 Apr 7.
PMID 21473668
Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder.
Gui Y, Guo G, Huang Y, Hu X, Tang A, Gao S, Wu R, Chen C, Li X, Zhou L, He M, Li Z, Sun X, Jia W, Chen J, Yang S, Zhou F, Zhao X, Wan S, Ye R, Liang C, Liu Z, Huang P, Liu C, Jiang H, Wang Y, Zheng H, Sun L, Liu X, Jiang Z, Feng D, Chen J, Wu S, Zou J, Zhang Z, Yang R, Zhao J, Xu C, Yin W, Guan Z, Ye J, Zhang H, Li J, Kristiansen K, Nickerson ML, Theodorescu D, Li Y, Zhang X, Li S, Wang J, Yang H, Wang J, Cai Z.
Nat Genet. 2011 Aug 7;43(9):875-8. doi: 10.1038/ng.907.
PMID 21822268
Characterization of chromosome arm 20q abnormalities in myeloid malignancies using genome-wide single nucleotide polymorphism array analysis.
Huh J, Tiu RV, Gondek LP, O'Keefe CL, Jasek M, Makishima H, Jankowska AM, Jiang Y, Verma A, Theil KS, McDevitt MA, Maciejewski JP.
Genes Chromosomes Cancer. 2010 Apr;49(4):390-9. doi: 10.1002/gcc.20748.
PMID 20095039
Deletion of the Chd6 exon 12 affects motor coordination.
Lathrop MJ, Chakrabarti L, Eng J, Rhodes CH, Lutz T, Nieto A, Liggitt HD, Warner S, Fields J, Stoger R, Fiering S.
Mamm Genome. 2010 Apr;21(3-4):130-42. doi: 10.1007/s00335-010-9248-8. Epub 2010 Jan 29.
PMID 20111866
CHD6 is a DNA-dependent ATPase and localizes at nuclear sites of mRNA synthesis.
Lutz T, Stoger R, Nieto A.
FEBS Lett. 2006 Oct 30;580(25):5851-7. Epub 2006 Oct 2.
PMID 17027977
The Chd family of chromatin remodelers.
Marfella CG, Imbalzano AN.
Mutat Res. 2007 May 1;618(1-2):30-40. Epub 2007 Jan 21. (REVIEW)
PMID 17350655
Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer.
Mouradov D, Sloggett C, Jorissen RN, Love CG, Li S, Burgess AW, Arango D, Strausberg RL, Buchanan D, Wormald S, O'Connor L, Wilding JL, Bicknell D, Tomlinson IP, Bodmer WF, Mariadason JM, Sieber OM.
Cancer Res. 2014 Jun 15;74(12):3238-47. doi: 10.1158/0008-5472.CAN-14-0013. Epub 2014 Apr 22.
PMID 24755471
The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation.
Nioi P, Nguyen T, Sherratt PJ, Pickett CB.
Mol Cell Biol. 2005 Dec;25(24):10895-906.
PMID 16314513
Isolated deletion of the long arm of chromosome 20 [del(20q12)] in myelodysplastic syndrome: a case report and literature review.
Padhi S, Varghese RG, Phansalkar MD, Sarangi R.
Singapore Med J. 2013 Sep;54(9):e185-9. (REVIEW)
PMID 24068064
CHD5 defines a new subfamily of chromodomain-SWI2/SNF2-like helicases.
Schuster EF, Stoger R.
Mamm Genome. 2002 Feb;13(2):117-9.
PMID 11889561
CHD chromatin remodelling enzymes and the DNA damage response.
Stanley FK, Moore S, Goodarzi AA.
Mutat Res. 2013 Oct;750(1-2):31-44. doi: 10.1016/j.mrfmmm.2013.07.008. Epub 2013 Aug 14. (REVIEW)
PMID 23954449
Identification of differentially transcribed genes in human lymphoblastoid cells irradiated with 0.5 Gy of gamma-ray and the involvement of low dose radiation inducible CHD6 gene in cell proliferation and radiosensitivity.
Wang HP, Long XH, Sun ZZ, Rigaud O, Xu QZ, Huang YC, Sui JL, Bai B, Zhou PK.
Int J Radiat Biol. 2006 Mar;82(3):181-90.
PMID 16638715
Characterization of a de novo balanced t(4;20)(q33;q12) translocation in a patient with mental retardation.
Yamada K, Fukushi D, Ono T, Kondo Y, Kimura R, Nomura N, Kosaki KJ, Yamada Y, Mizuno S, Wakamatsu N.
Am J Med Genet A. 2010 Dec;152A(12):3057-67. doi: 10.1002/ajmg.a.33174.
PMID 21086493


This paper should be referenced as such :
Melissa Lathrop, C Harker Rhodes, Steve Fiering
CHD6 (chromodomain helicase DNA binding protein 6)
Atlas Genet Cytogenet Oncol Haematol. 2015;19(6):379-382.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(6;20)(q13;q12) LMBRD1::CHD6

External links

HGNC (Hugo)CHD6   19057
Entrez_Gene (NCBI)CHD6    chromodomain helicase DNA binding protein 6
AliasesCHD-6; CHD5; RIGB
GeneCards (Weizmann)CHD6
Ensembl hg19 (Hinxton)ENSG00000124177 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000124177 [Gene_View]  ENSG00000124177 [Sequence]  chr20:41402083-41618377 [Contig_View]  CHD6 [Vega]
ICGC DataPortalENSG00000124177
TCGA cBioPortalCHD6
AceView (NCBI)CHD6
Genatlas (Paris)CHD6
SOURCE (Princeton)CHD6
Genetics Home Reference (NIH)CHD6
Genomic and cartography
GoldenPath hg38 (UCSC)CHD6  -     chr20:41402083-41618377 -  20q12   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CHD6  -     20q12   [Description]    (hg19-Feb_2009)
GoldenPathCHD6 - 20q12 [CytoView hg19]  CHD6 - 20q12 [CytoView hg38]
Genome Data Viewer NCBICHD6 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB037756 AF525085 AK026022 AK091551 AK098144
RefSeq transcript (Entrez)NM_032221
Consensus coding sequences : CCDS (NCBI)CHD6
Gene ExpressionCHD6 [ NCBI-GEO ]   CHD6 [ EBI - ARRAY_EXPRESS ]   CHD6 [ SEEK ]   CHD6 [ MEM ]
Gene Expression Viewer (FireBrowse)CHD6 [ Firebrowse - Broad ]
GenevisibleExpression of CHD6 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)84181
GTEX Portal (Tissue expression)CHD6
Human Protein AtlasENSG00000124177-CHD6 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)CHD6
Human Protein Atlas [tissue]ENSG00000124177-CHD6 [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed41 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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