CHD4
Chromodomain-helicase-DNA-binding protein 4
Also known as: CHD4_HUMAN, Mi-2b, Mi2-BETA
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q14839
- Gene
- CHD4
- Ensembl
- ENSG00000111642
- Chromosome
- 12
- Canonical length
- 1912 aa
- Protein class
- Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm
OverviewNCBI Gene
The product of this gene belongs to the SNF2/RAD54 helicase family. It represents the main component of the nucleosome remodeling and deacetylase complex and plays an important role in epigenetic transcriptional repression. Patients with dermatomyositis develop antibodies against this protein. Somatic mutations in this gene are associated with serous endometrial tumors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]
Canonical amino-acid sequenceUniProt
1912 residues, UniProt reviewed canonical sequence.
>Q14839|CHD4
1 MASGLGSPSP CSAGSEEEDM DALLNNSLPP PHPENEEDPE EDLSETETPK LKKKKKPKKP
61 RDPKIPKSKR QKKERMLLCR QLGDSSGEGP EFVEEEEEVA LRSDSEGSDY TPGKKKKKKL
121 GPKKEKKSKS KRKEEEEEED DDDDSKEPKS SAQLLEDWGM EDIDHVFSEE DYRTLTNYKA
181 FSQFVRPLIA AKNPKIAVSK MMMVLGAKWR EFSTNNPFKG SSGASVAAAA AAAVAVVESM
241 VTATEVAPPP PPVEVPIRKA KTKEGKGPNA RRKPKGSPRV PDAKKPKPKK VAPLKIKLGG
301 FGSKRKRSSS EDDDLDVESD FDDASINSYS VSDGSTSRSS RSRKKLRTTK KKKKGEEEVT
361 AVDGYETDHQ DYCEVCQQGG EIILCDTCPR AYHMVCLDPD MEKAPEGKWS CPHCEKEGIQ
421 WEAKEDNSEG EEILEEVGGD LEEEDDHHME FCRVCKDGGE LLCCDTCPSS YHIHCLNPPL
481 PEIPNGEWLC PRCTCPALKG KVQKILIWKW GQPPSPTPVP RPPDADPNTP SPKPLEGRPE
541 RQFFVKWQGM SYWHCSWVSE LQLELHCQVM FRNYQRKNDM DEPPSGDFGG DEEKSRKRKN
601 KDPKFAEMEE RFYRYGIKPE WMMIHRILNH SVDKKGHVHY LIKWRDLPYD QASWESEDVE
661 IQDYDLFKQS YWNHRELMRG EEGRPGKKLK KVKLRKLERP PETPTVDPTV KYERQPEYLD
721 ATGGTLHPYQ MEGLNWLRFS WAQGTDTILA DEMGLGKTVQ TAVFLYSLYK EGHSKGPFLV
781 SAPLSTIINW EREFEMWAPD MYVVTYVGDK DSRAIIRENE FSFEDNAIRG GKKASRMKKE
841 ASVKFHVLLT SYELITIDMA ILGSIDWACL IVDEAHRLKN NQSKFFRVLN GYSLQHKLLL
901 TGTPLQNNLE ELFHLLNFLT PERFHNLEGF LEEFADIAKE DQIKKLHDML GPHMLRRLKA
961 DVFKNMPSKT ELIVRVELSP MQKKYYKYIL TRNFEALNAR GGGNQVSLLN VVMDLKKCCN
1021 HPYLFPVAAM EAPKMPNGMY DGSALIRASG KLLLLQKMLK NLKEGGHRVL IFSQMTKMLD
1081 LLEDFLEHEG YKYERIDGGI TGNMRQEAID RFNAPGAQQF CFLLSTRAGG LGINLATADT
1141 VIIYDSDWNP HNDIQAFSRA HRIGQNKKVM IYRFVTRASV EERITQVAKK KMMLTHLVVR
1201 PGLGSKTGSM SKQELDDILK FGTEELFKDE ATDGGGDNKE GEDSSVIHYD DKAIERLLDR
1261 NQDETEDTEL QGMNEYLSSF KVAQYVVREE EMGEEEEVER EIIKQEESVD PDYWEKLLRH
1321 HYEQQQEDLA RNLGKGKRIR KQVNYNDGSQ EDRDWQDDQS DNQSDYSVAS EEGDEDFDER
1381 SEAPRRPSRK GLRNDKDKPL PPLLARVGGN IEVLGFNARQ RKAFLNAIMR YGMPPQDAFT
1441 TQWLVRDLRG KSEKEFKAYV SLFMRHLCEP GADGAETFAD GVPREGLSRQ HVLTRIGVMS
1501 LIRKKVQEFE HVNGRWSMPE LAEVEENKKM SQPGSPSPKT PTPSTPGDTQ PNTPAPVPPA
1561 EDGIKIEENS LKEEESIEGE KEVKSTAPET AIECTQAPAP ASEDEKVVVE PPEGEEKVEK
1621 AEVKERTEEP METEPKGAAD VEKVEEKSAI DLTPIVVEDK EEKKEEEEKK EVMLQNGETP
1681 KDLNDEKQKK NIKQRFMFNI ADGGFTELHS LWQNEERAAT VTKKTYEIWH RRHDYWLLAG
1741 IINHGYARWQ DIQNDPRYAI LNEPFKGEMN RGNFLEIKNK FLARRFKLLE QALVIEEQLR
1801 RAAYLNMSED PSHPSMALNT RFAEVECLAE SHQHLSKESM AGNKPANAVL HKVLKQLEEL
1861 LSDMKADVTR LPATIARIPP VAVRLQMSER NILSRLANRA PEPTPQQVAQ QQLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CHD4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.42
- Highest tissue expression
- 85 nTPM
Expression across tissuesHPA
Tissue
- thymus: 85 nTPM
- parathyroid gland: 55 nTPM
- tonsil: 53 nTPM
- thyroid gland: 51 nTPM
- smooth muscle: 47 nTPM
- skeletal muscle: 45 nTPM
Single-cell type
- astrocytes: 83 nCPM
- oligodendrocytes: 78 nCPM
- bergmann glia: 75 nCPM
- ependymal cells: 70 nCPM
- choroid plexus epithelial cells: 64 nCPM
- microglia: 63 nCPM
Immune cell
- T-reg: 16 nTPM
- plasmacytoid DC: 15 nTPM
- basophil: 12 nTPM
- NK-cell: 12 nTPM
- naive B-cell: 11 nTPM
- neutrophil: 11 nTPM
Brain region
- basal ganglia: 79 nTPM
- thalamus: 76 nTPM
- midbrain: 76 nTPM
- pons: 75 nTPM
- medulla oblongata: 74 nTPM
- white matter: 71 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CHD4.
Disease | AllUniProt
Conditions CHD4 is implicated in, by any mechanism.
- Sifrim-Hitz-Weiss syndrome (SIHIWES) MIM:617159
Disease | GeneticClinVar
72 pathogenic / likely-pathogenic of 829 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Sifrim-Hitz-Weiss syndrome
- Moyamoya angiopathy with developmental delay
- CHD4-related disorder
- Inborn genetic diseases
- Uterine corpus endometrial carcinoma
Disease | AutoantibodyPubMed
Conditions in which antibodies against CHD4 are reported. Each links to that disease's full target list.
ReferencesPubMed · IEDB
Publications for CHD4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
121 publications
- A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups.
1991 · Medicine (Baltimore) · RCR 27.5 · 789 citations - Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients.
2019 · J Autoimmun · RCR 13.6 · 238 citations - Autoantibody profiles in the sera of European patients with myositis.
2001 · Ann Rheum Dis · RCR 8.2 · 305 citations - Predictors of clinical improvement in rituximab-treated refractory adult and juvenile dermatomyositis and adult polymyositis.
2014 · Arthritis Rheumatol · RCR 7.3 · 199 citations - Cutaneous Manifestations in Dermatomyositis: Key Clinical and Serological Features-a Comprehensive Review.
2016 · Clin Rev Allergy Immunol · RCR 5.6 · 109 citations
Show 20 more of 121 total
- The association between Mi-2 antibodies and dermatomyositis.
1985 · Arthritis Rheum · RCR 5.4 · 203 citations - Myositis-specific autoantibodies recognising Mi2 also target the AIRE protein at a shared PHD zinc finger.
2026 · Ann Rheum Dis · RCR 5 · 5 citations - Comparison of clinical features between patients with anti-synthetase syndrome and dermatomyositis: results from the MYONET registry.
2024 · Rheumatology (Oxford) · RCR 5 · 19 citations - Transcriptional derepression of CHD4/NuRD-regulated genes in the muscle of patients with dermatomyositis and anti-Mi2 autoantibodies.
2023 · Ann Rheum Dis · RCR 4.3 · 35 citations - Pathogenic mechanisms of disease in idiopathic inflammatory myopathies: autoantibodies as clues.
2024 · Front Immunol · RCR 3.9 · 17 citations - The Type I Interferon Signature Reflects Multiple Phenotypic and Activity Measures in Dermatomyositis.
2023 · Arthritis Rheumatol · RCR 3.8 · 29 citations - Myositis autoantibodies and clinical phenotypes.
2014 · Auto Immun Highlights · RCR 3.8 · 95 citations - Muscle Biopsy Findings in Combination With Myositis-Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis.
2016 · Arthritis Rheumatol · RCR 3.7 · 80 citations - Association of Dermatomyositis Sine Dermatitis With Anti-Nuclear Matrix Protein 2 Autoantibodies.
2020 · JAMA Neurol · RCR 3.4 · 51 citations - Global surface ultraviolet radiation intensity may modulate the clinical and immunologic expression of autoimmune muscle disease.
2003 · Arthritis Rheum · RCR 3.4 · 119 citations - Enzyme-linked immunosorbent assays for detection of anti-transcriptional intermediary factor-1 gamma and anti-Mi-2 autoantibodies in dermatomyositis.
2016 · J Dermatol Sci · RCR 3.3 · 68 citations - Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women.
2009 · Arthritis Rheum · RCR 3.2 · 101 citations - Clinical characteristics of patients with myositis and autoantibodies to different fragments of the Mi-2 beta antigen.
2006 · Ann Rheum Dis · RCR 3.1 · 109 citations - Myositis-specific and myositis-associated antibodies in a series of eighty-eight Mediterranean patients with idiopathic inflammatory myopathy.
2006 · Arthritis Rheum · RCR 3 · 97 citations - Humoral immunity in polymyositis/dermatomyositis.
1993 · J Invest Dermatol · RCR 2.9 · 84 citations - Anti-Mi-2 antibodies.
2005 · Autoimmunity · RCR 2.8 · 95 citations - Use of a commercial line blot assay as a screening test for autoantibodies in inflammatory myopathies.
2009 · Autoimmun Rev · RCR 2.8 · 95 citations - Anti-Mi-2 antibodies characterize a distinct clinical subset of dermatomyositis with favourable prognosis.
2020 · Eur J Dermatol · RCR 2.7 · 38 citations - The Prevalence of Individual Histopathologic Features Varies according to Autoantibody Status in Muscle Biopsies from Patients with Dermatomyositis.
2015 · J Rheumatol · RCR 2.6 · 62 citations - Pathologic Features of Anti-Mi-2 Dermatomyositis.
2021 · Neurology · RCR 2.6 · 30 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.16
- gnomAD pLI
- 1
- gnomAD missense Z
- 6.34
- DepMap mean gene effect
- -1.08
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- chromatin remodeling
- double-strand break repair via homologous recombination
- negative regulation of DNA-templated transcription
- negative regulation of gene expression
- negative regulation of transcription by RNA polymerase II
- positive regulation of DNA-templated transcription
- regulation of cell fate specification
- regulation of stem cell differentiation
- regulation of synapse assembly
- terminal button organization
Molecular functions
- ATP binding
- ATP hydrolysis activity
- ATP-dependent chromatin remodeler activity
- chromatin binding
- DNA binding
- histone binding
- histone deacetylase binding
- RNA polymerase II-specific DNA-binding transcription factor binding
- transcription coregulator binding
- transcription corepressor activity
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- SNF2, N-terminal domain
- Chromo/chromo shadow domain
- Helicase, C-terminal domain-like
- Zinc finger, PHD-type
- DNA/RNA helicase, ATP-dependent, DEAH-box type, conserved site
- CHD subfamily II, SANT-like domain
- Domain of unknown function DUF1087
- Zinc finger, FYVE/PHD-type
- CHD, C-terminal 2
- CHD, N-terminal
- Zinc finger, RING/FYVE/PHD-type
- Helicase superfamily 1/2, ATP-binding domain
- Chromo-like domain superfamily
- Zinc finger, PHD-type, conserved site
- Zinc finger, PHD-finger
- Chromo domain
- P-loop containing nucleoside triphosphate hydrolase
- SNF2-like, N-terminal domain superfamily
- SNF2/RAD5-like, C-terminal helicase domain
- SNF2-related domain
- Helicase conserved C-terminal domain
- Chromo (CHRromatin Organisation MOdifier) domain
- PHD-finger
- CHD subfamily II, SANT-like domain
- CHD subfamily II, DUF1087
- CHDNT (NUC034) domain
- CHDCT2 (NUC038) domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CHD4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CHD4 as an antibody target. Whether an autoantibody or antibody against CHD4 could matter depends on whether native CHD4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CHD4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Source-annotated serology context
The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.
- Patients with dermatomyositis develop antibodies against this protein.
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