Chromodomain-helicase-DNA-binding protein 2 is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''CHD2''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
The
CHD family of proteins is characterized by the presence of
chromo (chromatin organization modifier) domains and
SNF2-related helicase/
ATPase
ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, ATP hydrolase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or ...
domains. CHD genes alter gene expression possibly by modification of
chromatin
Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...
structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. CHD2 catalyzes the assembly of
chromatin
Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...
into periodic arrays; and the
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
region of CHD2, which contains tandem chromodomains, serves an auto-inhibitory role in both the DNA-binding and ATPase activities of CHD2.
Alternatively spliced
Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...
transcript variants encoding distinct
isoforms
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...
have been found for this gene.
Clinical significance
De novo mutation
A de novo mutation (DNM) is any mutation or alteration in the genome of an individual organism (human, animal, plant, microbe, etc.) that was not inherited from its parents. This type of mutation spontaneously occurs during the process of DNA repl ...
s and deletions in this gene have been associated with cases of epileptic encephalopathies.
CHD2 epilepsy is increasingly being identified as a subpopulation of
Lennox-Gastaut Syndrome.
CHD2 myoclonic encephalopathy is a condition characterized by recurrent seizures (epilepsy), abnormal brain function (encephalopathy), and intellectual disability. Epilepsy begins in childhood, typically between ages 6 months and 4 years. Each individual may experience a variety of seizure types, most commonly myoclonic seizures.
Recently, de novo mutations or deletions in CHD2 has been linked to intellectual disability and to autism. Researchers found 27 genes which abolish function of the corresponding protein — in at least two people with autism, and 6 genes are mutated in three or more people with autism. These six genes —
CHD8
Chromodomain-helicase-DNA-binding protein 8 is an enzyme that in humans is encoded by the ''CHD8'' gene.
Function
The gene CHD8 encodes the protein chromodomain helicase DNA binding protein 8, which is a chromatin regulator enzyme that is ess ...
,
DYRK1A
Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the ''DYRK1A'' gene. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or ...
,
ANK2
Ankyrin-2, also known as Ankyrin-B, and Brain ankyrin, is a protein which in humans is encoded by the ''ANK2'' gene. Ankyrin-2 is ubiquitously expressed, but shows high expression in cardiac muscle. Ankyrin-2 plays an essential role in the locali ...
,
GRIN2B
Glutamate MDAreceptor subunit epsilon-2, also known as ''N''-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a protein that in humans is encoded by the ''GRIN2B'' gene.
NMDA receptors
''N''-methyl-D-aspartate (NMDA) receptors are ...
,
DSCAM and CHD2 — are the strongest autism candidates identified so far.
Family support
Syndromes associated with mutations or deletions in CHD2 can be devastating. Families of individuals with CHD2 mutations or deletions can join the CHD2 Support and Research Group on Facebook or find information and support through the non-profit organization Coalition to Cure CHD2.
References
Further reading
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External links
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* {{UCSC gene info, CHD2