GeneBe

CHD3

protein-coding

chromodomain helicase DNA binding protein 3, the group of Small nucleolar RNA protein coding host genes|PHD finger proteins|NuRD complex subunits

Gene summary

This gene encodes a member of the CHD family of proteins which are characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. This protein is one of the components of a histone deacetylase complex referred to as the Mi-2/NuRD complex which participates in the remodeling of chromatin by deacetylating histones. Chromatin remodeling is essential for many processes including transcription. Autoantibodies against this protein are found in a subset of patients with dermatomyositis. Three alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001005273.3

Inheritance

AD, AR

ClinVar variants

P:149U:540B:140

Top phenotype

Snijders Blok-Campeau syndrome

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr17:7,884,796-7,912,760

External References & Databases

Ensembl (ENSG00000170004)NCBI Gene (1107)OMIM (602120)HGNC:1918GenCCUniProt (Q12873)AlphaFoldClinVar (CHD3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~28.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Snijders Blok-Campeau syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0032600

Submitter: Illumina

Snijders Blok-Campeau syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032600

Submitter: Ambry Genetics

Snijders Blok-Campeau syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0032600

Submitter: ClinGen

*CHD3* was first reported in relation to autosomal dominant Snijders Blok-Campeau syndrome in 2018 (Snijders Blok et al., PMID: 30397230). Snijders Blok-Campeau syndrome is characterized by global developmental delay, delayed speech, intellectual disability, distinctive facial features including macrocephaly, prominent forehead and hypertelorism, hypotonia, and joint laxity. The severity of neurological deficits and non-neurological features is variable. Nineteen variants, including missense, nonsense, and frameshift variants, reported in 19 probands in 4 publications (PMIDs: 30397230, 32483341, 33571694, 34535214) are included in this curation. Of note, c.2953C>T (p.Arg985Trp) is a recurrent variant reported in 6 unrelated probands (PMID: 30397230). More evidence is available in the literature, but the maximum score for genetic evidence has been reached. This gene-disease relationship is also supported by protein interaction and functional assays (PMIDs: 26867680, 31949314). In summary, there is definitive evidence supporting the relationship between *CHD3* and autosomal dominant Snijders Blok-Campeau syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on March 2 2022 (SOP version 8).

Snijders Blok-Campeau syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032600

Submitter: Ambry Genetics

Snijders Blok-Campeau syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032600

Submitter: Labcorp Genetics (formerly Invitae)

Snijders Blok-Campeau syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032600

Submitter: G2P

Clinical Genomic Database (CGD)

Snijders Blok-Campeau syndromeAD

Manifestation: Craniofacial; Cardiovascular; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Cardiovascular

Rationale: Among other features, the condition can include congenital cardiac anomalies, and awareness may enable early identification and management

Refs: 29463886; 30397230; 32483341Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHD3 variants in ClinVar

17 Conditions Cataloged
not providedTotal: 385
Inborn genetic diseasesTotal: 246
Snijders Blok-Campeau syndromeTotal: 225
CHD3-related disorderTotal: 97
not specifiedTotal: 71
Intellectual disabilityTotal: 25
CHD3-related disordersTotal: 9
See casesTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001005273.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
6
clinvar
65
clinvar
8
clinvar
 80
missense
11
clinvar
77
clinvar
510
clinvar
67
clinvar
 665
nonsense
15
clinvar
10
clinvar
5
clinvar
 30
start loss
0
frameshift
14
clinvar
11
clinvar
7
clinvar
 32
splice donor/acceptor (+/-2bp)
2
clinvar
8
clinvar
12
clinvar
 22
Total421075401328829

Highest pathogenic variant AF is 0.000025509404

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001005273.3RefSeqNP_001005273.140MANE Select
ENST00000330494.12EnsemblENSP00000332628.740MANE Select
NM_001005271.3RefSeqNP_001005271.240Standard
NM_001437504.1RefSeqNP_001424433.140Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
chd3Danio rerio

Structure: head

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
  • Positive epigenetic regulation of rRNA expression
  • Signal Transduction
  • Epigenetic regulation of gene expression
  • Gene expression (Transcription)

Biological Process

  • chromatin assembly or disassembly
  • regulation of transcription, DNA-templated
  • regulation of transcription by RNA polymerase II
  • spindle organization
  • centrosome cycle

Molecular Function

  • DNA binding
  • RNA binding
  • ATP-dependent DNA helicase activity
  • helicase activity
  • histone deacetylase activity

Cellular Component

  • nucleus
  • nucleoplasm
  • nucleolus
  • cytoplasm
  • centrosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000380358
Coding exons
40
Length
27955
Individuals with no LoFs
125727
Homozygous LoFs
0
Heterozygous LoFs
21
Defined
125748
p
0.0000835
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense6.155911.19e+30.4980.000073513412
Missense (PolyPhen)49140.020.349961544
Synonymous0.04034674680.9980.00002953981
Loss of Function9.10101150.08660.000006981267

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000650.000062rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish0.000100.000099rare
East Asian0.000110.00011rare
Finnish00.0absent
European (Non-Finnish)0.000130.00013rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin by deacetylating histones. Required for anchoring centrosomal pericentrin in both interphase and mitosis, for spindle organization and centrosome integrity. {ECO:0000269|PubMed:17626165, ECO:0000269|PubMed:9804427}.;

Recessive Scores

pRec
0.129

Intolerance Scores

LoFtool
0.0137
RVIS EVS
-2.48
RVIS percentile EVS
0.97

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.859

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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