CHD5

chromodomain helicase DNA binding protein 5, the group of PHD finger proteins|NuRD complex subunits

Basic information

Region (hg38): 1:6101787-6180321

Links

ENSG00000116254

∙ NCBI:26038 ∙ OMIM:610771 ∙ HGNC:16816 ∙ Uniprot:Q8TDI0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

schizophrenia (Limited), mode of inheritance: Unknown
parenti-mignot neurodevelopmental syndrome (Strong), mode of inheritance: AD
parenti-mignot neurodevelopmental syndrome (Strong), mode of inheritance: AD
parenti-mignot neurodevelopmental syndrome (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parenti-Mignot neurodevelopmental syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	33944996

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHD5 gene.

not_provided (182 variants)
Inborn_genetic_diseases (178 variants)
Parenti-mignot_neurodevelopmental_syndrome (58 variants)
CHD5-related_disorder (29 variants)
not_specified (25 variants)
Global_developmental_delay (14 variants)
Seizure (10 variants)
Intellectual_disability (9 variants)
Neurodevelopmental_disorder (4 variants)
See_cases (2 variants)
CHD5-associated_Neurodevelopmental_disorder (1 variants)
Harel-Yoon_syndrome (1 variants)
Neurodevelopmental_delay (1 variants)
CHD5-related_Neurodevelopmental_disorder (1 variants)
Neurodevelopmental_abnormality (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHD5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015557.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	23 clinvar	6 clinvar	31
missense		19 clinvar	340 clinvar	14 clinvar		373
nonsense	3 clinvar	4 clinvar	4 clinvar			11
start loss			1			1
frameshift	4 clinvar	3 clinvar	1 clinvar			8
splice donor/acceptor (+/-2bp)		3 clinvar	1 clinvar			4
Total	7	29	349	37	6

Highest pathogenic variant AF is 0.0000131434

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHD5	protein_coding	protein_coding	ENST00000262450	41	78331

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.64e-10	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.32	668	1.18e+3	0.565	0.0000749	12905
Missense in Polyphen		143	453.16	0.31556		4698
Synonymous	-0.0510	518	517	1.00	0.0000371	3624
Loss of Function	8.44	9	100	0.0898	0.00000515	1178

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000608	0.0000544
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.0000805	0.0000791
Middle Eastern	0.0000608	0.0000544
South Asian	0.0000995	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Chromatin-remodeling protein that binds DNA through histones and regulates gene transcription. May specifically recognize and bind trimethylated 'Lys-27' (H3K27me3) and non- methylated 'Lys-4' of histone H3. Plays a role in the development of the nervous system by activating the expression of genes promoting neuron terminal differentiation. In parallel, it may also positively regulate the trimethylation of histone H3 at 'Lys- 27' thereby specifically repressing genes that promote the differentiation into non-neuronal cell lineages. Tumor suppressor, it regulates the expression of genes involved in cell proliferation and differentiation. Downstream activated genes may include CDKN2A that positively regulates the p53/TP53 pathway, which in turn, prevents cell proliferation. In spermatogenesis, it probably regulates histone hyperacetylation and the replacement of histones by transition proteins in chromatin, a crucial step in the condensation of spermatid chromatin and the production of functional spermatozoa. {ECO:0000269|PubMed:23948251}.;
Disease: DISEASE: Note=Defects in CHD5 may be a cause of the development of cancers from epithelial, neural and hematopoietic origin. CHD5 is one of the missing genes in the del(1p36), a deletion which is extremely common in this type of cancers. A decrease of its expression, results in increased susceptibility of cells to Ras- mediated transformation in vitro and in vivo (PubMed:17289567). {ECO:0000269|PubMed:17289567}.;

Recessive Scores

pRec: 0.116

Intolerance Scores

loftool: 0.0144
rvis_EVS: -3.07
rvis_percentile_EVS: 0.49

Haploinsufficiency Scores

pHI: 0.291
hipred: Y
hipred_score: 0.809
ghis: 0.631

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.256

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Chd5
Phenotype: cellular phenotype; reproductive system phenotype;

Zebrafish Information Network

Gene name: chd5
Affected structure: splanchnocranium
Phenotype tag: abnormal
Phenotype quality: absent

Gene ontology

Biological process: negative regulation of cell population proliferation;cerebral cortex neuron differentiation;spermatogenesis, exchange of chromosomal proteins;histone H4 acetylation;regulation of transcription involved in cell fate commitment;histone H3-K27 trimethylation;positive regulation of signal transduction by p53 class mediator
Cellular component: heterochromatin;nucleus;nucleoplasm;cytosol;membrane;NuRD complex;nuclear speck
Molecular function: DNA binding;helicase activity;ATP binding;metal ion binding;H3K27me3 modified histone binding