CHD5

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

Basic information

Region (hg38): 1:6101786-6180321

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

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 (91 variants)
• Inborn genetic diseases (57 variants)
• Parenti-mignot neurodevelopmental syndrome (22 variants)
• not specified (6 variants)
• Seizure;Global developmental delay;Intellectual disability (5 variants)
• CHD5-related condition (5 variants)
• Global developmental delay;Intellectual disability (4 variants)
• Global developmental delay (4 variants)
• Neurodevelopmental disorder (4 variants)
• Seizure (3 variants)
• Seizure;Global developmental delay (2 variants)
• Harel-Yoon syndrome (1 variants)
• Neurodevelopmental delay (1 variants)
• See cases (1 variants)
• CHD5-related Neurodevelopmental disorder (1 variants)
• CHD5-associated Neurodevelopmental disorder (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	10	16
missense		13	126	3	1	143
nonsense	2	4	2			8
start loss			1			1
frameshift	1	1	1			3
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region		1	5	2	5	13
non coding			3		3	6
Total	3	20	133	9	14

Highest pathogenic variant AF is 0.0000131

Variants in CHD5

This is a list of pathogenic ClinVar variants found in the CHD5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-6105431-C-A			Benign (Sep 01, 2022)
1-6106219-C-T		not specified	Uncertain significance (Oct 30, 2023)
1-6106409-C-T			Uncertain significance (Oct 09, 2022)
1-6106422-G-A			Pathogenic (Sep 01, 2022)
1-6106437-T-C		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
1-6106445-G-A		Inborn genetic diseases	Uncertain significance (Jan 19, 2022)
1-6106462-G-T		Inborn genetic diseases	Uncertain significance (Jan 19, 2022)
1-6106487-A-T			Uncertain significance (Apr 28, 2023)
1-6106500-C-G		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
1-6106508-C-G		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
1-6106629-G-A		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
1-6106632-TC-T			Uncertain significance (Jan 01, 2022)
1-6106639-C-T			Uncertain significance (Dec 14, 2023)
1-6106642-G-A		Inborn genetic diseases	Uncertain significance (Oct 20, 2021)
1-6106654-G-A		Inborn genetic diseases	Uncertain significance (May 30, 2023)
1-6106669-G-A			Uncertain significance (Nov 02, 2023)
1-6106691-G-A		Inborn genetic diseases	Likely benign (Nov 17, 2023)
1-6106702-G-C			Uncertain significance (Dec 21, 2022)
1-6106769-C-T			Likely benign (May 30, 2018)
1-6109928-C-T			Benign (Jul 31, 2018)
1-6109946-G-A			Likely benign (Jun 08, 2018)
1-6110468-C-G			Uncertain significance (Apr 21, 2022)
1-6110471-T-C		Neurodevelopmental disorder	Uncertain significance (Mar 31, 2022)
1-6110524-T-C			Uncertain significance (May 02, 2023)
1-6111775-G-A		Neurodevelopmental disorder	Uncertain significance (Jan 01, 2019)

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