CHD1

chromodomain helicase DNA binding protein 1

Basic information

Region (hg38): 5:98853985-98929007

Links

ENSG00000153922 ∙ NCBI:1105 ∙ OMIM:602118 ∙ HGNC:1915 ∙ Uniprot:O14646 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Pilarowski-Bjornsson syndrome (Limited), mode of inheritance: AD
• Pilarowski-Bjornsson syndrome (Supportive), mode of inheritance: AD
• Pilarowski-Bjornsson syndrome (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pilarowski-Bjornsson 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	28866611

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHD1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHD1 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				24		24
missense		2	144	13	5	164
nonsense			8			8
start loss						0
frameshift		2	3			5
inframe indel				1	1	2
splice donor/acceptor (+/-2bp)						0
splice region			6	1		7
non coding		1	1		2	4
Total	0	5	156	38	8

Variants in CHD1

This is a list of pathogenic ClinVar variants found in the CHD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-98856390-C-T		Pilarowski-Bjornsson syndrome	Uncertain significance (Jul 26, 2022)
5-98856391-G-A		not specified	Uncertain significance (Sep 21, 2023)
5-98856408-T-C		not specified	Uncertain significance (Mar 24, 2023)
5-98856411-G-A			Uncertain significance (Mar 01, 2023)
5-98856460-AAGG-A			Benign (Sep 01, 2020)
5-98856462-G-A		not specified	Uncertain significance (Feb 07, 2023)
5-98856471-T-C		not specified	Uncertain significance (Jul 09, 2021)
5-98856487-T-C		not specified	Uncertain significance (Aug 12, 2022)
5-98856537-C-G		Pilarowski-Bjornsson syndrome	Uncertain significance (Aug 25, 2023)
5-98856555-T-C		not specified	Uncertain significance (Dec 22, 2023)
5-98856555-T-G			Likely benign (Jun 01, 2023)
5-98856556-T-C		See cases	Uncertain significance (Oct 30, 2020)
5-98856564-G-A		CHD1-related disorder	Benign (Jan 01, 2024)
5-98856582-C-T		not specified	Uncertain significance (May 03, 2023)
5-98856600-C-T		not specified	Uncertain significance (Apr 25, 2022)
5-98856619-G-C		Pilarowski-Bjornsson syndrome	Uncertain significance (Dec 12, 2018)
5-98856627-G-C		Pilarowski-Bjornsson syndrome	Uncertain significance (Aug 17, 2020)
5-98856633-G-A			Uncertain significance (Mar 08, 2022)
5-98856658-A-G		CHD1-related disorder	Benign (Dec 31, 2019)
5-98856659-A-G		CHD1-related disorder	Likely benign (Jul 01, 2022)
5-98856663-G-A		not specified	Uncertain significance (Jul 23, 2024)
5-98856663-G-C		Pilarowski-Bjornsson syndrome	Uncertain significance (Sep 19, 2020)
5-98856721-A-G		Pilarowski-Bjornsson syndrome	Uncertain significance (Oct 26, 2020)
5-98858207-T-C		Pilarowski-Bjornsson syndrome	Uncertain significance (Aug 03, 2023)
5-98858214-G-A		Pilarowski-Bjornsson syndrome	Uncertain significance (Dec 24, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHD1	protein_coding	protein_coding	ENST00000284049	35	71333

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	8.98e-10	125728	0	17	125745	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.21	507	853	0.594	0.0000430	11327
Missense in Polyphen		48	255.07	0.18818		3227
Synonymous	0.531	277	288	0.960	0.0000142	2976
Loss of Function	8.28	9	96.9	0.0928	0.00000512	1289

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000470	0.0000462
European (Non-Finnish)	0.000107	0.000105
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (PubMed:18042460, PubMed:28866611). Required for maintaining open chromatin and pluripotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:P40201, ECO:0000269|PubMed:18042460, ECO:0000269|PubMed:28866611}.
• Disease: DISEASE: Pilarowski-Bjornsson syndrome (PILBOS) [MIM:617682]: An autosomal dominant disorder characterized by developmental delay, speech apraxia, intellectual disability, autism, and facial dysmorphic features. Some patients may have seizures. {ECO:0000269|PubMed:28866611}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase (Consensus)

Recessive Scores

• pRec: 0.173

Intolerance Scores

• loftool: 0.0234
• rvis_EVS: -0.81
• rvis_percentile_EVS: 12.05

Haploinsufficiency Scores

• pHI: 0.883
• hipred: Y
• hipred_score: 0.853
• ghis: 0.571

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.592

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chd1
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; growth/size/body region phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); craniofacial phenotype; cellular phenotype

Gene ontology

• Biological process: chromatin remodeling;regulation of transcription by RNA polymerase II;covalent chromatin modification;DNA duplex unwinding;positive regulation by host of viral transcription
• Cellular component: fibrillar center;nucleus;nucleoplasm;cytoplasm
• Molecular function: DNA binding;ATP-dependent DNA helicase activity;protein binding;ATP binding;methylated histone binding