CHD1L

protein-coding

chromodomain helicase DNA binding protein 1 like, the group of Macro domain containing

Gene summary

This gene encodes a DNA helicase protein involved in DNA repair. The protein converts ATP to add poly(ADP-ribose) as it regulates chromatin relaxation following DNA damage. Overexpression of this gene has been linked to several types of cancers. [provided by RefSeq, Feb 2017]

MANE transcript

NM_004284.6

Inheritance

—

ClinVar variants

U:169B:39

Top phenotype

CHD1L-related disorder

gnomAD constraint

pLI —, LoF o/e 1.04

Max pathogenic AF

—

Genomic locus

chr1:147,242,654-147,295,765

External References & Databases

Ensembl (ENSG00000131778)

Transcript & Mutation Effects

hg38 • Region Span ~53.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital anomaly of kidney and urinary tractLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0019719

Submitter: ClinGen

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHD1L variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 147

not providedTotal: 49

CHD1L-related disorderTotal: 38

Congenital anomaly of kidney and urinary tractTotal: 3

Short statureTotal: 1

Abnormality of the urinary systemTotal: 1

Decreased total neutrophil countTotal: 1

Hereditary breast ovarian cancer syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004284.6. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	14 clinvar	6 clinvar	23
missense			153 clinvar	13 clinvar	3 clinvar	169
nonsense			4 clinvar	1 clinvar		5
start loss				1 clinvar		1
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			5 clinvar	1 clinvar		6
Total	0	0	169	30	9	208

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 130 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004284.6	RefSeq	NP_004275.4	23	MANE Select
ENST00000369258.8	Ensembl	ENSP00000358262.4	23	MANE Select
NM_001256336.3	RefSeq	NP_001243265.1	21	Standard
NM_001256337.3	RefSeq	NP_001243266.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

DNA Repair
Formation of Incision Complex in GG-NER
Dual Incision in GG-NER
Global Genome Nucleotide Excision Repair (GG-NER)
Nucleotide Excision Repair

Biological Process

DNA repair
nucleotide-excision repair, preincision complex stabilization
nucleotide-excision repair, preincision complex assembly
nucleotide-excision repair, DNA incision, 5'-to lesion
chromatin remodeling

Molecular Function

nucleotide binding
ATP-dependent DNA helicase activity
protein binding
ATP binding
ATPase activity

Cellular Component

nucleus
nucleoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369258
Coding exons: 23
Length: 53153
Individuals with no LoFs: 125051
Homozygous LoFs: 2
Heterozygous LoFs: 695
Defined: 125748
p: 0.00278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.580	490	455	1.08	0.0000234	5808
Missense (PolyPhen)		154	151.5	1.0165		1894
Synonymous	-0.0463	167	166	1.00	0.00000830	1696
Loss of Function	-0.239	54	52.1	1.04	0.00000286	622

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0046	0.0044	notable
Latino/Admixed American	0.0027	0.0027	notable
Ashkenazi Jewish	0.00074	0.00069	rare
East Asian	0.0062	0.0062	notable
Finnish	0.00088	0.00088	rare
European (Non-Finnish)	0.0027	0.0027	notable
South Asian	0.0026	0.0024	notable
Other	0.0023	0.0023	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: DNA helicase which plays a role in chromatin-remodeling following DNA damage. Targeted to sites of DNA damage through interaction with poly(ADP-ribose) and functions to regulate chromatin during DNA repair. Able to catalyze nucleosome sliding in an ATP-dependent manner. Helicase activity is strongly stimulated upon poly(ADP-ribose)-binding. {ECO:0000269|PubMed:18023026, ECO:0000269|PubMed:19661379}.;

Recessive Scores

pRec: 0.127

Intolerance Scores

RVIS EVS: 1.09
RVIS percentile EVS: 91.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.884

Gene Damage Prediction

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