CHD1L

Chr 1

chromodomain helicase DNA binding protein 1 like

Also known as: ALC1, CHDL

NCBI Gene: 9557 ENSG00000131778 UniProt: Q86WJ1 OMIM: 613039

This gene encodes an ATP-dependent chromatin remodeler that recognizes poly-ADP-ribosylated histones at DNA damage sites and catalyzes nucleosome sliding to facilitate DNA repair. Mutations cause autosomal dominant intellectual disability with epilepsy and characteristic dysmorphic features, typically presenting in early childhood. The gene is not highly constrained against loss-of-function variants, and clinical presentations can include developmental delay, seizures, and craniofacial abnormalities.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Limited · congenital anomaly of kidney and urinary tract · AD · ClinGen 2016

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.30

LOEUF

—

Mechanism

📖

GeneReview available — CHD1L

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.30LOEUF

pLI 0.000

Z-score -0.24

OE 1.04 (0.83–1.30)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.58Z-score

OE missense 1.08 (1.00–1.16)

490 obs / 455.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.04 (0.83–1.30)

0≤0.351.4

Missense OE?1.08 (1.00–1.16)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 54 / 52.1Missense obs/exp: 490 / 455.2Syn Z: -0.05

Background carrier burden — how many people carry a rare variant somewhere in CHD1L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 47

1,268 rare PASS variants

Rare truncating (LoF)

1 in 230

296 rare PASS variants

Rare synonymous (reference)

1 in 120

432 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CHD1L; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 60	1 in 300
South Asian	~43k	1 in 44	1 in 160
Remaining (unassigned)	~30k	1 in 41	1 in 160
European (Finnish)	~27k	1 in 120	1 in 340
Admixed American	~22k	1 in 62	1 in 120
African / African American	~21k	1 in 39	1 in 190
East Asian	~20k	1 in 54	1 in 140
Ashkenazi Jewish	~13k	1 in 110	1 in 430
Middle Eastern	~2,884	1 in 42	1 in 170

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 22 of 23 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 23.? see exons ↓