CHD1

Chr 5AD

chromodomain helicase DNA binding protein 1

Also known as: CHD-1, PILBOS

NCBI Gene: 1105 ENSG00000153922 UniProt: O14646 OMIM: 602118

The CHD1 protein functions as a chromatin remodeler that uses its helicase/ATPase domains to alter chromatin structure and regulate gene expression by modifying access of transcriptional machinery to DNA. Loss-of-function mutations cause Pilarowski-Bjornsson syndrome through an autosomal dominant inheritance pattern. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the likely pathogenic mechanism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Pilarowski-Bjornsson syndromeMIM #617682

Clinical highlights

Gene–disease validity (ClinGen)

Limited · complex neurodevelopmental disorder · AD · ClinGen 2024

not for standalone diagnostic reporting

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.16

LOEUF· LoF intol.

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.16LOEUF

pLI 1.000

Z-score 8.28

OE 0.09 (0.06–0.16)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

4.21Z-score

OE missense 0.59 (0.55–0.64)

507 obs / 852.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.09 (0.06–0.16)

0≤0.351.4

Missense OE?0.59 (0.55–0.64)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 9 / 96.9Missense obs/exp: 507 / 852.9Syn Z: 0.53

Background carrier burden — how many people carry a rare variant somewhere in CHD1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 60

1,561 rare PASS variants

Rare truncating (LoF)

1 in 2,800

95 rare PASS variants

Rare synonymous (reference)

1 in 58

729 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHD1. 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 61	1 in 3,200
South Asian	~43k	1 in 47	1 in 1,600
Remaining (unassigned)	~30k	1 in 54	1 in 1,900
European (Finnish)	~27k	1 in 250	1 in 2,700
Admixed American	~22k	1 in 52	1 in 1,600
African / African American	~21k	1 in 54	≈ 1 in 5,300
East Asian	~20k	1 in 41	1 in 1,100
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 100	≈ 1 in 670

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 19 of 35 coding exons well covered in gnomAD exomes; exon 13 poorly covered; exons 2, 3, 5, 9, 10 and 10 more marginal. Genomes: 34 of 35 (exon 21 below).? see exons ↓