CHAF1B

protein-coding

chromatin assembly factor 1 subunit B, the group of WD repeat domain containing

Gene summary

Chromatin assembly factor I (CAF-I) is required for the assembly of histone octamers onto newly-replicated DNA. CAF-I is composed of three protein subunits, p50, p60, and p150. The protein encoded by this gene corresponds to the p60 subunit and is required for chromatin assembly after replication. The encoded protein is differentially phosphorylated in a cell cycle-dependent manner. In addition, it is normally found in the nucleus except during mitosis, when it is released into the cytoplasm. This protein is a member of the WD-repeat HIR1 family and may also be involved in DNA repair. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005441.3

Inheritance

ClinVar variants

P:1U:68B:10

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr21:36,385,392-36,419,015

External References & Databases

Ensembl (ENSG00000159259)

Transcript & Mutation Effects

hg38 • Region Span ~33.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disabilityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHAF1B variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 7

Prostate cancerTotal: 1

Global developmental delayTotal: 1

Attention deficit hyperactivity disorderTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005441.3. 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				2 clinvar	1 clinvar	3
missense		1 clinvar	63 clinvar	4 clinvar	3 clinvar	71
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	1	68	6	4	79

Highest pathogenic variant AF is 0.0000032225796

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005441.3	RefSeq	NP_005432.1	13	MANE Select
ENST00000314103.6	Ensembl	ENSP00000315700.4	13	MANE Select
ENST00000878604.1	Ensembl	ENSP00000548663.1	11	Standard
ENST00000878604.2	Ensembl	ENSP00000548663.1	11	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
chaf1b	Danio rerio	Structure: retinal ganglion cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

chaf1b

Danio rerio

Structure: retinal ganglion cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

btg family proteins and cell cycle regulation

Biological Process

DNA replication
DNA repair
nucleosome assembly
DNA replication-dependent nucleosome assembly
cell cycle

Molecular Function

chromatin binding
protein binding
histone binding
unfolded protein binding

Cellular Component

nuclear chromatin
nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314103
Coding exons: 13
Length: 33638
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.82	240	333	0.720	0.0000191	3634
Missense (PolyPhen)		48	109.18	0.43966		1181
Synonymous	0.439	129	136	0.952	0.00000896	1120
Loss of Function	3.77	6	27.2	0.220	0.00000131	321

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000063	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000057	0.000054	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Complex that is thought to mediate chromatin assembly in DNA replication and DNA repair. Assembles histone octamers onto replicating DNA in vitro. CAF-1 performs the first step of the nucleosome assembly process, bringing newly synthesized histones H3 and H4 to replicating DNA; histones H2A/H2B can bind to this chromatin precursor subsequent to DNA replication to complete the histone octamer. {ECO:0000269|PubMed:9813080}.;

Recessive Scores

pRec: 0.0832

Intolerance Scores

LoFtool: 0.333
RVIS EVS: 0.22
RVIS percentile EVS: 68.44

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.964

Gene Damage Prediction

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