CHAF1A
protein-codingchromatin assembly factor 1 subunit A
Gene summary
Chromatin assembly factor I (CAF1) is a nuclear complex consisting of p50, p60 (CHAF1B; MIM 601245), and p150 (CHAF1A) subunits that assembles histone octamers onto replicating DNA in vitro (Kaufman et al., 1995 [PubMed 7600578]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~42.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: LiferaOmics
Genetic evidence – Published: (AR assessment): No published cases with confirmed autosomal recessive inheritance Published Genetic Evidence= 0 Genetic evidence – Our cases: Family 1: One Proband = 0.5 (AR predicted null = 1.5, −0.5 for consanguinity, −0.5) Family total = 1.0; segregation = 0; case-control = 0 Family 2: One proband homozygous, nonsense, predicted null); consanguinity Family total = 1.0; segregation = 0; case-control = 0 Our cases contribution = 2.0 / 12 Total genetic evidence (published + current) = 2.0 / 12 Experimental evidence =0 / 6 Overall score (with current cases) = 2/18
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CHAF1A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005483.3. 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 | 4 | 1 | 5 | |||
| missense | 142 | 10 | 152 | |||
| nonsense | 1 | 1 | 2 | 4 | ||
| start loss | 0 | |||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 2 | 5 | |||
| Total | 1 | 7 | 150 | 10 | 1 | 169 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005474.2 | 15 | MANE Select | |
| Ensembl | ENSP00000301280.4 | 15 | MANE Select | |
| Ensembl | ENSP00000466888.1 | 2 | Standard | |
| Ensembl | ENSP00000465142.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- Nanoparticle triggered autophagic cell death
- 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
- identical protein binding
- unfolded protein binding
- chromo shadow domain binding
Cellular Component
- nuclear chromatin
- nucleus
- protein-containing complex
- CAF-1 complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000301280
- Coding exons
- 15
- Length
- 42357
- Individuals with no LoFs
- 125743
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125747
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.85 | 458 | 584 | 0.785 | 0.0000373 | 6282 |
| Missense (PolyPhen) | 94 | 166.82 | 0.56347 | 1743 | ||
| Synonymous | -0.909 | 269 | 251 | 1.07 | 0.0000180 | 1839 |
| Loss of Function | 5.72 | 1 | 40.1 | 0.0249 | 0.00000189 | 509 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Core component of the CAF-1 complex, a complex 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. CHAF1A binds to histones H3 and H4. It may play a role in heterochromatin maintenance in proliferating cells by bringing newly synthesized cbx proteins to heterochromatic DNA replication foci (By similarity). {ECO:0000250, ECO:0000269|PubMed:15327775}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- LoFtool
- 0.126
- RVIS EVS
- 0.32
- RVIS percentile EVS
- 72.85
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.972
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |