ASF1A

protein-coding

anti-silencing function 1A histone chaperone

Gene summary

This gene encodes a member of the H3/H4 family of histone chaperone proteins and is similar to the anti-silencing function-1 gene in yeast. The protein is a key component of a histone donor complex that functions in nucleosome assembly. It interacts with histones H3 and H4, and functions together with a chromatin assembly factor during DNA replication and repair. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014034.3

Inheritance

—

ClinVar variants

U:21B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr6:118,894,152-118,909,171

External References & Databases

Ensembl (ENSG00000111875)

Transcript & Mutation Effects

hg38 • Region Span ~15.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ASF1A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 15

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014034.3. 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			1 clinvar	1 clinvar		2
missense			19 clinvar			19
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	21	1	0	22

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014034.3	RefSeq	NP_054753.1	4	MANE Select
ENST00000229595.6	Ensembl	ENSP00000229595.5	4	MANE Select
ENST00000877924.1	Ensembl	ENSP00000547983.1	4	Standard
ENST00000877924.2	Ensembl	ENSP00000547983.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Formation of Senescence-Associated Heterochromatin Foci (SAHF)
DNA Damage/Telomere Stress Induced Senescence
Cellular Senescence
Cellular responses to stress
Cellular responses to external stimuli

Biological Process

osteoblast differentiation
DNA repair
nucleosome assembly
DNA replication-dependent nucleosome assembly
DNA replication-independent nucleosome assembly

Molecular Function

chromatin binding
protein binding
histone binding

Cellular Component

nuclear chromatin
nucleus
nucleoplasm
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000229595
Coding exons: 4
Length: 14949
Individuals with no LoFs: 124614
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 124617
p: 0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.39	37	106	0.348	0.00000484	1334
Missense (PolyPhen)		4	34.449	0.11611		441
Synonymous	-0.292	43	40.6	1.06	0.00000203	390
Loss of Function	2.60	1	9.77	0.102	4.78e-7	118

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly. Cooperates with chromatin assembly factor 1 (CAF-1) to promote replication-dependent chromatin assembly and with HIRA to promote replication-independent chromatin assembly. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit. {ECO:0000269|PubMed:10759893, ECO:0000269|PubMed:11897662, ECO:0000269|PubMed:12842904, ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:15621527, ECO:0000269|PubMed:15664198, ECO:0000269|PubMed:16151251}.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.496
RVIS EVS: 0.04
RVIS percentile EVS: 56.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.973

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low