ASF1A

Chr 6

anti-silencing function 1A histone chaperone

Also known as: CGI-98, CIA, HSPC146

NCBI Gene: 25842ENSG00000111875UniProt: Q9Y294

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]

44
ClinVar variants
25
Pathogenic / LP
0.81
pLI score
0
Active trials
Clinical Summary— ASF1A
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 18 VUS of 44 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.48LOEUF
pLI 0.805
Z-score 2.60
OE 0.10 (0.04–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.39Z-score
OE missense 0.35 (0.27–0.46)
37 obs / 106.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.10 (0.04–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.35 (0.27–0.46)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 1 / 9.8Missense obs/exp: 37 / 106.4Syn Z: -0.29

ClinVar Variant Classifications

44 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic5
VUS18
Likely Benign1
20
Pathogenic
5
Likely Pathogenic
18
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
5
0
5
VUS
0
15
3
0
18
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total01528144

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ASF1A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1β-mediated AML progression.
Lin HY et al.·Blood
2024
ASF1a inhibition induces p53-dependent growth arrest and senescence of cancer cells.
Wu Y et al.·Cell Death Dis
2019
Histone chaperone ASF1A accelerates chronic myeloid leukemia blast crisis by activating Notch signaling.
Yin X et al.·Cell Death Dis
2022
ASF1A regulates H4(Y72) phosphorylation and promotes autophagy in colon cancer cells via a kinase activity.
Qiu F et al.·Artif Cells Nanomed Biotechnol
2019
HIRA complex deposition of histone H3.3 is driven by histone tetramerization and histone-DNA binding.
Vogt A et al.·J Biol Chem
2024
Placing the HIRA histone chaperone complex in the chromatin landscape.
Pchelintsev NA et al.·Cell Rep
2013
Radionuclide-Labeled Antisilencing Function 1a Inhibitory Peptides for Tumor Identification and Individualized Therapy.
Shi X et al.·ACS Nano
2024
Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex.
Rai TS et al.·Mol Cell Biol
2011Functional
Asf1b, the necessary Asf1 isoform for proliferation, is predictive of outcome in breast cancer.
Corpet A et al.·EMBO J
2011
Cell reprogramming. Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming.
Gonzalez-Muñoz E et al.·Science
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools