DCAF8

Chr 1AD

DDB1 and CUL4 associated factor 8

Also known as: GAN2, H326, WDR42A

NCBI Gene: 50717ENSG00000132716UniProt: Q5TAQ9

This gene encodes a WD repeat-containing protein that interacts with the Cul4-Ddb1 E3 ligase macromolecular complex. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2009]

Primary Disease Associations & Inheritance

?Giant axonal neuropathy 2, autosomal dominantMIM #610100
AD
125
ClinVar variants
9
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DCAF8
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 82 VUS of 125 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.20LOEUF
pLI 1.000
Z-score 4.85
OE 0.06 (0.03–0.20)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
3.15Z-score
OE missense 0.53 (0.47–0.60)
191 obs / 359.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.06 (0.03–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.53 (0.47–0.60)
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.0.84
0≤1.21.6
LoF obs/exp: 2 / 31.3Missense obs/exp: 191 / 359.2Syn Z: 1.38

ClinVar Variant Classifications

125 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS82
Likely Benign13
Benign4
Conflicting1
7
Pathogenic
2
Likely Pathogenic
82
VUS
13
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
1
1
0
2
VUS
0
73
8
1
82
Likely Benign
0
1
3
9
13
Benign
0
0
3
1
4
Conflicting
—1
Total0752211109

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

View in ClinVar →

Protein Context — Lollipop Plot

DCAF8 · 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

?Giant axonal neuropathy 2, autosomal dominant

MIM #610100

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Loss of DCAF8 impairs hematopoietic stem cell function with cellular senescence via the DOCK11-CDC42 axis.
Xu P et al.·Blood
2025🔓 Open Access
Cisplatin-activated ERβ/DCAF8 positive feedback loop induces chemoresistance in non-small cell lung cancer via PTEN/Akt axis.
Hu Y et al.·Drug Resist Updat
2023
Systematic Profiling of DNMT3A Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor.
Huang YH et al.·Cancer Discov
2022🔓 Open Access
CRL4DCAF8 dependent opposing stability control over the chromatin remodeler LSH orchestrates epigenetic dynamics in ferroptosis.
Huang D et al.·Cell Death Differ
2021Functional
The small molecule PSSM0332 disassociates the CRL4ADCAF8 E3 ligase complex to decrease the ubiquitination of NcoR1 and inhibit the inflammatory response in a mouse sepsis-induced myocardial dysfunction model.
Peng Q et al.·Int J Biol Sci
2020🔓 Open AccessFunctional
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