DCAF15

Chr 19

DDB1 and CUL4 associated factor 15

NCBI Gene: 90379ENSG00000132017UniProt: Q66K64

Substrate-recognition component of the DCX(DCAF15) complex, a cullin-4-RING E3 ubiquitin-protein ligase complex that mediates ubiquitination and degradation of target proteins (PubMed:16949367, PubMed:31452512). The DCX(DCAF15) complex acts as a regulator of the natural killer (NK) cells effector functions, possibly by mediating ubiquitination and degradation of cohesin subunits SMC1A and SMC3 (PubMed:31452512). May play a role in the activation of antigen-presenting cells (APC) and their interaction with NK cells (PubMed:31452512)

104
ClinVar variants
12
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DCAF15
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 73 VUS of 104 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.27LOEUF
pLI 0.994
Z-score 4.43
OE 0.11 (0.05–0.27)
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.
2.27Z-score
OE missense 0.67 (0.61–0.75)
255 obs / 379.3 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.0.11 (0.05–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.61–0.75)
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.1.11
0≤1.21.6
LoF obs/exp: 3 / 28.5Missense obs/exp: 255 / 379.3Syn Z: -1.05

ClinVar Variant Classifications

104 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS73
Likely Benign3
Benign2
11
Pathogenic
1
Likely Pathogenic
73
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
1
0
1
VUS
0
70
3
0
73
Likely Benign
1
2
0
0
3
Benign
1
0
0
1
2
Total27215190

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

View in ClinVar →

Protein Context — Lollipop Plot

DCAF15 · 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
Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15.
Han T et al.·Science
2017
Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma.
Xu Y et al.·Cell Rep
2023
Targeting the E3 ubiquitin ligases DCAF15 and cereblon for cancer therapy.
Nguyen KM et al.·Semin Cancer Biol
2020Review
Development of targeted protein degradation therapeutics.
Chamberlain PP et al.·Nat Chem Biol
2019Review
Exploiting E3 ligases for lung cancer therapy: The promise of DCAF-PROTACs.
Hussain MS et al.·Pathol Res Pract
2025Review
RNA-binding motif protein 39 (RBM39): An emerging cancer target.
Xu Y et al.·Br J Pharmacol
2022Review
The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.
Cheng J et al.·Biochim Biophys Acta Rev Cancer
2019Review
Recent advances in anticancer mechanisms of molecular glue degraders: focus on RBM39-dgrading synthetic sulfonamide such as indisulam, E7820, tasisulam, and chloroquinoxaline sulfonamide.
Jang JH et al.·Genes Genomics
2024Review
Targeting RBM39 through indisulam induced mis-splicing of mRNA to exert anti-cancer effects in T-cell acute lymphoblastic leukemia.
Ji T et al.·J Exp Clin Cancer Res
2024
Targeting KRAS4A splicing through the RBM39/DCAF15 pathway inhibits cancer stem cells.
Chen WC et al.·Nat Commun
2021
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