DBF4

Chr 7

DBF4-CDC7 kinase regulatory subunit

Also known as: ASK, CHIF, DBF4A, ZDBF1

NCBI Gene: 10926ENSG00000006634UniProt: Q9UBU7

Predicted to enable protein serine/threonine kinase activator activity. Predicted to be involved in positive regulation of nuclear cell cycle DNA replication and regulation of cell cycle phase transition. Located in nuclear body. [provided by Alliance of Genome Resources, Jul 2025]

102
ClinVar variants
12
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DBF4
⚡
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· 84 VUS of 102 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.
0.28LOEUF
pLI 0.993
Z-score 4.63
OE 0.12 (0.06–0.28)
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.
0.98Z-score
OE missense 0.85 (0.77–0.94)
274 obs / 323.6 exp
Tolerant

Mild missense constraint

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.0.12 (0.06–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.77–0.94)
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.0.98
0≤1.21.6
LoF obs/exp: 4 / 32.4Missense obs/exp: 274 / 323.6Syn Z: 0.15

ClinVar Variant Classifications

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS84
Likely Benign3
Benign3
11
Pathogenic
1
Likely Pathogenic
84
VUS
3
Likely Benign
3
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
78
6
0
84
Likely Benign
0
3
0
0
3
Benign
0
2
0
1
3
Total083181102

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

View in ClinVar →

Protein Context — Lollipop Plot

DBF4 · 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
DBF4 ZINC FINGER; DBF4
MIM #604281 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Homozygous DBF4 mutation as a cause of severe congenital neutropenia.
Willemsen M et al.·J Allergy Clin Immunol
2023
Clinical significance and pro-oncogenic function of DBF4 in clear cell renal cell carcinoma.
Chen L et al.·BMC Urol
2025
Analysis of the expression and prognostic significance of DDK complex in Hepatocarcinoma.
Wang M et al.·BMC Cancer
2023
Budding yeast Dbf4 sequences required for Cdc7 kinase activation and identification of a functional relationship between the Dbf4 and Rev1 BRCT domains.
Harkins V et al.·Genetics
2009Functional
The role of Akkermansia muciniphila in colorectal cancer: A double-edged sword of treatment or disease progression?
Faghfuri E et al.·Biomed Pharmacother
2024Review
Dbf4-Dependent Kinase (DDK)-Mediated Proteolysis of CENP-A Prevents Mislocalization of CENP-A in Saccharomyces cerevisiae.
Eisenstatt JR et al.·G3 (Bethesda)
2020
Kinome expression profiling to target new therapeutic avenues in multiple myeloma.
de Boussac H et al.·Haematologica
2020
Not only P-glycoprotein: Amplification of the ABCB1-containing chromosome region 7q21 confers multidrug resistance upon cancer cells by coordinated overexpression of an assortment of resistance-related proteins.
Genovese I et al.·Drug Resist Updat
2017Review
Distinct surfaces on Cdc5/PLK Polo-box domain orchestrate combinatorial substrate recognition during cell division.
Almawi AW et al.·Sci Rep
2020
Cdc7 kinase - a new target for drug development.
Swords R et al.·Eur J Cancer
2010Review
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