DBF4B

Summary

DBF4B (DBF4B-CDC7 kinase regulatory subunit, HGNC:17883) is a protein-coding gene on chromosome 17q21.31, encoding Protein DBF4 homolog B (Q8NFT6). Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation.

This gene encodes a regulator of the cell division cycle 7 homolog (S. cerevisiae) protein, a serine-threonine kinase which links cell cycle regulation to genome duplication. This protein localizes to the nucleus and, in complex with the cell division cycle 7 homolog (S. cerevisiae) protein, may facilitate M phase progression. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 80174 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 99 total
• MANE Select transcript: NM_145663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17883
Approved symbol	DBF4B
Name	DBF4B-CDC7 kinase regulatory subunit
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13087, DRF1, ASKL1, chifb, ZDBF1B
Ensembl gene	ENSG00000161692
Ensembl biotype	protein_coding
OMIM	611661
Entrez	80174

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 retained_intron, 2 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000315005, ENST00000393547, ENST00000525140, ENST00000526915, ENST00000526924, ENST00000527862, ENST00000528353, ENST00000528766, ENST00000531699, ENST00000532789

RefSeq mRNA: 2 — MANE Select: NM_145663 NM_025104, NM_145663

CCDS: CCDS11485, CCDS45706

Canonical transcript exons

ENST00000315005 — 14 exons

Exon	Start	End
ENSE00001290216	44750595	44752264
ENSE00001319873	44748341	44748465
ENSE00001320514	44732178	44732265
ENSE00002154152	44708665	44708839
ENSE00003477745	44736830	44736866
ENSE00003481220	44734090	44734163
ENSE00003588807	44747391	44747515
ENSE00003595465	44741336	44741452
ENSE00003605826	44730965	44731015
ENSE00003634316	44738379	44738424
ENSE00003635762	44722880	44723022
ENSE00003641832	44709304	44709366
ENSE00003682083	44747083	44747191
ENSE00003691960	44729905	44730096

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 90.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4368 / max 149.6492, expressed in 1477 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161188	3.3216	1034
161187	3.1152	1248

Top tissues by expression

272 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	90.66	gold quality
left testis	UBERON:0004533	90.41	gold quality
oocyte	CL:0000023	87.57	gold quality
testis	UBERON:0000473	87.12	gold quality
secondary oocyte	CL:0000655	86.12	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.37	gold quality
ventricular zone	UBERON:0003053	83.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.45	gold quality
right uterine tube	UBERON:0001302	82.10	gold quality
spinal cord	UBERON:0002240	81.69	gold quality
right frontal lobe	UBERON:0002810	81.44	gold quality
apex of heart	UBERON:0002098	80.89	gold quality
nucleus accumbens	UBERON:0001882	80.03	gold quality
lower esophagus mucosa	UBERON:0035834	79.33	gold quality
left ovary	UBERON:0002119	79.31	gold quality
ganglionic eminence	UBERON:0004023	79.15	gold quality
anterior cingulate cortex	UBERON:0009835	79.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.04	gold quality
sural nerve	UBERON:0015488	79.03	gold quality
cingulate cortex	UBERON:0003027	78.98	gold quality
caudate nucleus	UBERON:0001873	78.74	gold quality
body of uterus	UBERON:0009853	78.54	gold quality
right ovary	UBERON:0002118	78.06	gold quality
putamen	UBERON:0001874	78.02	gold quality
cerebellar hemisphere	UBERON:0002245	77.98	gold quality
stromal cell of endometrium	CL:0002255	77.88	gold quality
cerebellar cortex	UBERON:0002129	77.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	77.74	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.66	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-98556	no	47.99
E-ANND-3	no	4.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting DBF4B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-571	95.38	66.54	671
HSA-MIR-6769A-3P	94.91	61.36	412
HSA-MIR-4747-3P	87.34	61.83	60

Literature-anchored findings (GeneRIF, showing 5)

• Results describe a novel human protein, Drf1, related to both human and yeast Dbf4. Drf1 is a nuclear cell cycle-regulated protein which binds to Cdc7 and activates the kinase. (PMID:12065429)
• ASKL1 in a complex with Cdc7 may play a role in normal progression of both S and M phases (PMID:15668232)
• These results indicate that Ddk functions as an upstream regulator to monitor S-phase checkpoint signaling. (PMID:19111665)
• Knockdown of the exon6-containing isoform (DBF4B-FL) significantly inhibits the tumorigenic potential of colon cancer. Overexpression of DBF4B-FL protects against DNA damage induced by SRSF1 knockdown. (PMID:29262322)
• DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks. (PMID:38865090)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	dbf4b	ENSDARG00000086550
drosophila_melanogaster	chif	FBGN0000307

Paralogs (1): DBF4 (ENSG00000006634)

Protein

Protein identifiers

Protein DBF4 homolog B — Q8NFT6 (reviewed: Q8NFT6)

Alternative names: Activator of S phase kinase-like protein 1, Chiffon homolog B, Dbf4-related factor 1

All UniProt accessions (2): B4E099, Q8NFT6

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S and M phases. The complex CDC7-DBF4B selectively phosphorylates MCM2 subunit at ‘Ser-40’ and then is involved in regulating the initiation of DNA replication during cell cycle.

Subunit / interactions. Forms a complex with CDC7. Note that CDC7 forms distinct complex either with DBF4/DBF4A or DBF4B. Such complexes are stable upon replication stress.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed. Highly expressed in testis.

Post-translational modifications. Phosphorylated.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8NFT6-1	1	yes
Q8NFT6-2	2
Q8NFT6-3	3
Q8NFT6-4	4

RefSeq proteins (2): NP_079380, NP_663696* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006572	Znf_DBF	Domain
IPR038545	Znf_DBF_sf	Homologous_superfamily
IPR051590	Replication_Regulatory_Kinase	Family

Pfam: PF07535

UniProt features (19 total): splice variant 6, binding site 4, region of interest 3, sequence conflict 2, chain 1, domain 1, zinc finger region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFT6-F1	55.60	0.22

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 320; 301; 304; 314

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 92 (showing top): GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_CELL_CYCLE_DNA_REPLICATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GEORGES_CELL_CYCLE_MIR192_TARGETS, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_REGULATION_OF_NUCLEAR_CELL_CYCLE_DNA_REPLICATION, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOMF_KINASE_ACTIVATOR_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, FISCHER_G2_M_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_MITOTIC_CELL_CYCLE

GO Biological Process (4): positive regulation of cell population proliferation (GO:0008284), positive regulation of nuclear cell cycle DNA replication (GO:0010571), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), regulation of cell cycle phase transition (GO:1901987)

GO Molecular Function (7): nucleic acid binding (GO:0003676), zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), protein kinase activator activity (GO:0030295), protein serine/threonine kinase activator activity (GO:0043539), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Dbf4-dependent protein kinase complex (GO:0031431)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
nuclear DNA replication	1
regulation of nuclear cell cycle DNA replication	1
positive regulation of cell cycle process	1
positive regulation of DNA-templated DNA replication	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G2/M phase transition	1
regulation of cell cycle process	1
cell cycle phase transition	1
transition metal ion binding	1
kinase binding	1
protein kinase activity	1
kinase activator activity	1
protein kinase regulator activity	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear protein-containing complex	1
serine/threonine protein kinase complex	1

Protein interactions and networks

STRING

630 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DBF4B	CDC7	O00311	901
DBF4B	CCNA2	P20248	510
DBF4B	RNF175	Q8N4F7	494
DBF4B	EXD3	Q8N9H8	471
DBF4B	THAP9	Q9H5L6	465
DBF4B	TOPBP1	Q92547	444
DBF4B	RECQL4	O94761	442
DBF4B	POLM	Q9NP87	434
DBF4B	MCM4	P33991	430
DBF4B	TICRR	Q7Z2Z1	430
DBF4B	CDC45	O75419	425
DBF4B	REV1	Q9UBZ9	422
DBF4B	ORC2	Q13416	419
DBF4B	CPO	Q8IVL8	419
DBF4B	CHEK2	O96017	413

IntAct

22 interactions, top by confidence:

A	B	Type	Score
DBF4B	LMO2	psi-mi:“MI:0915”(physical association)	0.560
DBF4B	CDC7	psi-mi:“MI:0914”(association)	0.530
MDFI	DBF4B	psi-mi:“MI:0915”(physical association)	0.490
DBF4B	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
LRRK2	DBF4B	psi-mi:“MI:0407”(direct interaction)	0.440
DBF4B	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
TRIM23	DBF4B	psi-mi:“MI:0915”(physical association)	0.370
MIER2	DBF4B	psi-mi:“MI:0915”(physical association)	0.370
TRIM27	DBF4B	psi-mi:“MI:0915”(physical association)	0.370
ADAMTSL4	DBF4B	psi-mi:“MI:0915”(physical association)	0.370
DBF4B	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
KRTAP4-12	DBF4B	psi-mi:“MI:0915”(physical association)	0.370
SUV39H1	DBF4B	psi-mi:“MI:0915”(physical association)	0.370
DBF4B	KDM1A	psi-mi:“MI:0915”(physical association)	0.370
DBF4B	TFAP2A	psi-mi:“MI:0915”(physical association)	0.370
DBF4B	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (46): DBF4B (Affinity Capture-MS), DBF4B (Two-hybrid), MAP1B (Affinity Capture-MS), MAP1S (Affinity Capture-MS), CDC7 (Affinity Capture-MS), EVA1C (Affinity Capture-MS), KRTAP4-12 (Two-hybrid), MAP1S (Affinity Capture-MS), CDC7 (Affinity Capture-MS), MAP1B (Affinity Capture-MS), EVA1C (Affinity Capture-MS), DBF4B (Affinity Capture-MS), DBF4B (Reconstituted Complex), DBF4B (Affinity Capture-MS), DBF4B (Proximity Label-MS)

ESM2 similar proteins: A0A5K7RLP0, A1YEX3, A2AGX3, A2AKB4, A7YWH3, A8MVX0, C9JSJ3, O08715, O88286, O88884, P24278, P97303, P97432, Q17RG1, Q1XFL1, Q3KNY0, Q3USH1, Q495C1, Q4V7B1, Q501R9, Q562E2, Q5SYB0, Q5VT97, Q5XIN1, Q6P2K3, Q6PCP7, Q6ZSG2, Q7TSX9, Q80SU3, Q80TL0, Q80W88, Q80XI1, Q8BLK9, Q8BSV3, Q8BW86, Q8K3E9, Q8K451, Q8N7W2, Q8NE31, Q8NFN8

Diamond homologs: Q283Q6, Q28FY7, Q7ZZH7, Q8NFT6, Q9QZ41, P32325, Q99MU0, Q9UBU7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

99 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3122 predictions. Top by Δscore:

Variant	Effect	Δscore
17:44708838:GG:G	donor_gain	1.0000
17:44708839:GG:G	donor_gain	1.0000
17:44722879:GGA:G	acceptor_gain	1.0000
17:44722929:G:GT	donor_gain	1.0000
17:44723018:GTGGG:G	donor_gain	1.0000
17:44738377:A:AG	acceptor_gain	1.0000
17:44738378:G:GA	acceptor_gain	1.0000
17:44738378:GT:G	acceptor_gain	1.0000
17:44738421:GCAG:G	donor_gain	1.0000
17:44738425:G:A	donor_loss	1.0000
17:44747382:C:A	acceptor_gain	1.0000
17:44747385:C:CA	acceptor_gain	1.0000
17:44747389:A:AG	acceptor_gain	1.0000
17:44747390:G:GA	acceptor_gain	1.0000
17:44747390:GC:G	acceptor_gain	1.0000
17:44747513:CAGGT:C	donor_loss	1.0000
17:44747516:G:GC	donor_loss	1.0000
17:44747517:T:A	donor_loss	1.0000
17:44708785:G:GT	donor_gain	0.9900
17:44708821:A:G	donor_gain	0.9900
17:44708835:A:T	donor_gain	0.9900
17:44720252:G:GG	donor_gain	0.9900
17:44722875:TCTA:T	acceptor_loss	0.9900
17:44722876:CTAG:C	acceptor_loss	0.9900
17:44722876:CTAGG:C	acceptor_gain	0.9900
17:44722877:TA:T	acceptor_loss	0.9900
17:44722877:TAGG:T	acceptor_gain	0.9900
17:44722877:TAGGA:T	acceptor_gain	0.9900
17:44722878:A:AC	acceptor_loss	0.9900
17:44722878:A:AG	acceptor_gain	0.9900

AlphaMissense

4013 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:44729917:T:C	F80L	0.998
17:44729919:T:A	F80L	0.998
17:44729919:T:G	F80L	0.998
17:44738403:T:C	L231P	0.997
17:44738399:T:C	F230L	0.996
17:44738401:C:A	F230L	0.996
17:44738401:C:G	F230L	0.996
17:44730990:T:C	L148P	0.995
17:44738407:A:C	K232N	0.995
17:44738407:A:T	K232N	0.995
17:44722955:T:C	F53S	0.994
17:44722961:T:C	L55S	0.994
17:44729918:T:C	F80S	0.994
17:44729927:A:T	K83I	0.994
17:44729945:T:A	V89E	0.994
17:44747174:T:C	F308L	0.994
17:44747176:C:A	F308L	0.994
17:44747176:C:G	F308L	0.994
17:44722954:T:C	F53L	0.993
17:44722956:T:A	F53L	0.993
17:44722956:T:G	F53L	0.993
17:44722957:T:G	Y54D	0.991
17:44722994:T:C	L66S	0.991
17:44730979:A:C	R144S	0.991
17:44730979:A:T	R144S	0.991
17:44732230:C:A	A174D	0.991
17:44741340:T:C	F240L	0.991
17:44741342:T:A	F240L	0.991
17:44741342:T:G	F240L	0.991
17:44723006:T:A	I70N	0.990

dbSNP variants (sampled 300 via entrez): RS1000081163 (17:44708737 T>C,G), RS1000131807 (17:44713652 AAAAC>A), RS1000189883 (17:44720862 GGCTTTTTTTTT>G), RS1000220902 (17:44752534 C>G), RS1000222818 (17:44721214 CT>C,CTT), RS1000244571 (17:44745455 G>A), RS1000273989 (17:44727101 A>G), RS1000284650 (17:44720447 C>G), RS1000350956 (17:44726097 C>T), RS1000398735 (17:44714099 A>T), RS1000475933 (17:44731999 G>C), RS1000528748 (17:44732287 C>T), RS1000590534 (17:44737746 A>G), RS1000699287 (17:44726032 C>T), RS1000700066 (17:44744935 T>C)

Disease associations

OMIM: gene MIM:611661 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010796_729	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09
GCST90000025_590	Appendicular lean mass	1.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment	4
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	decreases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Testosterone	decreases expression, affects cotreatment	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Vanadates	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Sodium Selenite	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SK39	HAP1 DBF4B (-) 1	Cancer cell line	Male
CVCL_SK40	HAP1 DBF4B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.