DCAF5

Summary

DCAF5 (DDB1 and CUL4 associated factor 5, HGNC:20224) is a protein-coding gene on chromosome 14q24.1, encoding DDB1- and CUL4-associated factor 5 (Q96JK2). Is a substrate receptor for the CUL4-DDB1 E3 ubiquitin-protein ligase complex (CRL4).

Predicted to be involved in negative regulation of fatty acid biosynthetic process. Part of Cul4-RING E3 ubiquitin ligase complex.

Source: NCBI Gene 8816 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 100 total
• MANE Select transcript: NM_003861

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20224
Approved symbol	DCAF5
Name	DDB1 and CUL4 associated factor 5
Location	14q24.1
Locus type	gene with protein product
Status	Approved
Aliases	BCRP2, D14S1461E, BCRG2, KIAA1824
Ensembl gene	ENSG00000139990
Ensembl biotype	protein_coding
OMIM	603812
Entrez	8816

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000341516, ENST00000389997, ENST00000553293, ENST00000553943, ENST00000554215, ENST00000554681, ENST00000556111, ENST00000556847, ENST00000557386, ENST00000867406, ENST00000927898, ENST00000954556

RefSeq mRNA: 4 — MANE Select: NM_003861 NM_001284206, NM_001284207, NM_001284208, NM_003861

CCDS: CCDS32106, CCDS61480, CCDS61481, CCDS73646

Canonical transcript exons

ENST00000341516 — 9 exons

Exon	Start	End
ENSE00001488127	69050881	69055611
ENSE00001488129	69062384	69062511
ENSE00002444984	69152765	69153119
ENSE00003566834	69118139	69118278
ENSE00003620710	69119194	69119230
ENSE00003631175	69122217	69122360
ENSE00003652236	69075345	69075411
ENSE00003689382	69116366	69116495
ENSE00003785146	69091674	69091887

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 98.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.0910 / max 143.5729, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143875	17.2172	1814
143874	6.6746	1709
143870	0.7568	481
143873	0.4035	211
143876	0.0390	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.14	gold quality
left ventricle myocardium	UBERON:0006566	96.38	gold quality
tibialis anterior	UBERON:0001385	96.29	gold quality
oocyte	CL:0000023	95.52	gold quality
deltoid	UBERON:0001476	95.44	gold quality
epithelial cell of pancreas	CL:0000083	95.06	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.75	gold quality
left testis	UBERON:0004533	94.66	gold quality
right testis	UBERON:0004534	94.41	gold quality
quadriceps femoris	UBERON:0001377	94.37	gold quality
skeletal muscle tissue	UBERON:0001134	94.35	gold quality
vastus lateralis	UBERON:0001379	94.05	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.02	gold quality
muscle tissue	UBERON:0002385	94.00	gold quality
biceps brachii	UBERON:0001507	93.88	gold quality
adult organism	UBERON:0007023	93.65	gold quality
smooth muscle tissue	UBERON:0001135	93.49	gold quality
muscle of leg	UBERON:0001383	93.26	gold quality
gastrocnemius	UBERON:0001388	93.25	gold quality
testis	UBERON:0000473	92.95	gold quality
tendon of biceps brachii	UBERON:0008188	92.61	gold quality
lower esophagus mucosa	UBERON:0035834	92.43	gold quality
upper arm skin	UBERON:0004263	92.38	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.20	silver quality
popliteal artery	UBERON:0002250	92.19	gold quality
tibial artery	UBERON:0007610	92.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.14	gold quality
myocardium	UBERON:0002349	92.11	gold quality
trabecular bone tissue	UBERON:0002483	92.01	gold quality
gall bladder	UBERON:0002110	91.94	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.70
E-MTAB-6058	no	61.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

108 targeting DCAF5, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3941	99.86	70.54	2735

Literature-anchored findings (GeneRIF, showing 1)

• Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF. (PMID:38538798)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dcaf5	ENSDARG00000060320
mus_musculus	Dcaf5	ENSMUSG00000049106
rattus_norvegicus	Dcaf5	ENSRNOG00000004556
drosophila_melanogaster	CG42233	FBGN0250755
caenorhabditis_elegans		WBGENE00011242

Paralogs (5): DCAF8 (ENSG00000132716), WDTC1 (ENSG00000142784), DCAF6 (ENSG00000143164), DCAF8L2 (ENSG00000189186), DCAF8L1 (ENSG00000226372)

Protein

Protein identifiers

DDB1- and CUL4-associated factor 5 — Q96JK2 (reviewed: Q96JK2)

Alternative names: Breakpoint cluster region protein 2, WD repeat-containing protein 22

All UniProt accessions (4): Q96JK2, G3V3S1, G3V4Z1, Q8TBB7

UniProt curated annotations — full annotation on UniProt →

Function. Is a substrate receptor for the CUL4-DDB1 E3 ubiquitin-protein ligase complex (CRL4). The complex CRL4-DCAF5 is involved in the ubiquitination of a set of methylated non-histone proteins, including SOX2, DNMT1 and E2F1.

Subunit / interactions. Interacts with DDB1, CUL4A or CUL4B. Interacts with L3MBTL3. Interacts with DNMT1. Interacts with E2F1. Interacts with SOX2.

Tissue specificity. Ubiquitous.

Pathway. Protein modification; protein ubiquitination.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96JK2-1	1	yes
Q96JK2-2	2
Q96JK2-3	3

RefSeq proteins (4): NP_001271135, NP_001271136, NP_001271137, NP_003852* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR045151	DCAF8	Family

Pfam: PF00400

UniProt features (72 total): strand 29, modified residue 9, repeat 6, compositionally biased region 6, turn 6, region of interest 5, sequence conflict 4, helix 4, splice variant 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8TL6	ELECTRON MICROSCOPY	2.63
3I89	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JK2-F1	61.00	0.31

Functional residue map

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

Post-translational modifications (9): 500, 531, 533, 626, 628, 645, 648, 651, 794

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 147 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_FATTY_ACID_METABOLIC_PROCESS, GTGCCTT_MIR506, GOBP_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, chr14q24, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_REGULATION_OF_KETONE_METABOLIC_PROCESS

GO Biological Process (2): protein ubiquitination (GO:0016567), negative regulation of fatty acid biosynthetic process (GO:0045717)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Cul4-RING E3 ubiquitin ligase complex (GO:0080008)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein modification by small protein conjugation	1
fatty acid biosynthetic process	1
regulation of fatty acid biosynthetic process	1
negative regulation of fatty acid metabolic process	1
negative regulation of lipid biosynthetic process	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

862 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCAF5	BCR	P11274	756
DCAF5	ACTN1	P12814	724
DCAF5	L3MBTL3	Q96JM7	719
DCAF5	RAD51B	O15315	670
DCAF5	BANF1	O75531	639
DCAF5	GRWD1	Q9BQ67	599
DCAF5	COPS7A	Q9UBW8	594
DCAF5	DDB1	Q16531	574
DCAF5	DCAF4	Q8WV16	574
DCAF5	DCAF12	Q5T6F0	563
DCAF5	DCAF10	Q5QP82	533
DCAF5	RIMBP3B	A6NNM3	523
DCAF5	DDB2	Q92466	475
DCAF5	ZNF564	Q8TBZ8	444
DCAF5	POM121L1P	Q3SYA9	435

IntAct

104 interactions, top by confidence:

A	B	Type	Score
CUL4B	COPS2	psi-mi:“MI:0914”(association)	0.790
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
L3MBTL3	DNMT1	psi-mi:“MI:0914”(association)	0.670
DCX	ZBTB5	psi-mi:“MI:0914”(association)	0.670
CUL4A	COPS2	psi-mi:“MI:0914”(association)	0.640
NUAK2	PPP1R12A	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT5	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT7	TXNDC9	psi-mi:“MI:0914”(association)	0.640
DCAF12L2	CETN3	psi-mi:“MI:0914”(association)	0.640
PYM1	CASC3	psi-mi:“MI:0914”(association)	0.620
DDB1	DCAF5	psi-mi:“MI:0407”(direct interaction)	0.590
DCAF5	DNMT1	psi-mi:“MI:0915”(physical association)	0.580
DCAF5	L3MBTL3	psi-mi:“MI:0915”(physical association)	0.580
DNMT1	DCAF5	psi-mi:“MI:0915”(physical association)	0.580
L3MBTL3	DCAF5	psi-mi:“MI:0915”(physical association)	0.580
SOST	KPNA4	psi-mi:“MI:0914”(association)	0.530
DCAF5	PFDN6	psi-mi:“MI:0914”(association)	0.530
ZNF816	LRP4	psi-mi:“MI:0914”(association)	0.530
SPATA24	GGPS1	psi-mi:“MI:0914”(association)	0.530
DCLK1	DCX	psi-mi:“MI:0914”(association)	0.530
GPBP1L1	CNOT1	psi-mi:“MI:0914”(association)	0.530

BioGRID (363): DDB1 (Affinity Capture-Western), CUL4A (Affinity Capture-Western), DCAF5 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), PFDN4 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), PFDN5 (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), PDRG1 (Affinity Capture-MS), PFDN6 (Affinity Capture-MS), VBP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PQ72, A7J1T0, A7J1T2, A7MBB4, A8MZ59, D3ZXW3, M0R5D6, O36371, O43283, O43310, O73622, O95073, P03177, P10242, P21705, P46200, Q0P4H6, Q1HKZ5, Q1HVD1, Q1LVK9, Q22811, Q2NKQ1, Q3KSQ2, Q3UPF5, Q535K8, Q562B4, Q567C6, Q5R8X7, Q5ZI27, Q6DGX3, Q6INH1, Q6J1H4, Q6PEE2, Q6ZTZ1, Q71M44, Q7SXL7, Q80T85, Q8BFX3, Q8BIL2, Q8BKE5

Diamond homologs: A1CH75, A1CXL0, A2QI22, A3LQ86, A4R2Q6, A5DL92, A5DST9, A6R3K5, A6S0T8, A6ZPA9, A7ECP3, A7TMF9, B0Y5V6, B2B5V0, B2VZH2, G0SFB5, O42937, O74184, Q0CLJ4, Q0UXP3, Q12024, Q1DJF7, Q1JQD2, Q2GXT0, Q2UGK1, Q40687, Q4WP10, Q54BI5, Q5APF0, Q5B4R1, Q6BLS5, Q6CEW7, Q6CU59, Q6FKK3, Q756D0, Q80T85, Q810D6, Q96JK2, Q9BQ67, Q9C2I5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 125 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Prefoldin mediated transfer of substrate to CCT/TriC	6	28.5×	2e-05
Association of TriC/CCT with target proteins during biosynthesis	5	17.6×	9e-04
DNA Damage Recognition in GG-NER	5	17.2×	9e-04
Formation of TC-NER Pre-Incision Complex	5	12.7×	2e-03
Neddylation	8	4.6×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1733 predictions. Top by Δscore:

Variant	Effect	Δscore
14:69055623:A:AC	acceptor_gain	1.0000
14:69055623:A:C	acceptor_gain	1.0000
14:69062378:CCTCA:C	donor_loss	1.0000
14:69062379:CTCA:C	donor_loss	1.0000
14:69062380:TCAC:T	donor_loss	1.0000
14:69062381:CACC:C	donor_loss	1.0000
14:69062382:A:C	donor_loss	1.0000
14:69062508:CCAC:C	acceptor_gain	1.0000
14:69062509:CAC:C	acceptor_gain	1.0000
14:69062509:CACC:C	acceptor_gain	1.0000
14:69062510:ACCTG:A	acceptor_loss	1.0000
14:69062512:C:CC	acceptor_gain	1.0000
14:69062512:CTGGG:C	acceptor_loss	1.0000
14:69062513:T:A	acceptor_loss	1.0000
14:69075408:TATA:T	acceptor_gain	1.0000
14:69075410:TA:T	acceptor_gain	1.0000
14:69075412:C:CC	acceptor_gain	1.0000
14:69091669:TTTA:T	donor_loss	1.0000
14:69091670:TTAC:T	donor_loss	1.0000
14:69091671:TA:T	donor_loss	1.0000
14:69091672:A:C	donor_loss	1.0000
14:69091883:GAGAA:G	acceptor_gain	1.0000
14:69091885:GAA:G	acceptor_gain	1.0000
14:69091886:AA:A	acceptor_gain	1.0000
14:69091887:ACTG:A	acceptor_loss	1.0000
14:69091888:C:CC	acceptor_gain	1.0000
14:69091888:C:T	acceptor_loss	1.0000
14:69116365:CCT:C	donor_gain	1.0000
14:69116491:GGGCT:G	acceptor_gain	1.0000
14:69116492:GGCT:G	acceptor_gain	1.0000

AlphaMissense

6187 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:69055421:A:G	L422P	1.000
14:69055427:T:A	D420V	1.000
14:69055427:T:C	D420G	1.000
14:69055427:T:G	D420A	1.000
14:69055428:C:G	D420H	1.000
14:69055429:A:C	F419L	1.000
14:69055429:A:T	F419L	1.000
14:69055430:A:C	F419C	1.000
14:69055430:A:G	F419S	1.000
14:69055431:A:C	F419V	1.000
14:69055431:A:G	F419L	1.000
14:69055431:A:T	F419I	1.000
14:69055432:G:C	F418L	1.000
14:69055432:G:T	F418L	1.000
14:69055433:A:C	F418C	1.000
14:69055433:A:G	F418S	1.000
14:69055434:A:G	F418L	1.000
14:69055434:A:T	F418I	1.000
14:69055441:C:A	M415I	1.000
14:69055441:C:G	M415I	1.000
14:69055441:C:T	M415I	1.000
14:69055442:A:C	M415R	1.000
14:69055442:A:G	M415T	1.000
14:69055442:A:T	M415K	1.000
14:69055451:T:A	D412V	1.000
14:69055451:T:C	D412G	1.000
14:69055454:T:A	E411V	1.000
14:69055476:A:G	Y404H	1.000
14:69055482:G:C	H402D	1.000
14:69055511:A:G	L392P	1.000

dbSNP variants (sampled 300 via entrez): RS1000002061 (14:69081289 C>T), RS1000139992 (14:69130814 T>C), RS1000156921 (14:69075887 T>C), RS1000177036 (14:69111458 C>T), RS1000209340 (14:69132749 G>A), RS1000238221 (14:69062118 T>C), RS1000276411 (14:69090451 A>C,G), RS1000292865 (14:69150499 A>G), RS1000376989 (14:69080739 A>C), RS1000388244 (14:69150947 C>A,G), RS1000423054 (14:69144274 A>G), RS1000431214 (14:69127994 T>C), RS1000475974 (14:69052897 C>T), RS1000479807 (14:69098470 T>C), RS1000514958 (14:69074327 G>A)

Disease associations

OMIM: gene MIM:603812 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004599_171	Mean platelet volume	8.000000e-42
GCST005232_25	Neuroticism	4.000000e-08
GCST005316_533	Intelligence (MTAG)	5.000000e-09
GCST010002_155	Refractive error	6.000000e-11
GCST90002395_208	Mean platelet volume	1.000000e-80
GCST90002402_190	Platelet count	6.000000e-46

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0004337	intelligence
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects expression, decreases expression	4
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases expression, increases abundance	1
K 7174	increases expression	1
abrine	increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Coumestrol	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Endosulfan	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ribonucleotides	affects binding	1
Rifampin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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