DCAF16

Summary

DCAF16 (DDB1 and CUL4 associated factor 16, HGNC:25987) is a protein-coding gene on chromosome 4p15.31, encoding DDB1- and CUL4-associated factor 16 (Q9NXF7). Functions as a substrate recognition component for CUL4-DDB1 E3 ubiquitin-protein ligase complex, which mediates ubiquitination and proteasome-dependent degradation of nuclear proteins.

Predicted to be involved in protein ubiquitination. Part of Cul4-RING E3 ubiquitin ligase complex.

Source: NCBI Gene 54876 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 40 total
• Druggable target: yes
• MANE Select transcript: NM_017741

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25987
Approved symbol	DCAF16
Name	DDB1 and CUL4 associated factor 16
Location	4p15.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20280
Ensembl gene	ENSG00000163257
Ensembl biotype	protein_coding
OMIM	620524
Entrez	54876

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000382247, ENST00000507731, ENST00000507768, ENST00000850885, ENST00000905203, ENST00000905204, ENST00000916753, ENST00000916754, ENST00000916755

RefSeq mRNA: 6 — MANE Select: NM_017741 NM_001345880, NM_001345881, NM_001345882, NM_001345884, NM_001345885, NM_017741

CCDS: CCDS3423

Canonical transcript exons

ENST00000382247 — 3 exons

Exon	Start	End
ENSE00001425755	17805107	17805225
ENSE00004282455	17800655	17804771
ENSE00004475513	17810447	17810757

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 94.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.8528 / max 270.4276, expressed in 1814 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51542	23.4629	1812
51540	0.2483	99
51541	0.1416	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.47	gold quality
ventricular zone	UBERON:0003053	91.27	gold quality
buccal mucosa cell	CL:0002336	91.10	gold quality
corpus epididymis	UBERON:0004359	90.85	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.66	gold quality
seminal vesicle	UBERON:0000998	90.52	gold quality
caput epididymis	UBERON:0004358	90.45	gold quality
nipple	UBERON:0002030	90.34	gold quality
penis	UBERON:0000989	89.97	gold quality
ganglionic eminence	UBERON:0004023	89.89	gold quality
cauda epididymis	UBERON:0004360	89.72	gold quality
left ovary	UBERON:0002119	89.59	gold quality
colonic epithelium	UBERON:0000397	89.37	gold quality
tendon	UBERON:0000043	89.32	gold quality
ovary	UBERON:0000992	89.21	gold quality
endometrium	UBERON:0001295	88.46	gold quality
adrenal tissue	UBERON:0018303	88.39	gold quality
right ovary	UBERON:0002118	87.85	gold quality
germinal epithelium of ovary	UBERON:0001304	87.84	gold quality
superficial temporal artery	UBERON:0001614	87.64	gold quality
body of uterus	UBERON:0009853	87.24	gold quality
cortical plate	UBERON:0005343	86.94	gold quality
cerebellar vermis	UBERON:0004720	86.91	gold quality
corpus callosum	UBERON:0002336	86.84	gold quality
stromal cell of endometrium	CL:0002255	86.78	gold quality
skin of hip	UBERON:0001554	86.72	gold quality
urethra	UBERON:0000057	86.42	gold quality
secondary oocyte	CL:0000655	85.94	gold quality
rectum	UBERON:0001052	85.93	gold quality
female reproductive system	UBERON:0000474	85.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting DCAF16, 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-3613-3P	100.00	76.36	7965
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6752-3P	99.72	66.71	1587

Literature-anchored findings (GeneRIF, showing 1)

• Selective degradation of PARP2 by PROTACs via recruiting DCAF16 for triple-negative breast cancer. (PMID:35430559)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

DDB1- and CUL4-associated factor 16 — Q9NXF7 (reviewed: Q9NXF7)

All UniProt accessions (1): Q9NXF7

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a substrate recognition component for CUL4-DDB1 E3 ubiquitin-protein ligase complex, which mediates ubiquitination and proteasome-dependent degradation of nuclear proteins.

Subunit / interactions. Interacts with DDB1 and CUL4A.

Subcellular location. Nucleus.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (6): NP_001332809, NP_001332810, NP_001332811, NP_001332813, NP_001332814, NP_060211* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028216	DCAF16	Family

Pfam: PF15349

UniProt features (19 total): helix 8, strand 2, turn 2, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8G46	ELECTRON MICROSCOPY	2.2
9S3R	ELECTRON MICROSCOPY	3.3
8OV6	ELECTRON MICROSCOPY	3.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXF7-F1	38.26	0.00

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 (1): 61

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 81 (showing top): MODULE_205, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, BASAKI_YBX1_TARGETS_DN, FISCHER_DREAM_TARGETS, GOBP_CHROMATIN_REMODELING, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOCC_TRANSFERASE_COMPLEX, GOCC_CUL4_RING_E3_UBIQUITIN_LIGASE_COMPLEX, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, chr4p15, GOCC_UBIQUITIN_LIGASE_COMPLEX, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, WHITFIELD_CELL_CYCLE_S, MARTENS_TRETINOIN_RESPONSE_DN

GO Biological Process (1): protein ubiquitination (GO:0016567)

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

GO Cellular Component (3): nucleoplasm (GO:0005654), Cul4-RING E3 ubiquitin ligase complex (GO:0080008), nucleus (GO:0005634)

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
protein modification by small protein conjugation	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
cullin-RING ubiquitin ligase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

708 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCAF16	RNF114	Q9Y508	790
DCAF16	FAM184B	Q9ULE4	757
DCAF16	RNF4	P78317	729
DCAF16	NCAPG	Q9BPX3	723
DCAF16	LCORL	Q8N3X6	714
DCAF16	DCAF15	Q66K64	606
DCAF16	CRBN	Q96SW2	576
DCAF16	FKBP1A	P20071	572
DCAF16	MED28	Q9H204	544
DCAF16	DDB1	Q16531	509
DCAF16	KEAP1	Q14145	495
DCAF16	MDM2	Q00987	471
DCAF16	BIRC2	Q13490	467
DCAF16	TRIM24	O15164	465
DCAF16	XIAP	P98170	452

IntAct

89 interactions, top by confidence:

A	B	Type	Score
RBPJ	NOTCH1	psi-mi:“MI:0914”(association)	0.910
CUL4B	COPS2	psi-mi:“MI:0914”(association)	0.790
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
CUL4A	COPS2	psi-mi:“MI:0914”(association)	0.640
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
GLMN	FKBP5	psi-mi:“MI:0914”(association)	0.640
PRPS1	NMT2	psi-mi:“MI:0914”(association)	0.640
tat	PPM1G	psi-mi:“MI:0914”(association)	0.560
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
C5orf24	MEIS1	psi-mi:“MI:0914”(association)	0.530
TXNIP	PER1	psi-mi:“MI:0914”(association)	0.530
CSNK1G2	GINS1	psi-mi:“MI:0914”(association)	0.530
CIAO3	INPPL1	psi-mi:“MI:0914”(association)	0.530
GREM2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
TCEANC2	HTATSF1	psi-mi:“MI:0914”(association)	0.530
SPIN4	PRMT6	psi-mi:“MI:0914”(association)	0.530

BioGRID (321): DDB1 (Affinity Capture-Western), CUL4A (Affinity Capture-Western), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTR0, A0A1B0GTY4, A0A1B0GVD1, A7WNB0, A8R0V4, E9Q7F5, O55779, O70552, O75818, O93036, P01586, P03212, P03319, P03321, P04823, P0DOE0, P10260, P13206, P16837, P20880, P28907, P36340, P47939, P47940, Q02484, Q03233, Q1HVF6, Q2HRD2, Q3KSS3, Q3TTJ4, Q5BK38, Q5QR91, Q5VAN0, Q64277, Q66669, Q66672, Q6GQU0, Q6GVM5, Q6UWF9, Q86WR6

Diamond homologs: Q2HJA2, Q9NXF7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
DNA Damage Recognition in GG-NER	9	36.2×	1e-09
Formation of TC-NER Pre-Incision Complex	9	26.8×	9e-09
Cargo recognition for clathrin-mediated endocytosis	7	10.3×	6e-04
Neddylation	12	8.0×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein neddylation	5	50.3×	1e-05
protein neddylation	6	45.3×	3e-06
negative regulation of cell population proliferation	10	4.5×	8e-03
protein ubiquitination	10	4.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

692 predictions. Top by Δscore:

Variant	Effect	Δscore
4:17810530:T:A	donor_gain	1.0000
4:17810442:CTAA:C	donor_loss	0.9900
4:17810443:TAACC:T	donor_loss	0.9900
4:17810444:AACC:A	donor_loss	0.9900
4:17810445:A:AT	donor_loss	0.9900
4:17810446:C:A	donor_loss	0.9900
4:17810486:C:CA	donor_gain	0.9900
4:17805232:C:CT	acceptor_gain	0.9700
4:17804566:TG:T	donor_gain	0.9500
4:17809538:T:TA	donor_gain	0.9500
4:17810362:G:GA	donor_gain	0.9500
4:17810413:AGG:A	donor_gain	0.9400
4:17809535:A:AC	donor_gain	0.9300
4:17809536:C:CC	donor_gain	0.9300
4:17810371:C:CA	donor_gain	0.9100
4:17810445:A:AC	donor_gain	0.9100
4:17810446:C:CC	donor_gain	0.9100
4:17810446:CCT:C	donor_gain	0.9000
4:17805222:TAAG:T	acceptor_gain	0.8900
4:17808373:ACT:A	acceptor_gain	0.8900
4:17808375:T:A	acceptor_gain	0.8900
4:17808370:ATTAC:A	acceptor_gain	0.8800
4:17808371:TTACT:T	acceptor_gain	0.8800
4:17808374:C:A	acceptor_gain	0.8800
4:17809536:CTT:C	donor_gain	0.8800
4:17805234:C:CT	acceptor_gain	0.8600
4:17805232:C:T	acceptor_gain	0.8300
4:17808372:TACT:T	acceptor_gain	0.8300
4:17804489:G:C	donor_gain	0.8200
4:17809532:A:AC	donor_gain	0.8200

AlphaMissense

1388 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:17803922:A:G	W74R	0.983
4:17803922:A:T	W74R	0.983
4:17803699:G:T	A148D	0.980
4:17803531:A:G	F204S	0.979
4:17803519:A:T	V208D	0.978
4:17803946:A:G	W66R	0.965
4:17803946:A:T	W66R	0.965
4:17803701:A:C	F147L	0.962
4:17803701:A:T	F147L	0.962
4:17803703:A:G	F147L	0.962
4:17803687:A:G	L152P	0.960
4:17803530:G:C	F204L	0.959
4:17803530:G:T	F204L	0.959
4:17803532:A:G	F204L	0.959
4:17803523:C:G	A207P	0.958
4:17803966:A:G	L59P	0.957
4:17803510:A:G	L211P	0.953
4:17803585:A:T	V186D	0.951
4:17803920:C:A	W74C	0.951
4:17803920:C:G	W74C	0.951
4:17803601:A:G	W181R	0.949
4:17803601:A:T	W181R	0.949
4:17803597:A:G	L182P	0.948
4:17803700:C:G	A148P	0.948
4:17803805:A:G	W113R	0.942
4:17803805:A:T	W113R	0.942
4:17803944:C:A	W66C	0.942
4:17803944:C:G	W66C	0.942
4:17803963:A:G	L60S	0.942
4:17803687:A:T	L152Q	0.939

dbSNP variants (sampled 300 via entrez): RS1000219646 (4:17802534 A>G), RS10002231 (4:17808840 C>G), RS1000272017 (4:17802278 G>A), RS1000308888 (4:17811378 A>G), RS1000791467 (4:17798290 C>T), RS1000848165 (4:17803185 C>T), RS1001010968 (4:17797299 A>C,G), RS1001118601 (4:17803911 A>C,G), RS1001252489 (4:17793838 A>G), RS1001406259 (4:17804689 T>C), RS1001463322 (4:17797612 T>C), RS1001754212 (4:17804517 G>A,C), RS1001958605 (4:17812360 T>C), RS1002071694 (4:17810866 T>A,G), RS1002250277 (4:17809788 T>C)

Disease associations

OMIM: gene MIM:620524 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002702_42	Height	2.000000e-40
GCST007293_20	Body fat distribution (arm fat ratio)	7.000000e-12
GCST007294_10	Body fat distribution (trunk fat ratio)	1.000000e-12
GCST007294_29	Body fat distribution (trunk fat ratio)	4.000000e-09
GCST007295_160	Body fat distribution (leg fat ratio)	7.000000e-08
GCST007295_51	Body fat distribution (leg fat ratio)	3.000000e-06
GCST008362_214	Birth weight	4.000000e-34
GCST008363_37	Offspring birth weight	4.000000e-12
GCST012227_1022	Hip circumference adjusted for BMI	2.000000e-14
GCST90090967_11	Height	8.000000e-14

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5465397 (PROTEIN-PROTEIN INTERACTION), CHEMBL6177907 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

24 potent at pChembl≥5 of 24 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.66	IC50	2.2	nM	CHEMBL6149118
8.59	IC50	2.59	nM	CHEMBL6175617
8.41	IC50	3.92	nM	CHEMBL6167907
8.40	IC50	3.98	nM	CHEMBL6175617
8.37	IC50	4.29	nM	CHEMBL6168941
8.30	IC50	4.96	nM	CHEMBL6166570
8.29	IC50	5.07	nM	CHEMBL6150672
8.12	IC50	7.58	nM	CHEMBL6173874
8.11	IC50	7.79	nM	CHEMBL6168537
8.09	IC50	8.08	nM	CHEMBL6173874
8.06	IC50	8.78	nM	CHEMBL6169562
7.99	IC50	10.14	nM	CHEMBL6167907
7.98	IC50	10.54	nM	CHEMBL6150672
7.95	IC50	11.16	nM	CHEMBL6168537
7.93	IC50	11.66	nM	CHEMBL6166570
7.90	IC50	12.49	nM	CHEMBL6168941
7.89	IC50	12.91	nM	CHEMBL6173766
7.81	IC50	15.5	nM	CHEMBL6174778
7.75	IC50	17.67	nM	CHEMBL6174778
7.74	IC50	18.21	nM	CHEMBL6164280
7.66	IC50	21.7	nM	CHEMBL6149118
7.57	IC50	26.99	nM	CHEMBL6164280
7.47	IC50	33.86	nM	CHEMBL6169562
7.31	IC50	48.6	nM	CHEMBL6160760

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	4
trichostatin A	decreases expression, affects cotreatment	2
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Hydrogen Peroxide	affects expression	1
Nicotine	increases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Thimerosal	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	decreases expression	1

ChEMBL screening assays

31 unique, capped per target: 31 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5369320	Binding	PROTAC activity at DCAF16/BRD4 in human PC-3 cells assessed as maximal degradation relative to control	Unlocking DCAFs To Catalyze Degrader Development: An Arena for Innovative Approaches. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7NF	Ubigene A-549 DCAF16 KO	Cancer cell line	Male
CVCL_D9D0	Ubigene HEK293 DCAF16 KO	Transformed cell line	Female
CVCL_E1VA	HAP1 DCAF16 (-) 1	Cancer cell line	Male
CVCL_E1VB	HAP1 DCAF16 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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