DCUN1D5

Summary

DCUN1D5 (defective in cullin neddylation 1 domain containing 5, HGNC:28409) is a protein-coding gene on chromosome 11q22.3, encoding DCN1-like protein 5 (Q9BTE7). Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes which is necessary for the activation of cullin-RING E3 ubiquitin ligases (CRLs).

Enables cullin family protein binding activity. Involved in DNA damage response; positive regulation of protein neddylation; and regulation of cell growth. Located in nucleus and spindle.

Source: NCBI Gene 84259 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 22 total
• Druggable target: yes
• MANE Select transcript: NM_032299

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28409
Approved symbol	DCUN1D5
Name	defective in cullin neddylation 1 domain containing 5
Location	11q22.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC2714, FLJ32431
Ensembl gene	ENSG00000137692
Ensembl biotype	protein_coding
OMIM	616522
Entrez	84259

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding, 7 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000260247, ENST00000525420, ENST00000527260, ENST00000527576, ENST00000527779, ENST00000529076, ENST00000529281, ENST00000529294, ENST00000531543, ENST00000531571, ENST00000583974, ENST00000858031, ENST00000914096, ENST00000914097, ENST00000914098

RefSeq mRNA: 4 — MANE Select: NM_032299 NM_001318739, NM_001318740, NM_001318741, NM_032299

CCDS: CCDS8325

Canonical transcript exons

ENST00000260247 — 8 exons

Exon	Start	End
ENSE00002148223	103050686	103062414
ENSE00002160059	103091787	103092160
ENSE00003541045	103064275	103064377
ENSE00003556202	103066459	103066567
ENSE00003570171	103089227	103089318
ENSE00003583569	103066269	103066373
ENSE00003623357	103082748	103082839
ENSE00003653170	103083256	103083326

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 98.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.0390 / max 1292.7694, expressed in 1827 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122034	51.6032	1826
122032	5.1073	1651
122033	3.3091	1500
122035	2.0193	1270

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.01	gold quality
oocyte	CL:0000023	97.77	gold quality
tibialis anterior	UBERON:0001385	94.43	silver quality
ventricular zone	UBERON:0003053	94.42	gold quality
ganglionic eminence	UBERON:0004023	94.11	gold quality
embryo	UBERON:0000922	94.10	gold quality
epithelial cell of pancreas	CL:0000083	93.98	gold quality
endothelial cell	CL:0000115	92.28	gold quality
deltoid	UBERON:0001476	92.18	gold quality
cortical plate	UBERON:0005343	92.07	gold quality
adrenal tissue	UBERON:0018303	91.92	gold quality
gastrocnemius	UBERON:0001388	91.82	gold quality
muscle of leg	UBERON:0001383	91.76	gold quality
skeletal muscle organ	UBERON:0014892	91.19	gold quality
stromal cell of endometrium	CL:0002255	91.09	gold quality
esophagus mucosa	UBERON:0002469	90.97	gold quality
cartilage tissue	UBERON:0002418	90.69	gold quality
left ventricle myocardium	UBERON:0006566	90.65	silver quality
islet of Langerhans	UBERON:0000006	90.51	gold quality
heart left ventricle	UBERON:0002084	90.42	gold quality
cardiac ventricle	UBERON:0002082	90.28	gold quality
right testis	UBERON:0004534	90.01	gold quality
tibia	UBERON:0000979	89.83	gold quality
myocardium	UBERON:0002349	89.83	silver quality
skeletal muscle tissue	UBERON:0001134	89.61	gold quality
heart	UBERON:0000948	89.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.58	gold quality
esophagus squamous epithelium	UBERON:0006920	89.58	gold quality
buccal mucosa cell	CL:0002336	89.48	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-81383	no	987.54
E-MTAB-9689	no	396.75
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

439 targeting DCUN1D5, 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-7110-3P	100.00	73.18	2486
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4682	100.00	68.89	1258
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467

Literature-anchored findings (GeneRIF, showing 5)

• Overexpression of DCUN1D5 is associated with laryngeal squamous cell carcinoma. (PMID:23098533)
• SCCRO5 has oncogenic potential that requires its function as a component of the neddylation E3. Neddylation activity and nuclear localization of SCCRO5 are important for its in vivo function. (PMID:24192928)
• evidence that DCNL5 may be involved in innate immunity, as it is a direct substrate of the kinase IKKalpha during immune signalling. (PMID:29958295)
• All reported DCN1 inhibitors are able to induce remarkable accumulation of cullin 3 and its substrate NRF2, indicating therapeutic potential of DCN1 inhibitors for human diseases that may benefit from upregulation of cullin 3 and NRF2 (PMID:31668094)
• YY1 mediated DCUN1D5 transcriptional activation promotes triple-negative breast cancer progression by targeting FN1/PI3K/AKT pathway. (PMID:38831379)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dcun1d5	ENSDARG00000100363
mus_musculus	Dcun1d5	ENSMUSG00000032002
rattus_norvegicus	Dcun1d5	ENSRNOG00000008390
drosophila_melanogaster	SCCRO	FBGN0036510
drosophila_melanogaster	SCCRO4	FBGN0036967
caenorhabditis_elegans		WBGENE00010428

Paralogs (4): DCUN1D1 (ENSG00000043093), DCUN1D4 (ENSG00000109184), DCUN1D2 (ENSG00000150401), DCUN1D3 (ENSG00000188215)

Protein

Protein identifiers

DCN1-like protein 5 — Q9BTE7 (reviewed: Q9BTE7)

Alternative names: DCUN1 domain-containing protein 5, Defective in cullin neddylation protein 1-like protein 5, Squamous cell carcinoma-related oncogene 5

All UniProt accessions (9): Q9BTE7, E9PLH8, E9PLS2, E9PM04, E9PM78, E9PQV9, H0YCN4, H0YD80, J3QQL8

UniProt curated annotations — full annotation on UniProt →

Function. Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes which is necessary for the activation of cullin-RING E3 ubiquitin ligases (CRLs). May play a role in DNA damage response and may participate in cell proliferation and anchorage-independent cell growth.

Subunit / interactions. Part of a complex that contains DCUN1D5, CUL1 and RBX1; this interaction is bridged by CUL1. Interacts (via the DCUN1 domain) with the unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5; these interactions promote the cullin neddylation and the identity of the cullin dictates the affinity of the interaction. Interacts (via DCUN1 domain) with UBE2M (N-terminally acetylated form) and probably with UBE2F (N-terminally acetylated form). May also interact with regulators or subunits of cullin-RING ligases such as RBX1, RNF7, ELOB and DDB1; these interactions are bridged by cullins. Interacts with CAND1; this interaction is bridged by cullins and strongly inhibits the neddylation of cullins. These CAND-cullin-DCNL complexes can only be neddylated in the presence of a substrate adapter.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle.

Tissue specificity. Weakly expressed in testis, skin and immune tissues (thymus, spleen and lymph nodes).

Post-translational modifications. Phosphorylation at Ser-41 is independent of cullin’s interaction. Phosphorylated in response to both TICAM1 and MYD88 dependent Toll-like receptor (TLR) pathway activation. Phosphorylated in response to IL1B stimulation.

Domain organisation. The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins. The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D5-cullin and DCUN1D5-E2 interaction affinities.

Induction. Expression is decreased in a time-dependent manner after UVC exposure.

RefSeq proteins (4): NP_001305668, NP_001305669, NP_001305670, NP_115675* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005176	PONY_dom	Domain
IPR014764	DCN-prot	Family
IPR042460	DCN1-like_PONY	Homologous_superfamily

Pfam: PF03556

Enzyme classification (BRENDA):

• EC 2.3.2.32 — cullin-RING-type E3 NEDD8 transferase (BRENDA: 6 organisms, 26 substrates, 31 inhibitors, 0 Km, 0 kcat entries)

UniProt features (13 total): mutagenesis site 7, modified residue 3, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTE7-F1	88.05	0.82

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 (3): 9, 41, 48

Mutagenesis-validated functional residues (7):

Position	Phenotype
225	loss of interaction with rbx1, cul1, cul2, cul3 and cand1. does not affect interaction with ube2m and nedd8. fails to au
226	loss of interaction with rbx1, cul1, cul2, cul3 and cand1. does not affect interaction with ube2m and nedd8. fails to au
5–8	affects nucleus localization.
195	loss of interaction with cul1, cul2, cul3, cul4a, cul5, cand1 and rbx1; when associated with r-219 and a-225. does not a
195	loss of interaction with rbx1, cul1 and cand1.
219	loss of interaction with rbx1, cul1 and cand1. loss of interaction with cul1, cul2, cul3, cul4a, cul5, cand1 and rbx1; w
225	loss of interaction with cul1, cul2, cul3, cul4a, cul5, cand1 and rbx1; when associated with a-195 and r-219. does not a

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 188 (showing top): chr11q22, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_GROWTH, GOBP_PROTEIN_NEDDYLATION, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GGGCATT_MIR365, GOBP_DNA_DAMAGE_RESPONSE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, BASAKI_YBX1_TARGETS_UP, GOBP_CELL_GROWTH, GOCC_SPINDLE, GOBP_REGULATION_OF_GROWTH, GOCC_TRANSFERASE_COMPLEX, GOBP_POSITIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS

GO Biological Process (5): regulation of cell growth (GO:0001558), DNA damage response (GO:0006974), protein neddylation (GO:0045116), regulation of protein neddylation (GO:2000434), positive regulation of protein neddylation (GO:2000436)

GO Molecular Function (4): ubiquitin conjugating enzyme binding (GO:0031624), ubiquitin-like protein binding (GO:0032182), cullin family protein binding (GO:0097602), protein binding (GO:0005515)

GO Cellular Component (6): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), spindle (GO:0005819), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020)

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 neddylation	2
protein binding	2
intracellular membraneless organelle	2
cellular anatomical structure	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
cellular response to stress	1
protein modification by small protein conjugation	1
regulation of protein modification by small protein conjugation or removal	1
positive regulation of protein modification by small protein conjugation or removal	1
regulation of protein neddylation	1
ubiquitin-like protein conjugating enzyme binding	1
binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membrane-bounded organelle	1
microtubule cytoskeleton	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCUN1D5	UBA3	Q8TBC4	589
DCUN1D5	SBK2	P0C263	525
DCUN1D5	UBE2M	P61081	506
DCUN1D5	UBE2F	Q969M7	493
DCUN1D5	NEDD8	Q15843	477
DCUN1D5	METTL21C	Q5VZV1	466
DCUN1D5	NAE1	Q13564	464
DCUN1D5	FHL1	Q13642	461
DCUN1D5	CAND1	Q86VP6	422
DCUN1D5	TMEM243	Q9BU79	391
DCUN1D5	SENP8	Q96LD8	362
DCUN1D5	ELAPOR2	A8MWY0	358
DCUN1D5	ACSBG2	Q5FVE4	348
DCUN1D5	ZNF555	Q8NEP9	348
DCUN1D5	RNF7	Q9UBF6	344

IntAct

76 interactions, top by confidence:

A	B	Type	Score
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
LNX1	DCUN1D5	psi-mi:“MI:0915”(physical association)	0.560
DCUN1D5	LNX1	psi-mi:“MI:0915”(physical association)	0.560
DCUN1D5	PLEKHG4	psi-mi:“MI:0915”(physical association)	0.560
DCUN1D5	PICK1	psi-mi:“MI:0915”(physical association)	0.560
HUS1	DCUN1D5	psi-mi:“MI:0915”(physical association)	0.560
DYNC1H1	DCUN1D5	psi-mi:“MI:0915”(physical association)	0.560
KLK6	DCUN1D5	psi-mi:“MI:0915”(physical association)	0.560
FAM177A1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
TMEM213	METAP2	psi-mi:“MI:0914”(association)	0.530
ORF38	PPT1	psi-mi:“MI:0914”(association)	0.500
DCUN1D5	RPL3	psi-mi:“MI:0915”(physical association)	0.400
DCUN1D5	AHNAK	psi-mi:“MI:0915”(physical association)	0.400
DCUN1D5	YMT1.42Ac	psi-mi:“MI:0915”(physical association)	0.370
DCUN1D5	RCHY1	psi-mi:“MI:0915”(physical association)	0.370
FOXL1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXL2	DDX39A	psi-mi:“MI:0914”(association)	0.350
TEAD2	DDX39A	psi-mi:“MI:0914”(association)	0.350
M2	ESYT2	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
CD70	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PACC1	DEGS1	psi-mi:“MI:0914”(association)	0.350
PNKD	EXOC5	psi-mi:“MI:0914”(association)	0.350
LYPD3	CLASP2	psi-mi:“MI:0914”(association)	0.350

BioGRID (139): LNX1 (Two-hybrid), CUL1 (Biochemical Activity), CUL2 (Biochemical Activity), CUL3 (Biochemical Activity), CUL4A (Biochemical Activity), CUL4B (Biochemical Activity), CUL5 (Biochemical Activity), UBE2M (Reconstituted Complex), UBE2F (Reconstituted Complex), DCUN1D5 (Affinity Capture-MS), DCUN1D5 (Affinity Capture-MS), DCUN1D5 (Affinity Capture-MS), DCUN1D5 (Affinity Capture-MS), DCUN1D5 (Affinity Capture-MS), SAC3D1 (Co-fractionation)

ESM2 similar proteins: A0PJX0, A1L1L6, A4IG32, B1A8Z2, B1H2N3, C7A278, D2HZB0, O88456, P04632, P06813, P07090, P22676, P47728, Q08331, Q0IIL1, Q17QE5, Q1RMX9, Q2HJF8, Q2KI69, Q32L26, Q32LU1, Q3T0E8, Q3ZBY3, Q4R518, Q5PPL2, Q5RDF9, Q5ZM73, Q6NVC5, Q6P6Q9, Q6P8Y1, Q6PHZ8, Q6PIL6, Q8BG51, Q8HYN7, Q8IXI2, Q8R426, Q8VCX5, Q8WWF8, Q99828, Q99MG9

Diamond homologs: A4IHK8, Q1RMX9, Q4V8B2, Q54GP1, Q5ADL9, Q5E9V1, Q5PPL2, Q5R9G1, Q5RDF9, Q5RHX6, Q5ZKU1, Q60YT5, Q6C0B6, Q6DFA1, Q6PH85, Q86JM4, Q8BZJ7, Q8CCA0, Q8IWE4, Q8K0V2, Q8T8S1, Q92564, Q96GG9, Q9BTE7, Q9CXV9, Q9QZ73, Q9U3C8, Q9VUQ8, Q9VWB1, Q5AWS1, Q8WZK4, Q9MBG8, Q12395, Q4PF67, Q750Y3, P0CN06, P0CN07, Q6FJR2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1030 predictions. Top by Δscore:

Variant	Effect	Δscore
11:103062412:GCCCT:G	acceptor_loss	1.0000
11:103062413:CC:C	acceptor_gain	1.0000
11:103062414:CC:C	acceptor_gain	1.0000
11:103062415:C:CC	acceptor_gain	1.0000
11:103062415:CTAG:C	acceptor_loss	1.0000
11:103062416:T:A	acceptor_loss	1.0000
11:103064266:TATAC:T	donor_loss	1.0000
11:103064267:ATAC:A	donor_loss	1.0000
11:103064268:TAC:T	donor_loss	1.0000
11:103064269:AC:A	donor_loss	1.0000
11:103064270:C:CT	donor_loss	1.0000
11:103064271:TTACA:T	donor_loss	1.0000
11:103064272:TACAA:T	donor_loss	1.0000
11:103064273:A:AC	donor_gain	1.0000
11:103064273:ACAA:A	donor_loss	1.0000
11:103064274:C:CC	donor_gain	1.0000
11:103064274:C:CT	donor_loss	1.0000
11:103064274:CA:C	donor_gain	1.0000
11:103064274:CAAG:C	donor_gain	1.0000
11:103064375:TTG:T	acceptor_gain	1.0000
11:103064375:TTGC:T	acceptor_loss	1.0000
11:103064376:TG:T	acceptor_gain	1.0000
11:103064376:TGCT:T	acceptor_loss	1.0000
11:103064377:GC:G	acceptor_loss	1.0000
11:103064378:C:CC	acceptor_gain	1.0000
11:103064378:CT:C	acceptor_loss	1.0000
11:103064379:T:A	acceptor_loss	1.0000
11:103066265:GTA:G	donor_loss	1.0000
11:103066267:A:AC	donor_gain	1.0000
11:103066267:ACCT:A	donor_gain	1.0000

AlphaMissense

1568 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:103062392:A:C	F227L	1.000
11:103062392:A:T	F227L	1.000
11:103062393:A:G	F227S	1.000
11:103062394:A:G	F227L	1.000
11:103062399:T:A	D225V	1.000
11:103062400:C:G	D225H	1.000
11:103062408:A:T	V222D	1.000
11:103062411:G:C	P221R	1.000
11:103062411:G:T	P221H	1.000
11:103062412:G:A	P221S	1.000
11:103064275:A:G	W220R	1.000
11:103064275:A:T	W220R	1.000
11:103064324:G:C	F203L	1.000
11:103064324:G:T	F203L	1.000
11:103064325:A:G	F203S	1.000
11:103064326:A:G	F203L	1.000
11:103064342:C:A	W197C	1.000
11:103064342:C:G	W197C	1.000
11:103064344:A:G	W197R	1.000
11:103064344:A:T	W197R	1.000
11:103064346:T:G	Q196P	1.000
11:103064348:A:C	D195E	1.000
11:103064348:A:T	D195E	1.000
11:103064349:T:A	D195V	1.000
11:103064349:T:C	D195G	1.000
11:103064349:T:G	D195A	1.000
11:103064350:C:G	D195H	1.000
11:103064350:C:T	D195N	1.000
11:103064351:T:A	K194N	1.000
11:103064351:T:G	K194N	1.000

dbSNP variants (sampled 300 via entrez): RS1000096707 (11:103054619 T>C), RS1000169709 (11:103077490 G>T), RS1000175232 (11:103059823 T>C), RS1000321727 (11:103052400 T>C), RS1000411967 (11:103061297 G>A), RS1000510950 (11:103061341 C>T), RS1000516487 (11:103080284 C>A,G), RS1000692370 (11:103092423 T>C), RS1000704670 (11:103079324 A>G,T), RS1000789842 (11:103068598 T>G), RS1000863496 (11:103091300 T>C), RS1000905093 (11:103068302 A>C), RS1000962118 (11:103085028 T>C,G), RS1001012468 (11:103054440 T>C), RS1001026634 (11:103054117 C>T)

Disease associations

OMIM: gene MIM:616522 | 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
GCST002198_22	Tuberculosis	2.000000e-06
GCST002665_4	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	2.000000e-44
GCST002671_10	Toenail selenium levels	2.000000e-06
GCST002875_148	Diisocyanate-induced asthma	1.000000e-09
GCST002875_71	Diisocyanate-induced asthma	2.000000e-06
GCST006102_13	Interleukin-10 levels	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004744	matrix metalloproteinase measurement
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0006995	response to diisocyanate
EFO:0004750	interleukin 10 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295937 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.67	Ki	2.14	nM	CHEMBL4592844

PubChem BioAssay actives

2 with measured affinity, of 12 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-(4-methylphenyl)-2-prop-2-ynylsulfanyl-6-(1,3-thiazol-2-ylsulfanyl)pyrimidine-5-carbonitrile	1599587: Binding affinity to N-terminal GST tagged recombinant DCN5 (unknown origin) (47 to 237 residues) expressed in Escherichia coli BL21(DE3) assessed as reduction in DCN1/FAM-labelled N-terminal acetylated UBE2M (1 to 21 residues) protein-protein interaction after 30 mins by HTRF assay	ki	0.0021	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Tretinoin	decreases expression, affects cotreatment	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
quercitrin	decreases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
ochratoxin A	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acrolein	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Estradiol	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	increases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4222552	Binding	Inhibition of human DCN5-mediated cullin neddylation assessed as reduction in transfer of fluorescein-5-maleimide-tagged NEDD8 from N-terminally acetylated human UBE2M to CUL2-CTD at 50 uM measured for 1 min by pulse-chase assay	Piperidinyl Ureas Chemically Control Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation. — J Med Chem

Clinical trials (associated diseases)

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