JUND

Summary

JUND (JunD proto-oncogene, AP-1 transcription factor subunit, HGNC:6206) is a protein-coding gene on chromosome 19p13.11, encoding Transcription factor JunD (P17535). Transcription factor binding AP-1 sites.

The protein encoded by this intronless gene is a member of the JUN family, and a functional component of the AP1 transcription factor complex. This protein has been proposed to protect cells from p53-dependent senescence and apoptosis. Alternative translation initiation site usage results in the production of different isoforms (PMID:12105216).

Source: NCBI Gene 3727 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 59 total
• Druggable target: yes
• Transcription factor: yes — 118 downstream targets (CollecTRI)
• MANE Select transcript: NM_005354

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6206
Approved symbol	JUND
Name	JunD proto-oncogene, AP-1 transcription factor subunit
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	AP-1
Ensembl gene	ENSG00000130522
Ensembl biotype	protein_coding
OMIM	165162
Entrez	3727

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000252818, ENST00000600972

RefSeq mRNA: 2 — MANE Select: NM_005354 NM_001286968, NM_005354

CCDS: CCDS32959

Canonical transcript exons

ENST00000252818 — 1 exons

Exon	Start	End
ENSE00000690246	18279694	18281622

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 243.5282 / max 14458.3153, expressed in 1828 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179976	213.8791	1825
179973	8.2125	1691
179975	6.5765	1739
179960	3.5657	1386
179974	3.0240	1313
179965	1.9941	891
179967	1.0559	545
179971	1.0519	522
179963	0.9806	403
179968	0.8636	346

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardia of stomach	UBERON:0001162	99.85	gold quality
vena cava	UBERON:0004087	99.82	gold quality
nipple	UBERON:0002030	99.81	gold quality
paraflocculus	UBERON:0005351	99.79	gold quality
pylorus	UBERON:0001166	99.74	gold quality
renal medulla	UBERON:0000362	99.71	gold quality
mammary duct	UBERON:0001765	99.69	gold quality
trachea	UBERON:0003126	99.69	gold quality
saphenous vein	UBERON:0007318	99.68	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.67	gold quality
buccal mucosa cell	CL:0002336	99.66	gold quality
middle frontal gyrus	UBERON:0002702	99.64	gold quality
epithelium of mammary gland	UBERON:0003244	99.63	gold quality
lower lobe of lung	UBERON:0008949	99.60	gold quality
trigeminal ganglion	UBERON:0001675	99.58	gold quality
parotid gland	UBERON:0001831	99.55	gold quality
medial globus pallidus	UBERON:0002477	99.55	gold quality
cerebellar vermis	UBERON:0004720	99.54	gold quality
urethra	UBERON:0000057	99.51	gold quality
parietal lobe	UBERON:0001872	99.51	gold quality
postcentral gyrus	UBERON:0002581	99.51	gold quality
CA1 field of hippocampus	UBERON:0003881	99.51	gold quality
frontal pole	UBERON:0002795	99.48	gold quality
tendon of biceps brachii	UBERON:0008188	99.48	gold quality
dorsal root ganglion	UBERON:0000044	99.45	gold quality
ventral tegmental area	UBERON:0002691	99.45	gold quality
type B pancreatic cell	CL:0000169	99.44	gold quality
globus pallidus	UBERON:0001875	99.43	gold quality
mucosa of urinary bladder	UBERON:0001259	99.41	gold quality
pericardium	UBERON:0002407	99.40	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	654.31
E-MTAB-8205	yes	371.61
E-HCAD-4	yes	179.75
E-CURD-88	yes	39.81
E-HCAD-1	yes	30.80
E-GEOD-135922	yes	30.64
E-MTAB-9221	yes	18.44
E-HCAD-10	yes	14.12
E-GEOD-130148	yes	9.22
E-HCAD-13	yes	9.14
E-GEOD-125970	yes	6.80
E-MTAB-10553	yes	6.36
E-CURD-122	yes	5.46
E-HCAD-36	no	6918.68
E-MTAB-10855	no	6215.01

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

118 targets.

Target	Regulation
AGT	Activation
AKR1B15
ALAS2
AP1	Activation
APOC3	Repression
BCL6	Activation
BGLAP	Activation
CCL5	Unknown
CCND1	Activation
CCR4	Activation
CD2AP
CD40LG	Unknown
CDK2	Repression
CDK4	Unknown
CDKN1A	Unknown
CEBPZ
CLU	Unknown
CSTA	Unknown
CXCL8	Activation
CYP11B1
CYP19A1
CYP2C9
DBH	Unknown
DDX53
DNAJB4
EGF
ERBB2	Unknown
ERVW-4
F3	Unknown
FGFBP1	Unknown

JASPAR motifs

Motif	Name	Family
MA0491.1	JUND	Jun-related
MA0491.2	JUND	Jun-related
MA0491.3	JUND	Jun-related
MA0492.1	JUND	Jun-related
MA0492.2	JUND	Jun-related
MA1141.1	FOS::JUND	Fos-related::Jun-related
MA1141.2	FOS::JUND	Fos-related::Jun-related
MA1142.1	FOSL1::JUND	Fos-related::Jun-related
MA1142.2	FOSL1::JUND	Fos-related::Jun-related
MA1143.1	FOSL1::JUND	Fos-related::Jun-related
MA1143.2	FOSL1::JUND	Fos-related::Jun-related
MA1144.1	FOSL2::JUND	Fos-related::Jun-related
MA1144.2	FOSL2::JUND	Fos-related::Jun-related
MA1145.1	FOSL2::JUND	Fos-related::Jun-related
MA1145.2	FOSL2::JUND	Fos-related::Jun-related

JASPAR matrix evidence (PMIDs): PMID:21526160, PMID:11988758

Upstream regulators (CollecTRI, top): DDIT3, FOS, GCM1, JUN, JUNB, JUND, MEN1, RBMX, RUNX1, SP1, STAT2, ZIC1

miRNA regulators (miRDB)

79 targeting JUND, 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-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
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-570-3P	99.96	72.41	4910
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 40)

• An alternative model of H ferritin promoter transactivation by c-Jun (PMID:11903046)
• JunD activated by LHRH acts as a modulator of cell proliferation and cooperates with the anti-apoptotic and anti-mitogenic functions of LHRH. (PMID:12054733)
• junD activation by ultraviolet rays plays a role in apoptosis in myeloblastic leukemia ML-1 cells (PMID:12082101)
• Translation initiation from alternative AUG and non-AUG sites in human, mouse and rat. (PMID:12105216)
• Constitutive activation of nuclear factor kappaB p50/p65 and Fra-1 and JunD is essential for deregulated interleukin 6 expression in prostate cancer. (PMID:12727841)
• Menin is important for recruiting an mSin3A-histone deacetylase complex to repress JunD transcriptional activity. (PMID:14559791)
• Data show that human T-cell leukemia virus type I (HTLV-I) bZIP factor can activate JunD-dependent transcription and that its amino-terminus is required. (PMID:15044019)
• c-jun, junD, junB, and c-fos and Notch2 are expressed in splenic marginal zone lymphoma (PMID:15507668)
• menin suppresses osteoblast maturation, in part, by inhibiting the differentiation actions of JunD (PMID:15563473)
• JunD is another ARE regulatory protein for transcriptional activation of the human ferritin H gene and probably other antioxidant genes containing the conserved ARE sequences by which JunD may confer cytoprotection during oxidative stress (PMID:16007120)
• JunD limits cardiomyocyte hypertrophy and protects the pressure-overloaded heart from cardiac apoptosis (PMID:16129800)
• Menin’s dynamic regulation of histone modifiers with JunD is responsible for PKC theta-synergistic effect on Nur77 expression in T cell (PMID:16264271)
• JunB and JunD contribute opposing effects; JunB activated whereas JunD repressed heme oxygenase-1 expression in human renal epithelial cells (PMID:17204476)
• Pyk2 regulation is associated with increased expression of Fra-1 and JunD, activator protein-1 transcription factors known to be required for involucrin expression. (PMID:17205062)
• Coordinated down- and up-regulation of the various AP-1 subunits in the course of epidermal wound healing is important for its undisturbed progress, putatively by influencing inflammation and cell-cell communication. (PMID:17495958)
• Our data suggest that JUND and CLDN4 are critical mediators of the antiproliferative and antiviral effects of type I IFNs and further confirm the functional importance of the DNA-binding domain of Stat2. (PMID:17651017)
• Dimerization with the Jun proteins inhibits c-Fos nuclear exit. (PMID:17681951)
• aberrantly expressed Fra-2 in association with JunD may play a major role in CCR4 expression and oncogenesis in adult t-cell leukemia. (PMID:18071306)
• evidence is provided that HBZ/JunD heterodimers interact with Sp1 transcription factors and that activation of hTERT transcription by these heterodimers is mediated through binding sites for Sp1 present in the hTERT promoter. (PMID:18078517)
• Damaging exercise induced the expression of capZalpha, MCIP1, CARP1, DNAJB2, c-myc, and junD, each of which are likely involved in skeletal muscle growth, remodeling, and stress management. (PMID:18321953)
• JunD overexpression increases production of reactive oxygen species in LNCaP cells in a low androgen environment. (PMID:18386285)
• JunD is a major determinant of macrophage activity and is associated with glomerulonephritis susceptibility. (PMID:18443593)
• JunD activation reduces the proliferation of cancer cells. (PMID:18454173)
• JunD is a biological suppressor of ZO-1 expression in intestinal epithelial cells and plays a critical role in maintaining epithelial barrier function (PMID:18562690)
• These results reveal the molecular bases of the expression specificity of PADI1 and PADI3 during keratinocyte differentiation through a long-range enhancer and support a model of PADI gene regulation depending on c-Jun-JunD competition. (PMID:18952102)
• Activated c-Jun is dimerized with JunD in response to adrenomedullin. (PMID:19166930)
• Data suggest that TGF-beta1 up-regulates angiotensinogen transcription through a mechanism that requires both JunD and HIF-1alpha binding to the AGT core promoter, and that a molecular mechanism links hypoxia signaling and fibrogenic stimuli in the lung. (PMID:19211927)
• Decreased Jun-D and myogenin expression in muscle wasting of human cachexia. (PMID:19470832)
• These results suggest that the induction of MMP-7 by Tax is regulated by JunD and that MMP-7 could facilitate visceral invasion in adult T-cell leukemia . (PMID:21315773)
• JunD mediates, whereas c-Jun modulates, prostaglandin E2 activation of aromatase promoters (PMID:21393445)
• data indicate that JunD is an inhibitor of RHOH gene expression. (PMID:21473742)
• CDK4-mediated regulation of cell functions via c-Jun phosphorylation and AP-1 activation (PMID:21559334)
• Apoptosis induction by dominant negative JunD is due to induction of growth arrest and DNA damage inducible proteins (GADD) 45 alpha and 45 gamma proteins. (PMID:21734453)
• crystal structures of human menin in its free form and in complexes with MLL1 or with JUND, or with an MLL1-LEDGF heterodimer (PMID:22327296)
• results demonstrate the presence of a common oncogenic cascade initiated by FRA2/JUND in CCR4-expressing mature T-cell malignancies such as ATLL and CTCLs (PMID:22493372)
• HTLV-1 bZIP factor(hbz) requires cellular JunD to upregulate HTLV-1 antisense transcription from the 3’ long terminal repeat. (PMID:22696638)
• This genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor (PMID:23376981)
• Jun proteins (pc-Jun and JunD) influence carcinogenesis and tumour progression, suggesting a significant role as prognostic predictors in human ovarian carcinoma. (PMID:23942796)
• Binding of specific AP-1 factors, we found JunD associated with the LILRB1 distal promoter. (PMID:24038602)
• BAG3 stabilized JunD mRNA. (PMID:24140207)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	jund	ENSDARG00000067850
mus_musculus	Jund	ENSMUSG00000071076
rattus_norvegicus	Jund	ENSRNOG00000019568
drosophila_melanogaster	Jra	FBGN0001291
caenorhabditis_elegans		WBGENE00008945

Paralogs (2): JUNB (ENSG00000171223), JUN (ENSG00000177606)

Protein

Protein identifiers

Transcription factor JunD — P17535 (reviewed: P17535)

Alternative names: Transcription factor AP-1 subunit JunD

All UniProt accessions (2): P17535, U3KPR5

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor binding AP-1 sites. Heterodimerizes with proteins of the FOS family to form an AP-1 transcription factor complex, thereby enhancing their DNA binding activity to an AP-1 consensus sequence 3’-TGA[GC]TCA-5’ and enhancing their transcriptional activity.

Subunit / interactions. Heterodimer; binds DNA as a heterodimer. Component of an AP-1 transcription factor complex composed of JUN-FOS heterodimers. As part of the AP-1 transcription factor complex, forms heterodimers with FOS proteins, thereby binding to the AP-1 consensus sequence and stimulating transcription. Forms heterodimers with FOSB; thereby binding to the AP-1 consensus sequence. Interacts (via MBM motif) with MEN1; this interaction represses transcriptional activation. Interacts with MAPK10; this interaction is inhibited in the presence of MEN1.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated by MAP kinases MAPK8 and MAPK10; phosphorylation is inhibited in the presence of MEN1.

Domain organisation. Binds DNA via bZIP domain; DNA-binding is under control of cellular redox homeostasis (in vitro). To enable DNA binding, the bZIP domain must undergo a conformational rearrangement which requires the reduction of the interchain disulfide bond between FosB and JunD (in vitro).

Similarity. Belongs to the bZIP family. Jun subfamily.

RefSeq proteins (2): NP_001273897, NP_005345* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002112	Leuzip_Jun	Family
IPR004827	bZIP	Domain
IPR005643	JNK	Domain
IPR008917	TF_DNA-bd_sf	Homologous_superfamily
IPR046347	bZIP_sf	Homologous_superfamily
IPR050946	AP-1_TF_bZIP	Family

Pfam: PF00170, PF03957

UniProt features (36 total): mutagenesis site 14, modified residue 6, region of interest 5, compositionally biased region 2, sequence conflict 2, short sequence motif 2, chain 1, domain 1, disulfide bond 1, sequence variant 1, helix 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
9OC3	X-RAY DIFFRACTION	1.73
7UCC	X-RAY DIFFRACTION	1.94
5VPE	X-RAY DIFFRACTION	2.05
5VPC	X-RAY DIFFRACTION	2.5
5VPB	X-RAY DIFFRACTION	2.69
5VPF	X-RAY DIFFRACTION	2.69
5VPD	X-RAY DIFFRACTION	2.79
5VPA	X-RAY DIFFRACTION	2.83
3U86	X-RAY DIFFRACTION	2.84
7UCD	X-RAY DIFFRACTION	3.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17535-F1	64.42	0.24

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 (6): 90, 100, 117, 251, 255, 259

Disulfide bonds (1): 285

Mutagenesis-validated functional residues (14):

Position	Phenotype
30	reduced interaction with men1.
31	reduced interaction with men1.
32	loss of interaction with men1.
33	loss of interaction with men1.
34	loss of interaction with men1.
35	reduced interaction with men1.
36	reduced interaction with men1.
37	reduced interaction with men1.
46	loss of phosphorylation; when associated with a-47.
46	reduced interaction with men1; when associated with e-47.
47	loss of phosphorylation; when associated with a-46.
47	reduced interaction with men1; when associated with e-46.
52	loss of phosphorylation; when associated with a-54.
54	loss of phosphorylation; when associated with a-52.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-162582	Signal Transduction
R-HSA-166520	Signaling by NTRKs
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-198725	Nuclear Events (kinase and transcription factor activation)
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 425 (showing top): GOBP_CIRCADIAN_RHYTHM, ATF_B, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_ACTIVATION, PAX4_01, GOBP_RESPONSE_TO_COLD, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_CELLULAR_RESPONSE_TO_LIPID, FISCHER_G1_S_CELL_CYCLE, ENK_UV_RESPONSE_KERATINOCYTE_UP, KEGG_MAPK_SIGNALING_PATHWAY, CMYB_01

GO Biological Process (22): negative regulation of transcription by RNA polymerase II (GO:0000122), osteoblast development (GO:0002076), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), circadian rhythm (GO:0007623), response to light stimulus (GO:0009416), response to mechanical stimulus (GO:0009612), response to lipopolysaccharide (GO:0032496), positive regulation of peroxisome proliferator activated receptor signaling pathway (GO:0035360), regulation of cell population proliferation (GO:0042127), positive regulation of macrophage activation (GO:0043032), response to peptide hormone (GO:0043434), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of transcription by RNA polymerase II (GO:0045944), response to steroid hormone (GO:0048545), regulation of cell cycle (GO:0051726), cellular response to calcium ion (GO:0071277), cellular response to fatty acid (GO:0071398), cellular response to hypoxia (GO:0071456), response to forskolin (GO:1904321), regulation of DNA-templated transcription (GO:0006355), gene expression (GO:0010467)

GO Molecular Function (14): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coregulator binding (GO:0001221), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), transcription coactivator activity (GO:0003713), nuclear receptor binding (GO:0016922), enzyme binding (GO:0019899), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), transcription repressor complex (GO:0017053), protein-DNA complex (GO:0032993), transcription factor AP-1 complex (GO:0035976), RNA polymerase II transcription regulator complex (GO:0090575), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Signal Transduction	2
ESR-mediated signaling	1
Nuclear Events (kinase and transcription factor activation)	1
Regulation of PD-L1(CD274) expression	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by NTRKs	1
Signaling by NTRK1 (TRKA)	1
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
response to lipid	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
osteoblast differentiation	2
regulation of DNA-templated transcription	2
response to oxygen-containing compound	2
regulation of cellular process	2
response to hormone	2
positive regulation of DNA-templated transcription	2
DNA binding	2
cellular anatomical structure	2
protein-containing complex	2
transcription regulator complex	2
negative regulation of DNA-templated transcription	1
cell development	1
DNA-templated transcription	1
rhythmic process	1
response to radiation	1
response to external stimulus	1
response to abiotic stimulus	1
response to molecule of bacterial origin	1
peroxisome proliferator activated receptor signaling pathway	1
regulation of peroxisome proliferator activated receptor signaling pathway	1
positive regulation of intracellular signal transduction	1
cell population proliferation	1
positive regulation of leukocyte activation	1
macrophage activation	1
regulation of macrophage activation	1
response to nitrogen compound	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
cell cycle	1
response to calcium ion	1
cellular response to metal ion	1
response to fatty acid	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
response to hypoxia	1
cellular response to stress	1

Protein interactions and networks

STRING

2874 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JUND	FOSL2	P15408	999
JUND	FOSB	P53539	998
JUND	FOS	P01100	998
JUND	FOSL1	P15407	998
JUND	MEN1	O00255	991
JUND	JUNB	P17275	984
JUND	JUN	P05412	983
JUND	ATF3	P18847	981
JUND	JDP2	Q8WYK2	932
JUND	CREB1	P16220	894
JUND	BATF	Q16520	887
JUND	HBZ	P02008	886
JUND	ATF7	P17544	851
JUND	MAPK8	P45983	848
JUND	CEBPB	P17676	836

IntAct

126 interactions, top by confidence:

A	B	Type	Score
FOS	JUN	psi-mi:“MI:0914”(association)	0.980
ATF2	JUN	psi-mi:“MI:0914”(association)	0.950
JUNB	FOS	psi-mi:“MI:0914”(association)	0.950
FOS	JUNB	psi-mi:“MI:0914”(association)	0.950
JUND	FOS	psi-mi:“MI:0407”(direct interaction)	0.930
JUND	FOS	psi-mi:“MI:0915”(physical association)	0.930
FOSL2	JUN	psi-mi:“MI:0914”(association)	0.930
FOSL1	JUN	psi-mi:“MI:0914”(association)	0.850
JUND	FOSL2	psi-mi:“MI:0407”(direct interaction)	0.810
FOSL2	JUND	psi-mi:“MI:0407”(direct interaction)	0.810
ATF2	BACH1	psi-mi:“MI:0914”(association)	0.780
ATF2	JUND	psi-mi:“MI:0407”(direct interaction)	0.760
JUND	ATF2	psi-mi:“MI:0407”(direct interaction)	0.760
ATF2	JUND	psi-mi:“MI:0914”(association)	0.760
JUND	FOSL1	psi-mi:“MI:0914”(association)	0.730
JUND	BATF3	psi-mi:“MI:0407”(direct interaction)	0.690
BATF3	JUND	psi-mi:“MI:0407”(direct interaction)	0.690
FOSB	JUN	psi-mi:“MI:0914”(association)	0.690
CREB5	JUN	psi-mi:“MI:0914”(association)	0.690
MEN1	JUND	psi-mi:“MI:0407”(direct interaction)	0.650
MEN1	JUND	psi-mi:“MI:0915”(physical association)	0.650

BioGRID (129): JUND (Reconstituted Complex), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS), JUND (Affinity Capture-MS)

ESM2 similar proteins: A4IHR5, A6H7J1, A6NKL6, A6NL88, A7UKY7, A7YY54, B8ZZ34, C9J069, C9JLR9, E9Q1P8, O15209, O35615, O35779, P04198, P15066, P17535, P39881, P52909, Q01101, Q0PHV7, Q14526, Q14934, Q15742, Q32KV8, Q4VA45, Q52KG4, Q5TJE2, Q61976, Q63ZV0, Q6NUJ5, Q6P0F9, Q7T3H2, Q7Z5L9, Q7Z6J2, Q8C3Q5, Q8IX07, Q8R4T5, Q8TF61, Q8VCG9, Q96B18

Diamond homologs: A0A0A2J9B3, A7YY54, B8NLU5, O77627, O93602, P05411, P05412, P05627, P09450, P11939, P12981, P15066, P15336, P16951, P17275, P17325, P17535, P17544, P18870, P23050, P24898, P27921, P52890, P52909, P54864, P56432, P78962, P79703, Q00969, Q02100, Q02930, Q09771, Q09926, Q0VBZ5, Q2U616, Q4WVQ7, Q59VR1, Q5R9C9, Q8K1L0, Q8R0S1

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
(-)-anisomycin	up-regulates	JUND	“chemical activation”
MAPK1	up-regulates	JUND	phosphorylation
MAPK3	up-regulates	JUND	phosphorylation
MAPK8	up-regulates	JUND	phosphorylation
JUND	“up-regulates quantity by expression”	FOSL1	“transcriptional regulation”
Gbeta	up-regulates	JUND	phosphorylation
ERK1/2	up-regulates	JUND	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
NGF-stimulated transcription	7	33.9×	5e-07
Toll Like Receptor 10 (TLR10) Cascade	5	18.3×	4e-04
Toll Like Receptor 5 (TLR5) Cascade	5	18.3×	4e-04
MyD88 cascade initiated on plasma membrane	5	17.3×	5e-04
Toll Like Receptor 3 (TLR3) Cascade	5	16.4×	5e-04
TRIF (TICAM1)-mediated TLR4 signaling	5	16.1×	5e-04
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	5	16.1×	5e-04
MyD88 dependent cascade initiated on endosome	5	16.1×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	7	65.5×	3e-09
positive regulation of miRNA transcription	7	27.1×	1e-06
cellular response to calcium ion	5	13.4×	4e-03
response to ethanol	5	9.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

32 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18280447:CGCGG:C	donor_gain	0.6500
19:18280448:GCGGG:G	donor_gain	0.6500
19:18280449:CGGGC:C	donor_gain	0.6500
19:18280049:C:CT	acceptor_gain	0.5500
19:18280888:G:C	donor_gain	0.5500
19:18280047:T:G	acceptor_gain	0.5100
19:18280050:A:T	acceptor_gain	0.5100
19:18280450:GGG:G	donor_gain	0.3700
19:18280517:TGCGC:T	donor_gain	0.3700
19:18280521:C:CT	donor_gain	0.3700
19:18280441:TCAG:T	donor_gain	0.3600
19:18280832:TCGGC:T	acceptor_gain	0.3600
19:18280522:C:CT	donor_gain	0.3400
19:18280590:T:A	donor_gain	0.3400
19:18280049:C:T	acceptor_gain	0.3300
19:18280046:TTCC:T	acceptor_gain	0.3000
19:18280506:T:A	donor_gain	0.3000
19:18280833:C:A	acceptor_gain	0.3000
19:18280584:TC:T	donor_gain	0.2900
19:18281105:T:TG	acceptor_gain	0.2600
19:18280451:G:GC	donor_gain	0.2500
19:18280595:T:TA	donor_gain	0.2500
19:18281310:C:CT	donor_gain	0.2500
19:18280453:C:CT	donor_gain	0.2400
19:18280685:T:A	donor_gain	0.2400
19:18281311:C:CT	donor_gain	0.2400
19:18280400:C:A	donor_gain	0.2300
19:18280442:CAGT:C	donor_gain	0.2300
19:18280443:AGTA:A	donor_gain	0.2300
19:18280831:TTCGG:T	acceptor_gain	0.2200

AlphaMissense

2209 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18280478:C:T	C336Y	1.000
19:18280479:A:G	C336R	1.000
19:18280492:G:C	H331Q	1.000
19:18280492:G:T	H331Q	1.000
19:18280493:T:C	H331R	1.000
19:18280493:T:G	H331P	1.000
19:18280494:G:C	H331D	1.000
19:18280494:G:T	H331N	1.000
19:18280510:C:A	K325N	1.000
19:18280510:C:G	K325N	1.000
19:18280514:A:G	L324P	1.000
19:18280514:A:T	L324H	1.000
19:18280521:C:G	A322P	1.000
19:18280526:T:G	Q320P	1.000
19:18280532:C:G	R318P	1.000
19:18280535:A:G	L317P	1.000
19:18280535:A:T	L317Q	1.000
19:18280545:C:G	A314P	1.000
19:18280554:C:G	A311P	1.000
19:18280556:A:G	L310P	1.000
19:18280556:A:T	L310Q	1.000
19:18280564:G:C	N307K	1.000
19:18280564:G:T	N307K	1.000
19:18280566:T:C	N307D	1.000
19:18280573:C:A	K304N	1.000
19:18280573:C:G	K304N	1.000
19:18280577:A:G	L303P	1.000
19:18280577:A:T	L303H	1.000
19:18280587:C:A	V300L	1.000
19:18280587:C:G	V300L	1.000

dbSNP variants (sampled 300 via entrez): RS1000078578 (19:18282018 CGGTGCCGGCCTCCGG>C), RS1000101088 (19:18280874 G>A), RS1000352178 (19:18280387 C>A,G,T), RS1000403598 (19:18281897 C>T), RS1000753295 (19:18282059 A>C,G), RS1000760675 (19:18279350 C>T), RS1001193359 (19:18282074 C>T), RS1001597217 (19:18279817 G>A,C), RS1001783352 (19:18279702 C>T), RS1002144888 (19:18281606 C>T), RS1002195580 (19:18281566 C>T), RS1002868479 (19:18283613 C>T), RS1003337591 (19:18279874 G>A,T), RS1003377537 (19:18280030 ACT>A), RS1004249399 (19:18281771 G>A)

Disease associations

OMIM: gene MIM:165162 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST002782_264	Waist-to-hip ratio adjusted for body mass index	1.000000e-07
GCST002782_265	Waist-to-hip ratio adjusted for body mass index	9.000000e-10
GCST002782_266	Waist-to-hip ratio adjusted for body mass index	3.000000e-07
GCST002782_267	Waist-to-hip ratio adjusted for body mass index	5.000000e-10
GCST002796_1	Bronchodilator response in asthma	2.000000e-10
GCST004063_30	Waist circumference adjusted for body mass index	7.000000e-06
GCST004063_63	Waist circumference adjusted for body mass index	1.000000e-08
GCST004129_9	White blood cell count (monocyte)	5.000000e-09
GCST004500_128	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	3.000000e-08
GCST004501_97	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-07
GCST004504_69	Waist circumference adjusted for BMI in non-smokers	6.000000e-08
GCST004505_52	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	5.000000e-09
GCST004505_64	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	3.000000e-09
GCST004505_65	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	3.000000e-11
GCST004507_41	Waist-to-hip ratio adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-06
GCST004507_45	Waist-to-hip ratio adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-08
GCST004508_11	Waist-to-hip ratio adjusted for BMI in non-smokers	7.000000e-09
GCST004508_12	Waist-to-hip ratio adjusted for BMI in non-smokers	5.000000e-07
GCST005830_137	Hand grip strength	2.000000e-09
GCST007344_72	Estimated glomerular filtration rate	4.000000e-08
GCST007876_77	Estimated glomerular filtration rate	2.000000e-10
GCST010571_74	Autoimmune thyroid disease	4.000000e-17
GCST011096_12	Systemic lupus erythematosus	5.000000e-08
GCST90000025_560	Appendicular lean mass	7.000000e-24

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference
EFO:0005091	monocyte count
EFO:0004318	smoking behavior
EFO:0006941	grip strength measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4630755 (PROTEIN COMPLEX), CHEMBL6067460 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases activity, increases expression, increases phosphorylation	4
(+)-JQ1 compound	decreases expression, increases expression	4
deoxynivalenol	affects cotreatment, increases expression	3
Resveratrol	decreases expression, increases expression, affects cotreatment	3
triphenyl phosphate	increases abundance, increases expression, affects expression	2
bisphenol A	affects binding, increases reaction, affects expression	2
Arsenic Trioxide	affects cotreatment, decreases expression, increases expression	2
Acetaminophen	increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Estradiol	affects expression, affects binding, increases reaction	2
Quercetin	increases expression, affects binding, increases reaction	2
Tetrachlorodibenzodioxin	increases expression	2
Tetradecanoylphorbol Acetate	decreases reaction, increases expression, affects binding, increases reaction	2
Dronabinol	increases expression, increases localization, decreases reaction, increases response to substance, affects expression	2
Tretinoin	increases expression	2
Cyclosporine	increases expression, affects cotreatment	2
Cadmium Chloride	affects cotreatment, increases expression	2
TAK-243	decreases sumoylation	1
quinomethionate	affects expression	1
fucoidan	decreases activity	1
geraniol	increases expression	1
pimaric acid	affects cotreatment, decreases expression	1
cinnamaldehyde	decreases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	decreases expression	1
2-tert-butylhydroquinone	affects binding, increases reaction, increases phosphorylation, decreases reaction, increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
benzo(e)pyrene	decreases methylation	1
4-hydroxy-2-nonenal	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4625230	Binding	Inhibition of recombinant Hi6-tagged deltaFOSB (unknown origin)/His6-tagged JUND (unknown origin) expressed in insect cells interaction with TAMRA labeled 5’-GTCGGTGACTCAAAACA-3’ AP1 oligonucleotide measured after 15 mins by fluorescence po	Discovery of phenanthridine analogues as novel chemical probes disrupting the binding of DNA to ΔFosB homodimers and ΔFosB/JunD heterodimers. — Bioorg Med Chem Lett

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A3K1	SEES3-1V human JUND, clone1	Embryonic stem cell	Male
CVCL_A3K2	SEES3-1V human JUND, clone2	Embryonic stem cell	Male
CVCL_A3K3	SEES3-1V human JUND, clone3	Embryonic stem cell	Male
CVCL_AW31	K562 eGFP-JUND	Cancer cell line	Female
CVCL_D1X6	Abcam A-549 JUND KO	Cancer cell line	Male
CVCL_D2BF	Abcam HCT 116 JUND KO	Cancer cell line	Male

Clinical trials (associated diseases)

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