BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

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Gene Report

Basic information

Related studies

Functional annotation

Related other genetic factors

Overlap with SZ and MDD

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Basic Info

Approved Symbol	TNF
Previous Symbol	TNFA
Symbol Alias	TNFSF2, DIF, TNF-alpha
Approved Name	tumor necrosis factor
Previous Name	tumor necrosis factor (TNF superfamily, member 2)
Name Alias	TNF superfamily, member 2
Location	6p21.3
Position	chr6:31575567-31578336, 1
External Links	HGNC: 11892 Entrez Gene: 7124 Ensembl: ENSG00000232810 UCSC: uc003nui.4
No. of Studies	4 (Positive: 2; Negative: 2; trend: 0)
Overlap with SZ?	YES
Overlap with MDD?	YES

Gene related studies (count: 4)

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Clerici, M.,2009	Other variant: TNF-alpha_308G/A	Our data reported a different genotype and allele distribution of -308 TNF-Î± and +874 IFN-Î³ in the bipolar II group that showed a higher percentage of subjects characterized by a lower production of both cytokines.	Positive	Comment on Study
Yosifova, A.,2009	SNP: rs1800629	No SNP of this gene had significant association with BD in our population.	Negative	Comment on Study
Meira-Lima, I.,2003(b)	Other variant: TNF_-G308A	The TNF-a gene variant did not present a significant difference in the allele and genotype distribution between the BPAD and the control groups.	Negative	Comment on Study
Pae, C. U.,2004(a)	Other variant: TNF_-G308A	The -G308A TNF-alpha gene polymorphism may confer a risk for BID in the Korean population.	Positive	Comment on Study

Gene functional annotation

Gene related GO terms (count: 130)

GO terms by PBA (count: 5)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0009615	response to virus	biological process	IDA[10490959]	5
GO:0005125	cytokine activity	molecular function	IDA[10748004]	13
GO:0005887	integral component of plasma membrane	cellular component	IDA[18355445]	158
GO:0006954	inflammatory response	biological process	IDA[10748004]	23
GO:0005886	plasma membrane	cellular component	TAS	360

GO terms by database search (count: 125)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0051222	positive regulation of protein transport	biological process	IDA[15310755]	1
GO:0097190	apoptotic signaling pathway	biological process	TAS	13
GO:0051023	regulation of immunoglobulin secretion	biological process	IEA	1
GO:0050766	positive regulation of phagocytosis	biological process	IMP[18201371]	3
GO:0033209	tumor necrosis factor-mediated signaling pathway	biological process	IMP[10748004]	2
GO:0050796	regulation of insulin secretion	biological process	IDA[8383325]	24
GO:0002020	protease binding	molecular function	IPI[12777399]	10
GO:0034116	positive regulation of heterotypic cell-cell adhesion	biological process	IDA[10604883]	2
GO:0032755	positive regulation of interleukin-6 production	biological process	IEA	8
GO:0050830	defense response to Gram-positive bacterium	biological process	IEA	7
GO:0051384	response to glucocorticoid	biological process	IDA[10443688]	11
GO:0043406	positive regulation of MAP kinase activity	biological process	IDA[12813029]	6
GO:0045840	positive regulation of mitotic nuclear division	biological process	IEA	5
GO:0031622	positive regulation of fever generation	biological process	ISS	3
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage	biological process	IEA	5
GO:2000343	positive regulation of chemokine (C-X-C motif) ligand 2 production	biological process	IDA[20551324]	1
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	IDA[15345745]; IGI[16803872]	91
GO:0050995	negative regulation of lipid catabolic process	biological process	IDA[19032770]	6
GO:0032715	negative regulation of interleukin-6 production	biological process	IDA[10443688]	4
GO:0043243	positive regulation of protein complex disassembly	biological process	IDA[12813029]	1
GO:0031334	positive regulation of protein complex assembly	biological process	IDA[12813029]	2
GO:2001240	negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	biological process	IDA[10666185]	8
GO:0060693	regulation of branching involved in salivary gland morphogenesis	biological process	IEA	1
GO:0009314	response to radiation	biological process	IEA	4
GO:0044212	transcription regulatory region DNA binding	molecular function	IDA[17350185]	17
GO:0048566	embryonic digestive tract development	biological process	IEP[20875417]	4
GO:0000060	protein import into nucleus, translocation	biological process	IDA[16280327]	4
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process	biological process	IDA[16723520]	7
GO:0045429	positive regulation of nitric oxide biosynthetic process	biological process	IDA[8383325]	13
GO:0071677	positive regulation of mononuclear cell migration	biological process	NAS[21319131]	1
GO:0097527	necroptotic signaling pathway	biological process	IDA[11101870]	1
GO:0045121	membrane raft	cellular component	IDA[17010968]	22
GO:0002925	positive regulation of humoral immune response mediated by circulating immunoglobulin	biological process	IEA	1
GO:0030198	extracellular matrix organization	biological process	IEA	26
GO:0051092	positive regulation of NF-kappaB transcription factor activity	biological process	IDA[10383454]	12
GO:0031663	lipopolysaccharide-mediated signaling pathway	biological process	IDA[21147091]	6
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity	biological process	IDA[10748004]	11
GO:0042493	response to drug	biological process	IEA	57
GO:0000185	activation of MAPKKK activity	biological process	IDA[15310755]	1
GO:0032741	positive regulation of interleukin-18 production	biological process	IEA	1
GO:0006006	glucose metabolic process	biological process	IEA	10
GO:0051798	positive regulation of hair follicle development	biological process	IEA	2
GO:0032729	positive regulation of interferon-gamma production	biological process	IEA	7
GO:0010628	positive regulation of gene expression	biological process	IDA[21559518]	23
GO:0044130	negative regulation of growth of symbiont in host	biological process	IEA	5
GO:0050715	positive regulation of cytokine secretion	biological process	IDA[10443688]	3
GO:0060664	epithelial cell proliferation involved in salivary gland morphogenesis	biological process	IEA	3
GO:0051533	positive regulation of NFAT protein import into nucleus	biological process	IDA[16803872]	2
GO:0005576	extracellular region	cellular component	TAS	97
GO:0071316	cellular response to nicotine	biological process	IDA[18676776]	2
GO:0071803	positive regulation of podosome assembly	biological process	IDA[15220135]	2
GO:0008285	negative regulation of cell proliferation	biological process	IEA	41
GO:0019722	calcium-mediated signaling	biological process	IEA	9
GO:0045071	negative regulation of viral genome replication	biological process	IDA[10490959]	1
GO:0043122	regulation of I-kappaB kinase/NF-kappaB signaling	biological process	IDA[10748004]	3
GO:0001819	positive regulation of cytokine production	biological process	IDA[17922812]	3
GO:0043068	positive regulation of programmed cell death	biological process	IDA[16611992]	1
GO:0043280	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	biological process	IDA[11577081]	4
GO:0045599	negative regulation of fat cell differentiation	biological process	NAS[16464856]	7
GO:0050901	leukocyte tethering or rolling	biological process	IDA[10820279]	1
GO:0014823	response to activity	biological process	IEA	11
GO:0002740	negative regulation of cytokine secretion involved in immune response	biological process	IDA[10443688]	2
GO:0002037	negative regulation of L-glutamate transport	biological process	IEA	1
GO:0050966	detection of mechanical stimulus involved in sensory perception of pain	biological process	IEA	4
GO:0010693	negative regulation of alkaline phosphatase activity	biological process	IEA	1
GO:0000165	MAPK cascade	biological process	IMP[21147091]	10
GO:0070374	positive regulation of ERK1 and ERK2 cascade	biological process	NAS[18606301]	14
GO:0045860	positive regulation of protein kinase activity	biological process	IDA[11821416]	8
GO:0060557	positive regulation of vitamin D biosynthetic process	biological process	IDA[1690216]	2
GO:0002876	positive regulation of chronic inflammatory response to antigenic stimulus	biological process	IEA	1
GO:0000187	activation of MAPK activity	biological process	IDA[10748004]	14
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological process	IDA[15345745]	62
GO:0010888	negative regulation of lipid storage	biological process	NAS[16464856]	2
GO:0045080	positive regulation of chemokine biosynthetic process	biological process	IDA[10490959]	3
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling	biological process	IDA[15310755]	14
GO:0045672	positive regulation of osteoclast differentiation	biological process	IDA[17888176]	5
GO:0043065	positive regulation of apoptotic process	biological process	IDA[16723520]	25
GO:0045668	negative regulation of osteoblast differentiation	biological process	IEA	3
GO:0045994	positive regulation of translational initiation by iron	biological process	IEA	1
GO:0030316	osteoclast differentiation	biological process	IEA	2
GO:0001891	phagocytic cup	cellular component	ISS	2
GO:0051897	positive regulation of protein kinase B signaling	biological process	IEA	11
GO:0001934	positive regulation of protein phosphorylation	biological process	IDA[10748004]	15
GO:0007254	JNK cascade	biological process	IEA	8
GO:0005515	protein binding	molecular function	IPI[11878931]	563
GO:0055037	recycling endosome	cellular component	ISS	14
GO:0045892	negative regulation of transcription, DNA-templated	biological process	IDA[16895791]	43
GO:0006927	transformed cell apoptotic process	biological process	IDA[3883195]	1
GO:0001666	response to hypoxia	biological process	IEA	24
GO:0045662	negative regulation of myoblast differentiation	biological process	IEA	1
GO:0030730	sequestering of triglyceride	biological process	IDA[19032770]	2
GO:0048661	positive regulation of smooth muscle cell proliferation	biological process	IDA[16518841]	11
GO:0045416	positive regulation of interleukin-8 biosynthetic process	biological process	IDA[20551324]	2
GO:0042802	identical protein binding	molecular function	IDA[14512626]	44
GO:0009651	response to salt stress	biological process	TAS[18355445]	4
GO:0002439	chronic inflammatory response to antigenic stimulus	biological process	IMP[14512626]	2
GO:0043507	positive regulation of JUN kinase activity	biological process	IDA[17389591]	2
GO:0051044	positive regulation of membrane protein ectodomain proteolysis	biological process	IDA[18373975]	5
GO:0009897	external side of plasma membrane	cellular component	ISS	21
GO:0071230	cellular response to amino acid stimulus	biological process	IEA	6
GO:0005615	extracellular space	cellular component	IDA[10443688]	85
GO:0050806	positive regulation of synaptic transmission	biological process	IEA	4
GO:0043491	protein kinase B signaling	biological process	IMP[21147091]	4
GO:0043242	negative regulation of protein complex disassembly	biological process	IDA[17389591]	1
GO:0003009	skeletal muscle contraction	biological process	IEA	4
GO:0060559	positive regulation of calcidiol 1-monooxygenase activity	biological process	IDA[1690216]	3
GO:0045893	positive regulation of transcription, DNA-templated	biological process	IDA[10748004]	58
GO:0032722	positive regulation of chemokine production	biological process	IDA[10490959]	4
GO:1990268	response to gold nanoparticle	biological process	IEA	1
GO:0006959	humoral immune response	biological process	IEA	5
GO:0032800	receptor biosynthetic process	biological process	IDA[10443688]	2
GO:0061048	negative regulation of branching involved in lung morphogenesis	biological process	IDA[17350185]	1
GO:0043525	positive regulation of neuron apoptotic process	biological process	IEA	11
GO:0009986	cell surface	cellular component	IDA[18355445]	40
GO:0010629	negative regulation of gene expression	biological process	IDA[15345745]	12
GO:0045760	positive regulation of action potential	biological process	IEA	3
GO:0046325	negative regulation of glucose import	biological process	IEA	1
GO:0071407	cellular response to organic cyclic compound	biological process	IDA[21147091]	5
GO:0001775	cell activation	biological process	IEA	2
GO:2000010	positive regulation of protein localization to cell surface	biological process	IDA[19366699]	1
GO:0008625	extrinsic apoptotic signaling pathway via death domain receptors	biological process	IDA[10521396]; NAS[21319131]	5
GO:0042346	positive regulation of NF-kappaB import into nucleus	biological process	IDA[17922812]	4
GO:0033138	positive regulation of peptidyl-serine phosphorylation	biological process	IDA[17389591]	10
GO:0005164	tumor necrosis factor receptor binding	molecular function	IDA[14512626]	2
GO:0097191	extrinsic apoptotic signaling pathway	biological process	IDA[11577081]	5

Gene related KEGG pathways (count: 18)

KEGG pathways by PBA (count: 4)

ID	Name	No. of Genes in BDgene
hsa04010	MAPK signaling pathway	39
hsa04350	TGF-beta signaling pathway	10
hsa04920	Adipocytokine signaling pathway	8
hsa04210	Apoptosis	12

KEGG pathways by database search (count: 14)

ID	Name	No. of Genes in BDgene
hsa04650	Natural killer cell mediated cytotoxicity	13
hsa04660	T cell receptor signaling pathway	13
hsa05010	Alzheimer's disease	4
hsa04640	Hematopoietic cell lineage	5
hsa05060	Prion disease	7
hsa04620	Toll-like receptor signaling pathway	10
hsa05310	Asthma	2
hsa05322	Systemic lupus erythematosus	4
hsa05330	Allograft rejection	6
hsa05332	Graft-versus-host disease	7
hsa04664	Fc epsilon RI signaling pathway	13
hsa04060	Cytokine-cytokine receptor interaction	17
hsa04940	Type I diabetes mellitus	10
hsa04930	Type II diabetes mellitus	11

Gene related BioCarta pathways (count: 21)

BioCarta pathways by PBA (count: 0)

BioCarta pathways by database search (count: 21)

ID	Name	No. of Genes in BDgene
granulocytesPathway	Adhesion and Diapedesis of Granulocytes	2
nfkbPathway	NF-kB Signaling Pathway	2
mspPathway	Msp/Ron Receptor Signaling Pathway	3
tnfr1Pathway	TNFR1 Signaling Pathway	1
pparaPathway	Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha)	12
il10Pathway	IL-10 Anti-inflammatory Signaling Pathway	4
tidPathway	Chaperones modulate interferon Signaling Pathway	3
cdMacPathway	Cadmium induces DNA synthesis and proliferation in macrophages	1
LairPathway	Cells and Molecules involved in local acute inflammatory response	2
hsp27Pathway	Stress Induction of HSP Regulation	2
soddPathway	SODD/TNFR1 Signaling Pathway	1
cytokinePathway	Cytokine Network	4
pmlPathway	Regulation of transcriptional activity by PML	3
freePathway	Free Radical Induced Apoptosis	2
inflamPathway	Cytokines and Inflammatory Response	4
vobesityPathway	Visceral Fat Deposits and the Metabolic Syndrome	2
stressPathway	TNF/Stress Related Signaling	2
il1rPathway	Signal transduction through IL1R	5
HivnefPathway	HIV-I Nef: negative effector of Fas and TNF	2
keratinocytePathway	Keratinocyte Differentiation	5
nthiPathway	NFkB activation by Nontypeable Hemophilus influenzae	5

Gene related interactors from protein-protein interactions data in HPRD (count: 12)

Gene	Interactor	Interactor in BDgene?	Experiment Type	PMID
TNF	PRTN3	NO	in vivo	10339575
TNF	IFNG	YES	in vitro;in vivo	3139842
TNF	TRAF2	NO	in vivo	12887920
TNF	TNFRSF1A	NO	in vitro;in vivo	10634209 , 14743216 , 19084540
TNF	ADAM17	NO	in vitro;in vivo	12135369 , 10799478
TNF	DCN	NO	in vitro	12387878
TNF	CSF1	NO	in vivo	8336080
TNF	MMP17	NO	in vitro	10799478
TNF	BGN	NO	in vitro	12387878
TNF	TNFRSF1B	NO	in vitro;in vivo	7664431 , 2158863 , 19084540
TNF	ADAM9	NO	in vitro	9920899
TNF	PDIK1L	NO	in vitro;in vivo	8597870

Related other genetic factors

Gene related SNPs (count: 1)

Literature-origin SNPs (count: 1)

rs_ID	Location	Functional Annotation	No. of Studies (Positive/Negative/Trend)
rs1800629	chrCHR_HSCHR6_MHC_SSTO_CTG1:31565999 - 31565999(1)	downstream_gene_variant; upstream_gene_variant	2(1/1/0)

LD-proxies (count: 0)

Gene related CNVs (count: 0)

Gene related other variants (count: 2)

Variant Name	Variant Type	Location in Gene	No. of Studies (Positive/Negative/Trend)
TNF_-G308A	point mutation		2 (1/1/0)
TNF-alpha_308G/A	point mutation		1 (1/0/0)

Gene related regions (count: 3)

Region Name	Position	No. of Studies (Positive/Negative/Trend)
Chr 6	chr6:0-170805979	3 (0/3/0)
6p21	chr6:30500000-46200000	1 (0/1/0)
6p23-p21.1	chr6:13400000-46200000	1 (1/0/0)

Overlap with schizophrenia (SZ) and major depressive disorder (MDD)

Gene relationship with SZ

Overlap with SZ from cross-disorder studies (count: 1)

Reference	Description	Result Category
12888800	Our larger sample suggests that these findings are not false-positive results, and supports the hypothesis that the TNF-a locus plays a role in susceptibility to schizophrenia.	Positive

Overlap with SZ from candidate gene intersection analysis (count: 21)

Reference	ID in SZGene	Result Category
14767724	404	Negative
17234379	404	Trend
15340354	404	Positive
15614591	404	Negative
14623370	404	Positive
14643088	404	Positive
15276234	404	Negative
19158809	404	Negative
15927374	404	Trend
11244489	404	Positive
16027740	404	Negative
12888800	404	Positive
16252073	404	Negative
12839521	404	Negative
17559942	404	Negative
14623371	404	Negative
12898567	404	Negative
12451465	404	Negative
16503400	404	Negative
16932925	404	Negative
17171665	404	Positive

Gene relationship with MDD

Overlap with MDD from cross-disorder studies (count: 0)

Overlap with MDD from candidate gene intersection analysis (count: 6)

Reference	Description	Category in MDD	Link in MK4MDD
20351714	the only gene for which the association with MDD remained significant after correction for multiple testing (rs76917; OR T = 1.35, 95% CI 1.13-1.63; P = 0.0034)	Pos	TNF
12960751	Genotype and allele distributions in patients with MDD (P=0.024 and P=0.0125, respectively), were significantly different from those of the controls. In particular, subjects with MDD had an increased frequency of the TNF2 (A) allele.	Pos	TNF
19836613	Our results evidenced a significantly higher percentage of the GG genotype in depressed subjects (84.0% vs. 68.3%; p=0.007) and consequently of the G allele (92.0% vs. 81.9%; p=0.05). The presence of the GG genotype raised the risk of developing MD (odds ratio=OR=2.433, confidence interval=Cl=1.09-5.43).	Pos	TNF
23064081		Pos	TNF
24424390	Thirty-four of the 47 monocyte inflammatory-related genes were significantly upregulated and 2 were significantly downregulated as compared to controls	Pos	TNF
19618378	In subjects affected by MD we found a higher percentage of the GG genotype (84 vs. 68,3%; p = 0.007) and thus of the G allele (92 vs. 81,9%; p = 0.05).The GG genotype was associated with a greater risk of developing the disease (OR 2.433, CI 1.09-5.43).	Pos	TNF

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Region: chr6:31575567..31578336 View in gBrowse