NFKBIE

Summary

NFKBIE (NFKB inhibitor epsilon, HGNC:7799) is a protein-coding gene on chromosome 6p21.1, encoding NF-kappa-B inhibitor epsilon (O00221). Sequesters NF-kappa-B transcription factor complexes in the cytoplasm, thereby inhibiting their activity. It is a selective cancer dependency (DepMap: 31.7% of cell lines).

The protein encoded by this gene binds to components of NF-kappa-B, trapping the complex in the cytoplasm and preventing it from activating genes in the nucleus. Phosphorylation of the encoded protein targets it for destruction by the ubiquitin pathway, which activates NF-kappa-B by making it available to translocate to the nucleus.

Source: NCBI Gene 4794 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 78 total
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 5 cancer types
• Cancer dependency (DepMap): dependent in 31.7% of screened cell lines
• MANE Select transcript: NM_004556

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7799
Approved symbol	NFKBIE
Name	NFKB inhibitor epsilon
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	IKBE
Ensembl gene	ENSG00000146232
Ensembl biotype	protein_coding
OMIM	604548
Entrez	4794

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000275015, ENST00000443607, ENST00000477930, ENST00000619360, ENST00000890578

RefSeq mRNA: 1 — MANE Select: NM_004556 NM_004556

CCDS: CCDS34463

Canonical transcript exons

ENST00000619360 — 6 exons

Exon	Start	End
ENSE00000974590	44262560	44262662
ENSE00002449589	44260451	44260539
ENSE00002481868	44260043	44260282
ENSE00002523703	44258166	44259284
ENSE00003690965	44261626	44261848
ENSE00003896869	44264982	44265551

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 88.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.0060 / max 1737.7270, expressed in 1798 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73758	29.0055	1785
73759	2.6296	1230
73757	0.3408	153
73753	0.0301	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.58	gold quality
granulocyte	CL:0000094	88.40	gold quality
spleen	UBERON:0002106	88.35	gold quality
monocyte	CL:0000576	87.57	gold quality
leukocyte	CL:0000738	87.39	gold quality
mononuclear cell	CL:0000842	87.31	gold quality
cartilage tissue	UBERON:0002418	86.01	gold quality
vermiform appendix	UBERON:0001154	85.99	gold quality
bone marrow cell	CL:0002092	84.63	gold quality
lymph node	UBERON:0000029	83.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.81	gold quality
cortical plate	UBERON:0005343	83.37	gold quality
blood	UBERON:0000178	83.31	gold quality
buccal mucosa cell	CL:0002336	81.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.91	gold quality
caecum	UBERON:0001153	81.21	gold quality
islet of Langerhans	UBERON:0000006	80.92	gold quality
bone marrow	UBERON:0002371	80.80	gold quality
mucosa of transverse colon	UBERON:0004991	80.62	gold quality
tonsil	UBERON:0002372	80.59	gold quality
prefrontal cortex	UBERON:0000451	80.25	gold quality
gall bladder	UBERON:0002110	79.87	gold quality
metanephros cortex	UBERON:0010533	79.71	gold quality
cingulate cortex	UBERON:0003027	79.68	gold quality
anterior cingulate cortex	UBERON:0009835	79.56	gold quality
ganglionic eminence	UBERON:0004023	79.53	gold quality
stromal cell of endometrium	CL:0002255	79.33	gold quality
cerebellar cortex	UBERON:0002129	79.27	gold quality
mucosa of urinary bladder	UBERON:0001259	79.23	silver quality
cerebellar hemisphere	UBERON:0002245	79.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.01
E-GEOD-110499	no	295.75

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CXCL8
ICAM1
SELE

Upstream regulators (CollecTRI, top): NFKB, RELA

miRNA regulators (miRDB)

23 targeting NFKBIE, 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-1184	99.99	68.19	1458
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-1301-5P	98.09	66.62	495
HSA-MIR-6502-5P	98.09	66.73	495
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-3972	97.19	66.46	808
HSA-MIR-6782-5P	96.45	64.42	612

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 31.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 14)

• Genomic mutation of the NFKBIE gene in primary Hodgkin/ Reed Sternberg cells (PMID:14595753)
• Protein phosphatase 6 subunit with conserved Sit4-associated protein domain targets IkappaBepsilon (PMID:16769727)
• An NFKBIE SNP associated with susceptibility to pneumococcal disease but not pneumococcal empyema. (PMID:17463416)
• Expression levels of GGT1 and possibly NFKBIE might be useful as biomarkers of genetic susceptibility to arsenite. (PMID:17976673)
• we identified two gene loci associated with rheumatoid arthritis susceptibility- NFKBIE and RTKN2 (PMID:23028356)
• Vitamin C forestalls cigarette smoke induced NF-kappaB activation in alveolar epithelial cells. (PMID:23615073)
• IkappaBepsilon has a role in NF-kappaB regulation in aggressive chronic lymphocytic leukemia (PMID:25987724)
• results show that Gal-1 acts by inhibiting the stimulation of the LPS-induced IkappaBzeta expression, an NF-kappaB regulator involved in IL-6 gene transcription. (PMID:26226212)
• Newly identified alterations included recurrent promoter mutations of NFKBIE, encoding NF-kappaB inhibitor varepsilon (IkappaBvarepsilon), in 14.5% of samples of desmoplastic melanoma (PMID:26343386)
• We suggest that the impairment of NFKBIE gene function can reduce the uptake of methotrexate into cells, suggesting that the gene is an important factor for rheumatoid arthritis outcome (PMID:26587663)
• A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis. (PMID:26870821)
• identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL. (PMID:27670424)
• NFKBIE mutations are selected by the tumor microenvironment and contribute to immune escape in chronic lymphocytic leukemia. (PMID:38486128)
• IkappaBepsilon deficiency accelerates disease development in chronic lymphocytic leukemia. (PMID:38575671)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nfkbie	ENSDARG00000068367
mus_musculus	Nfkbie	ENSMUSG00000023947
rattus_norvegicus	Nfkbie	ENSRNOG00000019907

Paralogs (16): BCL3 (ENSG00000069399), POTED (ENSG00000166351), POTEC (ENSG00000183206), POTEG (ENSG00000187537), POTEE (ENSG00000188219), POTEA (ENSG00000188877), POTEF (ENSG00000196604), POTEI (ENSG00000196834), POTEH (ENSG00000198062), POTEM (ENSG00000222036), POTEJ (ENSG00000222038), POTEB2 (ENSG00000230031), POTEB (ENSG00000233917), (ENSG00000276760), (ENSG00000277630), POTEB3 (ENSG00000278522)

Protein

Protein identifiers

NF-kappa-B inhibitor epsilon — O00221 (reviewed: O00221)

Alternative names: I-kappa-B-epsilon

All UniProt accessions (4): O00221, H0Y4W4, H3BNC2, Q7LC14

UniProt curated annotations — full annotation on UniProt →

Function. Sequesters NF-kappa-B transcription factor complexes in the cytoplasm, thereby inhibiting their activity. Sequestered complexes include NFKB1-RELA (p50-p65) and NFKB1-REL (p50-c-Rel) complexes. Limits B-cell activation in response to pathogens, and also plays an important role in B-cell development.

Subunit / interactions. Interacts with RELA, REL, NFKB1 nuclear factor NF-kappa-B p50 subunit and NFKB2 nuclear factor NF-kappa-B p52 subunit. Interacts with HNRNPA2B1; the interaction may be mediated by the RRM2 domain of HNRNPA2B1, and HNRNPA2B1 may interact simultaneously with FAM76B and either NFKBIA or NFKBIE to form a complex.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in spleen, testis and lung, followed by kidney, pancreas, heart, placenta and brain. Also expressed in granulocytes and macrophages.

Post-translational modifications. Serine phosphorylated; followed by proteasome-dependent degradation.

Similarity. Belongs to the NF-kappa-B inhibitor family.

RefSeq proteins (1): NP_004547* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR051070	NF-kappa-B_inhibitor	Family

Pfam: PF12796

UniProt features (25 total): repeat 6, sequence conflict 4, compositionally biased region 3, modified residue 3, mutagenesis site 3, region of interest 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00221-F1	62.07	0.39

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): 157, 161, 183

Mutagenesis-validated functional residues (3):

Position	Phenotype
145	no effect.
157	no degradation.
161	no degradation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells

MSigDB gene sets: 278 (showing top): KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, BOYLAN_MULTIPLE_MYELOMA_D_DN, TTGCWCAAY_CEBPB_02, MODULE_59, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, BOYLAN_MULTIPLE_MYELOMA_D_CLUSTER_DN, SIG_CD40PATHWAYMAP, HFH4_01, DIRMEIER_LMP1_RESPONSE_EARLY, BENPORATH_ES_CORE_NINE_CORRELATED, TIAN_TNF_SIGNALING_VIA_NFKB

GO Biological Process (1): D-serine transmembrane transport (GO:0042942)

GO Molecular Function (2): protein sequestering activity (GO:0140311), protein binding (GO:0005515)

GO Cellular Component (5): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Downstream signaling events of B Cell Receptor (BCR)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	2
amino acid transmembrane transport	1
serine transport	1
D-amino acid transport	1
carboxylic acid transmembrane transport	1
protein binding	1
molecular sequestering activity	1
binding	1
nucleolus	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2392 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFKBIE	REL	Q04864	992
NFKBIE	RELA	Q04206	959
NFKBIE	RELB	Q01201	937
NFKBIE	NFKBIB	Q15653	928
NFKBIE	PPP6C	O00743	901
NFKBIE	PPP6R1	Q9UPN7	838
NFKBIE	PPP6R2	O75170	827
NFKBIE	NFKBIA	P25963	814
NFKBIE	NFKB1	P19838	779
NFKBIE	IKBKB	O14920	767
NFKBIE	NFKB2	Q00653	764
NFKBIE	PPP6R3	Q5H9R7	706
NFKBIE	NFKBIZ	Q9BYH8	704
NFKBIE	CHUK	O15111	644
NFKBIE	TNF	P01375	625

IntAct

85 interactions, top by confidence:

A	B	Type	Score
RELB	NFKBIE	psi-mi:“MI:0914”(association)	0.670
REL	NFKBIE	psi-mi:“MI:0914”(association)	0.670
CDRT15P3	NFKBIE	psi-mi:“MI:0914”(association)	0.620
RELA	NFKBIE	psi-mi:“MI:0915”(physical association)	0.620
RELA	NFKBIE	psi-mi:“MI:0914”(association)	0.620
CDRT15P3	NFKBIE	psi-mi:“MI:0915”(physical association)	0.620
NFKB1	NFKBIE	psi-mi:“MI:2364”(proximity)	0.600
PPP6R1	NFKBIE	psi-mi:“MI:0915”(physical association)	0.590
NFKBIE	PPP6R2	psi-mi:“MI:0915”(physical association)	0.590
NFKBIE	ANKHD1	psi-mi:“MI:0915”(physical association)	0.570
NFKBIE	C1QBP	psi-mi:“MI:0915”(physical association)	0.570
NFKBIE	PRKN	psi-mi:“MI:0915”(physical association)	0.400
NFKBIE	PINK1	psi-mi:“MI:0915”(physical association)	0.400
NFKBIE	KBTBD7	psi-mi:“MI:0915”(physical association)	0.370
Tpx2	NFKBIE	psi-mi:“MI:0914”(association)	0.350
SKA3	AP3B1	psi-mi:“MI:0914”(association)	0.350
Ubr5	SFI1	psi-mi:“MI:0914”(association)	0.350
PRPF4		psi-mi:“MI:0914”(association)	0.350
NFKBIA	ATXN3	psi-mi:“MI:0914”(association)	0.350
YEATS4	ING3	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
NFKB1	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (61): BTRC (Affinity Capture-Western), NFKBIE (Affinity Capture-MS), NFKBIE (Affinity Capture-MS), NFKBIE (Two-hybrid), NFKBIE (Affinity Capture-MS), NFKBIE (Affinity Capture-MS), NFKBIE (Affinity Capture-MS), NFKBIE (Affinity Capture-MS), NFKBIE (Affinity Capture-MS), NFKBIE (Affinity Capture-MS), NFKBIE (Affinity Capture-MS), NFKBIE (Proximity Label-MS), NFKBIE (Affinity Capture-MS), NFKBIE (Affinity Capture-MS), NFKBIE (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RR11, A0A0U1RRI6, A6NCS6, A6NJG2, B0BN44, D3YXK1, E9PY61, E9Q0B3, F5H4A9, O00220, O00221, P09038, P0DPI3, P22083, P98077, Q08AU9, Q2M2W7, Q2M3V2, Q2TBI2, Q5F267, Q5FW56, Q5IS69, Q5R866, Q5T4W7, Q5TM52, Q5U4P2, Q5VTJ3, Q659K9, Q673H1, Q69ZB3, Q6AYE8, Q6IPT2, Q6PJ61, Q7RTU4, Q7TSX9, Q7YR31, Q80SU3, Q86SH2, Q86Y97, Q8NBR0

Diamond homologs: O00221, O54910, P19838, P20749, P25963, P83757, P98150, Q00653, Q08353, Q15653, Q60778, Q63369, Q63746, Q6F3J0, Q91974, Q9JIA3, Q9Z1E3, Q9Z2F6, Q04861, Q9WTK5, A2ARS0, C9JTQ0, L7XCU0, L7XDS4, O73630, O75762, O89019, P01125, P01126, P07207, P15307, P15330, P16236, P18954, P23631, P25799, P31695, P51509, P51510, P98149

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NFKBIE	down-regulates	NFKB1	binding
NFKBIE	down-regulates	NfKb-p65/p50	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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
RIP-mediated NFkB activation via ZBP1	6	73.3×	2e-08
MAP3K8 (TPL2)-dependent MAPK1/3 activation	5	64.9×	6e-07
TRAF6 mediated NF-kB activation	6	49.8×	2e-07
TAK1-dependent IKK and NF-kappa-B activation	6	32.8×	1e-06
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	5	32.4×	1e-05
Activation of NF-kappaB in B cells	9	32.2×	2e-09
RHO GTPases activate IQGAPs	5	31.5×	1e-05
Dectin-1 mediated noncanonical NF-kB signaling	7	27.4×	5e-07

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	7	101.7×	2e-10
protein refolding	5	53.8×	8e-06
canonical NF-kappaB signal transduction	8	50.5×	1e-09
mitotic cell cycle	6	13.8×	4e-04
regulation of apoptotic process	7	10.1×	5e-04
positive regulation of canonical NF-kappaB signal transduction	8	10.0×	1e-04
protein folding	5	8.9×	5e-03
protein stabilization	6	6.9×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 5 cancer types — CLLSLL, DLBCLNOS, LUAD, MLYM, NHL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

888 predictions. Top by Δscore:

Variant	Effect	Δscore
6:44260036:CACTT:C	donor_loss	1.0000
6:44260037:ACTTA:A	donor_loss	1.0000
6:44260039:TTA:T	donor_loss	1.0000
6:44260040:TA:T	donor_loss	1.0000
6:44260041:A:AC	donor_gain	1.0000
6:44260041:ACTT:A	donor_gain	1.0000
6:44260041:ACTTC:A	donor_gain	1.0000
6:44260042:C:CA	donor_loss	1.0000
6:44260042:C:CC	donor_gain	1.0000
6:44260042:CTT:C	donor_gain	1.0000
6:44260042:CTTC:C	donor_gain	1.0000
6:44260042:CTTCC:C	donor_gain	1.0000
6:44260044:T:TA	donor_gain	1.0000
6:44260045:C:A	donor_gain	1.0000
6:44260278:CCCTC:C	acceptor_gain	1.0000
6:44260279:CCTCC:C	acceptor_gain	1.0000
6:44260280:CTC:C	acceptor_gain	1.0000
6:44260281:TC:T	acceptor_gain	1.0000
6:44260282:CC:C	acceptor_gain	1.0000
6:44260283:C:CC	acceptor_gain	1.0000
6:44260284:T:A	acceptor_loss	1.0000
6:44260445:TCTCA:T	donor_loss	1.0000
6:44260446:CTCA:C	donor_loss	1.0000
6:44260447:TCA:T	donor_loss	1.0000
6:44260449:A:T	donor_loss	1.0000
6:44260450:C:CT	donor_loss	1.0000
6:44260535:CAGAC:C	acceptor_gain	1.0000
6:44260537:GAC:G	acceptor_gain	1.0000
6:44260538:ACC:A	acceptor_loss	1.0000
6:44260539:CCT:C	acceptor_loss	1.0000

AlphaMissense

2284 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:44262572:A:C	N291K	0.999
6:44262572:A:T	N291K	0.999
6:44262573:T:A	N291I	0.999
6:44264985:T:C	D260G	0.999
6:44261835:A:G	L300P	0.998
6:44261754:C:A	G327V	0.997
6:44262574:T:A	N291Y	0.997
6:44262651:A:G	L265P	0.997
6:44264985:T:G	D260A	0.997
6:44264988:C:A	G259V	0.997
6:44264997:G:A	S256F	0.997
6:44260079:A:C	N467K	0.996
6:44260079:A:T	N467K	0.996
6:44261633:G:C	N367K	0.996
6:44261633:G:T	N367K	0.996
6:44261634:T:A	N367I	0.996
6:44261763:T:A	D324V	0.996
6:44261832:G:T	A301D	0.996
6:44261833:C:G	A301P	0.996
6:44260152:A:G	L443P	0.995
6:44261764:C:G	D324H	0.995
6:44261805:A:T	V310D	0.995
6:44261841:A:T	L298H	0.995
6:44262561:T:G	Q295P	0.995
6:44262573:T:G	N291T	0.995
6:44262574:T:G	N291H	0.995
6:44264985:T:A	D260V	0.995
6:44264998:A:G	S256P	0.995
6:44260161:G:T	P440H	0.994
6:44260178:C:A	M434I	0.994

dbSNP variants (sampled 300 via entrez): RS1000289298 (6:44260996 G>A), RS1000856370 (6:44261563 C>A,G,T), RS1000894460 (6:44259307 G>A), RS1001042814 (6:44265743 C>G,T), RS1001189057 (6:44259908 T>G), RS1001859475 (6:44266408 T>C), RS1001885385 (6:44266223 T>C), RS1002388382 (6:44259719 A>G), RS1002861252 (6:44258598 C>T), RS1003349952 (6:44263813 C>T), RS1003427606 (6:44265368 G>A,C), RS1004011369 (6:44267546 G>A,T), RS1005431648 (6:44262096 C>A), RS1005851277 (6:44265844 T>A), RS1005922560 (6:44259991 C>G,T)

Disease associations

OMIM: gene MIM:604548 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001454_3	Rheumatoid arthritis	6.000000e-19
GCST001681_1	Rheumatoid arthritis	1.000000e-15
GCST002318_172	Rheumatoid arthritis	1.000000e-19
GCST002318_82	Rheumatoid arthritis	2.000000e-13
GCST002318_83	Rheumatoid arthritis	3.000000e-08
GCST004609_70	Monocyte percentage of white cells	2.000000e-10
GCST004625_84	Monocyte count	6.000000e-14
GCST006959_133	Rheumatoid arthritis	2.000000e-19
GCST006959_29	Rheumatoid arthritis	3.000000e-08
GCST006959_5	Rheumatoid arthritis	9.000000e-13
GCST011389_12	Rheumatoid arthritis	9.000000e-10
GCST90002393_80	Monocyte count	2.000000e-24
GCST90002394_159	Monocyte percentage of white cells	1.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3407 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression	3
Asbestos, Crocidolite	increases expression	3
Bortezomib	increases stability, decreases expression, decreases reaction	2
Arsenic Trioxide	decreases degradation, increases stability, decreases expression, decreases reaction	2
Nickel	increases expression	2
Silicon Dioxide	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
2-anisidine	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
kojic acid	increases expression	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
andrographolide	increases expression	1
pentanal	increases expression	1
casticin	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bardoxolone methyl	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
ON 01910	affects expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	affects expression	1
Gemcitabine	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5136270	Binding	Induction of NFKBIE degradation in human MINO cells at 100 nM measured after 8 hrs by proteomic analysis	Structural Feature Analyzation Strategies toward Discovery of Orally Bioavailable PROTACs of Bruton’s Tyrosine Kinase for the Treatment of Lymphoma. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TA66	HAP1 NFKBIE (-) 1	Cancer cell line	Male
CVCL_TA67	HAP1 NFKBIE (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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