NFKBID

Summary

NFKBID (NFKB inhibitor delta, HGNC:15671) is a protein-coding gene on chromosome 19q13.12, encoding NF-kappa-B inhibitor delta (Q8NI38). Regulates the expression of IL-2, IL-6, and other cytokines through regulation on NF-kappa-B activity.

Predicted to enable NF-kappaB binding activity. Predicted to be involved in T cell receptor signaling pathway; positive regulation of T-helper 17 cell differentiation; and regulation of gene expression. Predicted to act upstream of or within several processes, including negative regulation of NF-kappaB transcription factor activity; negative regulation of canonical NF-kappaB signal transduction; and positive regulation of thymocyte apoptotic process. Predicted to be active in nucleus.

Source: NCBI Gene 84807 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 44 total
• Transcription factor: yes — 35 downstream targets (CollecTRI)
• MANE Select transcript: NM_139239

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15671
Approved symbol	NFKBID
Name	NFKB inhibitor delta
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	TA-NFKBH, IkappaBNS, IkBNS
Ensembl gene	ENSG00000167604
Ensembl biotype	protein_coding
OMIM	618887
Entrez	84807

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000585544, ENST00000585925, ENST00000586361, ENST00000588039, ENST00000588497, ENST00000590094, ENST00000590828, ENST00000591730, ENST00000606253, ENST00000641389, ENST00000715565

RefSeq mRNA: 5 — MANE Select: NM_139239 NM_001321831, NM_001365705, NM_001365706, NM_032721, NM_139239

CCDS: CCDS42552, CCDS92601

Canonical transcript exons

ENST00000641389 — 12 exons

Exon	Start	End
ENSE00001114847	35896913	35897058
ENSE00001268039	35887952	35888612
ENSE00003673828	35896726	35896831
ENSE00003786790	35896392	35896538
ENSE00003807773	35897651	35897856
ENSE00003808249	35898719	35898822
ENSE00003810209	35898472	35898532
ENSE00003811546	35900442	35900540
ENSE00004027240	35889890	35890054
ENSE00004027244	35890374	35890490
ENSE00004027245	35895980	35896128
ENSE00004027247	35896218	35896269

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 94.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2439 / max 449.4196, expressed in 1301 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180595	5.2747	793
180594	1.1014	632
180591	0.4107	82
180592	0.3025	82
180590	0.1546	65

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	94.72	gold quality
granulocyte	CL:0000094	91.69	gold quality
sural nerve	UBERON:0015488	87.04	gold quality
monocyte	CL:0000576	86.45	gold quality
leukocyte	CL:0000738	86.28	gold quality
blood	UBERON:0000178	86.22	gold quality
vermiform appendix	UBERON:0001154	85.74	gold quality
omental fat pad	UBERON:0010414	84.78	gold quality
ileal mucosa	UBERON:0000331	84.73	gold quality
peritoneum	UBERON:0002358	84.66	gold quality
spleen	UBERON:0002106	84.44	gold quality
upper lobe of left lung	UBERON:0008952	84.25	gold quality
left lobe of thyroid gland	UBERON:0001120	83.94	gold quality
bone marrow	UBERON:0002371	83.81	gold quality
metanephros cortex	UBERON:0010533	83.76	gold quality
mucosa of stomach	UBERON:0001199	83.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.41	gold quality
adenohypophysis	UBERON:0002196	83.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.28	gold quality
left uterine tube	UBERON:0001303	83.25	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.11	gold quality
right lobe of thyroid gland	UBERON:0001119	83.08	gold quality
gall bladder	UBERON:0002110	83.04	gold quality
lower esophagus mucosa	UBERON:0035834	82.72	gold quality
cerebellar hemisphere	UBERON:0002245	82.47	gold quality
cerebellar cortex	UBERON:0002129	82.37	gold quality
tibial nerve	UBERON:0001323	82.24	gold quality
thyroid gland	UBERON:0002046	82.19	gold quality
upper lobe of lung	UBERON:0008948	82.10	gold quality
right ovary	UBERON:0002118	82.08	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-106540	yes	3287.57
E-HCAD-4	yes	105.68
E-GEOD-84465	yes	36.65
E-MTAB-9467	yes	35.81
E-ANND-3	yes	20.45
E-GEOD-135922	yes	12.74
E-MTAB-6678	yes	6.03
E-MTAB-6386	no	442.72

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

35 targets.

Target	Regulation
ABCA1
ADAM2
AHR
BCL2
BECN1
CD69
CDK4
CEBPD
CFLAR
CXCL10
CXCL8
CYP2A13
EPCAM
ERC1
FASLG
ICAM1
IFNG
IFNGR2
IL6
IRF6
ITCH
MICA
MUC5AC
MUC5B
MYD88
NDRG2
NFKBIA
NOS2
NOS3
SAG

Upstream regulators (CollecTRI, top): NFKB1, NFKB

Literature-anchored findings (GeneRIF, showing 1)

• The unique ability of p100/IkappaBdelta to stably interact with all NF-kappaB subunits by forming kappaBsomes demonstrates its importance in sequestering NF-kappaB subunits and releasing them as dictated by specific stimuli for developmental programs. (PMID:25349408)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nfkbid	ENSMUSG00000036931
rattus_norvegicus	Nfkbid	ENSRNOG00000025111

Paralogs (3): RFXANK (ENSG00000064490), NFKBIZ (ENSG00000144802), ANKRA2 (ENSG00000164331)

Protein

Protein identifiers

NF-kappa-B inhibitor delta — Q8NI38 (reviewed: Q8NI38)

Alternative names: I-kappa-B-delta, IkappaBNS, T-cell activation NFKB-like protein, TA-NFKBH

All UniProt accessions (5): A0A286YF31, A0AAQ5BIF9, K7EKM2, K7ENW9, Q8NI38

UniProt curated annotations — full annotation on UniProt →

Function. Regulates the expression of IL-2, IL-6, and other cytokines through regulation on NF-kappa-B activity. Functions in the regulation of inflammatory responses. Involved in the induction of T helper 17 cells (Th17) differentiation upon recognition of antigen by T cell antigen receptor (TCR). May also regulate TCR-induced negative selection of thymocytes.

Subunit / interactions. Interacts with NFKB1, RELA and RELB; in the nucleus.

Subcellular location. Nucleus.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NI38-1	1	yes
Q8NI38-2	2
Q8NI38-3	3

RefSeq proteins (5): NP_001308760, NP_001352634, NP_001352635, NP_116110, NP_640332* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF12796, PF13857

UniProt features (11 total): repeat 6, splice variant 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NI38-F1	88.20	0.76

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 227 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, CREL_01, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_T_HELPER_CELL_DIFFERENTIATION, CREBP1_Q2, NFKB_Q6

GO Biological Process (4): inflammatory response (GO:0006954), regulation of gene expression (GO:0010468), T cell receptor signaling pathway (GO:0050852), positive regulation of T-helper 17 cell differentiation (GO:2000321)

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

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	1
gene expression	1
regulation of macromolecule biosynthetic process	1
antigen receptor-mediated signaling pathway	1
positive regulation of immune effector process	1
positive regulation of T-helper cell differentiation	1
T-helper 17 cell differentiation	1
positive regulation of T-helper 17 type immune response	1
regulation of T-helper 17 cell differentiation	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1271 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFKBID	NFKBIB	Q15653	818
NFKBID	RELA	Q04206	760
NFKBID	RELB	Q01201	759
NFKBID	REL	Q04864	736
NFKBID	NFKB2	Q00653	665
NFKBID	NFKBIE	O00221	559
NFKBID	CD40	P25942	551
NFKBID	NFKBIA	P25963	517
NFKBID	BCL3	P20749	512
NFKBID	NFKB1	P19838	502
NFKBID	CHUK	O15111	447
NFKBID	NFKBIZ	Q9BYH8	438
NFKBID	IKBKB	O14920	432
NFKBID	IKBKG	Q9Y6K9	431
NFKBID	RC3H1	Q5TC82	419

IntAct

351 interactions, top by confidence:

A	B	Type	Score
NFKBID	C1orf94	psi-mi:“MI:0915”(physical association)	0.780
C1orf94	NFKBID	psi-mi:“MI:0915”(physical association)	0.780
SS18	NFKBID	psi-mi:“MI:0915”(physical association)	0.560
NFKBID	KRT40	psi-mi:“MI:0915”(physical association)	0.560
TRIM9	NFKBID	psi-mi:“MI:0915”(physical association)	0.560
KRT40	NFKBID	psi-mi:“MI:0915”(physical association)	0.560
NFKBID	SS18	psi-mi:“MI:0915”(physical association)	0.560
CYB5R2	NFKBID	psi-mi:“MI:0915”(physical association)	0.560
LMO4	NFKBID	psi-mi:“MI:0915”(physical association)	0.560
NFKBID	NDUFB7	psi-mi:“MI:0915”(physical association)	0.560
NFKBID	ZC2HC1B	psi-mi:“MI:0915”(physical association)	0.560
HSBP1L1	NFKBID	psi-mi:“MI:0915”(physical association)	0.560
NFKBID	E4	psi-mi:“MI:0915”(physical association)	0.370
NFKBID	SS18	psi-mi:“MI:0915”(physical association)	0.370
SS18	NFKBID	psi-mi:“MI:0915”(physical association)	0.370
NFKBID	NFKB1	psi-mi:“MI:0914”(association)	0.350
NFKBID	C1orf94	psi-mi:“MI:0915”(physical association)	0.000
NFKBID	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
NFKBID	KRT76	psi-mi:“MI:0915”(physical association)	0.000
NFKBID	SMAD4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (128): NFKBID (Two-hybrid), C1orf94 (Two-hybrid), TRIM9 (Two-hybrid), KRT40 (Two-hybrid), NFKB1 (Affinity Capture-MS), REL (Affinity Capture-MS), NFKB2 (Affinity Capture-MS), ERCC4 (Affinity Capture-MS), NFKBID (Affinity Capture-RNA), NFKBID (Two-hybrid), NFKBID (Two-hybrid), NFKBID (Two-hybrid), NFKBID (Two-hybrid), NFKBID (Two-hybrid), NFKBID (Two-hybrid)

ESM2 similar proteins: A2AS55, B2RXR6, O15084, O75832, P0C927, Q08DV6, Q0P5B9, Q29RM5, Q2TB02, Q3SX45, Q495B1, Q499M5, Q4V890, Q502K3, Q505D1, Q53RE8, Q5F478, Q5RFS1, Q5U2S6, Q5ZLC8, Q6GPE5, Q6P6B7, Q6P9Z4, Q70X92, Q7T3P8, Q810B6, Q8BTI7, Q8C0T1, Q8C6Y6, Q8K0L0, Q8N8A2, Q8NB46, Q8NI38, Q8WXH4, Q91ZT8, Q96AX9, Q96DX5, Q96NS5, Q96Q27, Q9BSK4

Diamond homologs: A2RUV0, B2RXR6, G3I6Z6, G5EDE9, P19838, P20749, P21783, P25799, P39010, P46530, P46531, Q00653, Q01705, Q04861, Q07008, Q19013, Q2TB02, Q63369, Q6F3J0, Q8BTI7, Q8NB46, Q8NI38, Q9BE45, Q9BYH8, Q9EST8, Q9P2R3, Q9WTK5, Q9Z2F6, O75762, P25963, Q08353, Q63746, Q6RI86, Q8BLA8, Q8N3C7, Q9Z1E3, Q9NU02

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 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.

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	7	16.2×	2e-04
anterior/posterior pattern specification	6	10.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1857 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35888626:A:T	acceptor_gain	1.0000
19:35889884:A:AC	donor_gain	1.0000
19:35889885:C:CC	donor_gain	1.0000
19:35889886:TTA:T	donor_loss	1.0000
19:35889887:TAC:T	donor_loss	1.0000
19:35889888:A:AC	donor_gain	1.0000
19:35889888:A:C	donor_loss	1.0000
19:35889888:AC:A	donor_gain	1.0000
19:35889888:ACC:A	donor_gain	1.0000
19:35889888:ACCC:A	donor_gain	1.0000
19:35889888:ACCCC:A	donor_gain	1.0000
19:35889889:C:CC	donor_gain	1.0000
19:35889889:CC:C	donor_gain	1.0000
19:35889889:CCC:C	donor_gain	1.0000
19:35889889:CCCC:C	donor_gain	1.0000
19:35889889:CCCCC:C	donor_gain	1.0000
19:35890050:TGGGC:T	acceptor_gain	1.0000
19:35890051:GGGC:G	acceptor_gain	1.0000
19:35890052:GGC:G	acceptor_gain	1.0000
19:35890053:GC:G	acceptor_gain	1.0000
19:35890054:CC:C	acceptor_gain	1.0000
19:35890054:CCTGG:C	acceptor_loss	1.0000
19:35890055:C:CC	acceptor_gain	1.0000
19:35890055:C:T	acceptor_gain	1.0000
19:35890369:CCCA:C	donor_loss	1.0000
19:35890371:CA:C	donor_loss	1.0000
19:35890373:C:A	donor_loss	1.0000
19:35890376:T:A	donor_gain	1.0000
19:35890486:ATCTC:A	acceptor_gain	1.0000
19:35890488:CTC:C	acceptor_gain	1.0000

AlphaMissense

2896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35889944:G:C	N278K	0.998
19:35889944:G:T	N278K	0.998
19:35890035:A:T	L248H	0.998
19:35896486:A:G	L104P	0.998
19:35890038:G:T	A247D	0.997
19:35889927:G:T	P284H	0.996
19:35889945:T:A	N278I	0.994
19:35890023:G:T	A252D	0.994
19:35890482:C:A	K205N	0.994
19:35890482:C:G	K205N	0.994
19:35896011:A:G	L192S	0.994
19:35896522:G:T	A92E	0.994
19:35896523:C:G	A92P	0.994
19:35896534:G:T	P88H	0.994
19:35896826:A:T	L53H	0.994
19:35889978:A:G	L267P	0.993
19:35890384:A:T	V238D	0.993
19:35896423:G:T	A125D	0.993
19:35896519:G:T	A93D	0.993
19:35896739:T:A	E82V	0.993
19:35896779:C:G	A69P	0.993
19:35890027:C:G	A251P	0.992
19:35890456:G:T	A214D	0.992
19:35890462:T:C	H212R	0.992
19:35889963:G:T	A272E	0.991
19:35890032:T:C	H249R	0.991
19:35890047:C:A	G244V	0.991
19:35890047:C:T	G244E	0.991
19:35890453:A:T	V215E	0.991
19:35896778:G:T	A69D	0.991

dbSNP variants (sampled 300 via entrez): RS1000000698 (19:35889120 G>A), RS1000269788 (19:35894633 G>A), RS1000275515 (19:35891043 A>C), RS1000396552 (19:35903100 C>A,T), RS1000968616 (19:35901240 C>A,T), RS1001008950 (19:35900813 C>T), RS1001097633 (19:35900676 A>G), RS1001124388 (19:35899793 C>A,G,T), RS1001278092 (19:35889762 T>A), RS1001352368 (19:35893784 C>T), RS1001481358 (19:35888462 C>A,T), RS1001783678 (19:35894230 G>A), RS1001864016 (19:35895465 G>A), RS1001969006 (19:35899902 G>A,C), RS1002231724 (19:35888123 C>A,T)

Disease associations

OMIM: gene MIM:618887 | disease phenotypes: MIM:616576

GenCC curated gene-disease

Mondo (1): immunodeficiency, common variable, 12 (MONDO:0014697)

Orphanet (2): OBSOLETE: Common variable immunodeficiency (Orphanet:1572), NFKB1-related immune dysregulation (Orphanet:696874)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	increases expression, decreases methylation	3
Benzo(a)pyrene	increases expression, affects methylation	2
Nickel	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
Glupearl 19S	increases expression	1
Asian ginseng	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases expression, decreases methylation	1
arsenite	affects expression	1
casticin	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
jinfukang	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	increases expression	1
Dieldrin	increases expression	1
Diethylhexyl Phthalate	affects cotreatment, decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Zinc	affects cotreatment, increases expression	1
Cyclosporine	decreases methylation	1

Clinical trials (associated diseases)

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