IKBIP

Summary

IKBIP (IKBKB interacting protein, HGNC:26430) is a protein-coding gene on chromosome 12q23.1, encoding Inhibitor of nuclear factor kappa-B kinase-interacting protein (Q70UQ0). Target of p53/TP53 with pro-apoptotic function.

Predicted to be involved in response to X-ray. Predicted to act upstream of or within several processes, including negative regulation of NF-kappaB transcription factor activity; response to interleukin-1; and response to tumor necrosis factor. Located in endoplasmic reticulum and nucleolus.

Source: NCBI Gene 121457 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_153687

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26430
Approved symbol	IKBIP
Name	IKBKB interacting protein
Location	12q23.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31051, IKIP
Ensembl gene	ENSG00000166130
Ensembl biotype	protein_coding
OMIM	609861
Entrez	121457

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000299157, ENST00000342502, ENST00000393042

RefSeq mRNA: 3 — MANE Select: NM_153687 NM_153687, NM_201612, NM_201613

CCDS: CCDS41822, CCDS9067, CCDS9068

Canonical transcript exons

ENST00000299157 — 3 exons

Exon	Start	End
ENSE00001100077	98634296	98634413
ENSE00001266558	98624249	98626766
ENSE00002517574	98644523	98644788

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 94.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.6601 / max 598.3145, expressed in 1804 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132834	48.6601	1804

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	94.64	gold quality
calcaneal tendon	UBERON:0003701	91.48	gold quality
monocyte	CL:0000576	89.41	gold quality
leukocyte	CL:0000738	89.26	gold quality
islet of Langerhans	UBERON:0000006	86.68	gold quality
smooth muscle tissue	UBERON:0001135	86.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.35	gold quality
epithelial cell of pancreas	CL:0000083	86.26	gold quality
ventricular zone	UBERON:0003053	85.67	gold quality
vermiform appendix	UBERON:0001154	85.16	gold quality
secondary oocyte	CL:0000655	85.07	gold quality
cartilage tissue	UBERON:0002418	85.02	gold quality
blood	UBERON:0000178	84.91	gold quality
gall bladder	UBERON:0002110	84.22	gold quality
oocyte	CL:0000023	83.84	gold quality
tibia	UBERON:0000979	83.78	gold quality
left coronary artery	UBERON:0001626	83.32	gold quality
omental fat pad	UBERON:0010414	83.21	gold quality
peritoneum	UBERON:0002358	83.16	gold quality
adrenal tissue	UBERON:0018303	82.90	gold quality
granulocyte	CL:0000094	82.68	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.61	gold quality
visceral pleura	UBERON:0002401	82.28	gold quality
coronary artery	UBERON:0001621	81.88	gold quality
thoracic aorta	UBERON:0001515	81.87	gold quality
placenta	UBERON:0001987	81.84	gold quality
ascending aorta	UBERON:0001496	81.83	gold quality
tendon	UBERON:0000043	81.58	gold quality
right lung	UBERON:0002167	81.50	gold quality
parietal pleura	UBERON:0002400	81.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.97
E-HCAD-13	no	3.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

120 targeting IKBIP, 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-3924	100.00	72.09	2394
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
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

Literature-anchored findings (GeneRIF, showing 6)

• We conclude that IKIP is a novel p53 target gene with proapoptotic function.(IKIP1 protein, human) (PMID:15389287)
• study identifies a previously unrecognized role for IKIP in the negative regulation of NF-kappaB activation by inhibition of IKKalpha/beta phosphorylation through the disruption of IKK complex formation (PMID:31826938)
• hsa_circ_0072389, hsa_circ_0072386, hsa_circ_0008621, hsa_circ_0072387, and hsa_circ_0072391 aggravate glioma via miR-338-5p/IKBIP. (PMID:34897031)
• IKBIP, a novel glioblastoma biomarker, maintains abnormal proliferation of tumor cells by inhibiting the ubiquitination and degradation of CDK4. (PMID:36244542)
• IKBIP is a Predictive Biomarker Related to Immunosuppressive Microenvironment in Digestive System Malignancies. (PMID:37024442)
• IKBIP promotes tumor development via the akt signaling pathway in esophageal squamous cell carcinoma. (PMID:38914958)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ikbip	ENSDARG00000078520
mus_musculus	Ikbip	ENSMUSG00000019975
rattus_norvegicus	Ikbip	ENSRNOG00000008247

Protein

Protein identifiers

Inhibitor of nuclear factor kappa-B kinase-interacting protein — Q70UQ0 (reviewed: Q70UQ0)

All UniProt accessions (1): Q70UQ0

UniProt curated annotations — full annotation on UniProt →

Function. Target of p53/TP53 with pro-apoptotic function.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in vein endothelial cells. Isoform 4 is expressed in lung, kidney, spleen, thymus and skeletal muscle.

Post-translational modifications. N-glycosylated. Isoform 4 is glycosylated at Asn-154.

Induction. By X-ray irradiation.

Miscellaneous. Shares a common promoter with APAF1 from which the 2 genes are transcribed in opposite directions.

Isoforms (4)

UniProt ID	Names	Canonical?
Q70UQ0-1	1, IKIP2	yes
Q70UQ0-2	2
Q70UQ0-3	3, IKIP3
Q70UQ0-4	4, IKIP1

RefSeq proteins (3): NP_710154, NP_963906, NP_963907 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024152	Inh_kappa-B_kinase-int	Family

UniProt features (13 total): splice variant 4, sequence variant 2, glycosylation site 2, chain 1, transmembrane region 1, region of interest 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q70UQ0-F1	83.32	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 144, 328

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9758274	Regulation of NF-kappa B signaling

MSigDB gene sets: 174 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_RESPONSE_TO_IONIZING_RADIATION, REACTOME_INNATE_IMMUNE_SYSTEM, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, TTGGGAG_MIR150, GOBP_RESPONSE_TO_RADIATION, GARY_CD5_TARGETS_DN, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, HNF1_C, GOBP_RESPONSE_TO_X_RAY, OSMAN_BLADDER_CANCER_DN

GO Biological Process (1): response to X-ray (GO:0010165)

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

GO Cellular Component (4): nucleolus (GO:0005730), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TAK1-dependent IKK and NF-kappa-B activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to ionizing radiation	1
binding	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

126 interactions, top by confidence:

A	B	Type	Score
STAM	HGS	psi-mi:“MI:0914”(association)	0.860
L3MBTL2	E2F6	psi-mi:“MI:0914”(association)	0.730
MYOG	IKBIP	psi-mi:“MI:0915”(physical association)	0.670
IKBIP	MYOG	psi-mi:“MI:0915”(physical association)	0.670
WNT2B	IKBIP	psi-mi:“MI:0403”(colocalization)	0.660
IKBIP	WNT2B	psi-mi:“MI:0915”(physical association)	0.660
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
COMMD8	VPS26C	psi-mi:“MI:0914”(association)	0.640
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
	DDX3X	psi-mi:“MI:0914”(association)	0.630
KRT15	IKBIP	psi-mi:“MI:0915”(physical association)	0.560
IKBIP	NUP62	psi-mi:“MI:0915”(physical association)	0.560
TPM3	IKBIP	psi-mi:“MI:0915”(physical association)	0.560
BBLN	IKBIP	psi-mi:“MI:0915”(physical association)	0.560
TFIP11	IKBIP	psi-mi:“MI:0915”(physical association)	0.560
IKBIP	KRT15	psi-mi:“MI:0915”(physical association)	0.560
NUP62	IKBIP	psi-mi:“MI:0915”(physical association)	0.560
IKBIP	BBLN	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (239): IKBIP (Two-hybrid), IKBIP (Two-hybrid), IKBIP (Two-hybrid), IKBIP (Two-hybrid), IKBIP (Two-hybrid), IKBIP (Two-hybrid), IKBIP (Affinity Capture-MS), IKBIP (Affinity Capture-MS), IKBIP (Affinity Capture-MS), IKBIP (Affinity Capture-MS), IKBIP (Affinity Capture-MS), IKBIP (Affinity Capture-MS), IKBIP (Proximity Label-MS), IKBIP (Proximity Label-MS), IKBIP (Proximity Label-MS)

ESM2 similar proteins: A2VE00, A2VE53, B0F9L7, F4HVS6, O75071, O82259, Q10MI0, Q28GJ0, Q2KJD6, Q2TLY2, Q2TLZ1, Q2TLZ2, Q2TLZ3, Q2TLZ4, Q2TLZ5, Q3SYZ9, Q4V7D3, Q502L1, Q561Q8, Q561X3, Q5EAJ6, Q5FVH8, Q5M8Y7, Q5R6R3, Q5ZM60, Q640L3, Q641E3, Q6NPP4, Q70UQ0, Q7TQE6, Q802A9, Q8BGQ6, Q8BIS8, Q8GSA7, Q8GYU3, Q8N5G2, Q8TEQ0, Q96EE4, Q9CQA5, Q9DBZ1

Diamond homologs: A2VE53, Q5EAJ6, Q70UQ0, Q9DBZ1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 137 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
ERAD pathway	8	11.8×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

505 predictions. Top by Δscore:

Variant	Effect	Δscore
12:98626773:T:C	acceptor_gain	1.0000
12:98634320:A:AC	donor_gain	1.0000
12:98634321:C:CC	donor_gain	1.0000
12:98644843:C:A	donor_gain	1.0000
12:98644857:T:TA	donor_gain	1.0000
12:98644942:T:TA	donor_gain	1.0000
12:98626763:CAAG:C	acceptor_gain	0.9900
12:98626767:C:CC	acceptor_gain	0.9900
12:98626773:T:TC	acceptor_gain	0.9900
12:98634292:TTAC:T	donor_loss	0.9900
12:98634293:TA:T	donor_loss	0.9900
12:98634295:C:CT	donor_loss	0.9900
12:98634409:CAAAC:C	acceptor_gain	0.9900
12:98634412:ACCT:A	acceptor_loss	0.9900
12:98634414:C:CA	acceptor_loss	0.9900
12:98644516:CACTT:C	donor_loss	0.9900
12:98644517:ACTT:A	donor_loss	0.9900
12:98644518:CTTA:C	donor_loss	0.9900
12:98644519:TTAC:T	donor_loss	0.9900
12:98644520:TACC:T	donor_loss	0.9900
12:98644521:A:AC	donor_gain	0.9900
12:98644522:C:CC	donor_gain	0.9900
12:98644522:CCAGG:C	donor_gain	0.9900
12:98644850:C:A	donor_gain	0.9900
12:98644868:T:TA	donor_gain	0.9900
12:98644870:A:AC	donor_gain	0.9900
12:98644871:C:CC	donor_gain	0.9900
12:98644926:TCA:T	donor_gain	0.9900
12:98626762:TCAAG:T	acceptor_gain	0.9800
12:98626763:CAAGC:C	acceptor_gain	0.9800

AlphaMissense

2521 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:98644539:A:G	C55R	0.958
12:98644558:G:C	S48R	0.950
12:98644558:G:T	S48R	0.950
12:98644560:T:G	S48R	0.950
12:98644545:C:G	G53R	0.947
12:98644545:C:T	G53R	0.947
12:98644524:A:G	W60R	0.939
12:98644524:A:T	W60R	0.939
12:98644533:C:G	G57R	0.937
12:98644532:C:T	G57D	0.916
12:98644544:C:T	G53E	0.900
12:98634404:A:C	F63L	0.897
12:98634404:A:T	F63L	0.897
12:98634406:A:G	F63L	0.897
12:98644526:G:T	A59D	0.867
12:98644529:A:G	L58P	0.853
12:98644529:A:C	L58R	0.850
12:98644547:A:C	L52R	0.849
12:98644553:A:C	L50R	0.837
12:98634397:A:G	S66P	0.830
12:98634357:A:G	L79P	0.828
12:98634327:A:G	L89P	0.827
12:98634335:G:C	F86L	0.827
12:98634335:G:T	F86L	0.827
12:98634337:A:G	F86L	0.827
12:98634386:A:C	F69L	0.826
12:98634386:A:T	F69L	0.826
12:98634388:A:G	F69L	0.826
12:98644537:G:C	C55W	0.825
12:98644541:G:T	T54K	0.808

dbSNP variants (sampled 300 via entrez): RS1000170618 (12:98638684 A>C), RS1000228426 (12:98616359 TGA>T), RS1000299152 (12:98619122 C>T), RS1000343935 (12:98624716 A>T), RS1000460142 (12:98624919 C>T), RS1000471035 (12:98645945 T>A), RS1000657891 (12:98639658 C>G), RS1000677923 (12:98623298 T>C,G), RS1000725555 (12:98631242 A>G), RS1000793587 (12:98623553 C>T), RS1000872158 (12:98616068 C>T), RS1000883066 (12:98626949 C>T), RS1000909887 (12:98629316 G>A), RS1001055876 (12:98637296 T>C), RS1001058225 (12:98643576 T>C)

Disease associations

OMIM: gene MIM:609861 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006528_2	Barrett’s esophagus x pack-years of smoking exposure interaction	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006526	pack-years measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	5
Valproic Acid	increases expression, affects expression	3
Cadmium Chloride	decreases expression, increases expression, decreases reaction, increases abundance, increases palmitoylation	3
bisphenol A	decreases expression	2
sodium arsenite	increases abundance, increases expression, decreases expression	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
methylparaben	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctanoic acid	decreases expression	1
ferrous chloride	decreases expression	1
avobenzone	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
deguelin	increases expression	1
entinostat	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pyrimidifen	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	increases expression	1

Clinical trials (associated diseases)

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