NFRKB

Summary

NFRKB (nuclear factor related to kappaB binding protein, HGNC:7802) is a protein-coding gene on chromosome 11q24.3, encoding Nuclear factor related to kappa-B-binding protein (Q6P4R8). Binds to the DNA consensus sequence 5’-GGGGAATCTCC-3’. It is a selective cancer dependency (DepMap: 42.2% of cell lines).

Enables protease binding activity. Involved in several processes, including positive regulation of DNA-templated transcription; regulation of DNA metabolic process; and regulation of chromosome organization. Located in Ino80 complex and nucleoplasm.

Source: NCBI Gene 4798 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 199 total
• GTEx eGene: eQTL in 49 tissues, sQTL in 21 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 42.2% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.54 (moderately constrained)
• MANE Select transcript: NM_001143835
• Notable: 199 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7802
Approved symbol	NFRKB
Name	nuclear factor related to kappaB binding protein
Location	11q24.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp547B2013, INO80G
Ensembl gene	ENSG00000170322
Ensembl biotype	protein_coding
OMIM	164013
Entrez	4798

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 27 protein_coding, 7 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000682444

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 4, TSL 4: 1, TSL 5: 4

ENST00000682444, ENST00000446488, ENST00000524746, ENST00000524794, ENST00000526884, ENST00000526940, ENST00000529319, ENST00000530278, ENST00000531318, ENST00000531755, ENST00000532147, ENST00000532225, ENST00000875000, ENST00000875001, ENST00000875002, ENST00000936753, ENST00000947152, ENST00000998697, ENST00000998698, ENST00000998699, ENST00000998700, ENST00000998701, ENST00000998702, ENST00000998703, ENST00000998704, ENST00001037414, ENST00001037415, ENST00001037416, ENST00001037417, ENST00001061036, ENST00001061037, ENST00001061038, ENST00001124360, ENST00001124361, ENST00001140236

RefSeq mRNA: 2 — MANE Select: NM_001143835 NM_001143835, NM_006165

CCDS: CCDS44770, CCDS8483

Canonical transcript exons

ENST00000682444 — 27 exons

Exon	Start	End
ENSE00001128659	129864966	129865101
ENSE00001128663	129865877	129865983
ENSE00001128670	129869494	129870261
ENSE00001128678	129872884	129873096
ENSE00001128685	129873745	129874015
ENSE00001128694	129874113	129874333
ENSE00001128703	129874501	129874580
ENSE00001128712	129874793	129874916
ENSE00001128722	129875357	129875463
ENSE00001128729	129876721	129876895
ENSE00001128735	129877325	129877385
ENSE00001128743	129878309	129878355
ENSE00001128750	129878464	129878543
ENSE00001128758	129881443	129881508
ENSE00001128764	129881727	129881853
ENSE00001128769	129882086	129882194
ENSE00001128778	129882451	129882631
ENSE00001128786	129884070	129884143
ENSE00001128815	129888594	129888795
ENSE00001131018	129883122	129883206
ENSE00001653418	129884745	129884846
ENSE00002167977	129894359	129894438
ENSE00002195691	129863636	129864850
ENSE00002200091	129892715	129892870
ENSE00003522010	129886317	129886444
ENSE00003604033	129885435	129885609
ENSE00003917857	129895496	129895578

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 96.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.3250 / max 45.8352, expressed in 1730 samples.

Highest expression (Bgee): buccal mucosa cell, secondary oocyte, oocyte, male germ line stem cell (sensu Vertebrata) in testis, endothelial cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NFRKB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 49 tissues and its splicing (sQTL) in 21 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 70 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	4.7e-58	-0.57	11:129884773:T:C
Whole Blood	eqtl	4.6e-49	-0.58	11:129822685:G:A
Adipose Subcutaneous	eqtl	1.4e-46	-0.59	11:129868653:T:G
Artery Tibial	eqtl	2.0e-31	-0.47	11:129861534:C:A
Esophagus Mucosa	eqtl	6.8e-31	-0.39	11:129853970:C:T
Thyroid	eqtl	2.1e-30	-0.26	11:129853970:C:T
Esophagus Muscularis	eqtl	1.1e-28	+0.53	11:129793142:T:C
Cells Cultured fibroblasts	eqtl	2.6e-27	-0.29	11:129862603:A:G
Muscle Skeletal	eqtl	1.5e-24	-0.36	11:129894970:C:T
Skin Sun Exposed Lower leg	eqtl	4.1e-23	-0.28	11:129898610:C:T
Colon Transverse	eqtl	7.3e-23	-0.53	11:129868653:T:G
Skin Not Sun Exposed Suprapubic	eqtl	1.1e-22	-0.35	11:129861534:C:A
Artery Aorta	eqtl	6.2e-21	-0.44	11:129894970:C:T
Cells EBV-transformed lymphocytes	eqtl	1.3e-20	-0.58	11:129868094:T:C
Brain Cerebellum	eqtl	3.1e-20	-0.51	11:129852887:C:A
Breast Mammary Tissue	eqtl	4.5e-19	+0.34	11:129793142:T:C
Adipose Visceral Omentum	eqtl	1.3e-18	-0.34	11:129894970:C:T
Esophagus Gastroesophageal Junction	eqtl	5.7e-16	-0.45	11:129854136:C:A
Lung	eqtl	1.0e-15	-0.36	11:129894970:C:T
Thyroid	sqtl	2.4e-15	-0.60	11:129875076:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
123143	6.3250	1730

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.23	gold quality
secondary oocyte	CL:0000655	93.46	gold quality
oocyte	CL:0000023	92.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.11	gold quality
endothelial cell	CL:0000115	88.75	gold quality
left lobe of thyroid gland	UBERON:0001120	88.67	gold quality
right uterine tube	UBERON:0001302	88.23	gold quality
thyroid gland	UBERON:0002046	88.23	gold quality
right lobe of thyroid gland	UBERON:0001119	88.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.91	gold quality
skin of leg	UBERON:0001511	87.15	gold quality
left ovary	UBERON:0002119	86.92	gold quality
ovary	UBERON:0000992	86.79	gold quality
testis	UBERON:0000473	86.78	gold quality
ventricular zone	UBERON:0003053	86.70	gold quality
tongue squamous epithelium	UBERON:0006919	86.66	silver quality
skin of abdomen	UBERON:0001416	86.63	gold quality
right testis	UBERON:0004534	86.40	gold quality
left testis	UBERON:0004533	86.36	gold quality
body of uterus	UBERON:0009853	86.35	gold quality
right ovary	UBERON:0002118	86.30	gold quality
vagina	UBERON:0000996	86.16	gold quality
adrenal tissue	UBERON:0018303	85.67	gold quality
gastrocnemius	UBERON:0001388	85.52	gold quality
body of pancreas	UBERON:0001150	85.51	gold quality
zone of skin	UBERON:0000014	85.33	gold quality
granulocyte	CL:0000094	85.30	gold quality
muscle of leg	UBERON:0001383	85.14	gold quality
mucosa of stomach	UBERON:0001199	84.92	gold quality
ectocervix	UBERON:0012249	84.88	gold quality
endocervix	UBERON:0000458	84.77	gold quality
esophagus mucosa	UBERON:0002469	84.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.58	gold quality
smooth muscle tissue	UBERON:0001135	84.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.26	gold quality
cerebellar hemisphere	UBERON:0002245	84.22	gold quality
popliteal artery	UBERON:0002250	84.22	gold quality
tibial artery	UBERON:0007610	84.22	gold quality
stromal cell of endometrium	CL:0002255	84.21	gold quality
descending thoracic aorta	UBERON:0002345	84.16	gold quality
cerebellar cortex	UBERON:0002129	84.05	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.99	gold quality
esophagus	UBERON:0001043	83.95	gold quality
fallopian tube	UBERON:0003889	83.95	gold quality
minor salivary gland	UBERON:0001830	83.93	gold quality
metanephros cortex	UBERON:0010533	83.86	gold quality
sperm	CL:0000019	83.83	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.83	gold quality
female reproductive system	UBERON:0000474	83.80	gold quality
lower esophagus mucosa	UBERON:0035834	83.80	gold quality
ganglionic eminence	UBERON:0004023	83.73	gold quality
aorta	UBERON:0000947	83.65	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	83.57	gold quality
body of stomach	UBERON:0001161	83.50	gold quality
oviduct epithelium	UBERON:0004804	83.50	gold quality
male germ cell	CL:0000015	83.47	gold quality
sural nerve	UBERON:0015488	83.41	gold quality
tibia	UBERON:0000979	83.30	gold quality
transverse colon	UBERON:0001157	83.30	gold quality
lower esophagus	UBERON:0013473	83.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.29	gold quality
rectum	UBERON:0001052	83.15	gold quality
right coronary artery	UBERON:0001625	83.15	gold quality
endometrium	UBERON:0001295	83.12	gold quality
pancreas	UBERON:0001264	83.10	gold quality
thoracic aorta	UBERON:0001515	83.06	gold quality
mouth mucosa	UBERON:0003729	82.98	gold quality
ascending aorta	UBERON:0001496	82.95	gold quality
gall bladder	UBERON:0002110	82.91	gold quality
uterus	UBERON:0000995	82.87	gold quality
upper lobe of left lung	UBERON:0008952	82.81	gold quality
tibial nerve	UBERON:0001323	82.76	gold quality
cerebellum	UBERON:0002037	82.74	gold quality
small intestine	UBERON:0002108	82.67	gold quality
right adrenal gland cortex	UBERON:0035827	82.60	gold quality
left uterine tube	UBERON:0001303	82.59	gold quality
saliva-secreting gland	UBERON:0001044	82.53	gold quality
blood	UBERON:0000178	82.50	gold quality
pituitary gland	UBERON:0000007	82.49	gold quality
right lobe of liver	UBERON:0001114	82.45	gold quality
lymph node	UBERON:0000029	82.44	gold quality
muscle organ	UBERON:0001630	82.39	gold quality
right lung	UBERON:0002167	82.39	gold quality
stomach	UBERON:0000945	82.38	gold quality
adenohypophysis	UBERON:0002196	82.29	gold quality
esophagus squamous epithelium	UBERON:0006920	82.26	gold quality
right adrenal gland	UBERON:0001233	82.18	gold quality
monocyte	CL:0000576	82.17	gold quality
leukocyte	CL:0000738	82.16	gold quality
upper lobe of lung	UBERON:0008948	82.14	gold quality
apex of heart	UBERON:0002098	82.08	gold quality
mononuclear cell	CL:0000842	82.03	gold quality
prostate gland	UBERON:0002367	82.00	gold quality
tonsil	UBERON:0002372	81.98	gold quality
left coronary artery	UBERON:0001626	81.81	gold quality
embryo	UBERON:0000922	81.79	gold quality
fundus of stomach	UBERON:0001160	81.72	gold quality
left adrenal gland	UBERON:0001234	81.69	gold quality
squamous epithelium	UBERON:0006914	81.67	gold quality
left adrenal gland cortex	UBERON:0035825	81.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.48

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	23.6
Nucleus accumbens	tissue	21.2
Bone marrow	tissue	21.0	not detected
Skin 1	tissue	20.3	low
Testis	tissue	18.4	low
Hippocampus	tissue	17.6	low
Postcentral gyrus	tissue	17.0
Epididymis	tissue	16.4	not detected
Fallopian tube	tissue	15.3	low
Thyroid gland	tissue	14.9	medium
Ovary	tissue	14.6	low
Locus coeruleus	tissue	14.5
Thymus	tissue	13.9
Skeletal muscle	tissue	13.8	medium
Endometrium 1	tissue	13.8	low
Lymph node	tissue	13.0	low
Salivary gland	tissue	12.8	not detected
Seminal vesicle	tissue	12.4	high
Tonsil	tissue	12.1	medium
Placenta	tissue	11.6	medium
Duodenum	tissue	11.4	low
Smooth muscle	tissue	11.2	not detected
Esophagus	tissue	11.1	low
Small intestine	tissue	11.1	low
Olfactory bulb	tissue	10.9
Pancreas	tissue	10.3	low
Cerebellum	tissue	10.3	low
Breast	tissue	10.2	low
Prostate	tissue	10.2	not detected
Vagina	tissue	10.1	low
Hippocampal formation	tissue	10.0
Parathyroid gland	tissue	9.8	not detected
Basal ganglia	tissue	9.8	medium
Lung	tissue	9.8	medium
Spleen	tissue	9.8	not detected
Appendix	tissue	9.8	low
Amygdala	tissue	9.7
Ventral forebrain	tissue	9.6
Cervix	tissue	9.5	medium
Septum	tissue	9.4
Cerebral cortex	tissue	9.2	low
Putamen	tissue	9.2
Insular cortex	tissue	9.2
Temporal cortex	tissue	9.1
Retina	tissue	9.0
Rectum	tissue	9.0	low
Tongue	tissue	9.0
Spinal cord	tissue	9.0
Periaqueductal gray	tissue	9.0
Urinary bladder	tissue	8.9	medium
Prefrontal cortex	tissue	8.8
Retrosplenial and cingulate cortex	tissue	8.8
Retrosplenial cortex	tissue	8.8
Colon	tissue	8.7	low
Corpus callosum	tissue	8.7
Entorhinal cortex	tissue	8.7
Occipital cortex	tissue	8.6
Hypothalamus	tissue	8.5
Gallbladder	tissue	8.5	medium
Pituitary gland	tissue	8.4

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Caudate nucleus (24.7), Cerebellar cortex (24.3), Flocculonodular lobe (23.8), Vermis (23.5), Hippocampus, CA3 (21.3).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
JUN	Activation

miRNA regulators (miRDB)

Targeting NFRKB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

28 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-4772-3P	98.04	65.60	1203
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-2278	97.30	66.19	1130
HSA-MIR-582-3P	96.69	67.38	1019

Functional genomics

gnomAD constraint: pLI 0.00163, LOEUF 0.543, missense Z 1.59 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000682444 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
11:129,864,728–129,874,525	753 / 804.3	0.94	no
11:129,874,526–129,877,336	114 / 211.0	0.54	no
11:129,877,337–129,892,849	678 / 646.7	1.05	no
DepMap (CRISPR cell-line fitness): dependent in 42.2% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): CL-40 (-1.451), Panc 08.13 (-1.409), EM-2 (-1.348), TUHR10TKB (-1.309), U343 (-1.271), KS-1 (-1.233), CL-11 (-1.216), SW 1990 (-1.212), JM1 (-1.211), Set-2 (-1.183), JHH-2 (-1.178), SK-BR-3 (-1.164), NCI-H661 (-1.16), NCI-N87 (-1.15), Li-7 (-1.135).

Literature-anchored findings (GeneRIF, showing 7)

• NFRKB may be involved in the disorders of transcriptional regulation commonly observed in minimal change nephrotic syndrome relapse. (PMID:22291976)
• The structure of a novel helical domain of NFRKB was determined to 2.18 A resolution. (PMID:22984442)
• Data show that DEUBAD domain in RPN13 (ADRM1) activates ubiquitin thioesterase L5 (UCH-L5), and the related DEUBAD domain in INO80G (NFRKB) inhibits UCH-L5. (PMID:25702870)
• LncRNA DRAIC inhibits proliferation and metastasis of gastric cancer cells through interfering with NFRKB deubiquitination mediated by UCHL5. (PMID:32351584)
• Nuclear Factor Related to KappaB Binding Protein (NFRKB) Is a Telomere-Associated Protein and Involved in Liver Cancer Development. (PMID:34591601)
• The biological function of metazoan-specific subunit nuclear factor related to kappaB binding protein of INO80 complex. (PMID:35093437)
• A large deletion in a non-coding regulatory region leads to NFKB1 haploinsufficiency in two adult siblings. (PMID:38423196)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nfrkb	ENSDARG00000091512
mus_musculus	Nfrkb	ENSMUSG00000042185
rattus_norvegicus	Nfrkb	ENSRNOG00000008278
drosophila_melanogaster	CG11970	FBGN0027503

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus tropicalis	Q6P4L9	65.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TMEM45B	protein-coding	120224
PRDM10-DT	ncRNA	440072
PRDM10	protein-coding	56980
LINC01395	ncRNA	101929557
APLP2	protein-coding	334

Protein

Protein identifiers

Nuclear factor related to kappa-B-binding protein — Q6P4R8 (reviewed: Q6P4R8)

Alternative names: DNA-binding protein R kappa-B, INO80 complex subunit G

All UniProt accessions (7): Q6P4R8, E9PJE1, E9PJG2, E9PJU3, E9PM88, E9PQ59, E9PQB0

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the DNA consensus sequence 5’-GGGGAATCTCC-3’. Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Modulates the deubiquitinase activity of UCHL5 in the INO80 complex.

Subunit / interactions. Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the N-terminus of INO80. Interacts with UCHL5; NFRKB competes with ADRM1 for interaction with UCHL5.

Subcellular location. Nucleus.

Tissue specificity. Expressed in thymus, brain, testes, spleen and liver.

Domain organisation. NFRKB seems to be mostly disordered. The wing-helix like domain doesn’t bind DNA.

Similarity. Belongs to the NFRKB family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6P4R8-1	1	yes
Q6P4R8-2	2
Q6P4R8-3	3

RefSeq proteins (2): NP_001137307, NP_006156 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024867	NFRKB	Family
IPR025220	NFRKB_WH_1	Domain
IPR038106	NFRKB_winged_sf	Homologous_superfamily
IPR044867	DEUBAD_dom	Domain
IPR057748	NFRKB_WH_2	Domain

Pfam: PF14465, PF25793

UniProt features (51 total): helix 14, compositionally biased region 7, modified residue 6, region of interest 6, strand 5, cross-link 4, splice variant 3, sequence conflict 2, turn 2, chain 1, domain 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
3U21	Crystal structure of a Fragment of Nuclear factor related to kappa-B-binding protein …	X-RAY DIFFRACTION	2.18
4WLP	Crystal structure of UCH37-NFRKB Inhibited Deubiquitylating Complex	X-RAY DIFFRACTION	3.1
4UF6	UCH-L5 in complex with ubiquitin-propargyl bound to an activating fragment of INO80G	X-RAY DIFFRACTION	3.69
4UF5	Crystal structure of UCH-L5 in complex with inhibitory fragment of INO80G	X-RAY DIFFRACTION	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P4R8-F1	56.56	0.13

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF enhanced

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 (10)

Type	Positions
Phosphoserine	228, 298, 351, 1022, 1291
N6-acetyllysine	1237
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	327, 469, 488
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	488

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-5696394	DNA Damage Recognition in GG-NER	curated
R-HSA-5689603	UCH proteinases	curated
R-HSA-73894	DNA Repair	—
R-HSA-5688426	Deubiquitination	—
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-5696398	Nucleotide Excision Repair	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 172 (showing top): MORF_RAGE, GOBP_CHROMOSOME_ORGANIZATION, FREAC2_01, MORF_ATRX, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, GOBP_TELOMERE_ORGANIZATION, MODULE_308, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE, MORF_PPP5C, MORF_FANCG, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_STRAND_ELONGATION

GO Biological Process (17): telomere maintenance (GO:0000723), regulation of DNA replication (GO:0006275), DNA repair (GO:0006281), DNA recombination (GO:0006310), chromatin remodeling (GO:0006338), DNA-templated transcription (GO:0006351), regulation of chromosome organization (GO:0033044), positive regulation of DNA repair (GO:0045739), positive regulation of DNA-templated transcription (GO:0045893), regulation of embryonic development (GO:0045995), regulation of cell cycle (GO:0051726), regulation of DNA strand elongation (GO:0060382), positive regulation of telomere maintenance in response to DNA damage (GO:1904507), regulation of DNA repair (GO:0006282), DNA damage response (GO:0006974), positive regulation of macromolecule metabolic process (GO:0010604), regulation of DNA metabolic process (GO:0051052)

GO Molecular Function (3): protease binding (GO:0002020), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), Ino80 complex (GO:0031011)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Deubiquitination	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
Post-translational protein modification	1
DNA Repair	1
Nucleotide Excision Repair	1
Metabolism of proteins	1

GO top-level categories

39 GO namespaces:

Category	Terms
DNA metabolic process	4
regulation of DNA metabolic process	3
DNA repair	2
positive regulation of response to stimulus	2
regulation of macromolecule metabolic process	2
telomere organization	1
DNA replication	1
DNA damage response	1
chromatin organization	1
gene expression	1
RNA biosynthetic process	1
regulation of organelle organization	1
chromosome organization	1
regulation of DNA repair	1
positive regulation of DNA metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
embryo development	1
regulation of multicellular organismal development	1
cell cycle	1
regulation of cellular process	1
DNA strand elongation	1
positive regulation of telomere maintenance	1
telomere maintenance in response to DNA damage	1
regulation of telomere maintenance in response to DNA damage	1
regulation of cellular response to stress	1
cellular response to stress	1
positive regulation of metabolic process	1
macromolecule metabolic process	1
regulation of nucleobase-containing compound metabolic process	1
enzyme binding	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear chromosome	1
INO80-type complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 23 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
chromatin remodeling	BP	direct assay
positive regulation of DNA-templated transcription	BP	mutant phenotype
regulation of DNA replication	BP	mutant phenotype
regulation of DNA strand elongation	BP	mutant phenotype
regulation of cell cycle	BP	mutant phenotype
regulation of chromosome organization	BP	mutant phenotype
Ino80 complex	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
protease binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,102 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFRKB	UCHL5	Q9Y5K5	658
NFRKB	ETS1	P14921	584
NFRKB	ADRM1	Q16186	570
NFRKB	ACTR5	Q9H9F9	552
NFRKB	PCBD2	Q9H0N5	511
NFRKB	TFPT	P0C1Z6	502
NFRKB	CBL	P22681	487
NFRKB	ACTR8	Q9H981	439
NFRKB	INO80C	Q6PI98	434
NFRKB	K7ENP7	K7ENP7	434
NFRKB	NFKB2	Q00653	432
NFRKB	BAP1	Q92560	414
NFRKB	GABPA	Q06546	412
NFRKB	INO80B	Q9C086	400
NFRKB	INO80E	Q8NBZ0	385

IntAct

Human interaction partners of NFRKB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
UCHL5	physical association	0.890	13
INO80	association	0.530	1
CDC37	physical association	0.400	1
HSP90AB1	physical association	0.400	1
EPHB3	physical association	0.370	1
TRDMT1	physical association	0.370	1
ADRM1	association	0.350	1
FMR1	physical association	0.000	1

BioGRID (212 interactions; top human partners by supporting records): UCHL5 (Two-hybrid; 16 records), INO80 (Affinity Capture-Western; 8 records), YY1 (Affinity Capture-MS; 7 records), INO80E (Co-fractionation; 6 records), RUVBL1 (Affinity Capture-MS; 6 records), RUVBL2 (Affinity Capture-MS; 6 records), ACTR5 (Co-fractionation; 4 records), ACTR8 (Co-fractionation; 4 records), TFPT (Affinity Capture-MS; 4 records), CARD8 (Affinity Capture-MS; 3 records), CCNDBP1 (Affinity Capture-MS; 3 records), DLK1 (Affinity Capture-MS; 3 records), INO80B (Affinity Capture-MS; 3 records), INO80C (Affinity Capture-MS; 3 records), INO80D (Affinity Capture-MS; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
NFRKB	“form complex”	“INO80 complex”	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
INO80 chromatin remodeling complex	13	INO80D, INO80E, TCF3, ACTR8, INO80B, INO80C, MCRS1, NFRKB, RUVBL1, RUVBL2, ACTL6A, ACTR5, INO80

Disease & clinical

Genetic variants

Variant evidence for NFRKB: 199 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	162
Likely benign	9
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 22 predictions of 2,889):

Position(s)	Effect	Δscore	Sites
11:129865875	donor_gain	1.0000	2
11:129865876	donor_loss	1.0000	2
11:129865984	acceptor_gain	1.0000
11:129865984–129865985	acceptor_loss	1.0000	4
11:129874499–129874500	donor_loss	1.0000	3
11:129874754	donor_gain	1.0000
11:129874796	donor_gain	1.0000
11:129874917–129874918	acceptor_loss	1.0000	6
11:129874921	acceptor_gain	1.0000
11:129874926	acceptor_gain	1.0000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	0.000116
Breast Invasive Carcinoma (validation)	favorable	0.000181
Rectum Adenocarcinoma (TCGA)	favorable	0.000464

Disease associations

OMIM: gene MIM:164013 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST90002405_520	Reticulocyte count	1e-10
GCST90002385_491	High light scatter reticulocyte count	3e-10
GCST003542_152	Night sleep phenotypes	1e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0007827	nighttime rest measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725193 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.18	Kd	66	nM	MOLIBRESIB
7.00	IC50	100	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179221: Binding affinity against NFRKB (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0660	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	decreases expression, affects cotreatment	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Valproic Acid	affects expression, decreases methylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
quercitrin	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
4-hydroxy-2-nonenal	decreases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	decreases expression	1
Lead	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Ozone	decreases expression, increases abundance	1
Phthalic Acids	decreases methylation	1
Smoke	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697599	Binding	Inhibition of NFRKB (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — *Nature*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for NFRKB across ~30M SureChEMBL compounds — explore on Sugi Predict.