NFKBIL1

Summary

NFKBIL1 (NFKB inhibitor like 1, HGNC:7800) is a protein-coding gene on chromosome 6p21.33, encoding NF-kappa-B inhibitor-like protein 1 (Q9UBC1). Involved in the regulation of innate immune response.

This gene encodes a divergent member of the I-kappa-B family of proteins. Its function has not been determined. The gene lies within the major histocompatibility complex (MHC) class I region on chromosome 6. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4795 — RefSeq curated summary.

At a glance

• GWAS associations: 44
• Clinical variants (ClinVar): 62 total
• Phenotypes (HPO): 16
• MANE Select transcript: NM_005007

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7800
Approved symbol	NFKBIL1
Name	NFKB inhibitor like 1
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	IKBL
Ensembl gene	ENSG00000204498
Ensembl biotype	protein_coding
OMIM	601022
Entrez	4795

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000376145, ENST00000376146, ENST00000376148, ENST00000473655, ENST00000496233

RefSeq mRNA: 4 — MANE Select: NM_005007 NM_001144961, NM_001144962, NM_001144963, NM_005007

CCDS: CCDS4700, CCDS47399, CCDS47400

Canonical transcript exons

ENST00000376148 — 4 exons

Exon	Start	End
ENSE00001639067	31557628	31557849
ENSE00001840883	31547608	31547751
ENSE00001911372	31558022	31558829
ENSE00003670784	31548163	31548439

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 92.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.5254 / max 177.4362, expressed in 1807 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66894	22.2731	1807
66893	0.9427	493
66892	0.3097	146

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.16	silver quality
body of pancreas	UBERON:0001150	90.68	gold quality
body of stomach	UBERON:0001161	89.76	gold quality
fundus of stomach	UBERON:0001160	89.58	gold quality
apex of heart	UBERON:0002098	89.55	gold quality
left ovary	UBERON:0002119	89.11	gold quality
mucosa of stomach	UBERON:0001199	88.34	gold quality
right ovary	UBERON:0002118	88.33	gold quality
ovary	UBERON:0000992	88.29	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.16	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.88	gold quality
gastrocnemius	UBERON:0001388	87.82	gold quality
lower esophagus mucosa	UBERON:0035834	87.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.58	gold quality
popliteal artery	UBERON:0002250	87.56	gold quality
tibial artery	UBERON:0007610	87.56	gold quality
lower esophagus	UBERON:0013473	87.56	gold quality
stomach	UBERON:0000945	87.43	gold quality
pituitary gland	UBERON:0000007	87.38	gold quality
sural nerve	UBERON:0015488	87.38	gold quality
adenohypophysis	UBERON:0002196	87.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.06	gold quality
muscle of leg	UBERON:0001383	86.96	gold quality
right adrenal gland cortex	UBERON:0035827	86.63	gold quality
ascending aorta	UBERON:0001496	86.59	gold quality
right lobe of thyroid gland	UBERON:0001119	86.56	gold quality
thoracic aorta	UBERON:0001515	86.52	gold quality
body of uterus	UBERON:0009853	86.51	gold quality
left lobe of thyroid gland	UBERON:0001120	86.49	gold quality
skin of abdomen	UBERON:0001416	86.34	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.52

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
PRRC2A

Upstream regulators (CollecTRI, top): MYC, TCF3, USF1

miRNA regulators (miRDB)

2 targeting NFKBIL1, 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-9903	98.47	66.70	748
HSA-MIR-3190-3P	97.61	66.95	1406

Literature-anchored findings (GeneRIF, showing 16)

• identifed the second rheumatoid arthritis -susceptibility locus within the HLA region, as the T allele of SNP 96452 (T/A), in the promoter region (position -62) of the I kappa BL gene (P=.0062) (PMID:12509789)
• study shows that the estimated haplotype IkBL -421 8T/-62 T tends to be associated with susceptibility to rheumatoid arthritis in Taiwan (PMID:16644022)
• analysis of the NFKB1 protein polymorphism interactions with CARD15/NOD2, IKBL, and IL-1RN genes (PMID:16804398)
• no association between polymorphisms and hypertension, myocardial infarct and angina in Irish (PMID:17485095)
• Minor homozygous genotypes of polymorphisms in NFKBIL1 were associated with moderately protective effects against myocardial infarction. (PMID:17517687)
• The IKBL locus itself or another critical gene in this region may confer susceptibility to the development of chronic Chagas cardiomyopathy. (PMID:17544510)
• IL1RN VNTR and the IKBL + 738T > C gene polymorphisms are not risk factors for myocardial infarct in Caucasians with type 2 diabetes (PMID:17847930)
• A potential role for NFkBL1 in the pathogenesis of rheumatoid arthritis and in mRNA processing or the regulation of translation. (PMID:17855452)
• IkappaBL allele polymorphisms influences risk of acquiring systemic lupus erythematosus and Sjogren’s syndrome. (PMID:18295675)
• The DPB1 gene controlled the severity of the vascular lesion, whereas the IKBL gene (NFKBIL1) was associated with a relatively mild phenotype. (PMID:19165231)
• results do not provide evidence for the association between the -62A/T NFKBIL1 polymorphism and obsessive-compulsive disorder in this Brazilian sample. (PMID:19578685)
• Results of the present study do not provide evidence for the association between the NFKBIL1 exon 4 polymorphism and MS predisposition in the investigated Polish population. (PMID:20568399)
• an association was noted between IKBL-62T and idiopathic inflammatory myopathy, with increased risk noted in anti-Jo-1- and -PM-Scl antibody-positive patients; the IKBL-62T association is dependent on TNF-308A and HLA-B*08, due to strong shared linkage disequilibrium between these alleles (PMID:22210660)
• These observations suggest a functional involvement of IkappaBL in the regulation of alternative splicing in both human and viral genes, which is a novel link of HLA locus to the regulation of immunity and infection in humans. (PMID:23953137)
• genetic association studies in a population of black women in South Africa: Data suggest that an SNP in NFKBIL1 (rs2071592) is associated with iron status/iron-deficiency anemia in the population studied. (PMID:25809685)
• Study found significant associations for two single nucleotide polymorphisms in NFKBIL1: rs2239707 showed a significant distribution of genotype frequencies in the case-control analysis both for all individuals combined and in boys only, and rs2230365 was significantly associated with the ALTs-module language impairment in boys only. (PMID:31162003)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nfkbil1	ENSDARG00000003157
mus_musculus	Nfkbil1	ENSMUSG00000042419
rattus_norvegicus	Nfkbil1	ENSRNOG00000000839

Protein

Protein identifiers

NF-kappa-B inhibitor-like protein 1 — Q9UBC1 (reviewed: Q9UBC1)

Alternative names: Inhibitor of kappa B-like protein, Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 1

All UniProt accessions (4): A0A0A0MRT5, F2Z390, Q9UBC1, Q5STV6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of innate immune response. Acts as negative regulator of Toll-like receptor and interferon-regulatory factor (IRF) signaling pathways. Contributes to the negative regulation of transcriptional activation of NF-kappa-B target genes in response to endogenous proinflammatory stimuli.

Subunit / interactions. Interacts with CACTIN (via N-terminal domain); the interaction occurs in a proinflammatory-independent manner.

Subcellular location. Nucleus.

Tissue specificity. Detected in different cell types including monocytes, T-cells, B-cells and hepatocytes.

Disease relevance. Rheumatoid arthritis (RA) [MIM:180300] An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Polymorphism. Arg-224 is found in the MHC 7.1 haplotype (HLA-A3,B7,DR15) population.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UBC1-1	1	yes
Q9UBC1-2	2
Q9UBC1-3	3

RefSeq proteins (4): NP_001138433, NP_001138434, NP_001138435, NP_004998* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR038753	NFKBIL1	Family

UniProt features (15 total): region of interest 3, compositionally biased region 3, repeat 2, splice variant 2, sequence conflict 2, chain 1, sequence variant 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBC1-F1	77.75	0.21

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 (1): 150

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 184 (showing top): GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, SIG_CD40PATHWAYMAP

GO Biological Process (8): negative regulation of lipopolysaccharide-mediated signaling pathway (GO:0031665), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), negative regulation of tumor necrosis factor production (GO:0032720), negative regulation of toll-like receptor signaling pathway (GO:0034122), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), cellular response to lipopolysaccharide (GO:0071222), negative regulation of signal transduction (GO:0009968), regulation of gene expression (GO:0010468)

GO Molecular Function (2): transcription regulator inhibitor activity (GO:0140416), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of signal transduction	2
negative regulation of response to biotic stimulus	1
lipopolysaccharide-mediated signaling pathway	1
regulation of lipopolysaccharide-mediated signaling pathway	1
negative regulation of response to external stimulus	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
toll-like receptor signaling pathway	1
negative regulation of immune system process	1
regulation of toll-like receptor signaling pathway	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
signal transduction	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
gene expression	1
regulation of macromolecule biosynthetic process	1
regulation of gene expression	1
transcription regulator activity	1
molecular function inhibitor activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFKBIL1	ATP6V1G2	O95670	916
NFKBIL1	LTA	P01374	720
NFKBIL1	LST1	O00453	716
NFKBIL1	CARMIL2	Q6F5E8	650
NFKBIL1	NCR3	O14931	644
NFKBIL1	HLA-DRB1	P01911	611
NFKBIL1	AIF1	P55008	606
NFKBIL1	TMOD4	Q9NZQ9	597
NFKBIL1	HLA-B	P01889	583
NFKBIL1	LTB	P78370	578
NFKBIL1	TMOD2	Q9NZR1	550
NFKBIL1	MCCD1	P59942	544
NFKBIL1	SLC22A4	Q9H015	538
NFKBIL1	MAPK8IP3	Q9UPT6	529
NFKBIL1	TNF	P01375	519

IntAct

54 interactions, top by confidence:

A	B	Type	Score
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
ZRANB2	PIP4K2A	psi-mi:“MI:0914”(association)	0.610
NFKBIL1	NME7	psi-mi:“MI:0915”(physical association)	0.560
DNAAF8	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
PEX14	NFKBIL1	psi-mi:“MI:0407”(direct interaction)	0.440
BMP2K	NFKBIL1	psi-mi:“MI:0915”(physical association)	0.370
NFKBIL1	CASP10	psi-mi:“MI:0915”(physical association)	0.370
NFKBIL1	ADIPOR1	psi-mi:“MI:0915”(physical association)	0.370
NFKBIL1	C2orf88	psi-mi:“MI:0915”(physical association)	0.370
CLEC18C	NFKBIL1	psi-mi:“MI:0915”(physical association)	0.370
ARRDC3	ESYT2	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
RNPS1	C1orf226	psi-mi:“MI:0914”(association)	0.350
HDGFL2	CIBAR1	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
CCDC85A	CIBAR1	psi-mi:“MI:0914”(association)	0.350
SULF2	CCDC85C	psi-mi:“MI:0914”(association)	0.350
AHCYL1	TRAF5	psi-mi:“MI:0914”(association)	0.350
TNFRSF1A	KHNYN	psi-mi:“MI:0914”(association)	0.350
JMJD6	U2SURP	psi-mi:“MI:0914”(association)	0.350
LUC7L	CASC3	psi-mi:“MI:0914”(association)	0.350
NFKBIL1	TNRC18	psi-mi:“MI:0914”(association)	0.350
TNFRSF1B	MAP3K7	psi-mi:“MI:0914”(association)	0.350
ARRB2	AHCYL1	psi-mi:“MI:0914”(association)	0.350
AHCYL2	AHCYL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (118): NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS)

ESM2 similar proteins: A1L515, A4D2P6, A6QQD2, A8VU90, E1BDF2, O75808, O88995, P0CG25, P22083, Q0IIA6, Q2TA57, Q3B7L1, Q3MIP1, Q3U5Q7, Q3UR50, Q3UR97, Q3UV16, Q400G9, Q5BKX5, Q5EBM0, Q5GH72, Q5SZI1, Q5TM19, Q5U4P2, Q62994, Q659K9, Q6PRD1, Q7Z736, Q861W0, Q86UR1, Q8BNN1, Q8C0R7, Q8CG70, Q8IUW3, Q8IVL6, Q8N398, Q8NAG6, Q8NCW0, Q8R2H1, Q8VCE9

Diamond homologs: O88995, Q5TM19, Q861W0, Q8R2H1, Q9TSV7, Q9UBC1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
mRNA Splicing	6	21.2×	7e-05
Processing of Capped Intron-Containing Pre-mRNA	6	15.9×	1e-04
mRNA Splicing - Major Pathway	7	12.3×	1e-04
Metabolism of RNA	6	8.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

550 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31548436:GATG:G	donor_gain	1.0000
6:31548438:TGG:T	donor_loss	1.0000
6:31548439:GGT:G	donor_loss	1.0000
6:31557626:A:AG	acceptor_gain	1.0000
6:31557627:G:GG	acceptor_gain	1.0000
6:31548438:TG:T	donor_gain	0.9900
6:31548439:GG:G	donor_gain	0.9900
6:31548440:G:GG	donor_gain	0.9900
6:31548442:GAG:G	donor_loss	0.9900
6:31557624:ACAG:A	acceptor_loss	0.9900
6:31557625:CAG:C	acceptor_loss	0.9900
6:31557627:GC:G	acceptor_gain	0.9900
6:31557627:GCCT:G	acceptor_gain	0.9900
6:31557627:GCCTA:G	acceptor_gain	0.9900
6:31557803:GG:G	donor_gain	0.9900
6:31557804:GG:G	donor_gain	0.9900
6:31557828:G:GT	donor_gain	0.9900
6:31558020:A:G	acceptor_loss	0.9900
6:31548162:GC:G	acceptor_gain	0.9800
6:31557624:A:G	acceptor_gain	0.9800
6:31557627:GCC:G	acceptor_gain	0.9800
6:31557652:T:A	acceptor_gain	0.9800
6:31558017:A:G	acceptor_gain	0.9800
6:31558020:AGGT:A	acceptor_gain	0.9800
6:31558021:GGT:G	acceptor_gain	0.9800
6:31558021:GGTG:G	acceptor_gain	0.9800
6:31547645:GCCT:G	donor_gain	0.9700
6:31547725:G:GT	donor_gain	0.9700
6:31548162:GCCCA:G	acceptor_gain	0.9700
6:31557623:A:AG	acceptor_gain	0.9700

AlphaMissense

2445 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31557706:C:A	P138H	1.000
6:31557688:A:T	N132I	0.999
6:31558486:T:A	W341R	0.999
6:31558486:T:C	W341R	0.999
6:31548419:C:A	A105D	0.998
6:31548422:C:A	A106D	0.998
6:31557689:T:A	N132K	0.998
6:31557689:T:G	N132K	0.998
6:31548215:T:C	F37S	0.997
6:31548323:G:A	C73Y	0.997
6:31548398:G:T	G98V	0.997
6:31548412:C:G	H103D	0.997
6:31557652:T:A	L120Q	0.997
6:31557687:A:T	N132Y	0.997
6:31557706:C:G	P138R	0.997
6:31558488:G:C	W341C	0.997
6:31558488:G:T	W341C	0.997
6:31558489:C:G	H342D	0.997
6:31558491:C:A	H342Q	0.997
6:31558491:C:G	H342Q	0.997
6:31558502:T:C	F346S	0.997
6:31548389:A:T	D95V	0.996
6:31548412:C:A	H103N	0.996
6:31548413:A:G	H103R	0.996
6:31548414:T:A	H103Q	0.996
6:31548414:T:G	H103Q	0.996
6:31557687:A:C	N132H	0.996
6:31558490:A:G	H342R	0.996
6:31558501:T:C	F346L	0.996
6:31558503:C:A	F346L	0.996

dbSNP variants (sampled 300 via entrez): RS1000800943 (6:31551068 C>T), RS1000828182 (6:31555518 C>G,T), RS1001035439 (6:31559051 A>G), RS1001549193 (6:31558842 C>T), RS1001801229 (6:31545076 C>T), RS1001958229 (6:31551781 T>C), RS1002059371 (6:31550350 T>C,G), RS1002153130 (6:31558449 G>A,T), RS1002480323 (6:31556294 C>T), RS1002622828 (6:31555016 A>G), RS1002674895 (6:31554790 G>A), RS1002978518 (6:31548002 A>G), RS1003685138 (6:31553264 C>A,G,T), RS1004187261 (6:31546150 G>A), RS1004199229 (6:31546191 T>C)

Disease associations

OMIM: gene MIM:601022 | disease phenotypes: MIM:180300

GenCC curated gene-disease

Mondo (1): rheumatoid arthritis (MONDO:0008383)

Orphanet (1): NON RARE IN EUROPE: Rheumatoid arthritis (Orphanet:284130)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0001370	Rheumatoid arthritis
HP:0001386	Joint swelling
HP:0001387	Joint stiffness
HP:0001824	Weight loss
HP:0001945	Fever
HP:0002633	Vasculitis
HP:0002829	Arthralgia
HP:0002923	Rheumatoid factor positive
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0005764	Polyarticular arthritis
HP:0006150	Swan neck-like deformities of the fingers
HP:0006252	Interphalangeal joint erosions
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0012276	Digital flexor tenosynovitis
HP:0012378	Fatigue
HP:0033034	Anti-citrullinated protein antibody positivity

GWAS associations

44 associations (top):

Study	Trait	p-value
GCST000738_5	Neonatal lupus	5.000000e-10
GCST001729_10	Crohn’s disease	5.000000e-28
GCST002876_4	Type 1 diabetes and autoimmune thyroid diseases	2.000000e-23
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_27	Autism spectrum disorder or schizophrenia	1.000000e-09
GCST004521_3	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST004611_98	High light scatter reticulocyte count	7.000000e-12
GCST004612_17	High light scatter reticulocyte percentage of red cells	7.000000e-11
GCST004619_165	Reticulocyte fraction of red cells	8.000000e-16
GCST004622_188	Reticulocyte count	5.000000e-17
GCST005542_1	Sarcoidosis (non-Lofgren’s syndrome without extrapulmonary manifestations)	7.000000e-06
GCST006867_48	Type 2 diabetes	6.000000e-14
GCST008163_329	Height	8.000000e-09
GCST008916_111	Asthma	2.000000e-14
GCST008916_114	Asthma	1.000000e-09
GCST008916_30	Asthma	1.000000e-09
GCST008917_2	Asthma (childhood onset)	4.000000e-07
GCST008921_1	Asthma and major depressive disorder	2.000000e-16
GCST010002_50	Refractive error	4.000000e-34
GCST010725_43	Malaria	5.000000e-07

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004352	mortality
EFO:0008039	BMI-adjusted hip circumference
EFO:0004842	eosinophil count
EFO:0004348	hematocrit
EFO:0007989	monocyte percentage of leukocytes
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001172	Arthritis, Rheumatoid	C05.550.114.154; C05.799.114; C17.300.775.099; C20.111.199

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
naringenin	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenite	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
abrine	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Caffeine	affects phosphorylation	1
Cisplatin	increases expression	1
Methyl Methanesulfonate	increases expression	1
Niclosamide	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Tetradecanoylphorbol Acetate	affects expression, affects cotreatment	1
Thiram	increases expression	1
Valproic Acid	affects expression	1
Zinc	affects cotreatment, affects expression	1
Cyclosporine	increases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00056667	PHASE4	COMPLETED	Relaxation Response Training for the Treatment of Rheumatoid Arthritis
NCT00094341	PHASE4	COMPLETED	Preference of Rheumatoid Arthritis (RA) Patients of Enbrel® (Etanercept) Auto-Injector Versus Enbrel® Pre-Filled Syringes
NCT00099554	PHASE4	COMPLETED	Effectiveness and Safety of Enbrel® (Etanercept) in Rheumatoid Arthritis Subjects Who Have Failed Remicade® (Infliximab)
NCT00111410	PHASE4	COMPLETED	Evaluating the Effect of Anakinra (r-metHuIL-1ra) on Vaccine AntibodyResponse in Subjects With Rheumatoid Arthritis (RA)
NCT00115219	PHASE4	COMPLETED	Evaluating Efficacy and Safety of Etanercept 50 mg Twice Weekly (BIW) in Rheumatoid Arthritis (RA) Subjects Who Are Sub-Optimal Responders to Etanercept 50 mg Once Weekly (QW)
NCT00121043	PHASE4	COMPLETED	Evaluating Kineret® (Anakinra) in Rheumatoid Arthritis (RA) Subjects Using aSelf-Reported Questionnaire
NCT00132418	PHASE4	COMPLETED	Study of Enbrel in Rheumatoid Arthritis (RA) Subjects With Comorbid Disorders
NCT00157872	PHASE4	COMPLETED	A Study of Rofecoxib Versus Naproxen in the Treatment of Chinese Patient With Rheumatoid Arthritis (0966-231)
NCT00195494	PHASE4	COMPLETED	Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis
NCT00208364	PHASE4	TERMINATED	A Two Centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Metal-on-Metal Bearing in Primary Total Hip Replacement
NCT00208377	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy ASR™ System in Primary Hip Resurfacing Surgery
NCT00208390	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the Summit™ Hip in Primary Total Hip Replacement
NCT00208429	PHASE4	WITHDRAWN	A Multi-centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Polyethylene-on-metal Bearing in Primary Total Hip Replacement
NCT00208455	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy PROXIMA™ Hip in Primary Total Hip Replacement
NCT00209859	PHASE4	COMPLETED	Methotrexate and Cyclosporine in Treatment of Early Rheumatoid Arthritis
NCT00216177	PHASE4	UNKNOWN	Comparison of Adalimumab and Infliximab Treatment of Rheumatoid Arthritis
NCT00233558	PHASE4	TERMINATED	Open-Label Steroid Reduction Study of Adalimumab With Methotrexate in Patients With Active Rheumatoid Arthritis
NCT00234234	PHASE4	COMPLETED	Predictors of the Response to Adalimumab in Rheumatoid Arthritis
NCT00234897	PHASE4	COMPLETED	Efficacy of HUMIRA in Subjects With Active Rheumatoid Arthritis
NCT00244556	PHASE4	COMPLETED	Study Comparing Enbrel (Etanercept) Plus Methotrexate Versus Enbrel Alone in Active Rheumatoid Arthritis Despite Current Methotrexate Therapy
NCT00252668	PHASE4	COMPLETED	Study Evaluating the Combination of Etanercept and Methotrexate in Rheumatoid Arthritis Subjects
NCT00259610	PHASE4	COMPLETED	Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)
NCT00291915	PHASE4	UNKNOWN	Multicenter Randomized Prospective Trial Comparing Methotrexate Alone or in Combination With Adalimumab in Early Arthritis
NCT00319917	PHASE4	COMPLETED	A Double Blind Placebo Controlled Study to Assess the Efficacy on Joint Damage in RA Patients
NCT00334620	PHASE4	COMPLETED	Effectiveness of Radon Spa Therapy in Multimodal Rehabilitative Treatment of Rheumatoid Arthritis
NCT00346294	PHASE4	COMPLETED	An Open-Label Study to Assess the Rate of Failure of an Enbrel® (Etanercept) SureClick™ Auto-injector in Subjects With Rheumatoid Arthritis
NCT00356473	PHASE4	COMPLETED	Effects of Atorvastatin on Disease Activity and HDL Cholesterol Function in Patients With Rheumatoid Arthritis
NCT00369187	PHASE4	COMPLETED	Study of a Large Protein Molecule Administered With Escalating Doses of Recombinant Human Hyaluronidase
NCT00385528	PHASE4	COMPLETED	Effects of a Multi-Faceted Psychiatric Intervention Targeted at the Complex Medically Ill: a Randomized Controlled Trial
NCT00396747	PHASE4	COMPLETED	A Comparison of Methotrexate Alone or Combined to Infliximab or to Pulse Methylprednisolone in Early Rheumatoid Arthritis: A Magnetic Resonance Imaging Study
NCT00420927	PHASE4	COMPLETED	Study of the Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early Rheumatoid Arthritis
NCT00422227	PHASE4	COMPLETED	Study Comparing Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis in the Asia Pacific Region
NCT00424502	PHASE4	COMPLETED	A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a TNF-Blocker.
NCT00434200	PHASE4	UNKNOWN	Rheumatoid Arthritis Patients in Training
NCT00439062	PHASE4	COMPLETED	Treatment of Rheumatoid Arthritis With Roxithromycin
NCT00447759	PHASE4	COMPLETED	The Standard Care Versus Celecoxib Outcome Trial
NCT00462072	PHASE4	COMPLETED	Centocor Microarray Study of Patients
NCT00462345	PHASE4	COMPLETED	A Study of MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Therapies.
NCT00480272	PHASE4	COMPLETED	Prospective Study on Intensive Early Rheumatoid Arthritis Treatment
NCT00502853	PHASE4	COMPLETED	A Pilot Study of MabThera (Rituximab) Evaluated by MRI in Patients With Rheumatoid Arthritis.