BTNL2

Summary

BTNL2 (butyrophilin like 2, HGNC:1142) is a protein-coding gene on chromosome 6p21.32, encoding Butyrophilin-like protein 2 (Q9UIR0). Negative regulator of T-cell proliferation.

This gene encodes a major histocompatibility complex, class II associated, type I transmembrane protein which belongs to the butyrophilin-like B7 family of immunoregulators. It is thought to be involved in immune surveillance, serving as a negative T-cell regulator by decreasing T-cell proliferation and cytokine release. The encoded protein contains an N-terminal signal peptide, two pairs of immunoglobulin-like domains, separated by a heptad peptide sequence, and a C-terminal transmembrane domain. Naturally occurring mutations in this gene are associated with sarcoidosis, rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, myositis, type 1 diabetes, systemic lupus erythematosus, acute coronary syndrome, and prostate cancer.

Source: NCBI Gene 56244 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sarcoidosis, susceptibility to, 2 (Limited, GenCC)
• GWAS associations: 133
• Clinical variants (ClinVar): 71 total
• Phenotypes (HPO): 88
• MANE Select transcript: NM_001304561

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1142
Approved symbol	BTNL2
Name	butyrophilin like 2
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	HSBLMHC1, BTL-II, BTN7
Ensembl gene	ENSG00000204290
Ensembl biotype	protein_coding
OMIM	606000
Entrez	56244

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000374993, ENST00000446536, ENST00000454136, ENST00000465865, ENST00000544175

RefSeq mRNA: 1 — MANE Select: NM_001304561 NM_001304561

CCDS: CCDS78126

Canonical transcript exons

ENST00000416387 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 62.93.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	62.93	silver quality
ventricular zone	UBERON:0003053	61.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	60.39	gold quality
ganglionic eminence	UBERON:0004023	59.36	gold quality
cortical plate	UBERON:0005343	57.30	gold quality
right ovary	UBERON:0002118	56.53	gold quality
ovary	UBERON:0000992	55.36	gold quality
lymph node	UBERON:0000029	54.62	gold quality
left ovary	UBERON:0002119	54.58	gold quality
superior frontal gyrus	UBERON:0002661	53.03	gold quality
smooth muscle tissue	UBERON:0001135	52.75	gold quality
endometrium	UBERON:0001295	52.46	gold quality
vermiform appendix	UBERON:0001154	51.22	gold quality
duodenum	UBERON:0002114	50.30	gold quality
small intestine	UBERON:0002108	50.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	49.91	gold quality
hypothalamus	UBERON:0001898	49.18	gold quality
metanephros cortex	UBERON:0010533	49.07	gold quality
nucleus accumbens	UBERON:0001882	48.35	gold quality
Ammon’s horn	UBERON:0001954	48.07	gold quality
amygdala	UBERON:0001876	47.94	gold quality
temporal lobe	UBERON:0001871	47.68	gold quality
spleen	UBERON:0002106	47.48	gold quality
anterior cingulate cortex	UBERON:0009835	47.39	gold quality
tibial nerve	UBERON:0001323	46.94	gold quality
tonsil	UBERON:0002372	46.78	gold quality
primary visual cortex	UBERON:0002436	46.61	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	46.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	46.18	gold quality
right frontal lobe	UBERON:0002810	45.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.31

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• Sarcoidosis is associated with a truncating splice site mutation in BTNL2 (PMID:15735647)
• BNTL2 associates with sarcoidosis in both White Americans and African-Americans, with risk effects in Whites independent of HLA-DRB1 associations, and negative interactions between BRNL2 and HLA classII in African-Americans. (PMID:16080124)
• Association of the truncating splice site mutation in BTNL2 with multiple sclerosis is secondary to HLA-DRB1*15. (PMID:16321988)
• resiults show that BTNL2 rs2076530 polymorphism is associated with type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus because of its strong linkage disequalibrium with predisposing HLA DQB1-DRB1 haplotypes in Caucasian populations (PMID:16690410)
• RAGE and its ligands with sarcoidosis and suggest that an intrinsic genetic factor could be in part involved in its expression. In Italian patients, the -374 T/A polymorphism seems to be significantly associated with this disease. (PMID:17170388)
• Structural analysis of BTNL2 shows a molecule with an extracellular region containing two sets of two Ig domains, a transmembrane region, and a previously unreported cytoplasmic tail (PMID:17237401)
• Coding regions of BTNL2 were sequenced to detect known and novel polymorphisms and genotyped 18 SNPs in 432 pulmonary tuberculosis cases and 482 controls. (PMID:17347014)
• a major effect of the BTNL2 rs2076530 (G –> A) SNP in Crohn’s disease and tuberculosis was excluded; there was an association with susceptibility to leprosy (P=0.04), however, this is most likely due to linkage disequilibrium with HLA-DR (PMID:17493147)
• Does not contribute to susceptibility to Crohn’s disease in Japan but is associated with Japanese ulcerative colitis because of strong linkage disequilibrium with HLA-DRB1*1502. (PMID:17610417)
• Some haplotypes are associated with non-Lofgren sarcoidosis. (PMID:17661910)
• Both DRB1*13 and BTNL2 rs3117099TT homozygosity are associated with chronic beryllium disease [CBD] in *Glu69-negative subjects, while DPB1*Glu69 is associated with CBD and Be sensitivity compared with Be exposed (PMID:17927685)
• BTNL2 gene might be one of the candidate genes that is responsible for the pathogenesis of Dermatophagoides farinae (Der f)-specific IgE responsiveness. (PMID:19050377)
• Genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 for ulcerative colitis. (PMID:19122664)
• The CNV_ID 507 was tested for association in a cohort of 89 sarcoidosis patients and 89 matched controls, but our results indicated that CNV_ID 507 does not affect the genomic structure of BTLN2 as previously described (PMID:19140834)
• Single-nucleotide polymorphism in the BTNL2 gene is associated with ulcerative colitis. (PMID:19659809)
• preliminary data suggest that BTNL2 polymorphism may be associated with susceptibility to Kawasaki disease and coronary artery lesions in Taiwanese children (PMID:19882345)
• This genetic study reveals a significant association between the rs3763313, rs9268494, rs9268492 SNPs in the BTNL2 gene and tuberculosis. (PMID:20176143)
• the absence of a membrane anchored BTNL2 protein may increase genetic susceptibility to sarcoidosis and familial occurrence of the disease. (PMID:20560297)
• The presence of a BTNL2G16071A variant allele almost doubles the risk of progressing to persistent pulmonary sarcoidosis in addition to increasing the risk of developing sarcoidosis. (PMID:21256912)
• The BTNL2 A allele variant occurs with a high frequency in Danish patients with sarcoidosis (PMID:21410903)
• The rs10947262 and rs7775228 variants are not associated with risk of knee osteoarthritis in European descent populations. (PMID:21853121)
• We unravel the role of unexplored immunologically important genes, BAT1 and BTNL2, and the haplotypes of the significantly associated SNPs therein, to understand susceptibility to the disease, leprosy and its differential severity. (PMID:22071774)
• Upon stratification analysis in search for a synergistic effect in sarcoidosis given the extensive linkage disequilibrium between BTNL2 rs2076530_A and HLA-DRB1*08:03; the risk-bearing allele of these two loci interact negatively. (PMID:22991420)
• Results show that single nucleotide polymorphism associated with BTNL2 gene is a risk factor for predisposition pulmonary sarcoidosis (PMID:23017494)
• sequenced single-nucleotide variants in an association study of 432 cases and 432 controls showed that 12 non-synonymous single-nucleotide polymorphisms (SNPs) in BTNL2 were significantly associated with RA (PMID:23364395)
• Rare BTNL2 variants play a role in susceptibility to both familial and sporadic prostate cancer. Results implicate BTNL2 as a novel prostate cancer susceptibility gene. (PMID:23833122)
• the BTNL2 splice site polymorphism (A variant of rs2076530) shows association with an increased risk for persistent sarcoidosis (PMID:23904553)
• These findings suggest that polymorphisms in the BTNL2 gene might play a vital role in determining the outcome of the immune response to hepatitis B vaccination. (PMID:24664813)
• Results confirm the association of BTNL2 rs2076530SNP with the susceptibility to develop sarcoidosis, but not with an increased risk of cancer in these patients. (PMID:25078641)
• No variation except in the 329-bp region containing the BTNL2 rs2076530 polymorphism was found in Turkish patients with sarcoidosis. (PMID:25551927)
• Two independent loci near BTNL2 (rs9461741) and HLA-B (rs2922994) in the HLA region significantly associated with Marginal Zone B-Cell Lymphoma risk. (PMID:25569183)
• The association of the rare variant p.G454C in BTNL2 reached genome-wide significance, and was independent of the known common risk variants for IBD in the HLA region in both a conditional and haplotype analysis (PMID:25671699)
• BTNL2 rs2076530 polymorphism contributes to the risk of sarcoidosis (PMID:25849037)
• genetic mutations within or around BTNL2 (rs3763313, rs9268494, rs9268492 and rs9268402) could alter susceptibility to grade IV of dilated cardiomyopathy in a Chinese population (PMID:26617759)
• BTNL2 may have an inhibitory effect on FOXP3(+) T cell proliferation, especially in patients homozygous for the risk alleles. (PMID:26679868)
• BTNL2 variant is associated with psoriasis. (PMID:27213287)
• The sarcoidosis risk variant BTNL2 c.1078G.A (rs2076530) was associated with disease in all OFG cases (P (1/4) 0.013; OR (1/4) 1.33; 95% CI, 1.06-1.67) and had a similar OR (1.56) and the same direction of effect as seen in sarcoidosis. However, no association was seen for the subphenotypes of OFG only or OFG+CD. (PMID:27306066)
• BTNL2 G16071A gene polymorphism may as a likelihood factor contributed to granulomatous disease susceptibility, especially increasing the sarcoidosis susceptibility. In addition, the polymorphism may be greatly associated with likelihood of granulomatous diseases among Caucasians. (PMID:27472712)
• Butyrophilin-like 2, expressed at various levels by UM cells and macrophages, might interfere with the immune control of the tumor. Butyrophilin-like 2 variants showed highly variable frequencies among ethnically related cohorts. There was no enrichment of BTNL2 variants in patients with UM compared with control patients. (PMID:27532663)
• Despite a significant difference in BTNL2 polymorphism between sarcoid patients and controls, there was no such difference between familial and sporadic sarcoidosis cases and no correlation between BTNL2 polymorphism and disease severity or outcome. Thus, BTNL2 difference cannot be considered as a key marker for disease classification or patient management. (PMID:27914482)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Btnl2	ENSMUSG00000024340
rattus_norvegicus	Btnl2	ENSRNOG00000028541

Paralogs (15): BTN3A1 (ENSG00000026950), CD276 (ENSG00000103855), BTN3A3 (ENSG00000111801), BTN2A1 (ENSG00000112763), BTNL8 (ENSG00000113303), HHLA2 (ENSG00000114455), BTN2A2 (ENSG00000124508), BTN1A1 (ENSG00000124557), VTCN1 (ENSG00000134258), ICOSLG (ENSG00000160223), ERMAP (ENSG00000164010), BTNL9 (ENSG00000165810), BTNL3 (ENSG00000168903), BTN3A2 (ENSG00000186470), MOG (ENSG00000204655)

Protein

Protein identifiers

Butyrophilin-like protein 2 — Q9UIR0 (reviewed: Q9UIR0)

All UniProt accessions (3): Q9UIR0, F6UPS5, F8WDK6

UniProt curated annotations — full annotation on UniProt →

Function. Negative regulator of T-cell proliferation.

Subcellular location. Membrane.

Tissue specificity. Expressed in brain, heart, kidney, liver, pancreas, ovary, leukocyte, small intestine, testis and thymus.

Disease relevance. Sarcoidosis 2 (SS2) [MIM:612387] An idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Induction. By pro-inflammatory cytokines such as TNF and IL1B/interleukin-1 beta.

Polymorphism. The sequence shown corresponds to the translation of the reference genome assembly (GRCh38/hg38) with Ser at position 360. This variant p.Gly360Ser is associated with an increased risk for sarcoidosis.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the immunoglobulin superfamily. BTN/MOG family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9UIR0-7	7	yes
Q9UIR0-1	1
Q9UIR0-2	2, Long
Q9UIR0-3	3, Short
Q9UIR0-4	4
Q9UIR0-8	8

RefSeq proteins (1): NP_001291490* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003597	Ig_C1-set	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050504	IgSF_BTN/MOG-like	Family
IPR053896	BTN3A2-like_Ig-C	Domain

Pfam: PF07686, PF22705

UniProt features (34 total): sequence variant 12, splice variant 8, disulfide bond 3, domain 3, topological domain 2, sequence conflict 2, glycosylation site 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UIR0-F1	85.97	0.61

Functional residue map

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

Disulfide bonds (3): 164–218, 267–341, 50–124

Glycosylation sites (2): 210, 427

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8851680	Butyrophilin (BTN) family interactions
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 238 (showing top): GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_CELL_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_LEUKOCYTE_PROLIFERATION, GOBP_CYTOKINE_PRODUCTION

GO Biological Process (5): regulation of cytokine production (GO:0001817), positive regulation of interleukin-2 production (GO:0032743), positive regulation of T cell proliferation (GO:0042102), T cell receptor signaling pathway (GO:0050852), negative regulation of T cell receptor signaling pathway (GO:0050860)

GO Molecular Function (1): signaling receptor binding (GO:0005102)

GO Cellular Component (3): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
positive regulation of cytokine production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of T cell activation	1
antigen receptor-mediated signaling pathway	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
protein binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

841 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BTNL2	ANXA11	P50995	841
BTNL2	HLA-DRB1	P01911	825
BTNL2	HLA-DRA	P01903	749
BTNL2	HLA-DQB1	P01917	726
BTNL2	HLA-DRB5	Q30154	707
BTNL2	TSBP1	Q5SRN2	697
BTNL2	HLA-DQA2	P01906	670
BTNL2	Q5Y7H0	Q5Y7H0	624
BTNL2	HSPA1L	P34931	610
BTNL2	NOD2	Q9HC29	600
BTNL2	EMC10	Q5UCC4	598
BTNL2	SRSF1	Q07955	582
BTNL2	SLC11A1	P49279	548
BTNL2	MRPL58	Q14197	545
BTNL2	HLA-A	P01891	535

IntAct

3 interactions, top by confidence:

A	B	Type	Score
BTNL2	HSPA5	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (154): OTOA (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), IKBIP (Affinity Capture-MS), NOMO1 (Affinity Capture-MS), ROR2 (Affinity Capture-MS), NLGN2 (Affinity Capture-MS), ABHD3 (Affinity Capture-MS), CLSTN1 (Affinity Capture-MS), PTGFRN (Affinity Capture-MS), TAPBP (Affinity Capture-MS), TTC17 (Affinity Capture-MS), CACNA2D2 (Affinity Capture-MS), ATF6 (Affinity Capture-MS), SEMA4G (Affinity Capture-MS), GAS6 (Affinity Capture-MS)

ESM2 similar proteins: A0A0E4BZH1, A4QPC6, A5D7V5, A7TZE6, A7TZF0, A7TZF3, A7XUX6, A7XV04, A7XV07, A8K4G0, A8MVZ5, O70355, P08508, P18892, P24071, P31994, P55803, P78410, P79391, Q13410, Q16653, Q29ZQ1, Q3KPI0, Q58DF9, Q5R7W8, Q5R960, Q5R996, Q61885, Q62556, Q63345, Q6Q8B3, Q6UXZ3, Q6XJV4, Q6XJV6, Q7KYR7, Q7TST0, Q7YR73, Q8BTP3, Q8K249, Q8TD46

Diamond homologs: A0A0E4BZH1, A4QPC6, A7TZE6, A7TZF0, A7TZF3, A7TZG1, A7TZG3, A7XUX6, A7XUY5, A7XUZ6, A7XV04, A7XV07, A7XV14, A8MVZ5, O00478, O00481, O70355, P18892, P55803, P78410, Q13410, Q16653, Q29ZQ1, Q5R7W8, Q5R960, Q5R996, Q61885, Q62556, Q63345, Q6MG97, Q6UX41, Q6UXE8, Q6UXG8, Q7KYR7, Q7TST0, Q8BJE2, Q8WVV5, Q96KV6, Q96PL5, Q9BGS7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	5
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1092 predictions. Top by Δscore:

Variant	Effect	Δscore
6:32396382:AGAAG:A	acceptor_gain	0.9900
6:32396383:GAAG:G	acceptor_gain	0.9900
6:32396384:AAGC:A	acceptor_loss	0.9900
6:32396385:AG:A	acceptor_gain	0.9900
6:32396386:GCTG:G	acceptor_loss	0.9900
6:32396387:C:A	acceptor_loss	0.9900
6:32396387:C:CC	acceptor_gain	0.9900
6:32396388:T:A	acceptor_loss	0.9900
6:32396390:T:TC	acceptor_gain	0.9900
6:32396394:A:AC	acceptor_gain	0.9900
6:32396394:A:C	acceptor_gain	0.9900
6:32396399:G:GC	acceptor_gain	0.9900
6:32407039:TCCTA:T	donor_loss	0.9900
6:32407040:CCTA:C	donor_loss	0.9900
6:32407041:CTA:C	donor_loss	0.9900
6:32407042:TA:T	donor_loss	0.9900
6:32407044:C:G	donor_loss	0.9900
6:32407044:CCTGA:C	donor_gain	0.9900
6:32396384:AAG:A	acceptor_gain	0.9800
6:32396390:T:C	acceptor_gain	0.9800
6:32403127:GCTCT:G	acceptor_gain	0.9800
6:32405298:G:GC	acceptor_gain	0.9800
6:32395024:ACCTG:A	acceptor_loss	0.9700
6:32395026:C:A	acceptor_loss	0.9700
6:32395027:T:A	acceptor_loss	0.9700
6:32396037:ACT:A	donor_loss	0.9700
6:32396038:CTT:C	donor_loss	0.9700
6:32396039:TTA:T	donor_loss	0.9700
6:32396040:TAC:T	donor_loss	0.9700
6:32396041:A:T	donor_loss	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000273906 (6:32394946 C>A,T), RS1000304271 (6:32396660 C>T), RS1000913980 (6:32405171 C>T), RS1001009345 (6:32399166 T>A), RS1001549956 (6:32398912 C>T), RS1001658282 (6:32400829 C>A), RS1001670172 (6:32402428 A>G), RS1001766182 (6:32408779 G>A), RS1002437534 (6:32405072 T>C), RS1002467036 (6:32398852 G>A), RS1002799314 (6:32403631 A>G), RS1002828812 (6:32393095 T>C), RS1003103966 (6:32393384 C>T), RS1003765824 (6:32403501 T>C), RS1003845105 (6:32394872 T>C,G)

Disease associations

OMIM: gene MIM:606000 | disease phenotypes: MIM:612387

GenCC curated gene-disease

Disease	Classification	Inheritance
sarcoidosis, susceptibility to, 2	Limited	Autosomal dominant

Mondo (2): breast ductal adenocarcinoma (MONDO:0005590), sarcoidosis, susceptibility to, 2 (MONDO:0012888)

Orphanet (1): Sarcoidosis (Orphanet:797)

HPO phenotypes

88 total (30 of 88 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000083	Renal insufficiency
HP:0000121	Nephrocalcinosis
HP:0000433	Abnormal nasal mucosa morphology
HP:0000501	Glaucoma
HP:0000502	Abnormal conjunctiva morphology
HP:0000518	Cataract
HP:0000554	Uveitis
HP:0000618	Blindness
HP:0000620	Dacryocystitis
HP:0000787	Nephrolithiasis
HP:0000821	Hypothyroidism
HP:0000834	Abnormality of the adrenal glands
HP:0000836	Hyperthyroidism
HP:0000873	Diabetes insipidus
HP:0000953	Hyperpigmentation of the skin
HP:0001010	Hypopigmentation of the skin
HP:0001097	Keratoconjunctivitis sicca
HP:0001217	Clubbing
HP:0001369	Arthritis
HP:0001386	Joint swelling
HP:0001399	Hepatic failure
HP:0001409	Portal hypertension
HP:0001410	Decreased liver function
HP:0001482	Subcutaneous nodule
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001878	Hemolytic anemia

GWAS associations

133 associations (top):

Study	Trait	p-value
GCST000243_1	Ulcerative colitis	6.000000e-18
GCST000311_1	Ulcerative colitis	1.000000e-16
GCST000356_1	Anti-cyclic Citrullinated Peptide Antibody	5.000000e-07
GCST000408_6	Primary biliary cholangitis	1.000000e-10
GCST000408_7	Primary biliary cholangitis	7.000000e-10
GCST000529_7	Ulcerative colitis	3.000000e-06
GCST000549_21	HIV-1 control	2.000000e-06
GCST000624_3	Ulcerative colitis	9.000000e-23
GCST000629_1	Knee osteoarthritis	5.000000e-09
GCST000662_5	Vitiligo	7.000000e-19
GCST000829_10	Waist-hip ratio	4.000000e-07
GCST000964_4	Ulcerative colitis	1.000000e-55
GCST000981_1	Vitiligo	8.000000e-11
GCST000984_11	Idiopathic membranous nephropathy	1.000000e-48
GCST001183_7	Asthma	5.000000e-12
GCST001587_6	Coronary heart disease	3.000000e-15
GCST001609_4	Lung adenocarcinoma	3.000000e-10
GCST001654_1	Sarcoidosis	3.000000e-11
GCST001701_2	Asthma	1.000000e-08
GCST001815_2	Hepatitis C induced liver cirrhosis	1.000000e-08
GCST001891_2	Multiple sclerosis (OCB status)	6.000000e-10
GCST001892_3	Multiple sclerosis (OCB status)	8.000000e-06
GCST001942_21	Prostate cancer	5.000000e-09
GCST002094_1	Crohn’s disease	5.000000e-12
GCST002094_4	Crohn’s disease	3.000000e-12
GCST002217_4	Sjögren’s syndrome	9.000000e-37
GCST002297_1	Hepatitis B vaccine response	3.000000e-19
GCST002516_2	Frontotemporal dementia	6.000000e-09
GCST002518_1	Food antigen IgG levels	9.000000e-08
GCST002742_1	Marginal zone lymphoma	4.000000e-15

EFO canonical traits (22, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0000180	HIV-1 infection
EFO:0004343	waist-hip ratio
EFO:0005206	oligoclonal band measurement
EFO:0004645	response to vaccine
EFO:0005844	response to dietary antigen
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0006319	HIV viral set point measurement
EFO:0007865	loneliness measurement
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0009180	rosacea severity measurement
EFO:0006941	grip strength measurement
EFO:0004509	hemoglobin measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0009936	Drugs affecting bone structure and mineralization use measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004918	age at diagnosis
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference
EFO:0004587	lymphocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, decreases methylation	1
bisphenol A	affects cotreatment, increases methylation	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery