BANK1

Summary

BANK1 (B cell scaffold protein with ankyrin repeats 1, HGNC:18233) is a protein-coding gene on chromosome 4q24, encoding B-cell scaffold protein with ankyrin repeats (Q8NDB2). Involved in B-cell receptor (BCR)-induced Ca(2+) mobilization from intracellular stores.

The protein encoded by this gene is a B-cell-specific scaffold protein that functions in B-cell receptor-induced calcium mobilization from intracellular stores. This protein can also promote Lyn-mediated tyrosine phosphorylation of inositol 1,4,5-trisphosphate receptors. Polymorphisms in this gene are associated with susceptibility to systemic lupus erythematosus. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55024 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Supportive, GenCC)
• GWAS associations: 43
• Clinical variants (ClinVar): 172 total — 5 pathogenic
• Phenotypes (HPO): 44
• MANE Select transcript: NM_017935

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18233
Approved symbol	BANK1
Name	B cell scaffold protein with ankyrin repeats 1
Location	4q24
Locus type	gene with protein product
Status	Approved
Aliases	BANK, FLJ20706
Ensembl gene	ENSG00000153064
Ensembl biotype	protein_coding
OMIM	610292
Entrez	55024

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000322953, ENST00000428908, ENST00000444316, ENST00000502990, ENST00000504403, ENST00000504592, ENST00000508653, ENST00000510950

RefSeq mRNA: 3 — MANE Select: NM_017935 NM_001083907, NM_001127507, NM_017935

CCDS: CCDS34038, CCDS47115, CCDS47116

Canonical transcript exons

ENST00000322953 — 17 exons

Exon	Start	End
ENSE00001008619	101862526	101862664
ENSE00001008622	101855035	101855189
ENSE00001080693	101870505	101870644
ENSE00001080699	102060211	102060389
ENSE00001080700	102063075	102063138
ENSE00001134639	102043839	102043907
ENSE00001134674	101917993	101918189
ENSE00001134687	101895305	101895410
ENSE00001283745	102029960	102030265
ENSE00002036780	102074005	102074812
ENSE00002044081	101790730	101790950
ENSE00003461909	102025201	102025509
ENSE00003499796	102021514	102021592
ENSE00003520190	101829808	101830206
ENSE00003611058	102072345	102072400
ENSE00003657238	102071275	102071304
ENSE00003657523	102073684	102073748

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 94.90.

FANTOM5 (CAGE): breadth broad, TPM avg 6.8126 / max 934.3658, expressed in 403 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49034	3.5328	137
49033	1.0157	316
49038	0.7469	54
49035	0.5726	66
49039	0.5314	53
49036	0.3189	35
49037	0.0475	17
203302	0.0467	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	94.90	gold quality
spleen	UBERON:0002106	94.56	gold quality
vermiform appendix	UBERON:0001154	93.21	gold quality
epithelium of nasopharynx	UBERON:0001951	92.29	gold quality
caecum	UBERON:0001153	88.47	gold quality
superficial temporal artery	UBERON:0001614	88.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.65	gold quality
buccal mucosa cell	CL:0002336	85.16	silver quality
granulocyte	CL:0000094	84.70	gold quality
blood	UBERON:0000178	84.27	gold quality
leukocyte	CL:0000738	83.80	gold quality
tonsil	UBERON:0002372	83.33	gold quality
monocyte	CL:0000576	83.32	gold quality
mononuclear cell	CL:0000842	83.30	gold quality
bone marrow	UBERON:0002371	82.25	gold quality
bone marrow cell	CL:0002092	81.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.22	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.46	gold quality
trabecular bone tissue	UBERON:0002483	78.20	gold quality
sural nerve	UBERON:0015488	78.11	gold quality
thyroid gland	UBERON:0002046	77.99	gold quality
left lobe of thyroid gland	UBERON:0001120	77.91	gold quality
right lobe of thyroid gland	UBERON:0001119	77.79	gold quality
colonic epithelium	UBERON:0000397	76.55	gold quality
lower lobe of lung	UBERON:0008949	75.79	gold quality
adipose tissue	UBERON:0001013	75.48	gold quality
small intestine	UBERON:0002108	75.23	gold quality
connective tissue	UBERON:0002384	75.06	gold quality
corpus epididymis	UBERON:0004359	74.73	gold quality
rectum	UBERON:0001052	74.70	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	3299.97
E-GEOD-150728	yes	1176.02
E-CURD-122	yes	792.11
E-CURD-55	yes	658.34
E-MTAB-9221	yes	647.70
E-HCAD-32	yes	611.50
E-GEOD-149689	yes	580.96
E-HCAD-4	yes	152.86
E-HCAD-1	yes	123.97
E-CURD-88	yes	80.30
E-MTAB-9467	yes	49.51
E-CURD-46	yes	44.13
E-ANND-3	yes	41.19
E-MTAB-8410	yes	40.38
E-MTAB-10553	yes	16.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting BANK1, 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-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
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-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
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-493-5P	99.96	72.47	2382
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786

Literature-anchored findings (GeneRIF, showing 40)

• Functional variants in the B-cell gene BANK1 are assoicated with systemic lupus erythematosus. (PMID:18204447)
• These results suggest that BANK1 SNPs and haplotypes may contribute to rheumatoid arthritis susceptibility with a low risk. (PMID:19180476)
• Study independently replicates and confirms the strong association of BANK1 variants rs17266594 and rs10516487 with the risk of systemic lupus erythematosus in the European-derived population. (PMID:19339986)
• Study confirmed the associations of BANK1 (rs3733197)and TNFSF4 (rs844648) with systemic lupus erythematosus in Hong Kong Chinese. (PMID:19357697)
• STAT4 and BLK displayed a strong genetic association with primary antiphospholipid syndrome, while a weak association with IRF5 and no association with BANK1 were observed. (PMID:19644876)
• results suggest that the BANK1 gene confers susceptibility to systemic sclerosis in general, and specifically to the diffuse cutanenous systemic sclerosis and anti-topoisomerase I antibody subsets. (PMID:19815934)
• BANK1 is a new systemic sclerosis genetic susceptibility factor. BANK1, IRF5, and STAT4 act with additive effects. (PMID:19877059)
• Results do not support a major implication of the BANK1 locus in susceptibility to giant cell arteritis. (PMID:20472928)
• This study implies that rs10516487 and rs17266594 polymorphisms might contribute to individual susceptibility to SLE (PMID:21078628)
• This meta-analysis demonstrates a significant association between BANK1 and TNFAIP3 gene polymorphism and systemic lupus erythematosus in multiple ethnic populations. (PMID:21208380)
• short Delta2 isoform of BANK1 displays a homogeneous cytoplasmic distribution (PMID:21900951)
• This study shows a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically. (PMID:21978998)
• Polymorphism in BANK1 is associated with susceptibility to psoriasis in Southern Han Chinese. (PMID:21989138)
• allelic variation in BANK1 does not play a major role in determining multifocal motor neuropathy susceptibility. (PMID:22003931)
• This study did not reveal a major role for BANK1 in humoral autoimmunity in chronic arthritis. (PMID:23065315)
• BANK1 and BLK have roles in B-cell signaling through phospholipase C gamma 2 (PMID:23555801)
• This study confirms BANK1 as an RA susceptibility gene and for the first time provides evidence for epistasis between BANK1 and BLK in RA. (PMID:23646104)
• SNPs of the FAM167A-BLK region, but not the BANK1 SNPs, were associated with the development of primary Sjogren’s syndrome in Han Chinese. (PMID:23899688)
• Our study confirms evidence for epistasis between BLK and BANK1 in systemic lupus erythematosis from a Chinese population for the first time. (PMID:24085759)
• Our findings suggest the existence of association between BANK1 gene and autoimmune thyroid diseases (PMID:24127308)
• BANK1 and IL15 as new T1D genetic susceptibility factors. (PMID:24342660)
• Authors identified a novel balanced reciprocal translocation, t(4;14)(q24;q32.) Sequence analysis identified the partner gene as BANK1. (PMID:24879116)
• Data show that single-nucleotide polymorphism rs3733197 located in the coding region of BANK1 (B-cell scaffold protein with ankyrin repeats 1) was significantly associated with serum LDL cholesterols. (PMID:25608828)
• Confirm the association of rs548234/ATG5, rs2736340/BLK and rs10516487/BANK1 with systemic lupus erythematosus in Chinese Han and reinforced our hypothesis of their epistasis effect in regulating B-cell signaling in SLE. (PMID:26420661)
• The systemic lupus erythematosus variant Ala71Thr of BLK severely decreases protein abundance and binding to BANK1 through impairment of the SH3 domain function. (PMID:26821283)
• Single-nucleotide polymorphism in BANK1 gene is associated with sclerotic graft-versus-host disease. (PMID:27313329)
• The results of this study suggesting a mechanism for the involvement of BANK1 in the BOLD response to working memory (PMID:27671502)
• The SLE susceptibility variants in the BANK1 gene may contribute to lupus by altering B cell signaling, increasing FOXO1 levels, and enhancing memory B cell development (PMID:27816669)
• This meta-analysis demonstrates that BANK1 rs10516487, rs3733197, and rs17266594 polymorphisms are associated with susceptibility to autoimmune diseases. (PMID:28466820)
• our results indicated that the BLK rs13277113 polymorphism was involved in the genetic background of RA in Chinese population and the association of BANK1 rs3733197 polymorphism with RA was dependent on the genotype of BLK rs13277113 polymorphism, highlighting B-cell response implicated in the pathogenesis of RA. (PMID:28925718)
• Our data defines a minimal set of risk associated eQTLs predicted to be involved in the expression of BANK1 modulated through epigenetic regulation and splicing. These findings allow us to suggest that the increased expression of BANK1 will have an impact on B-cell mediated disease pathways. (PMID:30096841)
• This study was the first to demonstrate that a BANK1 gene SNP (rs3733197) could confer genetic predisposition in polymyositis/dermatomyositis (PM/DM) patients and PM/DM patients with ILD in a Chinese Han population. (PMID:30145638)
• Study demonstrates the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines. (PMID:31101814)
• This is the first study showing an association of BLK rs2736340T/C and rs13277113A/G and BANK1 R61H with susceptibility to SLE in a Latin-American population. In addition, some BLK and BANK1 interactions were associated with susceptibility to SLE. (PMID:31134304)
• BLK and BANK1 variants and interactions are associated with susceptibility for primary Sjogren’s syndrome and with some clinical features. (PMID:33756160)
• Connection of BANK1, Tolerance, Regulatory B cells, and Apoptosis: Perspectives of a Reductionist Investigation. (PMID:33815360)
• The Role of BANK1 in B Cell Signaling and Disease. (PMID:34066164)
• Variants in BANK1 are associated with lupus nephritis of European ancestry. (PMID:34127828)
• IKBKE and BANK1 Polymorphisms and Clinical Characteristics in Chinese Women with Systemic Lupus Erythematosus. (PMID:35930382)
• Myelin oligodendrocyte glycoprotein-associated disease is associated with BANK1, RNASET2 and TNIP1 polymorphisms. (PMID:36054934)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bank1	ENSMUSG00000037922
rattus_norvegicus	Bank1	ENSRNOG00000032247
drosophila_melanogaster	stumps	FBGN0020299

Paralogs (1): PIK3AP1 (ENSG00000155629)

Protein

Protein identifiers

B-cell scaffold protein with ankyrin repeats — Q8NDB2 (reviewed: Q8NDB2)

All UniProt accessions (1): Q8NDB2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in B-cell receptor (BCR)-induced Ca(2+) mobilization from intracellular stores. Promotes Lyn-mediated phosphorylation of IP3 receptors 1 and 2.

Subunit / interactions. Interacts with LYN, ITPR1 and ITPR2.

Tissue specificity. Expressed in B-cell but not T-cell or myeloid cell lines. Highest expression in CD19(+) B-cells, with very low expression in other cell populations.

Post-translational modifications. Phosphorylated on tyrosines upon BCR activation.

Disease relevance. Systemic lupus erythematosus (SLE) [MIM:152700] A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8NDB2-1	1	yes
Q8NDB2-2	2
Q8NDB2-3	3
Q8NDB2-4	4, delta2

RefSeq proteins (3): NP_001077376, NP_001120979, NP_060405* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000157	TIR_dom	Domain
IPR017893	DBB_domain	Domain
IPR035897	Toll_tir_struct_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR041340	PIK3AP1_TIR	Domain
IPR052446	B-cell_PI3K-Signaling_Adptrs	Family

Pfam: PF14545, PF18567

UniProt features (25 total): sequence conflict 5, region of interest 5, splice variant 4, compositionally biased region 3, sequence variant 3, domain 2, repeat 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDB2-F1	61.25	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 334 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, chr4q24, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_B_CELL_ACTIVATION, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_B_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, TATTATA_MIR374, GOBP_TRANSLATIONAL_INITIATION, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_TRANSLATIONAL_INITIATION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (14): MAPK cascade (GO:0000165), response to bacterium (GO:0009617), negative regulation of interleukin-6 production (GO:0032715), B cell activation (GO:0042113), positive regulation of MAPK cascade (GO:0043410), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), negative regulation of translational initiation (GO:0045947), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), B cell receptor signaling pathway (GO:0050853), negative regulation of B cell activation (GO:0050869), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), regulation of immune system process (GO:0002682), signal transduction (GO:0007165), regulation of protein metabolic process (GO:0051246)

GO Molecular Function (6): protease binding (GO:0002020), signaling receptor binding (GO:0005102), signaling adaptor activity (GO:0035591), phospholipase binding (GO:0043274), protein tyrosine kinase binding (GO:1990782), protein binding (GO:0005515)

GO Cellular Component (1): perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular signaling cassette	2
enzyme binding	2
response to other organism	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
lymphocyte activation	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
translational initiation	1
regulation of translational initiation	1
negative regulation of translation	1
positive regulation of protein phosphorylation	1
peptidyl-tyrosine phosphorylation	1
regulation of peptidyl-tyrosine phosphorylation	1
antigen receptor-mediated signaling pathway	1
B cell activation	1
regulation of B cell activation	1
negative regulation of lymphocyte activation	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative regulation of intracellular signal transduction	1
immune system process	1
regulation of biological process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein metabolic process	1
regulation of macromolecule metabolic process	1
regulation of primary metabolic process	1
protein binding	1
protein-macromolecule adaptor activity	1
protein kinase binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

962 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BANK1	BLK	P51451	802
BANK1	LYN	P07948	779
BANK1	PXK	Q7Z7A4	779
BANK1	PHRF1	Q9P1Y6	765
BANK1	IRF5	Q13568	754
BANK1	PTPN22	Q9Y2R2	751
BANK1	ITPR3	Q14573	731
BANK1	TNFSF4	P23510	705
BANK1	ITPR1	Q14643	705
BANK1	TNFAIP3	P21580	697
BANK1	FAM167A	Q96KS9	664
BANK1	MS4A1	P08984	628
BANK1	MS4A2	Q01362	609
BANK1	PLCG2	P16885	601
BANK1	ITPR2	Q14571	599

IntAct

19 interactions, top by confidence:

A	B	Type	Score
LYN	BANK1	psi-mi:“MI:0915”(physical association)	0.590
BANK1	LYN	psi-mi:“MI:0915”(physical association)	0.590
BANK1	BLK	psi-mi:“MI:0915”(physical association)	0.560
BANK1	BLK	psi-mi:“MI:0403”(colocalization)	0.560
YWHAZ	LMNA	psi-mi:“MI:0914”(association)	0.560
	BANK1	psi-mi:“MI:0915”(physical association)	0.400
BANK1	SERPINH1	psi-mi:“MI:0915”(physical association)	0.400
FMR1	BANK1	psi-mi:“MI:0915”(physical association)	0.000
BANK1		psi-mi:“MI:0915”(physical association)	0.000
glgA	BANK1	psi-mi:“MI:0915”(physical association)	0.000
	BANK1	psi-mi:“MI:0915”(physical association)	0.000
BANK1	hemY	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): BANK1 (Affinity Capture-MS), BANK1 (Affinity Capture-Western), BANK1 (Co-localization), BANK1 (Affinity Capture-Western), TRAF6 (Co-localization), BANK1 (Reconstituted Complex), BANK1 (Proximity Label-MS), LYN (Affinity Capture-Western), ITPR1 (Affinity Capture-Western), LYN (Reconstituted Complex), BANK1 (Affinity Capture-MS), BANK1 (Affinity Capture-Western), BANK1 (Affinity Capture-MS), BANK1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMR6, A1A4L6, A1YG61, A2T737, O70273, O75747, P01105, P10157, P11308, P13474, P14921, P15036, P15037, P15062, P18755, P19102, P26323, P27577, P41156, P41157, P41212, P57782, P81270, P97360, Q08AW4, Q15052, Q32LN0, Q3SZL0, Q3US16, Q58DT0, Q60641, Q6GPJ8, Q6P3D7, Q7ZYI3, Q8BZ05, Q8C7R7, Q8HWS3, Q8N8B7, Q8NDB2, Q8VDK3

Diamond homologs: Q80VH0, Q8NDB2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	128
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1695119	GRCh37/hg19 4q24(chr4:102942671-103682051)x1	Pathogenic
2423442	NC_000004.11:g.(?102001669)(103806607_?)del	Pathogenic
2685124	GRCh37/hg19 4q23-24(chr4:100542119-103793167)x1	Pathogenic
3246728	NC_000004.11:g.(?101947022)(104640852_?)del	Pathogenic
688222	GRCh37/hg19 4q24(chr4:102980012-103706640)x1	Pathogenic

SpliceAI

2986 predictions. Top by Δscore:

Variant	Effect	Δscore
4:101855033:A:AG	acceptor_gain	1.0000
4:101855034:G:GG	acceptor_gain	1.0000
4:101855186:TGAGG:T	donor_loss	1.0000
4:101855190:G:A	donor_loss	1.0000
4:101855191:T:G	donor_loss	1.0000
4:101862254:G:GT	donor_gain	1.0000
4:101862662:TAGG:T	donor_loss	1.0000
4:101862663:AGG:A	donor_loss	1.0000
4:101862664:GG:G	donor_loss	1.0000
4:101862666:T:TC	donor_loss	1.0000
4:101870500:A:AG	acceptor_gain	1.0000
4:101870501:T:G	acceptor_gain	1.0000
4:101870502:A:AG	acceptor_gain	1.0000
4:101870503:A:AG	acceptor_gain	1.0000
4:101870504:G:GC	acceptor_loss	1.0000
4:101870504:G:GG	acceptor_gain	1.0000
4:101870504:GA:G	acceptor_gain	1.0000
4:101870504:GAGT:G	acceptor_gain	1.0000
4:101870641:CCAGG:C	donor_loss	1.0000
4:101870644:GGT:G	donor_loss	1.0000
4:101870645:GTAA:G	donor_loss	1.0000
4:101870646:T:G	donor_loss	1.0000
4:101895293:A:AG	acceptor_gain	1.0000
4:101895293:ACTT:A	acceptor_gain	1.0000
4:101895294:C:G	acceptor_gain	1.0000
4:101895304:GAATA:G	acceptor_gain	1.0000
4:101917989:ACAG:A	acceptor_loss	1.0000
4:101917990:CAG:C	acceptor_loss	1.0000
4:101917991:A:AG	acceptor_gain	1.0000
4:101917992:G:GG	acceptor_gain	1.0000

AlphaMissense

5229 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:102043841:T:C	F635L	0.996
4:102043843:T:A	F635L	0.996
4:102043843:T:G	F635L	0.996
4:101829855:T:A	W40R	0.994
4:101829855:T:C	W40R	0.994
4:101862590:T:C	F230S	0.991
4:102030195:A:C	R610S	0.991
4:102030195:A:T	R610S	0.991
4:101918140:C:A	A386D	0.990
4:102043842:T:C	F635S	0.988
4:101862589:T:C	F230L	0.987
4:101862591:T:A	F230L	0.987
4:101862591:T:G	F230L	0.987
4:101829857:G:C	W40C	0.986
4:101829857:G:T	W40C	0.986
4:101870529:T:A	V263D	0.985
4:101918034:G:C	A351P	0.984
4:102030194:G:C	R610T	0.984
4:102043842:T:G	F635C	0.983
4:101829982:T:C	L82P	0.979
4:102030193:A:G	R610G	0.978
4:102060342:T:C	F701L	0.978
4:102060344:T:A	F701L	0.978
4:102060344:T:G	F701L	0.978
4:101870576:T:G	Y279D	0.977
4:102060330:G:C	A697P	0.976
4:101862545:T:A	I215K	0.975
4:101918058:G:C	A359P	0.975
4:101918139:G:C	A386P	0.975
4:101830039:T:C	L101P	0.974

dbSNP variants (sampled 300 via entrez): RS1000007260 (4:102032361 CT>C,CTT), RS1000007626 (4:102010309 A>G), RS1000032534 (4:101890985 A>G), RS1000056675 (4:101837827 A>G), RS1000066026 (4:101974666 A>G), RS1000066749 (4:101792264 G>A,C), RS1000070862 (4:101812828 C>G), RS1000076993 (4:102025820 A>C), RS1000093472 (4:101974852 G>A), RS1000097459 (4:102016638 T>C), RS10000979 (4:101984885 A>C,G), RS1000106839 (4:102063844 A>G), RS1000115239 (4:101795091 A>G), RS1000118060 (4:101974371 G>T), RS1000120096 (4:102064272 T>G)

Disease associations

OMIM: gene MIM:610292 | disease phenotypes: MIM:152700, MIM:601744

GenCC curated gene-disease

Disease	Classification	Inheritance
systemic lupus erythematosus	Supportive	Unknown

Mondo (1): systemic lupus erythematosus (MONDO:0007915)

Orphanet (1): Systemic lupus erythematosus (Orphanet:536)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000093	Proteinuria
HP:0000155	Oral ulcer
HP:0000488	Retinopathy
HP:0000716	Depression
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000992	Cutaneous photosensitivity
HP:0001250	Seizure
HP:0001369	Arthritis
HP:0001596	Alopecia
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001878	Hemolytic anemia
HP:0001882	Decreased total leukocyte count
HP:0001945	Fever
HP:0002039	Anorexia
HP:0002072	Chorea
HP:0002716	Lymphadenopathy
HP:0003453	Antineutrophil antibody positivity
HP:0003493	Antinuclear antibody positivity
HP:0005421	Decreased circulating complement C3 concentration
HP:0005764	Polyarticular arthritis
HP:0007417	Discoid lupus rash
HP:0012085	Pyuria
HP:0012378	Fatigue
HP:0020151	Anti-dsDNA antibody positivity
HP:0025300	Malar rash
HP:0030880	Raynaud phenomenon
HP:0032235	Anti-La/SS-B antibody positivity
HP:0033028	Anti-U1 ribonucleoprotein antibody positivity

GWAS associations

43 associations (top):

Study	Trait	p-value
GCST000143_1	Systemic lupus erythematosus	4.000000e-10
GCST001598_2	Blood pressure	8.000000e-08
GCST001795_15	Systemic lupus erythematosus	5.000000e-06
GCST001877_71	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	4.000000e-06
GCST003155_47	Systemic lupus erythematosus	4.000000e-17
GCST003156_13	Systemic lupus erythematosus	8.000000e-08
GCST003468_24	Chronic lymphocytic leukemia	7.000000e-08
GCST003622_74	Systemic lupus erythematosus	5.000000e-10
GCST003876_5	Gut microbiota (beta diversity)	5.000000e-08
GCST004131_126	Inflammatory bowel disease	4.000000e-06
GCST004132_34	Crohn’s disease	4.000000e-08
GCST004146_23	Chronic lymphocytic leukemia	1.000000e-10
GCST004521_11	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004599_91	Mean platelet volume	2.000000e-15
GCST005316_602	Intelligence (MTAG)	2.000000e-09
GCST005316_605	Intelligence (MTAG)	2.000000e-13
GCST005537_18	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	3.000000e-10
GCST005752_160	Systemic lupus erythematosus	1.000000e-17
GCST005752_45	Systemic lupus erythematosus	5.000000e-07
GCST005830_88	Hand grip strength	1.000000e-08
GCST006269_1221	General cognitive ability	4.000000e-08
GCST006269_780	General cognitive ability	2.000000e-09
GCST006630_63	Diastolic blood pressure	4.000000e-26
GCST006666_13	Lipid traits (pleiotropy) (HIPO component 1)	3.000000e-08
GCST006803_8	Schizophrenia	1.000000e-16
GCST007267_36	Systolic blood pressure	2.000000e-16
GCST007324_120	Adventurousness	2.000000e-08
GCST007400_32	Systemic lupus erythematosus	1.000000e-12
GCST009685_35	Hypertension	1.000000e-09
GCST009797_5	Alcohol consumption (heavy vs. light/non-drinkers)	2.000000e-07

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0004337	intelligence
EFO:0006941	grip strength measurement
EFO:0006336	diastolic blood pressure
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006335	systolic blood pressure
EFO:0008579	risk-taking behaviour
EFO:0004346	neuroimaging measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0600001	ghrelin measurement
EFO:0010100	multisite chronic pain

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	3
Aflatoxin B1	decreases expression, decreases methylation	3
sodium arsenite	decreases expression	2
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Fonofos	increases methylation	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Gallic Acid	increases expression	1
Mercury	increases expression	1
Parathion	increases methylation	1
Silicon Dioxide	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)
NCT02953821	PHASE4	COMPLETED	Acthar Gel for Active Systemic Lupus Erythematosus (SLE)
NCT03042260	PHASE4	UNKNOWN	Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
NCT03098823	PHASE4	COMPLETED	A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT04447053	PHASE4	UNKNOWN	Sequential Belimumab and T-cell Based Therapy in SLE
NCT04515719	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in SLE Patients
NCT04893161	PHASE4	UNKNOWN	A Model About the Response of Belimumab in SLE
NCT04908865	PHASE4	COMPLETED	Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)
NCT04956484	PHASE4	COMPLETED	Belimumab In Early Systemic Lupus Erythematosus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus
NCT05666336	PHASE4	UNKNOWN	Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients
NCT05748925	PHASE4	COMPLETED	Cardio Renal Effects of SGLT2 Inhibitors Among Lupus Nephritis Patients