JAZF1

Summary

JAZF1 (JAZF zinc finger 1, HGNC:28917) is a protein-coding gene on chromosome 7p15.2-p15.1, encoding Juxtaposed with another zinc finger protein 1 (Q86VZ6). Acts as a transcriptional corepressor of orphan nuclear receptor NR2C2. It is a selective cancer dependency (DepMap: 27.9% of cell lines).

This gene encodes a nuclear protein with three C2H2-type zinc fingers, and functions as a transcriptional repressor. Chromosomal aberrations involving this gene are associated with endometrial stromal tumors. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized

Source: NCBI Gene 221895 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Supportive, GenCC)
• GWAS associations: 166
• Clinical variants (ClinVar): 34 total
• Phenotypes (HPO): 44
• Cancer dependency (DepMap): dependent in 27.9% of screened cell lines
• MANE Select transcript: NM_175061

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28917
Approved symbol	JAZF1
Name	JAZF zinc finger 1
Location	7p15.2-p15.1
Locus type	gene with protein product
Status	Approved
Aliases	TIP27, DKFZp761K2222, ZNF802
Ensembl gene	ENSG00000153814
Ensembl biotype	protein_coding
OMIM	606246
Entrez	221895

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000283928, ENST00000420835, ENST00000427814, ENST00000430432, ENST00000447620, ENST00000452993, ENST00000454041, ENST00000466516, ENST00000649905, ENST00000900291, ENST00000919133

RefSeq mRNA: 1 — MANE Select: NM_175061 NM_175061

CCDS: CCDS5416

Canonical transcript exons

ENST00000283928 — 5 exons

Exon	Start	End
ENSE00001285427	27991909	27991981
ENSE00001335148	28180463	28180795
ENSE00003508156	27840698	27840867
ENSE00003687721	27895220	27895416
ENSE00003843358	27830577	27832976

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 96.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.6869 / max 2855.8163, expressed in 1688 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83368	23.4199	1596
83367	8.8069	1551
83351	0.1653	65
83366	0.1586	57
83352	0.0939	27
83350	0.0424	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	96.10	gold quality
cauda epididymis	UBERON:0004360	95.82	gold quality
right adrenal gland cortex	UBERON:0035827	95.77	gold quality
right adrenal gland	UBERON:0001233	95.12	gold quality
adrenal cortex	UBERON:0001235	95.11	gold quality
left adrenal gland cortex	UBERON:0035825	94.94	gold quality
left adrenal gland	UBERON:0001234	94.89	gold quality
adrenal gland	UBERON:0002369	94.25	gold quality
urethra	UBERON:0000057	94.18	gold quality
endometrium	UBERON:0001295	94.17	gold quality
oocyte	CL:0000023	94.10	gold quality
decidua	UBERON:0002450	93.83	gold quality
secondary oocyte	CL:0000655	93.72	gold quality
smooth muscle tissue	UBERON:0001135	93.52	gold quality
cortical plate	UBERON:0005343	93.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.36	gold quality
synovial joint	UBERON:0002217	93.33	gold quality
endocervix	UBERON:0000458	93.29	gold quality
uterus	UBERON:0000995	93.25	gold quality
monocyte	CL:0000576	93.05	gold quality
blood	UBERON:0000178	93.03	gold quality
leukocyte	CL:0000738	92.95	gold quality
saphenous vein	UBERON:0007318	92.94	gold quality
myometrium	UBERON:0001296	92.83	gold quality
layer of synovial tissue	UBERON:0007616	92.25	gold quality
popliteal artery	UBERON:0002250	92.15	gold quality
tibial artery	UBERON:0007610	92.15	gold quality
cartilage tissue	UBERON:0002418	92.08	gold quality
body of uterus	UBERON:0009853	91.98	gold quality
uterine cervix	UBERON:0000002	91.69	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.83
E-CURD-119	yes	4.99
E-MTAB-6386	no	902.98
E-MTAB-9467	no	1.08

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
MEF2C	Repression

Upstream regulators (CollecTRI, top): PITX2, ZNF91

miRNA regulators (miRDB)

288 targeting JAZF1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3185	99.99	68.12	1959
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-6870-5P	99.99	68.55	2115
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 27.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 35)

• Endometrial stromal tumors(ESTs) are genetically heterogeneous, with prevalence of JAZF1-JJAZ1 fusion highest among ESTs of classic histology. Diagnostic utility of JAZF1-JJAZ1 fusion transcript assay in ESTs may be limited to classic histologic subset. (PMID:15043312)
• TIP27 (TAK1-interacting protein 27; sequence indentical to JAZF1) functions as a repressor of the nuclear orphan receptor TAK1/TR4. (PMID:15302918)
• The JAZF1-JJAZ1 fusion is a frequent, although nonuniform, feature of endometrial stromal neoplasia. (PMID:17197920)
• The JAFZ1-JJAZ1 fusion gene is present in the endometrial stromal and smooth muscle components of endometrial stromal tumors. (PMID:17667554)
• Both benign and malignant forms of endometrial stromal tumor have the JAZF1-JJAZ1 fusion, but only the malignant form also exhibits exclusion of the unrearranged JJAZ1 allele. (PMID:18077430)
• Study show that polymorphisms in JAZF1 were associated with type 2 diabetes risk in the studied population. (PMID:18694974)
• predicted 684-amino acid JAZF1/PHF1 chimeric protein retained one zinc finger domain from JAZF1 and the two zinc finger domains from PHF1, and its oncogenic mechanism should be similar to that of the JAZF1/SUZ12 protein (PMID:18722875)
• study shows normal endometrial stromal cells contain a specific chimeric RNA joining 5’ exons of JAZF1 gene on chromosome 7p15 to 3’ exons of JJAZ1/SUZ12 gene on chromosome 17q11; this RNA is translated into JAZF1-JJAZ1 with anti-apoptotic activity (PMID:18772439)
• Linkage and genome-wide association analyses independently identified the JAZF1 affecting human height. (PMID:18952825)
• The JAZF1-JJAZ1 gene fusion was not identified in any Uterine tumor resembling ovarian sex cord tumors (PMID:19542872)
• identified five new systemic lupus erythematosus susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). (PMID:19838195)
• The JAZF1 SNPs rs6968704 and rs10486567 were associated with decreased risk of prostate cancer but were not associated with diabetes. (PMID:19998368)
• Single-nucleotide polymorphism of rs10486567 in JAZF1 is associated with prostate cancer. (PMID:20406958)
• This study indicates a nominal role for JAZF1 and BCL11A variants in type 2 diabetes susceptibility in African-Americans. (PMID:22113416)
• Morphological features, immunoprofile and fluorescence in situ hybridization rearrangements of JAZF1 and PHF1 genes were correlated with tumor category and outcome in endometrial sarcomas (PMID:22918161)
• genetic association studies in a population in Utah: Data suggest that an SNP in JAZF1 (rs1635852) is associated with type 2 diabetes; this SNP in JAZF1 intron 1 is part of a cis-regulatory complex. (PMID:23328127)
• study determined that the previously described systemic lupus erythematosus susceptibility loci PXK (P = 3.27 x 10(-11), OR = 1.20) and JAZF1 (P = 1.11 x 10(-8), OR = 1.13) are shared with systemic sclerosis (PMID:23740937)
• In African American men, the association between JAZF1 rs10486567 and prostate cancer may be modified by exposure to heavy metals such as Pb. (PMID:24801046)
• genetic association study in Han population in China: Data suggest an SNP in PXK [rs2176082(C/T); but not rs6445975(G/T)] is associated with recurrent pregnancy loss; SNPs in KIAA0319L [rs2275247(A/G)] or JAZF1 [rs1635852(C/T)] are not associated. (PMID:25596907)
• study found SNP rs7754840 in CDKAL1, rs864745 in JAZF1, and rs35767 in IGF1 might serve as potential susceptibility loci for type 2 diabetes in the Uyghur population (PMID:25785549)
• PNPLA3 and JAZF1 were associated with non-hepatitis B virus and non-hepatitis C virus-related hepatocellular carcinoma development among Japanese patients with type 2 diabetes mellitus (PMID:26337813)
• We discovered three significant associations at rs6679677 on 1p13.2 (P=6.15x10-5, OR=5.07), rs16861329 on 3q27.3 (P=2.02x10-4, OR=0.87) and rs849135 on 7p15.1 (P=6.59x10-9, OR=1.78), which suggested PTPN22, ST6GAL1 and JAZF1 as novel susceptibility genes for psoriasis in Chinese population. (PMID:28603863)
• Case Report: JAZF1/SUZ12 translocation in a low-grade endometrioid stromal sarcoma originating in the paratestis. (PMID:29394168)
• The roles of JAZF1 were partially attenuated by Compound C. (PMID:30154417)
• This review provides an update of the latest research advances on JAZF1 and its regulatory network in T2 diabetes mellitus (T2DM). The association between JAZF1 polymorphisms and T2DM is discussed as well. The information provided is of importance for guiding future studies as well as for the design of JAZF1-based T2DM therapy. [review] (PMID:30838734)
• JAZF1 was identified as a direct miR-1275 target. miR-1275 supresses migration and invasion of gastric cancer cells in vitro and in vivo, which was restored by JAZF1 overexpression. Moreover, JAZF1 was recognized as a direct regulator of Vimentin. (PMID:31357957)
• The Diabetes Gene JAZF1 Is Essential for the Homeostatic Control of Ribosome Biogenesis and Function in Metabolic Stress. (PMID:32640216)
• TFAP2B, AP-1 and JAZF1 Expression in Tissues of Papillary Thyroid Carcinoma Patients; Clinical, Pathological and Prognostic Values. (PMID:32856873)
• The relationship between chimeric RNAs and gene fusions: Potential implications of reciprocity in cancer. (PMID:33008771)
• Correlation analysis of epicardial adipose tissue thickness, C-reactive protein, interleukin-6, visfatin, juxtaposed with another zinc finger protein 1, and type 2 diabetic macroangiopathy. (PMID:33722242)
• RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells. (PMID:34928964)
• Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in beta(0)-thalassemia/HbE. (PMID:35322124)
• JAZF1-SUZ12 dysregulates PRC2 function and gene expression during cell differentiation. (PMID:35649353)
• Rs864745 in JAZF1, an Islet Function Associated Variant, Correlates With Plasma Lipid Levels in Both Type 1 and Type 2 Diabetes Status, but Not Healthy Subjects. (PMID:35846288)
• JAZF1: A Metabolic Regulator of Sensitivity to a Polyamine-Targeted Therapy. (PMID:36166196)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	jazf1b	ENSDARG00000056793
danio_rerio	jazf1a	ENSDARG00000102551
mus_musculus	Jazf1	ENSMUSG00000063568
rattus_norvegicus	Jazf1	ENSRNOG00000027026
drosophila_melanogaster	CG12054	FBGN0039831

Protein

Protein identifiers

Juxtaposed with another zinc finger protein 1 — Q86VZ6 (reviewed: Q86VZ6)

Alternative names: TAK1-interacting protein 27, Zinc finger protein 802

All UniProt accessions (6): Q86VZ6, A0A3B3ISK8, C9JGY8, C9JWY1, F8WD35, H0Y403

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional corepressor of orphan nuclear receptor NR2C2. Inhibits expression of the gluconeogenesis enzyme PCK2 through inhibition of NR2C2 activity. Also involved in transcriptional activation of NAMPT by promoting expression of PPARA and PPARD. Plays a role in lipid metabolism by suppressing lipogenesis, increasing lipolysis and decreasing lipid accumulation in adipose tissue. Plays a role in glucose homeostasis by improving glucose metabolism and insulin sensitivity.

Subunit / interactions. Interacts with NR2C2 (via ligand-binding region).

Subcellular location. Nucleus.

Tissue specificity. Highest expression in testis with moderate levels in colon, placenta, prostate and ovary and low levels in brain, spleen, liver and small intestine.

Disease relevance. A chromosomal aberration involving JAZF1 may be a cause of endometrial stromal tumors. Translocation t(7;17)(p15;q21) with SUZ12. The translocation generates the JAZF1-SUZ12 oncogene consisting of the N-terminus part of JAZF1 and the C-terminus part of SUZ12. It is frequently found in all cases of endometrial stromal tumors, except in endometrial stromal sarcomas, where it is rarer. Translocation t(6;7)(p21;p22) with PHF1.

Miscellaneous. Under hypoxic conditions, the precursor SUZ12 RNA undergoes regulated trans-splicing with the JAZF1 RNA, resulting in a chimeric isoform which may be protective against apoptosis. The chimeric transcript is characterized by JAZF1 exons 1-3 joined to SUZ12 exon 2-16. The chimeric transcript is expressed primarily in the endometrium from late secretory and early proliferative phases of the menstrual cycle, but not in normal myometrium at any phase of the cycle. Its expression is slightly induced by low levels of progesterone, but suppressed by both estrogen and high levels of progesterone.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86VZ6-1	1	yes
Q86VZ6-3	3

RefSeq proteins (1): NP_778231* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051580	ZnF-Chromatin_assoc	Family

UniProt features (18 total): mutagenesis site 4, zinc finger region 3, compositionally biased region 3, modified residue 2, region of interest 2, chain 1, splice variant 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VZ6-F1	70.25	0.10

Functional residue map

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

Catalytic / active sites (1): 129–130 (breakpoint for translocation to form jazf1-suz12 oncogene)

Post-translational modifications (2): 109, 113

Mutagenesis-validated functional residues (4):

Position	Phenotype
47	little effect on interaction with nr2c2.
60	abolishes interaction with nr2c2.
69	little effect on interaction with nr2c2.
76	reduces interaction with nr2c2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 294 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, AHRARNT_01, TTTGTAG_MIR520D, CACCAGC_MIR138, AATGGAG_MIR136, EVI1_05, CAGCAGG_MIR370, NF1_Q6_01, WTGAAAT_UNKNOWN, TGTGTGA_MIR377, OCT1_07, TGANTCA_AP1_C, MYOD_Q6, GOBP_LIPID_METABOLIC_PROCESS, AFP1_Q6

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), lipid metabolic process (GO:0006629)

GO Molecular Function (4): transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), transcription repressor complex (GO:0017053), ciliary tip (GO:0097542)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
negative regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
primary metabolic process	1
transcription coregulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
transcription regulator complex	1
cilium	1

Protein interactions and networks

STRING

1476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JAZF1	SUZ12	Q15022	912
JAZF1	CDC123	O75794	820
JAZF1	CDKAL1	Q5VV42	762
JAZF1	PHF1	O43189	714
JAZF1	MBTD1	Q05BQ5	701
JAZF1	CAMK1D	Q8IU85	699
JAZF1	NUTM2A	Q8IVF1	699
JAZF1	NR2C2	P49116	697
JAZF1	MEAF6	Q9HAF1	697
JAZF1	ADAMTS9	Q9P2N4	697
JAZF1	HHEX	Q03014	696
JAZF1	TSPAN8	P19075	696
JAZF1	SLC30A8	Q8IWU4	696
JAZF1	HNF1B	P35680	672
JAZF1	WFS1	O76024	668

IntAct

36 interactions, top by confidence:

A	B	Type	Score
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
NR2C2	JAZF1	psi-mi:“MI:0915”(physical association)	0.790
NR2C2	JAZF1	psi-mi:“MI:0403”(colocalization)	0.790
YEATS4	ZNHIT1	psi-mi:“MI:0914”(association)	0.790
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
MORF4L1	SIN3B	psi-mi:“MI:0914”(association)	0.730
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
FAM9B	JAZF1	psi-mi:“MI:0915”(physical association)	0.560
JAZF1	FAM9B	psi-mi:“MI:0915”(physical association)	0.560
YEATS4	ACTL6B	psi-mi:“MI:0914”(association)	0.530
JAZF1	YEATS4	psi-mi:“MI:0914”(association)	0.530
DMAP1	DR1	psi-mi:“MI:0914”(association)	0.530
JAZF1	DMAP1	psi-mi:“MI:0914”(association)	0.530
Ruvbl1	AAR2	psi-mi:“MI:0914”(association)	0.350
TRRAP	TTI2	psi-mi:“MI:0914”(association)	0.350
YEATS4	ING3	psi-mi:“MI:0914”(association)	0.350
JAZF1	TNPO2	psi-mi:“MI:0914”(association)	0.350
	KIF5C	psi-mi:“MI:0914”(association)	0.350
ING5	CCDC85C	psi-mi:“MI:0914”(association)	0.350
MYCL	CASK	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): JAZF1 (Affinity Capture-MS), JAZF1 (Affinity Capture-MS), JAZF1 (Affinity Capture-MS), JAZF1 (Affinity Capture-MS), JAZF1 (Affinity Capture-MS), JAZF1 (Affinity Capture-MS), JAZF1 (Affinity Capture-MS), JAZF1 (Affinity Capture-MS), JAZF1 (Affinity Capture-MS), JAZF1 (Affinity Capture-MS), JAZF1 (Affinity Capture-MS), FAM9B (Two-hybrid), JAZF1 (Affinity Capture-MS), SUZ12 (Reconstituted Complex), SUZ12 (Affinity Capture-MS)

ESM2 similar proteins: A2AFR3, A4FV57, B3KU38, F1LXF1, G3V9M2, O00287, O09112, O88450, P0C6S7, P11274, P22681, P22682, P49797, Q03353, Q03354, Q03355, Q13387, Q14CM0, Q3UR85, Q5RDF5, Q5T6S3, Q68FF6, Q69Z61, Q6GR30, Q6PAJ1, Q6ZMZ0, Q6ZN18, Q6ZWB6, Q7SXV2, Q7Z6G8, Q80ZQ5, Q86VZ6, Q8BIE6, Q8BIZ1, Q8CE64, Q8R3B7, Q8TEK3, Q8WXI2, Q96N64, Q9CXG9

Diamond homologs: P32432, Q5RDF5, Q61103, Q80ZQ5, Q86VZ6, Q92785, Q9UTH8, Q9W636, Q9W638, O15014, Q56A10, Q9ULD9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
JAZF1	down-regulates	NR2C2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
HATs acetylate histones	12	45.3×	4e-16
Chromatin organization	8	31.1×	6e-09
Chromatin modifying enzymes	8	27.5×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
regulation of double-strand break repair	8	160.3×	2e-14
positive regulation of double-strand break repair via homologous recombination	8	105.7×	4e-13
regulation of cell cycle	11	28.3×	3e-12
regulation of apoptotic process	8	23.0×	5e-08
chromatin remodeling	6	15.1×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3050 predictions. Top by Δscore:

Variant	Effect	Δscore
7:27833892:A:C	donor_gain	1.0000
7:27840716:T:TA	donor_gain	1.0000
7:27840864:CTGC:C	acceptor_gain	1.0000
7:27840865:TGC:T	acceptor_gain	1.0000
7:27840866:GC:G	acceptor_gain	1.0000
7:27840866:GCC:G	acceptor_loss	1.0000
7:27840867:CC:C	acceptor_gain	1.0000
7:27840868:C:CC	acceptor_gain	1.0000
7:27840869:T:A	acceptor_loss	1.0000
7:27895215:CTCA:C	donor_loss	1.0000
7:27895216:TCA:T	donor_loss	1.0000
7:27895217:CA:C	donor_loss	1.0000
7:27895218:A:C	donor_loss	1.0000
7:27991902:GGCTT:G	donor_loss	1.0000
7:27991903:GCTTA:G	donor_loss	1.0000
7:27991904:CTTA:C	donor_loss	1.0000
7:27991905:TTACC:T	donor_loss	1.0000
7:27991906:TA:T	donor_loss	1.0000
7:27991907:A:AC	donor_gain	1.0000
7:27991908:C:CC	donor_gain	1.0000
7:27991977:TGTAT:T	acceptor_gain	1.0000
7:27991979:TAT:T	acceptor_gain	1.0000
7:27991979:TATC:T	acceptor_loss	1.0000
7:27991980:AT:A	acceptor_gain	1.0000
7:27991981:TC:T	acceptor_loss	1.0000
7:27991982:C:CA	acceptor_loss	1.0000
7:27991982:C:CC	acceptor_gain	1.0000
7:27991987:A:AC	acceptor_gain	1.0000
7:27832973:CATT:C	acceptor_gain	0.9900
7:27832975:TT:T	acceptor_gain	0.9900

AlphaMissense

1601 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:27832844:G:C	H230D	1.000
7:27832857:G:C	H225Q	1.000
7:27832857:G:T	H225Q	1.000
7:27832858:T:A	H225L	1.000
7:27832858:T:C	H225R	1.000
7:27832858:T:G	H225P	1.000
7:27832859:G:A	H225Y	1.000
7:27832859:G:C	H225D	1.000
7:27832859:G:T	H225N	1.000
7:27832867:A:G	L222P	1.000
7:27832870:C:T	G221D	1.000
7:27832871:C:G	G221R	1.000
7:27832886:A:C	Y216D	1.000
7:27832886:A:G	Y216H	1.000
7:27832892:T:C	K214E	1.000
7:27832896:A:C	C212W	1.000
7:27832897:C:A	C212F	1.000
7:27832897:C:G	C212S	1.000
7:27832897:C:T	C212Y	1.000
7:27832898:A:G	C212R	1.000
7:27832898:A:T	C212S	1.000
7:27832902:A:C	C210W	1.000
7:27832903:C:A	C210F	1.000
7:27832903:C:G	C210S	1.000
7:27832903:C:T	C210Y	1.000
7:27832904:A:G	C210R	1.000
7:27832904:A:T	C210S	1.000
7:27832914:T:A	K206N	1.000
7:27832914:T:G	K206N	1.000
7:27832916:T:C	K206E	1.000

dbSNP variants (sampled 300 via entrez): RS1000005943 (7:28039752 A>G), RS1000022346 (7:28147507 T>C), RS1000029441 (7:28106527 C>G), RS1000032103 (7:27847614 A>G,T), RS1000033653 (7:28147747 T>G), RS1000042667 (7:28121954 T>C), RS1000046843 (7:27889292 G>T), RS1000052916 (7:28016221 A>G), RS1000058820 (7:27989674 CAT>C), RS1000059601 (7:27958054 A>G), RS1000083591 (7:28016009 T>C), RS1000086342 (7:27876193 T>G), RS1000090125 (7:27958366 C>A), RS1000121417 (7:28101265 A>G), RS1000121555 (7:28039264 C>T)

Disease associations

OMIM: gene MIM:606246 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
systemic lupus erythematosus	Supportive	Unknown

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

Orphanet (0):

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

166 associations (top):

Study	Trait	p-value
GCST000154_5	Prostate cancer	2.000000e-06
GCST000167_1	Type 2 diabetes	5.000000e-14
GCST000254_1	Height	9.000000e-10
GCST000372_11	Height	3.000000e-11
GCST000712_20	Type 2 diabetes	3.000000e-09
GCST000817_193	Height	6.000000e-25
GCST001356_30	Gout	1.000000e-07
GCST001729_16	Crohn’s disease	4.000000e-09
GCST001859_11	Thiazide-induced adverse metabolic effects in hypertensive patients	9.000000e-06
GCST001956_57	Height	8.000000e-14
GCST002069_5	Systemic lupus erythematosus and Systemic sclerosis	2.000000e-08
GCST002318_20	Rheumatoid arthritis	3.000000e-09
GCST002318_21	Rheumatoid arthritis	4.000000e-09
GCST002352_11	Type 2 diabetes	2.000000e-09
GCST002418_2	Free thyroxine concentration	6.000000e-06
GCST002647_66	Height	9.000000e-46
GCST003155_5	Systemic lupus erythematosus	9.000000e-11
GCST003156_34	Systemic lupus erythematosus	3.000000e-08
GCST003252_6	Systemic lupus erythematosus	8.000000e-06
GCST003619_3	Type 2 diabetes	6.000000e-13
GCST004063_10	Waist circumference adjusted for body mass index	5.000000e-17
GCST004063_21	Waist circumference adjusted for body mass index	5.000000e-13
GCST004063_41	Waist circumference adjusted for body mass index	4.000000e-07
GCST004067_114	Hip circumference adjusted for BMI	2.000000e-16
GCST004067_152	Hip circumference adjusted for BMI	5.000000e-07
GCST004067_45	Hip circumference adjusted for BMI	7.000000e-13
GCST004093_6	Prostate-specific antigen levels	4.000000e-19
GCST004500_29	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	3.000000e-07
GCST004500_55	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	3.000000e-07
GCST004500_99	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	3.000000e-12

EFO canonical traits (24, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0003924	hair color
EFO:0004341	body fat distribution
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0004314	forced expiratory volume
EFO:0004847	age at onset
EFO:1002011	adult onset asthma
EFO:0009924	Drugs used in diabetes use measurement
EFO:0004340	body mass index
EFO:0600021	response to dietary selenium supplementation
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004980	appendicular lean mass
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	9
bisphenol A	affects cotreatment, increases methylation, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
bisphenol S	increases expression, affects cotreatment, increases methylation	2
Panobinostat	increases expression, affects cotreatment	2
Aflatoxin B1	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
trichostatin A	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	1
belinostat	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
Grape Seed Proanthocyanidins	increases expression, affects cotreatment	1
dorsomorphin	decreases expression, affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Troglitazone	increases expression	1
Vorinostat	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases 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