PACSIN1

Summary

PACSIN1 (protein kinase C and casein kinase substrate in neurons 1, HGNC:8570) is a protein-coding gene on chromosome 6p21.31, encoding Protein kinase C and casein kinase substrate in neurons protein 1 (Q9BY11). Plays a role in the reorganization of the microtubule cytoskeleton via its interaction with MAPT; this decreases microtubule stability and inhibits MAPT-induced microtubule polymerization.

Enables phospholipid binding activity. Involved in plasma membrane tubulation. Located in cytoplasm.

Source: NCBI Gene 29993 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Limited, GenCC)
• GWAS associations: 20
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_020804

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8570
Approved symbol	PACSIN1
Name	protein kinase C and casein kinase substrate in neurons 1
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	SDPI
Ensembl gene	ENSG00000124507
Ensembl biotype	protein_coding
OMIM	606512
Entrez	29993

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000244458, ENST00000374043, ENST00000486120, ENST00000487760, ENST00000493633, ENST00000538621, ENST00000620693, ENST00000965139

RefSeq mRNA: 2 — MANE Select: NM_020804 NM_001199583, NM_020804

CCDS: CCDS4793

Canonical transcript exons

ENST00000244458 — 10 exons

Exon	Start	End
ENSE00000849537	34529666	34529841
ENSE00000849538	34530243	34530363
ENSE00000849539	34530460	34530587
ENSE00000849540	34531600	34531787
ENSE00003491352	34526243	34526368
ENSE00003677741	34528642	34528877
ENSE00003686101	34527332	34527488
ENSE00003692094	34529397	34529552
ENSE00003729195	34532421	34535223
ENSE00003845194	34466076	34466270

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 98.56.

FANTOM5 (CAGE): breadth broad, TPM avg 11.0198 / max 590.8912, expressed in 483 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67361	7.8956	452
67364	2.8207	116
67363	0.1542	52
67360	0.0969	51
67362	0.0523	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	98.56	gold quality
superior frontal gyrus	UBERON:0002661	98.47	gold quality
postcentral gyrus	UBERON:0002581	98.44	gold quality
entorhinal cortex	UBERON:0002728	98.36	gold quality
primary visual cortex	UBERON:0002436	98.19	gold quality
middle temporal gyrus	UBERON:0002771	98.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.90	gold quality
parietal lobe	UBERON:0001872	97.88	gold quality
anterior cingulate cortex	UBERON:0009835	97.74	gold quality
cingulate cortex	UBERON:0003027	97.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.67	gold quality
prefrontal cortex	UBERON:0000451	97.59	gold quality
frontal cortex	UBERON:0001870	97.54	gold quality
temporal lobe	UBERON:0001871	97.46	gold quality
cerebellar hemisphere	UBERON:0002245	97.42	gold quality
cerebellar cortex	UBERON:0002129	97.40	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.24	gold quality
amygdala	UBERON:0001876	97.10	gold quality
cerebellum	UBERON:0002037	96.91	gold quality
nucleus accumbens	UBERON:0001882	96.88	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.69	gold quality
neocortex	UBERON:0001950	96.65	gold quality
occipital lobe	UBERON:0002021	96.62	gold quality
cerebellar vermis	UBERON:0004720	96.51	gold quality
endothelial cell	CL:0000115	96.50	gold quality
cerebral cortex	UBERON:0000956	96.47	gold quality
Ammon’s horn	UBERON:0001954	96.35	gold quality
telencephalon	UBERON:0001893	96.10	gold quality
caudate nucleus	UBERON:0001873	95.47	gold quality
vena cava	UBERON:0004087	95.45	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8911	yes	174.04
E-MTAB-9067	yes	11.94
E-MTAB-8498	yes	11.67
E-ANND-3	no	2.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3

miRNA regulators (miRDB)

139 targeting PACSIN1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6721-5P	99.93	68.92	2981

Literature-anchored findings (GeneRIF, showing 13)

• The regulated deformation of membranes and promotion of tubule constrictions by Pacsin suggests a more versatile function of these proteins in vesiculation and endocytosis. (PMID:19549836)
• PACSIN 1 (1-344) was crystallized & diffracted to resolution of 3.0 A. The crystal belonged to space group C2, with unit-cell parameters a=158.65, b=87.38, c=91.76 A, alpha=90.00, beta=113.61, gamma=90.00 degrees. There are 2 molecules in asymmetric unit. (PMID:20057076)
• Phosphorylation of syndapin I F-BAR domain at two helix-capping motifs regulates membrane tubulation (PMID:22355135)
• PACSIN1 represents a pDC-specific adaptor molecule that plays an important role in the TLR7/9-mediated type I IFN responses by pDCs in vitro and in vivo. (PMID:22488361)
• Pacsin-1 plays a versatile role in sculpting cellular membranes that is likely dependent both on protein structure and membrane properties. (PMID:23236520)
• Data indicate that the structural capacity of N17 to fold back toward distal regions within huntingtin requires an interacting protein, protein kinase C and casein kinase 2 substrate in neurons 1 (PACSIN1). (PMID:23898200)
• Specifically, CKS1B and MAP2K5 significantly inhibited hepatitis C viral RNA replication. PACSIN1, by contrast, inhibited hepatitis C virus infection by decreasing the level of viral protein p7. (PMID:24205826)
• syndapin I functions reflected direct, SH3 domain-mediated associations and functional interactions with ProSAP1/Shank2. (PMID:24751538)
• PACSIN1 and EHD1 assemble membrane tubules from the developing intracellular cilium that attach to the plasma membrane, creating an extracellular membrane channel to the outside of the cell. (PMID:30683896)
• Curvature induction and sensing of the F-BAR protein Pacsin1 on lipid membranes via molecular dynamics simulations. (PMID:31601944)
• Regulation of Synapse Weakening through Interactions of the Microtubule Associated Protein Tau with PACSIN1. (PMID:34290082)
• De Novo PACSIN1 Gene Variant Found in Childhood Lupus and a Role for PACSIN1/TRAF4 Complex in Toll-like Receptor 7 Activation. (PMID:36622335)
• PACSIN1 promotes immunosuppression in gastric cancer by degrading MHC-I. (PMID:38826133)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pacsin1a	ENSDARG00000032865
danio_rerio	pacsin1b	ENSDARG00000042128
mus_musculus	Pacsin1	ENSMUSG00000040276
rattus_norvegicus	Pacsin1	ENSRNOG00000054603
drosophila_melanogaster	Synd	FBGN0053094
caenorhabditis_elegans		WBGENE00018467

Paralogs (2): PACSIN2 (ENSG00000100266), PACSIN3 (ENSG00000165912)

Protein

Protein identifiers

Protein kinase C and casein kinase substrate in neurons protein 1 — Q9BY11 (reviewed: Q9BY11)

Alternative names: Syndapin-1

All UniProt accessions (3): F6U236, Q9BY11, Q5TZC3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the reorganization of the microtubule cytoskeleton via its interaction with MAPT; this decreases microtubule stability and inhibits MAPT-induced microtubule polymerization. Plays a role in cellular transport processes by recruiting DNM1, DNM2 and DNM3 to membranes. Plays a role in the reorganization of the actin cytoskeleton and in neuron morphogenesis via its interaction with COBL and WASL, and by recruiting COBL to the cell cortex. Plays a role in the regulation of neurite formation, neurite branching and the regulation of neurite length. Required for normal synaptic vesicle endocytosis; this process retrieves previously released neurotransmitters to accommodate multiple cycles of neurotransmission. Required for normal excitatory and inhibitory synaptic transmission. Binds to membranes via its F-BAR domain and mediates membrane tubulation.

Subunit / interactions. May form heterooligomers with other PACSINs. Interacts with MAPT. Interacts with TRPV4. Interacts (via SH3 domain) with SYNJ1 and WASL. Interacts with DNM2 and DNM3. Interacts with both COBL and DBNL. Identified in a complex composed of COBL, PACSIN1 and WASL. Interacts with EHD1 and EHD3. Homodimer. Interacts (via SH3 domain) with DNM1; the interaction is reduced by DNM1 phosphorylation.

Subcellular location. Cytoplasm. Cell projection. Synapse. Synaptosome. Ruffle membrane. Membrane. Cytoplasmic vesicle membrane. Cytosol. Cell membrane.

Tissue specificity. Highly expressed in brain and, at much lower levels, in heart and pancreas.

Post-translational modifications. Phosphorylated by casein kinase 2 (CK2) and protein kinase C (PKC).

Domain organisation. The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation. In the autoinhibited conformation, interaction with the SH3 domain inhibits membrane tubulation mediated by the F-BAR domain. DNM1 binding abolishes autoinhibition.

Similarity. Belongs to the PACSIN family.

RefSeq proteins (2): NP_001186512, NP_065855* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001060	FCH_dom	Domain
IPR001452	SH3_domain	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR031160	F_BAR_dom	Domain
IPR035743	PACSIN1/PACSIN2_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR037454	PACSIN1_F-BAR	Domain

Pfam: PF00611, PF14604

UniProt features (34 total): modified residue 11, helix 8, turn 3, domain 2, mutagenesis site 2, region of interest 2, compositionally biased region 2, chain 1, sequence variant 1, strand 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3HAH	X-RAY DIFFRACTION	2.77
3Q84	X-RAY DIFFRACTION	2.8
3QNI	X-RAY DIFFRACTION	2.8
3HAI	X-RAY DIFFRACTION	2.88

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY11-F1	85.37	0.72

Functional residue map

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

Post-translational modifications (11): 184, 346, 348, 349, 361, 365, 394, 405, 430, 2, 79

Mutagenesis-validated functional residues (2):

Position	Phenotype
125	reduces membrane-binding. abolishes membrane tubulation.
126	reduces membrane-binding. abolishes membrane tubulation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8856828	Clathrin-mediated endocytosis

MSigDB gene sets: 185 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_DENDRITE_DEVELOPMENT, GGGACCA_MIR133A_MIR133B, GCACCTT_MIR18A_MIR18B, RNGTGGGC_UNKNOWN, RORA1_01, GOBP_PLASMA_MEMBRANE_ORGANIZATION, AMIT_SERUM_RESPONSE_20_MCF10A, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, REACTOME_MEMBRANE_TRAFFICKING, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY

GO Biological Process (12): cytoskeleton organization (GO:0007010), actin filament organization (GO:0007015), regulation of endocytosis (GO:0030100), negative regulation of endocytosis (GO:0045806), synaptic vesicle endocytosis (GO:0048488), neuron projection morphogenesis (GO:0048812), protein localization to membrane (GO:0072657), protein localization to plasma membrane (GO:0072659), plasma membrane tubulation (GO:0097320), positive regulation of dendrite development (GO:1900006), endocytosis (GO:0006897), neuron development (GO:0048666)

GO Molecular Function (6): phospholipid binding (GO:0005543), cytoskeletal protein binding (GO:0008092), identical protein binding (GO:0042802), protein binding (GO:0005515), lipid binding (GO:0008289), kinase activity (GO:0016301)

GO Cellular Component (16): cytoplasm (GO:0005737), endosome (GO:0005768), cytosol (GO:0005829), plasma membrane (GO:0005886), COPI-coated vesicle (GO:0030137), cytoplasmic vesicle membrane (GO:0030659), ruffle membrane (GO:0032587), axon terminus (GO:0043679), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), photoreceptor ribbon synapse (GO:0098684), presynaptic endocytic zone (GO:0098833), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	3
endocytosis	2
protein binding	2
binding	2
cytoplasmic vesicle	2
presynapse	2
organelle organization	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
regulation of endocytosis	1
negative regulation of transport	1
negative regulation of cellular component organization	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
intracellular protein localization	1
localization within membrane	1
protein localization to membrane	1
protein localization to cell periphery	1
plasma membrane organization	1
positive regulation of neuron projection development	1
dendrite development	1
regulation of dendrite development	1
positive regulation of developmental process	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
neuron differentiation	1
cell development	1
lipid binding	1
transferase activity, transferring phosphorus-containing groups	1
intracellular anatomical structure	1
endomembrane system	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PACSIN1	SYNJ1	O43426	833
PACSIN1	WASL	O00401	828
PACSIN1	SOBP	A7XYQ1	803
PACSIN1	HTT	P42858	788
PACSIN1	DNM1	Q05193	753
PACSIN1	TRIP10	Q15642	746
PACSIN1	EHD1	Q9H4M9	728
PACSIN1	EHD3	Q9NZN3	632
PACSIN1	AMPH	P49418	594
PACSIN1	EHBP1	Q8NDI1	568
PACSIN1	BIN1	O00499	564
PACSIN1	FNBP1	Q96RU3	555
PACSIN1	EHD4	Q9H223	546
PACSIN1	FES	P07332	534
PACSIN1	ZDHHC17	Q8IUH5	521

IntAct

94 interactions, top by confidence:

A	B	Type	Score
PACSIN1	PACSIN2	psi-mi:“MI:0915”(physical association)	0.930
PACSIN2	PACSIN1	psi-mi:“MI:0915”(physical association)	0.930
PACSIN1	PACSIN3	psi-mi:“MI:0915”(physical association)	0.900
PACSIN3	PACSIN1	psi-mi:“MI:0915”(physical association)	0.900
PACSIN1	COBL	psi-mi:“MI:0914”(association)	0.750
PACSIN1	COBLL1	psi-mi:“MI:0914”(association)	0.660
PACSIN1	HTT	psi-mi:“MI:0407”(direct interaction)	0.590
FASLG	PACSIN1	psi-mi:“MI:0915”(physical association)	0.590
PACSIN1	FASLG	psi-mi:“MI:0915”(physical association)	0.590
HTT	PACSIN1	psi-mi:“MI:0915”(physical association)	0.590
PACSIN1	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
NME4	PACSIN1	psi-mi:“MI:0915”(physical association)	0.560
SNX12	PACSIN1	psi-mi:“MI:0915”(physical association)	0.560
PACSIN1	SLFN12	psi-mi:“MI:0915”(physical association)	0.560
CCDC26	PACSIN1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (104): PACSIN1 (Two-hybrid), PACSIN1 (Two-hybrid), PACSIN1 (Two-hybrid), PACSIN1 (Affinity Capture-MS), PACSIN1 (Affinity Capture-MS), PACSIN1 (Affinity Capture-MS), PACSIN1 (Affinity Capture-MS), PACSIN1 (FRET), PACSIN1 (Affinity Capture-Western), PACSIN1 (Far Western), PACSIN1 (Reconstituted Complex), COBLL1 (Affinity Capture-MS), COBL (Affinity Capture-MS), PACSIN2 (Affinity Capture-MS), MPRIP (Affinity Capture-MS)

ESM2 similar proteins: A7MBI0, D3ZYR1, O13154, O43586, O55148, O60749, O60861, P09760, P16591, P70451, P97531, P97814, Q0JRZ9, Q15642, Q2HWF0, Q3KR97, Q3UQN2, Q4V920, Q5R411, Q5R807, Q5RCJ1, Q5T0N5, Q5U3Q6, Q60780, Q61644, Q6DCZ7, Q6GNV5, Q6GUF4, Q8CJ53, Q8I190, Q8I1A6, Q8I1C0, Q8I1I3, Q8K012, Q8T390, Q91VH2, Q99JB8, Q99M15, Q99N27, Q9BY11

Diamond homologs: A0A0G2JV04, A0JNB0, A1A5H8, A1CEK6, A1DFN5, A1Y2K1, A2QW93, A3LXQ8, A4RF61, A5D8S5, A6H7G2, A6QLK6, A7MBI0, D3ZG83, F1RDG9, O13154, O42287, O43125, O55043, O74749, O75791, O89100, P00523, P00525, P00526, P00528, P05480, P06241, P09324, P10936, P12931, P13115, P13116, P13406, P14084, P14085, P15054, P25020, P27446, P27447

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PAK6	“up-regulates activity”	PACSIN1	phosphorylation
PAK4	“up-regulates activity”	PACSIN1	phosphorylation
PAK5	“up-regulates activity”	PACSIN1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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
Clathrin-mediated endocytosis	6	16.0×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1974 predictions. Top by Δscore:

Variant	Effect	Δscore
6:34466268:CAGGT:C	donor_loss	1.0000
6:34466269:AG:A	donor_loss	1.0000
6:34466270:GG:G	donor_loss	1.0000
6:34526242:GT:G	acceptor_gain	1.0000
6:34526296:C:CA	acceptor_gain	1.0000
6:34528640:A:AG	acceptor_gain	1.0000
6:34528640:A:AT	acceptor_loss	1.0000
6:34528640:AG:A	acceptor_gain	1.0000
6:34528641:G:GT	acceptor_gain	1.0000
6:34528641:GG:G	acceptor_gain	1.0000
6:34528865:G:GT	donor_gain	1.0000
6:34528869:A:G	donor_gain	1.0000
6:34528875:G:GT	donor_gain	1.0000
6:34528875:G:T	donor_gain	1.0000
6:34528876:AGG:A	donor_loss	1.0000
6:34528877:GG:G	donor_loss	1.0000
6:34528885:G:GG	donor_gain	1.0000
6:34529393:A:AG	acceptor_gain	1.0000
6:34529393:ACAG:A	acceptor_loss	1.0000
6:34529394:C:G	acceptor_gain	1.0000
6:34529395:A:AG	acceptor_gain	1.0000
6:34529395:AGC:A	acceptor_loss	1.0000
6:34529395:AGCT:A	acceptor_gain	1.0000
6:34529395:AGCTG:A	acceptor_gain	1.0000
6:34529396:G:GG	acceptor_gain	1.0000
6:34529396:GC:G	acceptor_gain	1.0000
6:34529396:GCT:G	acceptor_gain	1.0000
6:34529396:GCTG:G	acceptor_gain	1.0000
6:34529396:GCTGG:G	acceptor_gain	1.0000
6:34529517:G:GT	donor_gain	1.0000

AlphaMissense

2968 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:34527447:T:C	L60P	1.000
6:34527455:T:A	W63R	1.000
6:34527455:T:C	W63R	1.000
6:34531773:T:A	L404H	1.000
6:34531773:T:C	L404P	1.000
6:34531779:T:C	F406S	1.000
6:34532430:T:C	L412P	1.000
6:34532462:T:A	W423R	1.000
6:34532462:T:C	W423R	1.000
6:34532463:G:C	W423S	1.000
6:34532464:G:C	W423C	1.000
6:34532464:G:T	W423C	1.000
6:34532471:G:A	G426R	1.000
6:34532471:G:C	G426R	1.000
6:34532471:G:T	G426W	1.000
6:34532472:G:A	G426E	1.000
6:34532496:G:A	G434D	1.000
6:34532501:T:A	Y436N	1.000
6:34532501:T:G	Y436D	1.000
6:34532504:C:A	P437T	1.000
6:34532504:C:T	P437S	1.000
6:34532505:C:A	P437H	1.000
6:34527360:G:C	R31P	0.999
6:34527393:T:C	L42P	0.999
6:34527413:C:A	R49S	0.999
6:34527414:G:C	R49P	0.999
6:34527416:G:C	A50P	0.999
6:34527467:T:A	W67R	0.999
6:34527467:T:C	W67R	0.999
6:34528671:T:A	W84R	0.999

dbSNP variants (sampled 300 via entrez): RS1000028980 (6:34521252 G>A), RS1000038758 (6:34526835 T>C), RS1000052470 (6:34485947 C>G), RS1000079916 (6:34527763 A>G), RS1000204051 (6:34501920 T>A,C), RS1000261764 (6:34504743 G>A), RS1000292936 (6:34505100 C>T), RS1000342462 (6:34467280 G>A,T), RS1000377458 (6:34533697 G>A), RS1000398139 (6:34470067 T>G), RS1000442670 (6:34498958 G>A), RS1000462002 (6:34516855 A>C,G), RS1000512708 (6:34481127 C>A,T), RS1000534291 (6:34481083 T>C), RS1000606374 (6:34480792 T>C)

Disease associations

OMIM: gene MIM:606512 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
systemic lupus erythematosus	Limited	Autosomal dominant

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

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST003602_15	Inflammatory bowel disease	1.000000e-07
GCST004557_192	Body mass index	3.000000e-07
GCST004557_221	Body mass index	2.000000e-08
GCST004558_64	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-06
GCST004558_91	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-07
GCST004559_84	Body mass index in physically active individuals	2.000000e-06
GCST004559_95	Body mass index in physically active individuals	9.000000e-06
GCST006896_18	Free thyroxine concentration	2.000000e-07
GCST007202_16	High density lipoprotein cholesterol levels	9.000000e-06
GCST007294_103	Body fat distribution (trunk fat ratio)	3.000000e-11
GCST007295_123	Body fat distribution (leg fat ratio)	1.000000e-12
GCST008129_47	Body mass index	3.000000e-26
GCST008159_14	Waist-to-hip ratio adjusted for BMI	2.000000e-07
GCST010002_50	Refractive error	4.000000e-34
GCST011010_61	Electrocardiographic traits (multivariate)	4.000000e-06
GCST012227_947	Hip circumference adjusted for BMI	1.000000e-09
GCST012227_948	Hip circumference adjusted for BMI	3.000000e-13
GCST90020028_670	Hip circumference adjusted for BMI	5.000000e-15
GCST90020028_671	Hip circumference adjusted for BMI	6.000000e-11
GCST90020029_1578	Waist circumference adjusted for body mass index	4.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008002	physical activity measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004341	body fat distribution
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004327	electrocardiography
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference

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

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, increases reaction, affects cotreatment	3
Valproic Acid	increases expression, increases methylation	3
trichostatin A	affects expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Aflatoxin B1	increases methylation	2
propionaldehyde	decreases expression	1
bisphenol A	increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
entinostat	increases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases methylation, increases methylation	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Bortezomib	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Calcitriol	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Phthalic Acids	increases methylation	1
Silicon Dioxide	decreases expression	1
Testosterone	increases expression, affects cotreatment	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	affects 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