PXK

Summary

PXK (PX domain containing serine/threonine kinase like, HGNC:23326) is a protein-coding gene on chromosome 3p14.3, encoding PX domain-containing protein kinase-like protein (Q7Z7A4). Binds to and modulates brain Na,K-ATPase subunits ATP1B1 and ATP1B3 and may thereby participate in the regulation of electrical excitability and synaptic transmission.

This gene encodes a phox (PX) domain-containing protein which may be involved in synaptic transmission and the ligand-induced internalization and degradation of epidermal growth factors. Variations in this gene may be associated with susceptibility to systemic lupus erythematosus (SLE). Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 54899 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Supportive, GenCC)
• GWAS associations: 34
• Clinical variants (ClinVar): 104 total — 1 pathogenic
• Phenotypes (HPO): 44
• MANE Select transcript: NM_017771

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23326
Approved symbol	PXK
Name	PX domain containing serine/threonine kinase like
Location	3p14.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20335, Slob
Ensembl gene	ENSG00000168297
Ensembl biotype	protein_coding
OMIM	611450
Entrez	54899

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 23 protein_coding, 2 nonsense_mediated_decay

ENST00000302779, ENST00000356151, ENST00000383715, ENST00000383716, ENST00000459676, ENST00000463280, ENST00000468776, ENST00000477308, ENST00000479134, ENST00000479241, ENST00000484288, ENST00000491164, ENST00000493474, ENST00000495557, ENST00000877066, ENST00000877067, ENST00000877068, ENST00000877069, ENST00000877070, ENST00000877071, ENST00000877072, ENST00000877073, ENST00000940460, ENST00000944947, ENST00000944948

RefSeq mRNA: 58 — MANE Select: NM_017771 NM_001289095, NM_001289096, NM_001289098, NM_001289099, NM_001289100, NM_001289101, NM_001349488, NM_001349489, NM_001349490, NM_001349491, NM_001349492, NM_001349493, NM_001349494, NM_001349495, NM_001349496, NM_001349497, NM_001349498, NM_001349499, NM_001349500, NM_001349501, NM_001349502, NM_001349503, NM_001349504, NM_001349506, NM_001349507, NM_001349508, NM_001349509, NM_001349510, NM_001349511, NM_001349512, NM_001349513, NM_001349514, NM_001349515, NM_001349516, NM_001349517, NM_001349518, NM_001349519, NM_001349520, NM_001349521, NM_001349522, NM_001349524, NM_001349525, NM_001349526, NM_001349527, NM_001349528, NM_001349529, NM_001349530, NM_001349531, NM_001349532, NM_001349533, NM_001349534, NM_001349535, NM_001349536, NM_001349537, NM_001349538, NM_001349539, NM_001349540, NM_017771

CCDS: CCDS2889, CCDS74952, CCDS74954, CCDS74955, CCDS87097, CCDS87098

Canonical transcript exons

ENST00000356151 — 18 exons

Exon	Start	End
ENSE00001235112	58382514	58382700
ENSE00001235118	58369431	58369478
ENSE00001235124	58365874	58365924
ENSE00003522461	58391773	58391847
ENSE00003529475	58397039	58397200
ENSE00003610499	58391147	58391220
ENSE00003612872	58395658	58395759
ENSE00003622991	58390582	58390659
ENSE00003667166	58394998	58395102
ENSE00003686000	58412901	58412963
ENSE00003695854	58408924	58409001
ENSE00003697409	58409532	58409618
ENSE00003698435	58403862	58403910
ENSE00003698701	58397605	58397722
ENSE00003701554	58399299	58399377
ENSE00003701683	58410090	58410159
ENSE00003890389	58424752	58426127
ENSE00003893457	58332892	58333090

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.6864 / max 712.3731, expressed in 1794 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37042	25.4192	1792
37043	0.1648	73
37045	0.1024	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	98.92	gold quality
inferior vagus X ganglion	UBERON:0005363	98.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.04	gold quality
subthalamic nucleus	UBERON:0001906	98.03	gold quality
spinal cord	UBERON:0002240	97.75	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.69	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.90	gold quality
lateral globus pallidus	UBERON:0002476	96.83	gold quality
medulla oblongata	UBERON:0001896	96.68	gold quality
superior vestibular nucleus	UBERON:0007227	96.58	gold quality
substantia nigra pars compacta	UBERON:0001965	96.56	gold quality
substantia nigra	UBERON:0002038	96.55	gold quality
midbrain	UBERON:0001891	96.54	gold quality
ventral tegmental area	UBERON:0002691	95.83	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.31	gold quality
secondary oocyte	CL:0000655	95.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.00	gold quality
putamen	UBERON:0001874	94.88	gold quality
endocervix	UBERON:0000458	94.87	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.77	gold quality
cerebellar hemisphere	UBERON:0002245	94.73	gold quality
cartilage tissue	UBERON:0002418	94.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.67	gold quality
cerebellar cortex	UBERON:0002129	94.60	gold quality
Ammon’s horn	UBERON:0001954	94.48	gold quality
cerebellum	UBERON:0002037	94.33	gold quality
globus pallidus	UBERON:0001875	94.22	gold quality
left lobe of thyroid gland	UBERON:0001120	94.14	gold quality
right lobe of thyroid gland	UBERON:0001119	93.94	gold quality
thyroid gland	UBERON:0002046	93.79	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-6075	yes	284.49
E-HCAD-25	yes	52.30
E-CURD-119	yes	30.49
E-MTAB-5061	yes	15.58
E-GEOD-81608	yes	10.60
E-GEOD-84465	yes	9.96
E-ANND-3	yes	7.21
E-HCAD-31	yes	4.69
E-MTAB-7249	no	2549.41
E-ENAD-27	no	3.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting PXK, 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-3120-5P	100.00	65.56	965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4694-3P	99.79	69.53	2640

Literature-anchored findings (GeneRIF, showing 11)

• First described as part of human kinome analysis, named Slob after Drosophila ortholog. (PMID:15289607)
• MONaKA modulates brain Na,K-ATPase by binding tightly to its beta1 and beta3 subunits, and may thereby participate in the regulation of electrical excitability and synaptic transmission [MONaKA] (PMID:16135750)
• study presents four new regions having genetic associations with systemic lupus erythematosus in women of European descent: ITGAM, KIAA1542, PXK and rs10798269 (PMID:18204446)
• These results indicate that PXK plays a critical role in epidermal growth factor receptor trafficking through modulating ligand-induced ubiquitination of the receptor. (PMID:20086096)
• The association of PXK rs6445975 with systemic lupus erythematosus that was previously observed in Caucasians was not replicated in Koreans or in Hong Kong Chinese. (PMID:21243490)
• The rs6445975 polymorphism of PXK and the rs2304256 polymorphism of tyrosine kinase 2 are associated with the development of systemic lupus erythematosus in Europeans (PMID:22592861)
• 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)
• Results confirm the genetic association of the locus 3p14.3 with systemic lupus erythematosus in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. (PMID:24534757)
• 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)
• Two of these kinases that were classified as resistors were PX domain-containing serine/threonine kinase (PXK) and AP2-associated kinase 1 (AAK1), which promote receptor endocytosis and may enable cells to resist TRAIL-induced apoptosis (PMID:25852190)
• Telomere Length and Male Fertility. (PMID:33921254)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pxk	ENSDARG00000063195
mus_musculus	Pxk	ENSMUSG00000033885
rattus_norvegicus	Pxk	ENSRNOG00000008024
drosophila_melanogaster	CG8726	FBGN0033244

Paralogs (1): SNX16 (ENSG00000104497)

Protein

Protein identifiers

PX domain-containing protein kinase-like protein — Q7Z7A4 (reviewed: Q7Z7A4)

Alternative names: Modulator of Na,K-ATPase

All UniProt accessions (13): A0A0C4DG95, C9IYJ2, E9PD56, Q7Z7A4, F8WAW8, F8WDF7, H7BYG4, H7C4V0, H7C4W2, H7C529, U3KQS4, W5RWE6, W5RX72

UniProt curated annotations — full annotation on UniProt →

Function. Binds to and modulates brain Na,K-ATPase subunits ATP1B1 and ATP1B3 and may thereby participate in the regulation of electrical excitability and synaptic transmission. May not display kinase activity.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Widely expressed in all tissues examined except in heart. Isoform 1 is expressed in high levels in the brain, skeletal muscle, spleen and testis. Isoform 7 expression has yet to be demonstrated.

Domain organisation. The protein kinase domain is predicted to be catalytically inactive.

Similarity. Belongs to the protein kinase superfamily.

Isoforms (7)

UniProt ID	Names	Canonical?
Q7Z7A4-1	1, Long, v1	yes
Q7Z7A4-2	2, Short
Q7Z7A4-3	3, v3
Q7Z7A4-4	4
Q7Z7A4-5	5, v4
Q7Z7A4-6	6, v2
Q7Z7A4-7	7, v5

RefSeq proteins (58): NP_001276024, NP_001276025, NP_001276027, NP_001276028, NP_001276029, NP_001276030, NP_001336417, NP_001336418, NP_001336419, NP_001336420, NP_001336421, NP_001336422, NP_001336423, NP_001336424, NP_001336425, NP_001336426, NP_001336427, NP_001336428, NP_001336429, NP_001336430, NP_001336431, NP_001336432, NP_001336433, NP_001336435, NP_001336436, NP_001336437, NP_001336438, NP_001336439, NP_001336440, NP_001336441, NP_001336442, NP_001336443, NP_001336444, NP_001336445, NP_001336446, NP_001336447, NP_001336448, NP_001336449, NP_001336450, NP_001336451, NP_001336453, NP_001336454, NP_001336455, NP_001336456, NP_001336457, NP_001336458, NP_001336459, NP_001336460, NP_001336461, NP_001336462, NP_001336463, NP_001336464, NP_001336465, NP_001336466, NP_001336467, NP_001336468, NP_001336469, NP_060241* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001683	PX_dom	Domain
IPR003124	WH2_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR037903	MONaKA_PX	Domain
IPR051837	SortingNexin/PXDomain-PKLike	Family

Pfam: PF00787, PF02205

UniProt features (28 total): splice variant 7, compositionally biased region 5, sequence variant 4, domain 3, mutagenesis site 3, sequence conflict 3, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7A4-F1	86.42	0.70

Functional residue map

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

Mutagenesis-validated functional residues (3):

Position	Phenotype
54	no effect on subcellular location.
56	results in redistribution of protein from cytoplasm throughout entire cell.
92	results in redistribution of protein from cytoplasm throughout entire cell.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 256 (showing top): GOBP_INFLAMMATORY_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_ATP_DEPENDENT_ACTIVITY, MORI_IMMATURE_B_LYMPHOCYTE_UP, FOXO4_01, GOBP_CELL_CELL_SIGNALING, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_UP, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_SYNAPTIC_SIGNALING, GOMF_ACTIN_BINDING, GOBP_REGULATION_OF_ATP_DEPENDENT_ACTIVITY, GOBP_REGULATION_OF_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, P53_DECAMER_Q2

GO Biological Process (5): inflammatory response (GO:0006954), negative regulation of ATP-dependent activity (GO:0032780), negative regulation of monoatomic ion transport (GO:0043271), modulation of chemical synaptic transmission (GO:0050804), protein phosphorylation (GO:0006468)

GO Molecular Function (5): actin binding (GO:0003779), phosphatidylinositol binding (GO:0035091), protein kinase activity (GO:0004672), protein binding (GO:0005515), ATP binding (GO:0005524)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), centriolar satellite (GO:0034451), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
defense response	1
regulation of ATP-dependent activity	1
negative regulation of molecular function	1
ATP-dependent activity	1
monoatomic ion transport	1
regulation of monoatomic ion transport	1
negative regulation of transport	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
phosphorylation	1
protein modification process	1
cytoskeletal protein binding	1
anion binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cellular_component	1
centrosome	1

Protein interactions and networks

STRING

572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PXK	PHRF1	Q9P1Y6	821
PXK	BANK1	Q8NDB2	779
PXK	KCNMA1	Q12791	747
PXK	TNFSF4	P23510	735
PXK	NKAIN1	Q4KMZ8	693
PXK	PTPN22	Q9Y2R2	691
PXK	IRF5	Q13568	666
PXK	ATP1B1	P05026	648
PXK	TNFAIP3	P21580	622
PXK	FAM167A	Q96KS9	608
PXK	ZNF676	Q8N7Q3	604
PXK	BLK	P51451	588
PXK	ZNF208	O43345	573
PXK	MARK2	Q7KZI7	561
PXK	ACYP2	P14621	544

IntAct

16 interactions, top by confidence:

A	B	Type	Score
TBK1	TBKBP1	psi-mi:“MI:0914”(association)	0.860
CCKBR	PRKAG1	psi-mi:“MI:0914”(association)	0.640
PXK	TUBB1	psi-mi:“MI:0915”(physical association)	0.400
PXK	YBX3	psi-mi:“MI:0914”(association)	0.350
PXK	CSNK2B	psi-mi:“MI:0914”(association)	0.350
ACTB	ENAH	psi-mi:“MI:0914”(association)	0.350
ACTG1	ENAH	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
EDNRB	EXOC5	psi-mi:“MI:0914”(association)	0.350
PXK	ANKRD28	psi-mi:“MI:0914”(association)	0.350
DDX55	URB1	psi-mi:“MI:0914”(association)	0.350
GPRC5C	NMT2	psi-mi:“MI:0914”(association)	0.350
USP48	UBB	psi-mi:“MI:0914”(association)	0.350
TMC6	PXK	psi-mi:“MI:0914”(association)	0.350
CLEC14A	PXK	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): YBX3 (Affinity Capture-MS), FBL (Affinity Capture-MS), HNRNPA0 (Affinity Capture-MS), ALYREF (Affinity Capture-MS), PXK (Affinity Capture-MS), PXK (Affinity Capture-MS), PXK (Affinity Capture-MS), PXK (Affinity Capture-MS), PXK (Affinity Capture-MS), PXK (Affinity Capture-MS), HBB (Affinity Capture-MS), DIEXF (Affinity Capture-MS), SUPT4H1 (Affinity Capture-MS), CTR9 (Affinity Capture-MS), KIAA0196 (Affinity Capture-MS)

ESM2 similar proteins: A0A571BF63, A0JMA8, A1A535, A1A5P5, A1ZBE8, A6H8H2, A8XSV3, B0BF33, B2RS91, E7F187, O17237, O43150, P25054, P30630, Q05B30, Q09263, Q14156, Q14738, Q14D04, Q19317, Q1AAU6, Q21106, Q2KI89, Q5PQS3, Q5R4N9, Q5R629, Q5RAY1, Q5SPP5, Q5U245, Q5VZ89, Q61315, Q61QK6, Q620W3, Q641A2, Q6ZQ18, Q7SIG6, Q7Z3E5, Q7Z401, Q7Z7A4, Q8BG67

Diamond homologs: P40959, P57768, P57769, Q08DX0, Q3MPQ4, Q4FZZ1, Q559T8, Q5AG56, Q5PNP1, Q5R6Q7, Q5R7A7, Q5R903, Q7Z7A4, Q8BHY8, Q8BX57, Q8C080, Q8R4V0, Q8TEQ0, Q96BR1, Q9D3S3, Q9ERE3, Q9FG38, Q9Y5W7, Q9Y5W8, Q05B62, Q13596, Q4R503, Q6BIS2, Q99N27, Q9WV80, A1QZ05, B1AVY7, Q2KHV6, Q54TC3, Q54WZ5, Q6CUC4, Q6PHS6, Q75CC3, Q8CFD4, Q8IPH9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 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
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	48.2×	2e-05
Membrane Trafficking	5	11.6×	3e-03
Vesicle-mediated transport	5	10.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	68
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
685671	GRCh37/hg19 3p14.3-14.1(chr3:57076136-65716956)x1	Pathogenic

SpliceAI

3315 predictions. Top by Δscore:

Variant	Effect	Δscore
3:58333090:GGTG:G	donor_loss	1.0000
3:58333091:G:GA	donor_loss	1.0000
3:58365869:TTAA:T	acceptor_loss	1.0000
3:58365870:TAA:T	acceptor_loss	1.0000
3:58365871:A:AG	acceptor_gain	1.0000
3:58365871:AAG:A	acceptor_gain	1.0000
3:58365872:A:G	acceptor_gain	1.0000
3:58365873:G:GG	acceptor_gain	1.0000
3:58365920:GGCAG:G	donor_gain	1.0000
3:58365921:GCAGG:G	donor_gain	1.0000
3:58365923:AGGTA:A	donor_loss	1.0000
3:58365925:G:GG	donor_gain	1.0000
3:58365926:T:A	donor_loss	1.0000
3:58370179:GCA:G	donor_gain	1.0000
3:58370182:G:GG	donor_gain	1.0000
3:58370189:A:T	donor_gain	1.0000
3:58382511:A:G	acceptor_gain	1.0000
3:58382512:A:G	acceptor_gain	1.0000
3:58382513:GA:G	acceptor_gain	1.0000
3:58382656:TTAAG:T	donor_gain	1.0000
3:58382697:ACTGG:A	donor_loss	1.0000
3:58382698:CTGGT:C	donor_loss	1.0000
3:58382699:TGGTA:T	donor_loss	1.0000
3:58382700:GGT:G	donor_loss	1.0000
3:58382701:G:GC	donor_loss	1.0000
3:58382702:TAAG:T	donor_loss	1.0000
3:58391141:TGGCA:T	acceptor_loss	1.0000
3:58391142:GGCA:G	acceptor_loss	1.0000
3:58391143:GCAGG:G	acceptor_loss	1.0000
3:58391144:CAGGT:C	acceptor_loss	1.0000

AlphaMissense

3764 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:58365877:T:C	Y36H	1.000
3:58365877:T:G	Y36D	1.000
3:58369441:G:C	R55T	1.000
3:58369441:G:T	R55I	1.000
3:58369442:A:C	R55S	1.000
3:58369442:A:T	R55S	1.000
3:58369443:T:C	Y56H	1.000
3:58369443:T:G	Y56D	1.000
3:58369444:A:G	Y56C	1.000
3:58369453:T:C	F59S	1.000
3:58382545:A:T	K78I	1.000
3:58382546:A:C	K78N	1.000
3:58382546:A:T	K78N	1.000
3:58382574:T:C	F88L	1.000
3:58382575:T:C	F88S	1.000
3:58382576:C:A	F88L	1.000
3:58382576:C:G	F88L	1.000
3:58382587:G:C	R92T	1.000
3:58382587:G:T	R92M	1.000
3:58382588:G:C	R92S	1.000
3:58382588:G:T	R92S	1.000
3:58382590:A:C	Q93P	1.000
3:58382599:T:C	L96P	1.000
3:58382611:T:C	L100P	1.000
3:58333059:T:A	I24N	0.999
3:58333085:C:G	H33D	0.999
3:58365878:A:C	Y36S	0.999
3:58365878:A:G	Y36C	0.999
3:58365884:T:A	I38N	0.999
3:58365890:T:A	V40E	0.999

dbSNP variants (sampled 300 via entrez): RS1000008204 (3:58334098 C>G), RS1000016734 (3:58382622 A>G), RS1000024547 (3:58425060 T>G), RS1000050489 (3:58402029 C>G), RS1000107305 (3:58384052 G>A), RS1000112462 (3:58353248 C>T), RS1000126095 (3:58402348 C>T), RS1000176943 (3:58419768 C>T), RS1000216446 (3:58402069 G>A), RS1000224934 (3:58375977 T>C), RS1000237509 (3:58420046 A>C), RS1000261236 (3:58357766 A>G), RS1000284786 (3:58369751 G>A), RS1000358869 (3:58364387 G>A), RS1000389898 (3:58364128 A>C)

Disease associations

OMIM: gene MIM:611450 | 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

34 associations (top):

Study	Trait	p-value
GCST000142_1	Systemic lupus erythematosus	7.000000e-09
GCST002069_3	Systemic lupus erythematosus and Systemic sclerosis	5.000000e-11
GCST002221_33	Cholesterol, total	4.000000e-08
GCST002318_144	Rheumatoid arthritis	5.000000e-08
GCST003155_45	Systemic lupus erythematosus	3.000000e-14
GCST003622_72	Systemic lupus erythematosus	5.000000e-06
GCST004601_43	Red blood cell count	5.000000e-09
GCST004604_87	Hematocrit	2.000000e-10
GCST005534_11	Systemic sclerosis	4.000000e-08
GCST005568_17	Rheumatoid arthritis (ACPA-positive)	1.000000e-06
GCST005569_40	Rheumatoid arthritis	2.000000e-07
GCST005752_17	Systemic lupus erythematosus	2.000000e-08
GCST005752_58	Systemic lupus erythematosus	2.000000e-06
GCST006197_6	Type 1 diabetes autoantibodies in high risk HLA genotype individuals (time to event)	9.000000e-06
GCST006612_69	LDL cholesterol	4.000000e-08
GCST006959_32	Rheumatoid arthritis	5.000000e-08
GCST006979_72	Heel bone mineral density	4.000000e-10
GCST007400_44	Systemic lupus erythematosus	2.000000e-08
GCST007446_42	vWF levels	6.000000e-09
GCST007446_43	vWF levels	9.000000e-09
GCST007446_82	vWF levels	3.000000e-08
GCST007446_83	vWF levels	5.000000e-09
GCST008129_10	Body mass index	8.000000e-12
GCST009131_6	Systemic sclerosis	1.000000e-10
GCST010002_426	Refractive error	5.000000e-14
GCST010083_211	Hemoglobin levels	1.000000e-12
GCST010083_274	Hemoglobin levels	1.000000e-16
GCST010083_42	Hemoglobin levels	2.000000e-16
GCST010204_196	Low density lipoprotein cholesterol levels	4.000000e-18
GCST90002383_368	Hematocrit	2.000000e-24

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0000482	event free survival time
EFO:0004866	autoantibody measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0009270	heel bone mineral density
EFO:0004340	body mass index
EFO:0004509	hemoglobin measurement
EFO:0007985	platelet crit
EFO:0004736	aspartate aminotransferase measurement

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)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Slob family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Cyclosporine	increases expression	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Vorinostat	decreases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Estradiol	increases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
jinfukang	affects cotreatment, decreases expression	1
fatostatin	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3FG	Abcam HEK293T PXK KO	Transformed cell line	Female
CVCL_TH80	HAP1 PXK (-) 1	Cancer cell line	Male
CVCL_TH81	HAP1 PXK (-) 2	Cancer cell line	Male

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