STOX1

Summary

STOX1 (storkhead box 1, HGNC:23508) is a protein-coding gene on chromosome 10q22.1, encoding Storkhead-box protein 1 (Q6ZVD7). Involved in regulating the levels of reactive oxidative species and reactive nitrogen species and in mitochondrial homeostasis in the placenta.

Enables RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in several processes, including cellular response to nitrosative stress; positive regulation of mitotic cell cycle phase transition; and regulation of macromolecule metabolic process. Located in centrosome; cytosol; and nuclear lumen. Implicated in pre-eclampsia. Biomarker of Alzheimer’s disease.

Source: NCBI Gene 219736 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 157 total
• Phenotypes (HPO): 31
• MANE Select transcript: NM_152709

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23508
Approved symbol	STOX1
Name	storkhead box 1
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25162
Ensembl gene	ENSG00000165730
Ensembl biotype	protein_coding
OMIM	609397
Entrez	219736

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000298596, ENST00000399162, ENST00000399165, ENST00000399169, ENST00000642869, ENST00000909986

RefSeq mRNA: 4 — MANE Select: NM_152709 NM_001130159, NM_001130160, NM_001130161, NM_152709

CCDS: CCDS41535, CCDS44416, CCDS44417

Canonical transcript exons

ENST00000298596 — 4 exons

Exon	Start	End
ENSE00001536803	68884260	68886618
ENSE00003671821	68881958	68882110
ENSE00003692698	68892589	68893060
ENSE00003847963	68827531	68827933

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 95.68.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1995 / max 91.4799, expressed in 726 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105270	2.3949	633
105269	0.5488	290
105268	0.2557	139

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	95.68	gold quality
bronchus	UBERON:0002185	94.14	gold quality
ventricular zone	UBERON:0003053	90.83	gold quality
oviduct epithelium	UBERON:0004804	89.84	gold quality
amygdala	UBERON:0001876	88.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.80	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.29	gold quality
endothelial cell	CL:0000115	86.78	gold quality
anterior cingulate cortex	UBERON:0009835	86.69	gold quality
nucleus accumbens	UBERON:0001882	86.59	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.45	gold quality
putamen	UBERON:0001874	86.34	gold quality
caudate nucleus	UBERON:0001873	86.33	gold quality
right frontal lobe	UBERON:0002810	84.68	gold quality
temporal lobe	UBERON:0001871	84.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.29	gold quality
right uterine tube	UBERON:0001302	84.10	gold quality
hypothalamus	UBERON:0001898	83.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.32	gold quality
telencephalon	UBERON:0001893	82.94	gold quality
substantia nigra	UBERON:0002038	82.71	gold quality
Ammon’s horn	UBERON:0001954	82.39	gold quality
epithelium of nasopharynx	UBERON:0001951	82.35	gold quality
forebrain	UBERON:0001890	82.26	gold quality
ganglionic eminence	UBERON:0004023	82.22	gold quality
embryo	UBERON:0000922	82.21	gold quality
prefrontal cortex	UBERON:0000451	81.95	gold quality
neocortex	UBERON:0001950	81.93	gold quality
cerebral cortex	UBERON:0000956	81.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.22
E-MTAB-8060	no	35.79

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
CCNA2	Activation
CCNB1	Activation
CCNC	Repression
CCNE1	Activation
CNTNAP2	Repression

miRNA regulators (miRDB)

29 targeting STOX1, 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-340-5P	100.00	72.50	4437
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-4676-5P	97.54	65.29	715
HSA-MIR-575	97.54	65.18	718
HSA-MIR-4642	97.52	67.60	916
HSA-MIR-6750-3P	96.79	67.50	740
HSA-MIR-4436B-5P	96.71	68.37	1346
HSA-MIR-203A-5P	96.33	65.03	714
HSA-MIR-5687	96.10	64.83	226

Literature-anchored findings (GeneRIF, showing 21)

• In conclusion, we are unable to validate STOX1 as a common preeclampsia susceptibility gene. (PMID:17290274)
• Anomalies in STOX1 expression are associated with the onset of preeclampsia. (PMID:19079545)
• role in placental development and preeclampsia (Review) (PMID:19577309)
• The data of this study indicated that STOX1 controls a conserved pathway shared between placenta and brain with overexpression in late-onset Alzheimer’s disease. (PMID:20110611)
• The risk allele (Y153H) of the preeclampsia susceptibility gene STOX1 negatively regulates trophoblast invasion by upregulation of the cell-cell adhesion protein a-T-catenin (CTNNA3). (PMID:20400461)
• STOX1 does not show differential expression in deciduas from pregnancies complicated by both pre-eclampsia and FGR as compared with controls. (PMID:20643876)
• methylation is independent of parental origin, but regulates STOX1 expression with the Y153H genotype directing the level of methylation. (PMID:20716964)
• STOX1 is one of the genes that give susceptibility for preeclampsia. (PMID:21490791)
• Upregulation of total tau expression (SFRS7-independent) and tau exon 10 splicing (SFRS7-dependent), as shown in this study to be both affected by STOX1A, is known to have implications in neurodegeneration. (PMID:21755018)
• Mitotic entry is enhanced through the direct upregulation of cyclin B1 expression effectuated by STOX1A. (PMID:22253775)
• Transcription factor STOX1A and its target gene, CNTNAP2, are potentially involved in the etiology of Alzheimer’s disease. (PMID:22728895)
• A STOX1A-dependent effect on tau phosphorylation found in neurodegenerative diseases such as Alzheimer’s disease. (PMID:22995177)
• The STOX1 mice could help to better understand the endothelial dysfunction in the context of preeclampsia, and guide the search for efficient therapies able to protect the maternal endothelium during the disease and its aftermath. (PMID:26758611)
• expressions of STOX1 is gradually increasing along with the normal pregnancy progression (PMID:30955313)
• STOX1 protein in early onset group, late onset group and control group were 0.78+/-0.04,0.59+/-0.020 and 0.54+/-0.018 respectively, which is higher in early onset group than that in late onset group(P<0.05) (PMID:31189268)
• Investigation of the STOX1 polymorphism on lumbar disc herniation. (PMID:31724315)
• STOX1 gene single nucleotide polymorphism is associated with early-onset preeclampsia. (PMID:32534058)
• circ-ZUFSP regulates trophoblasts migration and invasion through sponging miR-203 to regulate STOX1 expression. (PMID:32807495)
• Functional Evaluation of STOX1 (STORKHEAD-BOX PROTEIN 1) in Placentation, Preeclampsia, and Preterm Birth. (PMID:33356399)
• STOX1 promotor region -922 T > C polymorphism is associated with Early-Onset preeclampsia. (PMID:36369889)
• Modeling Preeclampsia In Vitro: Polymorphic Variants of STOX1-A/B Genes Can Downregulate CD24 in Trophoblast Cell Lines. (PMID:36555567)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stox1	ENSDARG00000062593
mus_musculus	Stox1	ENSMUSG00000036923
rattus_norvegicus	Stox1	ENSRNOG00000023712
drosophila_melanogaster	ko	FBGN0020294
caenorhabditis_elegans		WBGENE00001820

Paralogs (1): STOX2 (ENSG00000173320)

Protein

Protein identifiers

Storkhead-box protein 1 — Q6ZVD7 (reviewed: Q6ZVD7)

Alternative names: Winged-helix domain-containing protein

All UniProt accessions (2): A0A2R8Y5I4, Q6ZVD7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in regulating the levels of reactive oxidative species and reactive nitrogen species and in mitochondrial homeostasis in the placenta. Required for regulation of inner ear epithelial cell proliferation via the AKT signaling pathway. Involved in cell cycle regulation by binding to the CCNB1 promoter, up-regulating its expression and promoting mitotic entry. Induces phosphorylation of MAPT/tau.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Microtubule organizing center. Centrosome Nucleus Nucleus. Nucleolus.

Tissue specificity. Expressed in placenta, including the invasive extravillus trophoblast cells.

Disease relevance. Pre-eclampsia/eclampsia 4 (PEE4) [MIM:609404] A hypertensive disorder of pregnancy characterized by new hypertension (blood pressure 140/90 or greater) presenting after 20 weeks’ gestation with clinically relevant proteinuria. It impacts 2 individuals, the mother and her child, both of whom can be severely affected. Preeclampsia is one of the causes of maternal mortality and morbidity worldwide. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZVD7-1	A	yes
Q6ZVD7-2	B
Q6ZVD7-3	C

RefSeq proteins (4): NP_001123631, NP_001123632, NP_001123633, NP_689922* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019391	Storkhead-box_WHD	Domain
IPR040126	STOX1/2	Family

Pfam: PF10264

UniProt features (19 total): region of interest 5, sequence variant 5, splice variant 4, compositionally biased region 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZVD7-F1	48.87	0.11

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 223 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_MITOCHONDRIAL_DNA_METABOLIC_PROCESS, GOBP_OTIC_VESICLE_DEVELOPMENT, GOBP_PEPTIDYL_SERINE_MODIFICATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_G1_S_TRANSITION_OF_MITOTIC_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY

GO Biological Process (20): regulation of transcription by RNA polymerase II (GO:0006357), regulation of gene expression (GO:0010468), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of peptidyl-threonine phosphorylation (GO:0010800), regulation of mitochondrion organization (GO:0010821), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), positive regulation of peptidyl-serine phosphorylation (GO:0033138), inner ear development (GO:0048839), cell division (GO:0051301), regulation of mitochondrial membrane potential (GO:0051881), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cellular response to nitrosative stress (GO:0071500), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), regulation of mitochondrial DNA metabolic process (GO:1901858), regulation of response to oxidative stress (GO:1902882), positive regulation of cyclin-dependent protein kinase activity (GO:1904031), positive regulation of otic vesicle morphogenesis (GO:1904120), regulation of mitotic cell cycle (GO:0007346), positive regulation of cell cycle (GO:0045787)

GO Molecular Function (4): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity (GO:0003700), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (9): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), cell cortex (GO:0005938), nucleolus (GO:0005730), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
gene expression	3
regulation of DNA-templated transcription	2
regulation of gene expression	2
positive regulation of protein phosphorylation	2
positive regulation of mitotic cell cycle phase transition	2
regulation of cell cycle	2
transcription cis-regulatory region binding	2
nuclear lumen	2
cytoplasm	2
intracellular membraneless organelle	2
transcription by RNA polymerase II	1
regulation of macromolecule biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
regulation of peptidyl-threonine phosphorylation	1
peptidyl-threonine phosphorylation	1
mitochondrion organization	1
regulation of organelle organization	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of cell cycle G2/M phase transition	1
peptidyl-serine phosphorylation	1
regulation of peptidyl-serine phosphorylation	1
ear development	1
anatomical structure development	1
cellular process	1
regulation of membrane potential	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
response to nitrosative stress	1
cellular response to chemical stress	1
G1/S transition of mitotic cell cycle	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
mitochondrial DNA metabolic process	1
regulation of DNA metabolic process	1
response to oxidative stress	1
regulation of response to stress	1

Protein interactions and networks

STRING

782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STOX1	F5	P12259	672
STOX1	AGTR2	P50052	599
STOX1	EPHX1	P07099	594
STOX1	GSTP1	P09211	555
STOX1	ACVR2A	P27037	544
STOX1	MTHFR	P42898	516
STOX1	CCAR1	Q8IX12	507
STOX1	DDX50	Q9BQ39	501
STOX1	AADACL2	Q6P093	492
STOX1	AGTR1	P30556	489
STOX1	NR3C2	P08235	469
STOX1	HLA-C	P04222	448
STOX1	AGT	P01019	443
STOX1	CLCA2	Q9UQC9	434
STOX1	LRRC3B	Q96PB8	431

IntAct

24 interactions, top by confidence:

A	B	Type	Score
STOX1	GORASP2	psi-mi:“MI:0915”(physical association)	0.670
GORASP2	STOX1	psi-mi:“MI:0915”(physical association)	0.670
ADARB1	STOX1	psi-mi:“MI:0915”(physical association)	0.560
NFYC	STOX1	psi-mi:“MI:0915”(physical association)	0.560
POU2F1	STOX1	psi-mi:“MI:0915”(physical association)	0.560
ROR2	STOX1	psi-mi:“MI:0915”(physical association)	0.560
STOX1	BANP	psi-mi:“MI:0915”(physical association)	0.560
GCLM	STOX1	psi-mi:“MI:0915”(physical association)	0.370
STOX1	TPM2	psi-mi:“MI:0914”(association)	0.350
DNAL4	WDR91	psi-mi:“MI:0914”(association)	0.350
DNAL4	ZMPSTE24	psi-mi:“MI:0914”(association)	0.350
STOX1	ADARB1	psi-mi:“MI:0915”(physical association)	0.000
NFYC	STOX1	psi-mi:“MI:0915”(physical association)	0.000
POU2F1	STOX1	psi-mi:“MI:0915”(physical association)	0.000
ROR2	STOX1	psi-mi:“MI:0915”(physical association)	0.000
BANP	STOX1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): STOX1 (Two-hybrid), TPM2 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), STOX1 (Affinity Capture-MS), STOX1 (Two-hybrid), STOX1 (Two-hybrid), ROR2 (Two-hybrid), BANP (Two-hybrid), ADARB1 (Two-hybrid), STOX1 (Affinity Capture-MS), STOX1 (Biochemical Activity), DDX21 (Cross-Linking-MS (XL-MS)), STOX1 (Cross-Linking-MS (XL-MS)), STOX1 (Two-hybrid)

ESM2 similar proteins: A0A087WRU1, A0JNH1, A2RUB1, A6QNQ6, B0S6S9, B1WC58, D3Z987, D3ZJ47, E1BC15, O60673, P28358, P28359, P56716, P70347, Q0P5X5, Q0VAV2, Q0VBV7, Q15468, Q2M2Z5, Q3UXL4, Q3V089, Q49A88, Q569L8, Q5BQN8, Q5CZC0, Q5QGS0, Q5T1N1, Q5VWN6, Q60988, Q61493, Q62924, Q6ZP01, Q6ZU52, Q6ZVD7, Q80U59, Q80WQ8, Q86WS4, Q86YC2, Q8CB14, Q8IUR6

Diamond homologs: B2RQL2, G5EEC5, Q499E5, Q6ZVD7, Q95K63, Q9P2F5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STOX1	“down-regulates quantity by repression”	CNTNAP2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	121
Likely benign	24
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1123 predictions. Top by Δscore:

Variant	Effect	Δscore
10:68881944:A:G	acceptor_gain	1.0000
10:68882277:GG:G	donor_gain	1.0000
10:68882278:GG:G	donor_gain	1.0000
10:68884255:TTTA:T	acceptor_loss	1.0000
10:68884256:TTA:T	acceptor_loss	1.0000
10:68884257:TA:T	acceptor_loss	1.0000
10:68884258:A:AG	acceptor_gain	1.0000
10:68884259:G:GA	acceptor_loss	1.0000
10:68884259:G:GG	acceptor_gain	1.0000
10:68884259:GGC:G	acceptor_gain	1.0000
10:68874300:T:G	donor_gain	0.9900
10:68874300:T:TG	donor_gain	0.9900
10:68881951:A:AG	acceptor_gain	0.9900
10:68881952:A:G	acceptor_gain	0.9900
10:68881954:TTAG:T	acceptor_loss	0.9900
10:68881955:TAGGT:T	acceptor_loss	0.9900
10:68881956:AGG:A	acceptor_loss	0.9900
10:68881957:G:GC	acceptor_loss	0.9900
10:68881957:GGT:G	acceptor_gain	0.9900
10:68882106:CCCAG:C	donor_loss	0.9900
10:68882107:CCAG:C	donor_loss	0.9900
10:68882108:CAGG:C	donor_loss	0.9900
10:68882109:AGGT:A	donor_loss	0.9900
10:68882110:GGTAG:G	donor_loss	0.9900
10:68882111:G:A	donor_loss	0.9900
10:68882112:T:A	donor_loss	0.9900
10:68884252:T:TA	acceptor_gain	0.9900
10:68884258:AG:A	acceptor_gain	0.9900
10:68884259:GG:G	acceptor_gain	0.9900
10:68884259:GGCA:G	acceptor_gain	0.9900

AlphaMissense

6531 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:68884820:T:A	W342R	0.998
10:68884820:T:C	W342R	0.998
10:68884822:G:C	W342C	0.996
10:68884822:G:T	W342C	0.996
10:68884805:T:C	F337L	0.993
10:68884807:C:A	F337L	0.993
10:68884807:C:G	F337L	0.993
10:68884902:T:C	L369S	0.990
10:68884917:T:C	L374S	0.989
10:68884887:G:C	R364P	0.988
10:68882036:T:A	I130K	0.986
10:68884870:A:C	E358D	0.986
10:68884870:A:T	E358D	0.986
10:68827922:T:C	I100T	0.982
10:68827933:G:C	G104R	0.982
10:68884821:G:C	W342S	0.982
10:68827742:T:C	F40S	0.981
10:68827882:T:A	W87R	0.981
10:68827882:T:C	W87R	0.981
10:68884793:T:C	F333L	0.981
10:68884795:C:A	F333L	0.981
10:68884795:C:G	F333L	0.981
10:68884806:T:C	F337S	0.981
10:68884881:T:A	I362N	0.979
10:68882036:T:G	I130R	0.978
10:68884349:T:C	F185L	0.978
10:68884351:C:A	F185L	0.978
10:68884351:C:G	F185L	0.978
10:68884356:T:A	V187D	0.978
10:68827813:G:C	G64R	0.976

dbSNP variants (sampled 300 via entrez): RS1000028676 (10:68866883 C>T), RS1000042413 (10:68863555 G>A), RS1000122250 (10:68853268 C>T), RS1000141741 (10:68827731 G>A,C,T), RS1000142876 (10:68867090 G>A), RS1000167950 (10:68861878 T>C), RS1000178550 (10:68867111 T>C), RS1000207526 (10:68829335 G>T), RS1000262933 (10:68872851 G>C), RS1000351707 (10:68881357 C>T), RS1000368911 (10:68873260 T>C), RS1000411675 (10:68849604 A>G), RS1000467831 (10:68826513 C>G,T), RS1000587481 (10:68886422 G>A), RS1000626118 (10:68861559 C>T)

Disease associations

OMIM: gene MIM:609397 | disease phenotypes: MIM:609404, MIM:618372

GenCC curated gene-disease

Mondo (2): preeclampsia/eclampsia 4 (MONDO:0012266), cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder (MONDO:0018794)

Orphanet (1): Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder (Orphanet:477787)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000077	Abnormality of the kidney
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000147	Polycystic ovaries
HP:0000504	Abnormality of vision
HP:0000707	Abnormality of the nervous system
HP:0000822	Hypertension
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0001873	Thrombocytopenia
HP:0001919	Acute kidney injury
HP:0002027	Abdominal pain
HP:0002315	Headache
HP:0002360	Sleep disturbance
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0002960	Autoimmunity
HP:0003259	Elevated circulating creatinine concentration
HP:0004421	Elevated systolic blood pressure
HP:0005117	Elevated diastolic blood pressure
HP:0005202	Helicobacter pylori infection
HP:0006707	Abnormality of the hepatic vasculature
HP:0010982	Polygenic inheritance
HP:0011462	Young adult onset
HP:0012622	Chronic kidney disease
HP:0031418	Increased body mass index
HP:0100598	Pulmonary edema
HP:0100601	Eclampsia
HP:0100602	Preeclampsia
HP:0100651	Type I diabetes mellitus
HP:0100767	Abnormal placenta morphology

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002337_140	Amyotrophic lateral sclerosis (sporadic)	5.000000e-06
GCST90020028_82	Hip circumference adjusted for BMI	2.000000e-11
GCST90020028_83	Hip circumference adjusted for BMI	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563724	Preeclampsia Eclampsia 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
manganese chloride	affects cotreatment, decreases expression, increases abundance	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Manganese	decreases expression, increases abundance, affects cotreatment	2
Oxygen	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Aflatoxin B1	decreases expression	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	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
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Panobinostat	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Caffeine	decreases phosphorylation	1
Diethylhexyl Phthalate	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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