MTUS1

Summary

MTUS1 (microtubule associated scaffold protein 1, HGNC:29789) is a protein-coding gene on chromosome 8p22, encoding Microtubule-associated tumor suppressor 1 (Q9ULD2). Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation.

This gene encodes a protein which contains a C-terminal domain able to interact with the angiotension II (AT2) receptor and a large coiled-coil region allowing dimerization. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the transcript variants has been shown to encode a mitochondrial protein that acts as a tumor suppressor and partcipates in AT2 signaling pathways. Other variants may encode nuclear or transmembrane proteins but it has not been determined whether they also participate in AT2 signaling pathways.

Source: NCBI Gene 57509 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 136 total
• MANE Select transcript: NM_001363059

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29789
Approved symbol	MTUS1
Name	microtubule associated scaffold protein 1
Location	8p22
Locus type	gene with protein product
Status	Approved
Aliases	MTSG1, KIAA1288, DKFZp586D1519, FLJ14295, ATIP1, MP44, ATBP, ICIS, ATIP3
Ensembl gene	ENSG00000129422
Ensembl biotype	protein_coding
OMIM	609589
Entrez	57509

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 24 protein_coding, 16 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000262102, ENST00000297488, ENST00000381861, ENST00000381869, ENST00000517413, ENST00000517721, ENST00000517818, ENST00000518138, ENST00000518713, ENST00000518755, ENST00000518792, ENST00000518889, ENST00000518891, ENST00000518975, ENST00000519066, ENST00000519263, ENST00000520196, ENST00000521635, ENST00000521772, ENST00000521882, ENST00000522149, ENST00000522757, ENST00000523183, ENST00000523471, ENST00000523718, ENST00000524044, ENST00000524371, ENST00000544260, ENST00000634613, ENST00000693296, ENST00000855900, ENST00000855901, ENST00000855902, ENST00000855903, ENST00000917856, ENST00000917857, ENST00000960147, ENST00000960148, ENST00000960149, ENST00000960150, ENST00000960151, ENST00000960152, ENST00000960153, ENST00000960154, ENST00000960155

RefSeq mRNA: 12 — MANE Select: NM_001363059 NM_001001924, NM_001001925, NM_001001931, NM_001166393, NM_001330470, NM_001363057, NM_001363058, NM_001363059, NM_001363060, NM_001363061, NM_001363062, NM_020749

CCDS: CCDS43716, CCDS43717, CCDS43718, CCDS43719, CCDS55204, CCDS83254

Canonical transcript exons

ENST00000693296 — 15 exons

Exon	Start	End
ENSE00003497250	17723672	17723833
ENSE00003506224	17646982	17647079
ENSE00003520313	17654561	17654666
ENSE00003526449	17743604	17743799
ENSE00003540710	17684328	17684542
ENSE00003545801	17653186	17653281
ENSE00003550629	17655863	17656065
ENSE00003554488	17715767	17715901
ENSE00003571827	17675186	17675252
ENSE00003655015	17753717	17755961
ENSE00003671698	17649846	17649962
ENSE00003676154	17713214	17713252
ENSE00003685743	17653425	17653498
ENSE00003932781	17643802	17646139
ENSE00003933182	17801061	17801094

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.1651 / max 868.3864, expressed in 1121 samples.

FANTOM5 promoters (29 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92008	8.0291	520
92030	2.2129	471
92034	1.8164	483
92002	1.1171	314
92013	0.9714	181
92031	0.7076	275
92006	0.6161	197
92022	0.5510	130
92033	0.2939	143
92007	0.2221	119

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	99.24	gold quality
inferior vagus X ganglion	UBERON:0005363	98.75	gold quality
inferior olivary complex	UBERON:0002127	98.70	gold quality
body of pancreas	UBERON:0001150	98.42	gold quality
diaphragm	UBERON:0001103	98.23	gold quality
heart right ventricle	UBERON:0002080	98.10	gold quality
subthalamic nucleus	UBERON:0001906	98.08	gold quality
biceps brachii	UBERON:0001507	98.00	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.99	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.85	gold quality
cerebellar hemisphere	UBERON:0002245	97.76	gold quality
medulla oblongata	UBERON:0001896	97.75	gold quality
calcaneal tendon	UBERON:0003701	97.75	gold quality
cerebellar cortex	UBERON:0002129	97.74	gold quality
cerebellum	UBERON:0002037	97.73	gold quality
pericardium	UBERON:0002407	97.73	gold quality
lateral globus pallidus	UBERON:0002476	97.73	gold quality
spinal cord	UBERON:0002240	97.71	gold quality
mucosa of stomach	UBERON:0001199	97.56	gold quality
jejunal mucosa	UBERON:0000399	97.46	gold quality
cardia of stomach	UBERON:0001162	97.44	gold quality
lower lobe of lung	UBERON:0008949	97.38	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.35	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.33	gold quality
sural nerve	UBERON:0015488	97.32	gold quality
triceps brachii	UBERON:0001509	97.30	gold quality
pancreas	UBERON:0001264	97.29	gold quality
jejunum	UBERON:0002115	97.27	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.24	gold quality
germinal epithelium of ovary	UBERON:0001304	97.23	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	42.32
E-CURD-46	yes	31.18
E-MTAB-8410	yes	22.33
E-MTAB-5061	yes	18.33
E-GEOD-81547	yes	18.06
E-HCAD-1	yes	17.16
E-MTAB-6678	yes	12.81
E-MTAB-7316	yes	12.52
E-GEOD-130148	yes	10.79
E-CURD-112	yes	8.02
E-ENAD-27	yes	6.98
E-GEOD-81608	yes	5.47
E-GEOD-137537	yes	4.39
E-MTAB-10137	no	3.68
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1, PARP1

miRNA regulators (miRDB)

146 targeting MTUS1, 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-4500	99.99	72.72	2367
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AN	99.97	70.91	2817
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-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-3919	99.87	69.45	2489

Literature-anchored findings (GeneRIF, showing 38)

• identified a tumor suppressor gene named MTSG1 at chromosome 8p21.3-22, encoding a mitochondrial protein, controlling cellular proliferation (PMID:12692079)
• Results identify ATIP1 (angiotensin II AT2 receptor-interacting protein) as a novel early component of growth inhibitory signaling cascade (PMID:15123706)
• Nucleotide variations result in amino-acid substitution or deletion of conserved structural motifs and also exonic splicing enhancer motifs and physiological splice sites, suggesting deleterious effects on ATIP function and/or expression. [REVIEW] (PMID:16650523)
• MTUS1 encodes a family of proteins(ATIP1, ATIP3 and ATIP4), with potential important biological roles in tumor suppression and/or brain function. (PMID:16887298)
• There is an association of the deletion variant of MTUS1 with a decreased risk for both familial and high-risk familial BC supporting its role in human cancer. (PMID:17301065)
• two transcriptional start sites in the ATIP1 promoter were identified; PARP-1 activates the ATIP1 gene (PMID:19344625)
• ATIP3 is a novel microtubule-associated protein isoform of MTUS1, with a role in invasiveness and progression of breast neoplasms. (PMID:19794912)
• ATIP3 is a novel microtubule-associated protein related to MTUS1, with a role in invasiveness and progression of breast neoplasms (PMID:19794912)
• MTUS1 could be involved in the loss of proliferative control in human colon cancer (PMID:19956880)
• Results in human prostate cancer cell lines demonstrate the presence of ATIP in both cell lines examined. (PMID:20687230)
• MTUS1 plays major roles in the progression of oral tongue squamous cell carcinoma. (PMID:22153618)
• analysis of a functional ATIP3 domain that associates with microtubules and recapitulates the effects of ATIP3 on microtubule dynamics, cell proliferation, and migration in breast cancer (PMID:23396587)
• The present data suggested MTUS1 as a potential tumor suppressor in gastric cancer and might lead to a better understanding of gastric carcinogenesis. (PMID:24299308)
• Data identifies MTUS1 as a tumour suppressor gene in cultured bladder cancer cells and in advanced bladder tumours. (PMID:24650297)
• Our studies confirm that MTUS1 plays an important role in the progression of salivary adenoid cystic carcinoma , and may serve as a biomarker or therapeutic target for patients with salivary adenoid cystic carcinoma (PMID:25885343)
• We propose a novel mechanism by which ATIP3-EB1 interaction indirectly reduces the kinetics of EB1 exchange on its recognition site, thereby accounting for negative regulation of microtubule dynamic instability (PMID:26498358)
• Deregulated microRNA (miRNA) expression has been shown to be involved in the pathogenesis of several types of cancers including colorectal cancer (CRC). MTUS1 targeting miRNAs may play key roles in the development of CRC by downregulating tumor suppressor MTUS1. (PMID:26643896)
• MTUS1 targeting miRNAs may play key roles in the development of CRC by downregulating tumor suppressor MTUS1. (PMID:26643896)
• Study reports differential expression of MTUS1 and its regulatory miRNAs in breast cancer and fibroadenoma tissues; among MTUS1 targeting miRNAs, miR-183-5p was overexpressed in breast cancer and down-regulated in fibroadenoma tissues; expression levels of MTUS1 and miR-183-5p correlated with clinical parameters. In particular, MTUS1 was found to be diminished and miR-183-5p was elevated with advancing stage. (PMID:27155522)
• Our findings showed that MTUS1 regulates the p38 MAPK-mediated cytokine production in ECs. MTUS1 gene probably plays a protective role against pro-inflammatory response of ECs. (PMID:27789289)
• findings have provided the first clues regarding the roles of miR-19a/b, which appear to function as oncomirs in lung cancer by downregulating MTUS1. (PMID:28364280)
• MTUS1 is not only involved in the formation and progression of human cancers but also involved in the complex pathological conditions such as cardiac hypertrophy, atherosclerosis, and SLE-like lymphoproliferative diseases. Several molecular mechanisms such as proliferation, differentiation, DNA repair, inflammation, vascular remodeling and senescence appear to be tightly regulated by the MTUS1-encoded proteins. (PMID:28499941)
• angiotensin II type 2 receptor-interacting protein 3a presents potential in suppressing the proliferation and aggressiveness of ovarian carcinoma cells through the high mobility group AT-hook 2-mediated extracellular signal-regulated kinase/epithelial-to-mesenchymal transition signal pathway. (PMID:28651497)
• The N-terminal coiled-coil domain of MTUS1 interacted with the mitochondrial membrane proteins. (PMID:29558204)
• studies emphasize the importance of studying combinatorial expression of EB1 and ATIP3 genes and proteins rather than each biomarker alone. A population of highly aggressive breast tumors expressing high-EB1/low-ATIP3 may be considered for the development of new molecular therapies. (PMID:30368744)
• Low expression of MTUS1 correlates to DNA methylation and histone deacetylation in human NSCLC. (PMID:30528566)
• MicroRNA-765 targets MTUS1 to promote the progression of osteosarcoma via mediating ERK/EMT pathway. (PMID:31210288)
• ATIP3 is an important regulator of mitotic integrity. (PMID:31685623)
• MTUS1 may act as tumor suppressor and might be a potential biomarker for predicting prognosis in GBC. (PMID:31882471)
• Reduced long non-coding RNA PTENP1 contributed to proliferation and invasion via miR-19b/MTUS1 axis in patients with cervical cancer. (PMID:32373949)
• Reciprocal regulation of Aurora kinase A and ATIP3 in the control of metaphase spindle length. (PMID:32789689)
• RNA-binding protein SORBS2 suppresses clear cell renal cell carcinoma metastasis by enhancing MTUS1 mRNA stability. (PMID:33311452)
• Microtubule-Associated Protein ATIP3, an Emerging Target for Personalized Medicine in Breast Cancer. (PMID:34062782)
• In silico analysis of deleterious SNPs of human MTUS1 gene and their impacts on subsequent protein structure and function. (PMID:34125870)
• MTUS1 is a promising diagnostic and prognostic biomarker for colorectal cancer. (PMID:35962436)
• Long Noncoding RNA MIR600HG Binds to MicroRNA-125a-5p to Prevent Pancreatic Cancer Progression Via Mitochondrial Tumor Suppressor 1-Dependent Suppression of Extracellular Regulated Protein Kinases Signaling Pathway. (PMID:37099789)
• ATIP/ATIP1 regulates prostate cancer metastasis through mitochondrial dynamic-dependent signaling. (PMID:38282475)
• [Microtubule-associated tumor suppressor 1 inhibits hemin-induced apoptosis of vascular endothelial cells via hemeoxygenase 1]. (PMID:38658371)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtus1b	ENSDARG00000034105
danio_rerio	mtus1a	ENSDARG00000071562
mus_musculus	Mtus1	ENSMUSG00000045636
rattus_norvegicus	Mtus1	ENSRNOG00000010748

Paralogs (2): MTUS2 (ENSG00000132938), CCDC69 (ENSG00000198624)

Protein

Protein identifiers

Microtubule-associated tumor suppressor 1 — Q9ULD2 (reviewed: Q9ULD2)

Alternative names: AT2 receptor-binding protein, Angiotensin-II type 2 receptor-interacting protein, Mitochondrial tumor suppressor 1

All UniProt accessions (3): Q9ULD2, A0A0U1RQI2, H0YC63

UniProt curated annotations — full annotation on UniProt →

Function. Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation. Isoform 1 inhibits breast cancer cell proliferation, delays the progression of mitosis by prolonging metaphase and reduces tumor growth.

Subunit / interactions. Homodimer. Interacts with AGTR2. Interacts with PTPN6. Isoform 1 associates with microtubules.

Subcellular location. Mitochondrion. Golgi apparatus. Cell membrane. Nucleus Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Cytoplasm. Spindle.

Tissue specificity. Ubiquitously expressed (at protein level). Highly expressed in brain. Down-regulated in ovarian carcinoma, pancreas carcinoma, colon carcinoma and head and neck squamous cell carcinoma (HNSCC). Isoform 1 is the major isoform in most peripheral tissues. Isoform 2 is abundant in most peripheral tissues. Isoform 3 is the major isoform in brain, female reproductive tissues, thyroid and heart. Within brain it is highly expressed in corpus callosum and pons. Isoform 6 is brain-specific, it is the major isoform in cerebellum and fetal brain.

Disease relevance. Hepatocellular carcinoma (HCC) [MIM:114550] A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. The gene represented in this entry may be involved in disease pathogenesis.

Induction. Down-regulated in invasive breast carcinomas (at protein level).

Miscellaneous. Expressed at very low levels in most tissues.

Similarity. Belongs to the MTUS1 family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q9ULD2-1	1, ATIP3a	yes
Q9ULD2-2	2, ATIP3b
Q9ULD2-3	3, ATIP1
Q9ULD2-4	4
Q9ULD2-5	5, ATIP2
Q9ULD2-6	6, ATIP4
Q9ULD2-7	7

RefSeq proteins (12): NP_001001924, NP_001001925, NP_001001931, NP_001159865, NP_001317399, NP_001349986, NP_001349987, NP_001349988, NP_001349989, NP_001349990, NP_001349991, NP_065800 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR051293	MTUS1/CCDC69	Family

UniProt features (56 total): modified residue 13, sequence variant 12, splice variant 10, compositionally biased region 9, region of interest 6, sequence conflict 4, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULD2-F1	52.58	0.22

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 (13): 186, 381, 399, 443, 629, 1203, 1224, 1245, 1255, 1259, 1261, 1264, 1268

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 312 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, AGGAAGC_MIR5163P, GCM_MAP4K4, LEE_NEURAL_CREST_STEM_CELL_DN, YAATNRNNNYNATT_UNKNOWN, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GCANCTGNY_MYOD_Q6, AREB6_03, AAGCCAT_MIR135A_MIR135B, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, TGACCTY_ERR1_Q2, CHX10_01, GGGTGGRR_PAX4_03, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION

GO Biological Process (1): regulation of macrophage chemotaxis (GO:0010758)

GO Molecular Function (2): microtubule binding (GO:0008017), protein binding (GO:0005515)

GO Cellular Component (13): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleolus (GO:0005730), mitochondrion (GO:0005739), Golgi apparatus (GO:0005794), centrosome (GO:0005813), spindle (GO:0005819), microtubule (GO:0005874), plasma membrane (GO:0005886), microtubule cytoskeleton (GO:0015630), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	3
intracellular membraneless organelle	3
cytoplasm	2
microtubule cytoskeleton	2
cellular anatomical structure	2
regulation of leukocyte chemotaxis	1
macrophage chemotaxis	1
regulation of macrophage migration	1
tubulin binding	1
binding	1
nuclear lumen	1
endomembrane system	1
centriole	1
microtubule organizing center	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
cytoskeleton	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1841 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTUS1	CTLA4	P16410	925
MTUS1	CD274	Q9NZQ7	909
MTUS1	PDCD1	Q15116	884
MTUS1	AGTR2	P50052	826
MTUS1	HAVCR2	Q8TDQ0	817
MTUS1	CD4	P01730	802
MTUS1	TIGIT	Q495A1	783
MTUS1	AURKB	Q96GD4	781
MTUS1	CD8A	P01732	780
MTUS1	KIF2C	Q99661	735
MTUS1	LAG3	P18627	724
MTUS1	BDKRB2	P30411	720
MTUS1	PDCD1LG2	Q9BQ51	720
MTUS1	EGFR	P00533	713
MTUS1	ALK	Q9UM73	699

IntAct

62 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
RING1	CBX4	psi-mi:“MI:0914”(association)	0.730
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
FNBP4	PRPF40A	psi-mi:“MI:0914”(association)	0.550
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
MTUS1	GLS	psi-mi:“MI:0915”(physical association)	0.400
MTUS1	H1-4	psi-mi:“MI:0915”(physical association)	0.400
POLM	MTUS1	psi-mi:“MI:0915”(physical association)	0.400
MTUS1	ORC4	psi-mi:“MI:0915”(physical association)	0.370
MTUS1	HTT	psi-mi:“MI:0915”(physical association)	0.370
NEURL4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
PB2	DNAJB6	psi-mi:“MI:0914”(association)	0.350
HSPA4	HSPA8	psi-mi:“MI:0914”(association)	0.350
TRIM52	MEIOC	psi-mi:“MI:0914”(association)	0.350
SKP1	BHLHE40	psi-mi:“MI:0914”(association)	0.350
MTUS2	CCP110	psi-mi:“MI:0914”(association)	0.350
FHL3	COBL	psi-mi:“MI:0914”(association)	0.350
MTUS1	IRF9	psi-mi:“MI:0914”(association)	0.350
B4GALT2	LENG9	psi-mi:“MI:0914”(association)	0.350
FAM167A	IFT56	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
NPAS1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
PLEKHG7	MROH6	psi-mi:“MI:0914”(association)	0.350
D2HGDH	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
SULT1C4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PUDP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
LOXL4	ARHGAP32	psi-mi:“MI:0914”(association)	0.350

BioGRID (105): MTUS1 (Affinity Capture-MS), MTUS1 (Proximity Label-MS), MTUS1 (Proximity Label-MS), MTUS1 (Proximity Label-MS), MTUS1 (Proximity Label-MS), MTUS1 (Proximity Label-MS), MTUS1 (Proximity Label-MS), MTUS1 (Proximity Label-MS), MTUS1 (Affinity Capture-MS), MTUS1 (Affinity Capture-MS), MTUS1 (Affinity Capture-MS), MTUS1 (Affinity Capture-MS), MTUS1 (Affinity Capture-MS), MTUS1 (Affinity Capture-MS), MTUS1 (Affinity Capture-MS)

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: A0JMQ7, A6NI79, A6QNP9, A7MC22, Q08AV7, Q0IHN7, Q17QT2, Q3TCJ8, Q3UHD3, Q5HZI1, Q5JR59, Q5R9I1, Q6DCD4, Q6IMY1, Q7SZL5, Q9ULD2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
Loss of Nlp from mitotic centrosomes	6	15.3×	1e-04
Loss of proteins required for interphase microtubule organization from the centrosome	6	15.3×	1e-04
AURKA Activation by TPX2	6	14.7×	1e-04
Regulation of PLK1 Activity at G2/M Transition	7	14.3×	1e-04
Recruitment of mitotic centrosome proteins and complexes	6	13.2×	2e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	12.4×	1e-03
Recruitment of NuMA to mitotic centrosomes	6	11.3×	5e-04
Anchoring of the basal body to the plasma membrane	6	10.9×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
cell division	9	5.2×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	13
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2040 predictions. Top by Δscore:

Variant	Effect	Δscore
8:17646976:TTTTA:T	donor_loss	1.0000
8:17646977:TTTAC:T	donor_loss	1.0000
8:17646978:TTACC:T	donor_loss	1.0000
8:17646979:TA:T	donor_loss	1.0000
8:17647077:CAC:C	acceptor_gain	1.0000
8:17647077:CACCT:C	acceptor_gain	1.0000
8:17647079:CCT:C	acceptor_gain	1.0000
8:17647080:C:CC	acceptor_gain	1.0000
8:17647081:T:C	acceptor_gain	1.0000
8:17647081:T:TC	acceptor_gain	1.0000
8:17647085:C:CT	acceptor_gain	1.0000
8:17647086:A:AC	acceptor_gain	1.0000
8:17647086:A:C	acceptor_gain	1.0000
8:17647091:C:CT	acceptor_gain	1.0000
8:17647092:A:T	acceptor_gain	1.0000
8:17649866:A:C	donor_gain	1.0000
8:17649959:TTTT:T	acceptor_gain	1.0000
8:17649960:TTT:T	acceptor_gain	1.0000
8:17649961:TTCTG:T	acceptor_loss	1.0000
8:17649962:TCTGG:T	acceptor_loss	1.0000
8:17649963:C:CA	acceptor_loss	1.0000
8:17649963:C:CC	acceptor_gain	1.0000
8:17649964:T:A	acceptor_loss	1.0000
8:17653181:CTTA:C	donor_loss	1.0000
8:17653184:A:AC	donor_gain	1.0000
8:17653184:AC:A	donor_gain	1.0000
8:17653185:C:CT	donor_gain	1.0000
8:17653185:CC:C	donor_gain	1.0000
8:17653185:CCA:C	donor_gain	1.0000
8:17653185:CCAA:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008807 (8:17727725 A>G), RS1000019362 (8:17768464 T>C), RS1000043443 (8:17647531 T>C), RS1000053455 (8:17650281 G>A), RS1000056845 (8:17727422 G>C), RS1000057942 (8:17673022 G>C,T), RS1000070521 (8:17754825 T>C), RS1000086609 (8:17714863 T>C), RS1000098969 (8:17702747 T>A,C), RS1000110324 (8:17677925 A>G,T), RS1000112520 (8:17719177 A>C,G), RS1000127723 (8:17744273 A>G), RS1000140850 (8:17670176 G>C), RS1000172460 (8:17670351 A>G), RS1000191040 (8:17791978 T>C,G)

Disease associations

OMIM: gene MIM:609589 | disease phenotypes: MIM:189800

GenCC curated gene-disease

Mondo (1): preeclampsia (MONDO:0005081)

Orphanet (1): Preeclampsia (Orphanet:275555)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007004_2	Hippocampal volume in normal cognition	5.000000e-09
GCST010320_85	PR interval	2.000000e-09
GCST010321_36	PR interval	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0004462	PR interval

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011225	Pre-Eclampsia	C12.050.703.395.249

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
Acetaminophen	decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
Aflatoxin B1	affects expression, increases methylation	3
methylmercuric chloride	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Cisplatin	increases expression, decreases expression, affects cotreatment	2
Lipopolysaccharides	affects cotreatment, decreases expression, affects response to substance, increases expression	2
Nickel	decreases expression	2
Quercetin	decreases expression, increases phosphorylation	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	increases methylation, increases expression	2
Zinc	affects cotreatment, decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	affects methylation	1
lead acetate	decreases expression	1
sodium arsenate	increases abundance, increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, increases expression	1
ochratoxin A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	PHASE4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	PHASE4	UNKNOWN	co Ihibtory Receptor in Preeclampsia
NCT05514847	PHASE4	ACTIVE_NOT_RECRUITING	Low Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373	PHASE4	COMPLETED	Ibuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102	PHASE4	COMPLETED	Optimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335	PHASE4	NOT_YET_RECRUITING	Effect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia
NCT06281665	PHASE4	RECRUITING	Treatment With Aspirin After Preeclampsia: TAP Trial