AMOT

Summary

AMOT (angiomotin, HGNC:17810) is a protein-coding gene on chromosome Xq23, encoding Angiomotin (Q4VCS5). Plays a central role in tight junction maintenance via the complex formed with ARHGAP17, which acts by regulating the uptake of polarity proteins at tight junctions.

This gene belongs to the motin family of angiostatin binding proteins characterized by conserved coiled-coil domains and C-terminal PDZ binding motifs. The encoded protein is expressed predominantly in endothelial cells of capillaries as well as larger vessels of the placenta where it may mediate the inhibitory effect of angiostatin on tube formation and the migration of endothelial cells toward growth factors during the formation of new blood vessels. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 154796 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 263 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001113490

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17810
Approved symbol	AMOT
Name	angiomotin
Location	Xq23
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1071
Ensembl gene	ENSG00000126016
Ensembl biotype	protein_coding
OMIM	300410
Entrez	154796

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000304758, ENST00000371958, ENST00000371959, ENST00000371962, ENST00000462114

RefSeq mRNA: 4 — MANE Select: NM_001113490 NM_001113490, NM_001386998, NM_001386999, NM_133265

CCDS: CCDS14563, CCDS48154

Canonical transcript exons

ENST00000371959 — 14 exons

Exon	Start	End
ENSE00000860417	112778997	112779680
ENSE00001024367	112832294	112832370
ENSE00001604167	112804947	112805092
ENSE00001657953	112790592	112790782
ENSE00001695122	112811249	112811393
ENSE00001702937	112780886	112781118
ENSE00001757018	112809894	112809986
ENSE00001775673	112782540	112782662
ENSE00001805641	112791832	112791981
ENSE00001954583	112825072	112825220
ENSE00002105833	112822255	112823188
ENSE00003558963	112815358	112815877
ENSE00003906777	112840452	112840831
ENSE00003921863	112774877	112778664

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 96.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.2153 / max 405.6447, expressed in 1233 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200214	7.3997	884
200216	3.3157	1023
200213	0.9018	394
200212	0.7426	367
200207	0.4377	222
200210	0.3715	228
200209	0.2482	145
200206	0.2237	91
200215	0.2199	113
200202	0.1786	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle frontal gyrus	UBERON:0002702	96.42	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.82	gold quality
frontal pole	UBERON:0002795	93.77	gold quality
paraflocculus	UBERON:0005351	93.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.97	gold quality
secondary oocyte	CL:0000655	89.22	gold quality
muscle of leg	UBERON:0001383	86.26	gold quality
gastrocnemius	UBERON:0001388	85.87	gold quality
oocyte	CL:0000023	84.79	gold quality
anterior cingulate cortex	UBERON:0009835	84.29	gold quality
cingulate cortex	UBERON:0003027	84.19	gold quality
amygdala	UBERON:0001876	83.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.17	gold quality
right frontal lobe	UBERON:0002810	82.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.79	gold quality
caudate nucleus	UBERON:0001873	82.74	gold quality
ganglionic eminence	UBERON:0004023	82.65	gold quality
nucleus accumbens	UBERON:0001882	82.03	gold quality
ventricular zone	UBERON:0003053	82.01	gold quality
putamen	UBERON:0001874	81.30	gold quality
prefrontal cortex	UBERON:0000451	80.51	gold quality
skeletal muscle organ	UBERON:0014892	79.83	gold quality
muscle organ	UBERON:0001630	79.81	gold quality
corpus epididymis	UBERON:0004359	79.29	gold quality
sural nerve	UBERON:0015488	79.14	gold quality
stromal cell of endometrium	CL:0002255	78.92	gold quality
right uterine tube	UBERON:0001302	78.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.56	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	374.87
E-ANND-3	yes	7.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

178 targeting AMOT, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-497-5P	99.92	71.83	2674

Literature-anchored findings (GeneRIF, showing 40)

• PDZ binding motif of angiomotin plays a critical role in regulating the responsiveness of endothelial cells to chemotactic cues (PMID:12902404)
• angiomotin, in addition to controlling cell motility, may play a role in the assembly of endothelial cell-cell junctions (PMID:16043488)
• p80- and p130-angiomotin play coordinating roles in vascular tube formation by affecting cell migration and cell shape, respectively. (PMID:16640563)
• Results show that DNA vaccination targeting angiomotin may be used to mimic the effect of angiostatin. (PMID:16754857)
• the directional migration of capillaries in the embryo is governed by the Amot:Patj/Mupp1:Syx signaling that controls local GTPase activity (PMID:18824598)
• The angiomotin-like 1 is involved in actin-cytoskeleton-based processes, in part, via its interaction with a p80-angiomotin-containing complex and the actin cytoskeleton (PMID:19565639)
• Amot and AmotL1 have similar effects on endothelial migration and tight junction formation in vitro. In vivo Amot appears to control the cell polarity and AmotL1 affects the stability of cell-cell junctions. (PMID:19590046)
• a novel lipid binding domain within Amot is shown to selectively bind with high affinity to membranes containing monophosphorylated phosphatidylinositols and cholesterol (PMID:20080965)
• novel mechanism to restrict the activity of TAZ and YAP through physical interaction with Amot and AmotL1 (PMID:21224387)
• Data show that Amot expression is required for proliferation of breast cancer cells in specific microenvironmental contexts that require ERK1/2 signaling. (PMID:21285250)
• ADepletion of Angiomotin in Nf2(-/-) Schwann cells attenuates the Ras-MAPK signaling pathway, impedes cellular proliferation in vitro and tumorigenesis in vivo (PMID:21481793)
• Three L/P-PXY motifs of AMOT/p130 and the WW domains of Nedd4 mediate the interaction of Nedd4, Nedd4-2 and Itch. (PMID:22385262)
• Soluble melanoma cell adhesion molecule (sMCAM/sCD146) promotes angiogenic effects on endothelial progenitor cells through angiomotin (PMID:23389031)
• Amot130 repurposes AIP4 from its previously described role in degrading large tumor suppressor 1 to the inhibition of YAP and cell growth. (PMID:23564455)
• High levels of Amot transcripts were associated with poor differentiation, venous invasion and decreased survival in patients with clear cell renal cell carcinoma. (PMID:23588948)
• Scaffold proteins angiomotin (Amot) and angiomotin-related AmotL1 and AmotL2 were recently identified as negative regulators of YAP and TAZ by preventing their nuclear translocation. (PMID:24003252)
• Within the nucleus, Amot-p130 was associated with the transcriptional complex containing Yap and Teads (TEA domain family members) and contributed to the regulation of a subset of Yap target genes, many of which are associated with tumorigenesis. (PMID:24003254)
• Data indicate that the phosphorylation of Amot130 by LATS1/2 is found to be a key feature that enables it to inhibit Yes-associated protein (YAP) dependent signaling and cell growth. (PMID:24101513)
• Thus AMOT is a direct substrate of Lats1/2 mediating functions of the Hippo pathway in endothelial cell migration and angiogenesis. (PMID:24106267)
• These results collectively suggest that the Hippo pathway negatively regulates the actin-binding activity of Amot family members through direct phosphorylation. (PMID:24225952)
• expression is upregulated in sinonasal inverted papilloma (PMID:24532565)
• function of Angiomotins and other members of the Motin protein family (PMID:24548561)
• angiomotin proteins connect F-actin architecture to YAP regulation. (PMID:24648494)
• AMOT is a crucial suppressor of lung cancer metastasis and highlight its critical role as a tumor suppressor and its potential as a prognostic biomarker and therapeutic target for lung cancer. (PMID:25381822)
• experiments indicate that AMOT and other motin family members function together with NEDD4L to help complete immature virion assembly prior to ESCRT-mediated virus budding (PMID:25633977)
• Amot was highly expressed in breast cancer tissues and was important in the promotion of breast cancer cell proliferation and invasion. Amot knockdown in MCF-7 cells decreased the expression of YAP, YAP/TAZ and LATS1. (PMID:25647626)
• angiomotin and Merlin respectively interface cortical actin filaments and core kinases in Hippo signaling (PMID:26045165)
• Study shows miR-205 significantly downregulated and directly target the 3’-UTR of AMOT in breast cancer. In vitro, miR-205 regulates the proliferation and invasion of breast cancer cells through suppression of AMOT expression. (PMID:26239614)
• The lncRNA SNHG12 promotes cell proliferation and migration by upregulating AMOT gene expression in osteosarcoma cells in vivo and in vitro. (PMID:26486328)
• Data indicate that Amot is crucial for the maintenance of nuclear YAP to promote renal epithelial and RCC proliferation. (PMID:26848622)
• AMOT may function as an oncogene in the progression of colon cancer by activating the YAP-ERK/PI3K-AKT signaling pathway. (PMID:27779692)
• Angiomotin promotes prostate cancer cell proliferation by signaling through the Hippo-YAP pathway. (PMID:28052036)
• The authors propose that phosphorylation of Amot(S176) is a critical post-translational modification that suppresses YAP’s ability to promote cell proliferation and tumorigenesis by altering the subcellular localization of an essential YAP co-factor. (PMID:28464980)
• Decreased AMOT-p130 expression coupled with high nuclear YAP1 expression resulted in shorter overall survival and disease-free survival in patients with advanced gastric cancer. (PMID:28885730)
• Study focused on the methylation profile of the AMOT promoter CpG island during development, comparing it in circulating cord blood endothelial progenitor cells (ECFC) of cord blood from term versus preterm newborns. Findings highlight importance of pro-angiogenic AMOT gene methylation in ECFC, suggesting that epigenetic mechanisms may control the regulation of angiogenesis during development. (PMID:29036193)
• We have been suggested that AmotP130 suppressed the invasion ability through remodelling of the cytoskeleton of breast cancer cells, involving regulation of the Rho pathway. The cytoskeleton-related pathway components may provide novel, clinically therapeutic targets for breast cancer treatment. (PMID:29377471)
• AMOT expression is regulated by MiR-4463 in the vascular smooth muscle cell migration. (PMID:29752344)
• AMOT, AMOTL1, and AMOTL2 enhance Hippo signaling by stimulating LATS1/2 autophosphorylation and by connecting LATS1/2 with both its activator SAV1-MST1/2 and its substrate YAP. (PMID:30266805)
• Amot-p130 functions as a tumor suppressor gene in breast cancer, disrupting beta-catenin stability by competing with Axin for binding to tankyrase. (PMID:30792381)
• AMOT is primarily expressed in migratory extravillous trophoblast cells (EVTs) and its expression increases after 10 weeks of gestation when oxygen tension rises and EVT migration/invasion peaks. In preeclampsia, however, AMOT expression is decreased and its localization to migratory fetomaternal interface EVTs is disrupted. JMJD6 an oxygen sensor, positively regulates AMOT via oxygen-dependent lysyl hydroxylation. (PMID:30996134)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	amot	ENSDARG00000078335
mus_musculus	Amot	ENSMUSG00000041688
rattus_norvegicus	Amot	ENSRNOG00000007345

Paralogs (2): AMOTL2 (ENSG00000114019), AMOTL1 (ENSG00000166025)

Protein

Protein identifiers

Angiomotin — Q4VCS5 (reviewed: Q4VCS5)

All UniProt accessions (3): Q4VCS5, A6NP16, E7ERM3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a central role in tight junction maintenance via the complex formed with ARHGAP17, which acts by regulating the uptake of polarity proteins at tight junctions. Appears to regulate endothelial cell migration and tube formation. May also play a role in the assembly of endothelial cell-cell junctions. Repressor of YAP1 and WWTR1/TAZ transcription of target genes, potentially via regulation of Hippo signaling-mediated phosphorylation of YAP1 which results in its recruitment to tight junctions.

Subunit / interactions. Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3. Interacts with MAGI1. Interacts with angiostatin. Interacts with YAP1; the interaction facilitates translocation of YAP1 to the cytoplasm and tight junctions. Interacts with WWTR1/TAZ (via WW domain); the interaction facilitates translocation of WWTR1/TAZ to the cytoplasm.

Subcellular location. Cell junction. Tight junction.

Tissue specificity. Expressed in placenta and skeletal muscle. Found in the endothelial cells of capillaries as well as larger vessels of the placenta.

Post-translational modifications. Polyubiquitinated by NEDD4, NEDD4L and ITCH, leading to proteasomal degradation.

Domain organisation. The coiled coil domain interacts directly with the BAR domain of ARHGAP17. The angiostatin binding domain (871-1005) allows the binding to angiostatin.

Miscellaneous. ‘Motus’ means ‘motility’ in Latin.

Similarity. Belongs to the angiomotin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q4VCS5-1	1, p130	yes
Q4VCS5-2	2, p80

RefSeq proteins (4): NP_001106962, NP_001373927, NP_001373928, NP_573572 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009114	Angiomotin	Family
IPR024646	Angiomotin_C	Domain
IPR051747	Angiomotin-like	Family

Pfam: PF12240

UniProt features (23 total): region of interest 7, compositionally biased region 5, cross-link 2, helix 2, coiled-coil region 2, chain 1, short sequence motif 1, modified residue 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
7NP2	X-RAY DIFFRACTION	1.27
7OQS	X-RAY DIFFRACTION	1.34
7NPB	X-RAY DIFFRACTION	1.37
7NPG	X-RAY DIFFRACTION	1.37
7NND	X-RAY DIFFRACTION	1.4
7OQJ	X-RAY DIFFRACTION	1.4
7OQU	X-RAY DIFFRACTION	1.4
7NMW	X-RAY DIFFRACTION	1.5
7OQG	X-RAY DIFFRACTION	1.5
7LP3	X-RAY DIFFRACTION	1.61
7NMA	X-RAY DIFFRACTION	1.75
7NN2	X-RAY DIFFRACTION	1.8
7LP2	X-RAY DIFFRACTION	1.88
7OQW	X-RAY DIFFRACTION	1.9
7NNE	X-RAY DIFFRACTION	1.96
6JJX	X-RAY DIFFRACTION	2
7NMX	X-RAY DIFFRACTION	2.3
7LP5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4VCS5-F1	58.16	0.24

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 (3): 714, 594, 595

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2028269	Signaling by Hippo
R-HSA-9762292	Regulation of CDH11 function

MSigDB gene sets: 317 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, MORF_MSH3, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOCC_CELL_SURFACE, GOBP_HIPPO_SIGNALING, GOCC_RUFFLE, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5

GO Biological Process (23): negative regulation of transcription by RNA polymerase II (GO:0000122), angiogenesis (GO:0001525), vasculogenesis (GO:0001570), in utero embryonic development (GO:0001701), gastrulation with mouth forming second (GO:0001702), establishment of cell polarity involved in ameboidal cell migration (GO:0003365), chemotaxis (GO:0006935), cell-cell junction assembly (GO:0007043), intracellular protein localization (GO:0008104), negative regulation of angiogenesis (GO:0016525), actin cytoskeleton organization (GO:0030036), regulation of cell migration (GO:0030334), hippo signaling (GO:0035329), positive regulation of embryonic development (GO:0040019), cell migration involved in gastrulation (GO:0042074), negative regulation of vascular permeability (GO:0043116), blood vessel endothelial cell migration (GO:0043534), positive regulation of blood vessel endothelial cell migration (GO:0043536), positive regulation of cell size (GO:0045793), regulation of small GTPase mediated signal transduction (GO:0051056), positive regulation of stress fiber assembly (GO:0051496), regulation of modification of postsynaptic actin cytoskeleton (GO:1905274), blood vessel morphogenesis (GO:0048514)

GO Molecular Function (3): signaling receptor activity (GO:0038023), angiostatin binding (GO:0043532), protein binding (GO:0005515)

GO Cellular Component (17): stress fiber (GO:0001725), ruffle (GO:0001726), cytoplasm (GO:0005737), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), postsynaptic density (GO:0014069), membrane (GO:0016020), lamellipodium (GO:0030027), endocytic vesicle (GO:0030139), cytoplasmic vesicle (GO:0031410), glutamatergic synapse (GO:0098978), COP9 signalosome (GO:0008180), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signal Transduction	1
Regulation of CDH11 Expression and Function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
blood vessel morphogenesis	2
gastrulation	2
ameboidal-type cell migration	2
cell leading edge	2
plasma membrane bounded cell projection	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
anatomical structure formation involved in morphogenesis	1
cell differentiation	1
chordate embryonic development	1
establishment of cell polarity	1
response to chemical	1
taxis	1
cell junction assembly	1
cell-cell junction organization	1
macromolecule localization	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
cytoskeleton organization	1
actin filament-based process	1
cell migration	1
regulation of cell motility	1
intracellular signal transduction	1
embryo development	1
regulation of embryonic development	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of vascular permeability	1
endothelial cell migration	1
positive regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1
regulation of blood vessel endothelial cell migration	1
regulation of cell size	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
molecular transducer activity	1

Protein interactions and networks

STRING

1718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMOT	ARHGAP17	Q68EM7	998
AMOT	PATJ	Q8NI35	998
AMOT	PLG	P00747	993
AMOT	PALS1	Q8N3R9	984
AMOT	NF2	P35240	939
AMOT	WWTR1	Q9GZV5	911
AMOT	YAP1	P46937	906
AMOT	MPDZ	O75970	897
AMOT	ARHGAP1	Q07960	864
AMOT	LATS1	O95835	852
AMOT	PARD3	Q8TEW0	839
AMOT	NEDD4L	Q96PU5	743
AMOT	PTPN14	Q15678	739
AMOT	WWC1	Q8IX03	736
AMOT	TEAD1	P28347	728

IntAct

163 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
NF2	AMOT	psi-mi:“MI:0915”(physical association)	0.880
NF2	AMOT	psi-mi:“MI:0403”(colocalization)	0.880
AMOT	NF2	psi-mi:“MI:0915”(physical association)	0.880
PALS1	LIN7A	psi-mi:“MI:0914”(association)	0.870
MLH1	PMS1	psi-mi:“MI:0914”(association)	0.830
YAP1	MPDZ	psi-mi:“MI:0914”(association)	0.780
MED4	MED14	psi-mi:“MI:0914”(association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AMOT	MPDZ	psi-mi:“MI:0914”(association)	0.670
MAGEA4	AMOT	psi-mi:“MI:0915”(physical association)	0.660
LURAP1	AMOT	psi-mi:“MI:0915”(physical association)	0.660
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
MPDZ	SMCHD1	psi-mi:“MI:0914”(association)	0.590
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570

BioGRID (514): AMOT (Affinity Capture-MS), AMOT (Two-hybrid), AMOT (Two-hybrid), AMOT (Two-hybrid), AMOT (Two-hybrid), AMOT (Two-hybrid), AMOT (Two-hybrid), AMOT (Two-hybrid), AMOT (Two-hybrid), AMOT (Two-hybrid), AMOT (Two-hybrid), AMOT (Two-hybrid), AMOT (Two-hybrid), AMOT (Two-hybrid), LURAP1 (Two-hybrid)

ESM2 similar proteins: A0A087WPF7, A0A0R4IBL7, O09000, O54972, O70305, O75081, O75376, P15806, P15881, P15884, P15923, P21677, P30985, P51514, P98180, Q05AQ8, Q14157, Q14687, Q1LY51, Q2VPM4, Q3U3C9, Q4KKX4, Q4VCS5, Q566L4, Q5F3B1, Q5SFM8, Q5T6F2, Q60722, Q60974, Q61286, Q62655, Q6DIH5, Q7ZWN6, Q7ZXS3, Q80X50, Q86YP4, Q8BZ47, Q8CHY6, Q8IXK0, Q8VHG2

Diamond homologs: A0A8I3QA39, A1YB07, B8A5S6, E1BEQ5, F1MRK3, G3V735, Q4VCS5, Q8IY63, Q8K371, Q8VHG2, Q9D4H4, Q9Y2J4

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
AMOT	down-regulates	WWTR1	relocalization
AMOT	down-regulates	YAP1	relocalization
AMOT	“down-regulates activity”	YAP/TAZ	binding
LATS1	“up-regulates quantity by stabilization”	AMOT	phosphorylation
LATS2	“up-regulates quantity by stabilization”	AMOT	phosphorylation
WWP1	“up-regulates quantity by stabilization”	AMOT	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 170 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
Signaling by Hippo	7	30.9×	1e-06
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	5	14.5×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
hippo signaling	9	42.8×	3e-10
sarcomere organization	6	14.9×	2e-03
intracellular protein localization	9	6.1×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	112
Likely benign	11
Benign	8

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
154252	GRCh38/hg38 Xq21.1-28(chrX:78187188-156004066)x1	Pathogenic
224811	NM_001113490.2(AMOT):c.1926G>C (p.Gln642His)	Likely pathogenic

SpliceAI

2098 predictions. Top by Δscore:

Variant	Effect	Δscore
X:112779676:AATGC:A	acceptor_gain	1.0000
X:112779677:ATGC:A	acceptor_gain	1.0000
X:112779678:TGC:T	acceptor_gain	1.0000
X:112779678:TGCCT:T	acceptor_loss	1.0000
X:112779679:GC:G	acceptor_gain	1.0000
X:112779680:CC:C	acceptor_gain	1.0000
X:112779680:CCTA:C	acceptor_loss	1.0000
X:112779681:C:CC	acceptor_gain	1.0000
X:112779681:C:T	acceptor_gain	1.0000
X:112779684:CAAA:C	acceptor_gain	1.0000
X:112779687:A:AC	acceptor_gain	1.0000
X:112779687:A:C	acceptor_gain	1.0000
X:112780880:CATTA:C	donor_loss	1.0000
X:112780882:TTA:T	donor_loss	1.0000
X:112780885:C:CA	donor_loss	1.0000
X:112780888:AGGCT:A	donor_gain	1.0000
X:112780898:T:TA	donor_gain	1.0000
X:112781117:TCCTA:T	acceptor_loss	1.0000
X:112781120:T:A	acceptor_loss	1.0000
X:112782566:ATTGG:A	donor_gain	1.0000
X:112782585:T:TA	donor_gain	1.0000
X:112782661:CC:C	acceptor_gain	1.0000
X:112782662:CC:C	acceptor_gain	1.0000
X:112782662:CCTGG:C	acceptor_loss	1.0000
X:112782663:C:A	acceptor_loss	1.0000
X:112782664:T:A	acceptor_loss	1.0000
X:112790587:CTTA:C	donor_gain	1.0000
X:112790588:TTA:T	donor_loss	1.0000
X:112790589:TA:T	donor_loss	1.0000
X:112790590:A:AC	donor_gain	1.0000

AlphaMissense

7025 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:112781065:A:G	L765P	1.000
X:112781081:C:G	A760P	1.000
X:112781107:A:G	L751P	1.000
X:112790661:T:G	Q683P	1.000
X:112790668:A:G	W681R	1.000
X:112790668:A:T	W681R	1.000
X:112790683:C:G	A676P	1.000
X:112790688:A:G	L674P	1.000
X:112791854:A:G	L635P	1.000
X:112791866:A:G	L631P	1.000
X:112791875:C:G	R628P	1.000
X:112791878:A:G	L627P	1.000
X:112791890:A:G	L623P	1.000
X:112791899:C:G	R620P	1.000
X:112791917:T:G	Q614P	1.000
X:112791920:A:G	L613P	1.000
X:112791929:A:G	L610P	1.000
X:112791933:C:G	A609P	1.000
X:112791980:A:G	L593P	1.000
X:112804957:A:G	L589P	1.000
X:112804979:C:G	A582P	1.000
X:112804987:A:G	L579P	1.000
X:112804991:C:G	A578P	1.000
X:112804999:C:G	R575P	1.000
X:112811254:A:G	L511P	1.000
X:112811350:A:G	L479P	1.000
X:112815365:A:G	L462P	1.000
X:112815428:A:G	L441P	1.000
X:112822594:A:G	L178P	1.000
X:112822602:A:C	S175R	1.000

dbSNP variants (sampled 300 via entrez): RS1000229454 (X:112835097 T>A,C), RS1000485035 (X:112800185 C>T), RS1000520564 (X:112797736 G>A), RS1000551512 (X:112807803 A>C), RS1000557291 (X:112833276 T>TA), RS1000611089 (X:112833554 ACTCT>A,ACT,ACTCTCT), RS1000659172 (X:112838339 GATGGGGAAGA>G), RS1000788268 (X:112842243 G>A), RS1000900287 (X:112825454 G>A), RS1000920957 (X:112780399 A>T), RS1000929512 (X:112825130 G>A,C), RS1001095332 (X:112815835 C>A,G,T), RS1001142597 (X:112789246 T>A), RS1001225384 (X:112798062 C>T), RS1001249106 (X:112833883 G>A)

Disease associations

OMIM: gene MIM:300410 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3392949 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects acetylation, affects methylation, decreases expression, increases expression	4
Valproic Acid	affects cotreatment, increases expression, decreases methylation	4
Aflatoxin B1	decreases expression, increases methylation	3
Benzo(a)pyrene	affects methylation, increases methylation	2
Estradiol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
beryllium sulfate	decreases expression	1
potassium chromate(VI)	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
evodiamine	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
monomethylarsonous acid	affects acetylation, affects methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3395018	Binding	Binding affinity to human leukocyte angiomotin extracellular domain (E458-T596) after 3 hrs by microplate-based T7 phage display biopanning method	Multimodal biopanning of T7 phage-displayed peptides reveals angiomotin as a potential receptor of the anti-angiogenic macrolide Roxithromycin. — Eur J Med Chem

Clinical trials (associated diseases)

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