AMOT

protein-coding

angiomotin, the group of MicroRNA protein coding host genes

Gene summary

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001113490.2

Inheritance

—

ClinVar variants

P:1U:228B:18

Top phenotype

Cerebral visual impairment and intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chrX:112,774,503-112,840,831

External References & Databases

Ensembl (ENSG00000126016)

Transcript & Mutation Effects

hg38 • Region Span ~66.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AMOT variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 112

not providedTotal: 19

Cerebral visual impairment and intellectual disabilityTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001113490.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			21 clinvar	2 clinvar	5 clinvar	28
missense		1 clinvar	167 clinvar	9 clinvar	2 clinvar	179
nonsense			18 clinvar			18
start loss			1 clinvar			1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			20 clinvar			20
Total	0	1	228	11	7	247

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001113490.2	RefSeq	NP_001106962.1	11	MANE Select
ENST00000371959.9	Ensembl	ENSP00000361027.3	11	MANE Select
NM_001386998.1	RefSeq	NP_001373927.1	11	Standard
NM_001386999.1	RefSeq	NP_001373928.1	11	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
amot	Danio rerio	Structure: endothelial tip cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

amot

Danio rerio

Structure: endothelial tip cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tight junction - Homo sapiens (human)
Hippo signaling pathway - Homo sapiens (human)
VEGFA-VEGFR2 Signaling Pathway
Signal Transduction
Signaling by Hippo

Biological Process

angiogenesis
vasculogenesis
in utero embryonic development
gastrulation with mouth forming second
establishment of cell polarity involved in ameboidal cell migration

Molecular Function

protein binding
signaling receptor activity
angiostatin binding

Cellular Component

ruffle
nucleus
cytosol
actin filament
bicellular tight junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371959
Coding exons: 11
Length: 66313
Individuals with no LoFs: 125688
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125690
p: 0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.09	363	426	0.851	0.0000345	6993
Missense (PolyPhen)		16	13.682	1.1694		257
Synonymous	0.327	157	162	0.967	0.0000127	2276
Loss of Function	4.81	4	34.4	0.116	0.00000291	502

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000024	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:11257124, ECO:0000269|PubMed:16678097}.;

Recessive Scores

pRec: 0.0949

Intolerance Scores

LoFtool: 0.111
RVIS EVS: 0.22
RVIS percentile EVS: 68.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.964

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium