AMOTL2

protein-coding

angiomotin like 2, the group of MicroRNA protein coding host genes

Gene summary

Angiomotin is a protein that binds angiostatin, a circulating inhibitor of the formation of new blood vessels (angiogenesis). Angiomotin mediates angiostatin inhibition of endothelial cell migration and tube formation in vitro. The protein encoded by this gene is related to angiomotin and is a member of the motin protein family. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

MANE transcript

NM_016201.4

Inheritance

—

ClinVar variants

U:143B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr3:134,355,347-134,375,479

External References & Databases

Ensembl (ENSG00000114019)

Transcript & Mutation Effects

hg38 • Region Span ~20.1 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 AMOTL2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 141

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016201.4. 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			1 clinvar		1 clinvar	2
missense			141 clinvar	2 clinvar	1 clinvar	144
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	143	2	2	147

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016201.4	RefSeq	NP_057285.3	9	MANE Select
ENST00000249883.10	Ensembl	ENSP00000249883.5	9	MANE Select
NM_001278683.1	RefSeq	NP_001265612.1	10	Standard
NM_001278685.2	RefSeq	NP_001265614.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
amotl2b	Danio rerio	Structure: dorsal longitudinal anastomotic vessel Quality: closed abnormal

Gene / Model

Organism

Observed Phenotype

amotl2b

Danio rerio

Structure: dorsal longitudinal anastomotic vessel

Quality: closed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tight junction - Homo sapiens (human)
Signal Transduction
Signaling by Hippo

Biological Process

angiogenesis
establishment of cell polarity involved in ameboidal cell migration
Wnt signaling pathway
actin cytoskeleton organization
regulation of cell migration

Molecular Function

protein binding
identical protein binding

Cellular Component

cytosol
bicellular tight junction
apical plasma membrane
cytoplasmic vesicle
recycling endosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000249883
Coding exons: 9
Length: 19606
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0754	483	488	0.990	0.0000314	4978
Missense (PolyPhen)		204	246.6	0.82725		2533
Synonymous	0.347	197	203	0.969	0.0000124	1670
Loss of Function	4.24	9	36.7	0.245	0.00000220	338

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000095	0.000092	rare
European (Non-Finnish)	0.00014	0.00013	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites. Required for proper architecture of actin filaments. Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. Participates in angiogenesis. May play a role in the polarity, proliferation and migration of endothelial cells. Selectively promotes FGF-induced MAPK activation through SRC. {ECO:0000269|PubMed:17293535, ECO:0000269|PubMed:21937427, ECO:0000269|PubMed:22362771}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.467
RVIS EVS: 0.8
RVIS percentile EVS: 87.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.922

Gene Damage Prediction

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