AMOTL1

protein-coding

angiomotin like 1

Gene summary

The protein encoded by this gene is a peripheral membrane protein that is a component of tight junctions or TJs. TJs form an apical junctional structure and act to control paracellular permeability and maintain cell polarity. This protein is related to angiomotin, an angiostatin binding protein that regulates endothelial cell migration and capillary formation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

MANE transcript

NM_130847.3

Inheritance

ClinVar variants

P:6U:162B:12

Top phenotype

Mendelian syndromes with cleft lip/palate

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr11:94,706,431-94,876,748

External References & Databases

Ensembl (ENSG00000166025)

Transcript & Mutation Effects

hg38 • Region Span ~170.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

orofacial clefting-cardiac anomalies-facial dysmorphism syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0971064

Submitter: G2P

Mendelian syndromes with cleft lip/palateSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0015335

Submitter: PanelApp Australia

orofacial cleftMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0000358

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AMOTL1 variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 142

not providedTotal: 26

Craniofaciocardiohepatic syndromeTotal: 9

AMOTL1-associated disorderTotal: 2

Long fingersTotal: 1

Cleft lip/palateTotal: 1

Tethered cordTotal: 1

Abnormal pinna morphologyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_130847.3. 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				4 clinvar	6 clinvar	10
missense	3 clinvar	3 clinvar	156 clinvar	2 clinvar		164
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	3	3	162	6	6	180

Highest pathogenic variant AF is 0.000005642598

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_130847.3	RefSeq	NP_570899.1	13	MANE Select
ENST00000433060.3	Ensembl	ENSP00000387739.2	13	MANE Select
NM_001301007.2	RefSeq	NP_001287936.1	12	Standard
ENST00000299004.13	Ensembl	ENSP00000299004.9	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
amotl1	Danio rerio	Structure: intersegmental vessel Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

amotl1

Danio rerio

Structure: intersegmental vessel

Quality: decreased length

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
COP9 signalosome
apical plasma membrane
lamellipodium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000433060
Coding exons: 13
Length: 170322
Individuals with no LoFs: 124655
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 124686
p: 0.000124

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.22	471	552	0.854	0.0000323	6193
Missense (PolyPhen)		206	254.17	0.81047		2735
Synonymous	0.301	221	227	0.975	0.0000141	1882
Loss of Function	4.41	14	46.4	0.301	0.00000273	487

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00030	0.00028	rare
Finnish	0.00010	0.000093	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.000066	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. {ECO:0000269|PubMed:22362771}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.671
RVIS EVS: -0.44
RVIS percentile EVS: 24.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.695

Gene Damage Prediction

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