TNS1

protein-coding

tensin 1, the group of MicroRNA protein coding host genes|Protein phosphatase 1 regulatory subunits|SH2 domain containing|C2 tensin-type domain containing|PTEN protein phosphatases

Gene summary

The protein encoded by this gene localizes to focal adhesions, regions of the plasma membrane where the cell attaches to the extracellular matrix. This protein crosslinks actin filaments and contains a Src homology 2 (SH2) domain, which is often found in molecules involved in signal transduction. This protein is a substrate of calpain II. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

Previous symbols:

TNS
MXRA6

MANE transcript

NM_001387777.1

Inheritance

—

ClinVar variants

U:313B:59

Top phenotype

TNS1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr2:217,799,588-218,033,982

External References & Databases

Ensembl (ENSG00000079308)

Transcript & Mutation Effects

hg38 • Region Span ~234.4 kb

Loading mutation effect viewer...

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 TNS1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 302

TNS1-related disorderTotal: 57

not providedTotal: 26

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001387777.1. 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			2 clinvar	16 clinvar	13 clinvar	31
missense			303 clinvar	16 clinvar	14 clinvar	333
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	313	32	27	372

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001387777.1	RefSeq	NP_001374706.1	33	MANE Select
ENST00000682258.1	Ensembl	ENSP00000506917.1	33	MANE Select
NM_001308022.2	RefSeq	NP_001294951.1	27	Standard
NM_001308023.2	RefSeq	NP_001294952.1	26	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tns1b	Danio rerio	Structure: endothelial cell Quality: decreased accumulation abnormal

Gene / Model

Organism

Observed Phenotype

tns1b

Danio rerio

Structure: endothelial cell

Quality: decreased accumulation

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Integrin-mediated Cell Adhesion
erk and pi-3 kinase are necessary for collagen binding in corneal epithelia
integrin signaling pathway
EGFR1
Integrin-linked kinase signaling

Biological Process

cell-substrate junction assembly
fibroblast migration

Molecular Function

RNA binding
actin binding
protein binding

Cellular Component

cytoplasm
cytoskeleton
focal adhesion
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000171887
Coding exons: 28
Length: 203207
Individuals with no LoFs: 125645
Homozygous LoFs: 0
Heterozygous LoFs: 103
Defined: 125748
p: 0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.552	979	1.03e+3	0.952	0.0000627	11147
Missense (PolyPhen)		373	423.75	0.88024		4544
Synonymous	0.222	419	425	0.986	0.0000275	3634
Loss of Function	6.00	18	73.6	0.245	0.00000410	797

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00032	0.00026	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0040	0.0040	notable
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000091	0.000088	rare
South Asian	0.00017	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in fibrillar adhesion formation. May be involved in cell migration, cartilage development and in linking signal transduction pathways to the cytoskeleton. {ECO:0000269|PubMed:21768292}.;

Recessive Scores

pRec: 0.156

Intolerance Scores

LoFtool: 0.0123
RVIS EVS: 1.59
RVIS percentile EVS: 95.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.662

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High