TLN1

protein-coding

talin 1, the group of FERM domain containing|MicroRNA protein coding host genes

Gene summary

This gene encodes a cytoskeletal protein that is concentrated in areas of cell-substratum and cell-cell contacts. The encoded protein plays a significant role in the assembly of actin filaments and in spreading and migration of various cell types, including fibroblasts and osteoclasts. It codistributes with integrins in the cell surface membrane in order to assist in the attachment of adherent cells to extracellular matrices and of lymphocytes to other cells. The N-terminus of this protein contains elements for localization to cell-extracellular matrix junctions. The C-terminus contains binding sites for proteins such as beta-1-integrin, actin, and vinculin. [provided by RefSeq, Feb 2009]

Previous symbols:

MANE transcript

NM_006289.4

Inheritance

ClinVar variants

P:1U:284B:24

Top phenotype

TLN1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr9:35,696,948-35,732,195

External References & Databases

Ensembl (ENSG00000137076)

Transcript & Mutation Effects

hg38 • Region Span ~35.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

thrombocytopeniaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0002049

Submitter: PanelApp Australia

idiopathic spontaneous coronary artery dissectionMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007385

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TLN1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 246

not providedTotal: 22

TLN1-related disorderTotal: 7

Capillary leak syndromeTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006289.4. 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			7 clinvar	14 clinvar	6 clinvar	27
missense			253 clinvar	4 clinvar		257
nonsense			3 clinvar			3
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)		1 clinvar	19 clinvar			20
Total	0	1	284	18	6	309

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006289.4	RefSeq	NP_006280.3	56	MANE Select
ENST00000314888.10	Ensembl	ENSP00000316029.9	56	MANE Select
ENST00000706939.1	Ensembl	ENSP00000516659.1	57	Standard
ENST00000706939.2	Ensembl	ENSP00000516659.1	57	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tln1	Danio rerio	Structure: cardiac muscle cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

tln1

Danio rerio

Structure: cardiac muscle cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Platelet activation - Homo sapiens (human)
Focal adhesion - Homo sapiens (human)
HTLV-I infection - Homo sapiens (human)
Rap1 signaling pathway - Homo sapiens (human)
Integrin-mediated Cell Adhesion

Biological Process

platelet degranulation
muscle contraction
cytoskeletal anchoring at plasma membrane
cell-cell junction assembly
cell-substrate junction assembly

Molecular Function

phosphatidylserine binding
integrin binding
structural constituent of cytoskeleton
protein binding
vinculin binding

Cellular Component

ruffle
extracellular region
cytosol
cytoskeleton
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314888
Coding exons: 56
Length: 35448
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125748
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.67	970	1.48e+3	0.658	0.0000872	16375
Missense (PolyPhen)		358	660.06	0.54237		7348
Synonymous	1.47	535	580	0.922	0.0000337	5324
Loss of Function	9.84	10	132	0.0757	0.00000743	1422

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0014	0.0014	notable
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably involved in connections of major cytoskeletal structures to the plasma membrane. High molecular weight cytoskeletal protein concentrated at regions of cell-substratum contact and, in lymphocytes, at cell-cell contacts (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.390

Intolerance Scores

LoFtool: 0.268
RVIS EVS: -3.42
RVIS percentile EVS: 0.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.937

Gene Damage Prediction

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