TLN2

protein-coding

talin 2, the group of FERM domain containing|MicroRNA protein coding host genes

Gene summary

This gene encodes a protein related to talin 1, a cytoskeletal protein that plays a significant role in the assembly of actin filaments and in spreading and migration of various cell types, including fibroblasts and osteoclasts. This protein has a different pattern of expression compared to talin 1 but, like talin 1, is thought to associate with unique transmembrane receptors to form novel linkages between extracellular matrices and the actin cytoskeleton. [provided by RefSeq, Jul 2008]

MANE transcript

NM_015059.3

Inheritance

ClinVar variants

U:410B:47

Top phenotype

Myoepithelial tumor

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr15:62,390,526-62,844,631

External References & Databases

Ensembl (ENSG00000171914)

Transcript & Mutation Effects

hg38 • Region Span ~454.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Tourette syndromeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0007661

Submitter: Labcorp Genetics (formerly Invitae)

camptodactyly of fingersLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007250

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TLN2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 384

not providedTotal: 56

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015059.3. 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	25 clinvar	9 clinvar	38
missense			392 clinvar	7 clinvar	6 clinvar	405
nonsense			1 clinvar			1
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	410	32	15	457

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015059.3	RefSeq	NP_055874.2	56	MANE Select
ENST00000636159.2	Ensembl	ENSP00000490662.2	56	MANE Select
NM_001394547.1	RefSeq	NP_001381476.1	56	Standard
ENST00000472902.1	Ensembl	ENSP00000453812.1	7	Standard

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)
Focal Adhesion

Biological Process

cytoskeletal anchoring at plasma membrane
cell-cell junction assembly
cell adhesion

Molecular Function

actin binding
structural molecule activity
structural constituent of cytoskeleton
protein binding
actin filament binding

Cellular Component

ruffle
cytoplasm
plasma membrane
focal adhesion
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000561311
Coding exons: 56
Length: 454106
Individuals with no LoFs: 125692
Homozygous LoFs: 0
Heterozygous LoFs: 56
Defined: 125748
p: 0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.41	1341	1.49e+3	0.897	0.0000907	16479
Missense (PolyPhen)		250	352.57	0.70908		3916
Synonymous	-2.28	700	627	1.12	0.0000444	5141
Loss of Function	8.41	26	129	0.201	0.00000651	1501

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000095	0.000092	rare
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.00026	0.00026	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: As a major component of focal adhesion plaques that links integrin to the actin cytoskeleton, may play an important role in cell adhesion. Recruits PIP5K1C to focal adhesion plaques and strongly activates its kinase activity (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.447

Intolerance Scores

LoFtool: 0.525
RVIS EVS: -3.47
RVIS percentile EVS: 0.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.701

Gene Damage Prediction

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