TLN1

Chr 9

talin 1

Also known as: ILWEQ, TLN, talin-1

NCBI Gene: 7094ENSG00000137076UniProt: Q9Y490

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]

428
ClinVar variants
46
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TLN1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 252 VUS of 428 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.13LOEUF
pLI 1.000
Z-score 9.84
OE 0.08 (0.05–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.67Z-score
OE missense 0.66 (0.62–0.69)
970 obs / 1475.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.05–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.62–0.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 10 / 132.1Missense obs/exp: 970 / 1475.0Syn Z: 1.47

ClinVar Variant Classifications

428 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic9
VUS252
Likely Benign18
Benign8
37
Pathogenic
9
Likely Pathogenic
252
VUS
18
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
1
0
8
0
9
VUS
1
242
9
0
252
Likely Benign
0
4
2
12
18
Benign
0
0
1
7
8
Total22465719324

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TLN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TALIN 1; TLN1
MIM #186745 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
miR-3154: Novel Pathogenic and Therapeutic Target in Abdominal Aortic Aneurysm.
Hou Q et al.·Circ Res
2025
Variants of Focal Adhesion Scaffold Genes Cause Thoracic Aortic Aneurysm.
Li Y et al.·Circ Res
2021
Characterization of immune features and discovery of potential biomarkers for ankylosing spondylitis using deep plasma proteomics.
Xu X et al.·J Adv Res
2026
TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity.
Gallego-Paez LM et al.·J Cell Biol
2023
Talin1 dysfunction is genetically linked to systemic capillary leak syndrome.
Elefant N et al.·JCI Insight
2024Case report
Genome-wide screening and validation of exosome-derived TLN1 as a regulator of epithelial-mesenchymal transition in lung cancer.
Ruan X et al.·Sci Rep
2025
The genetics of spontaneous coronary artery dissection: a scoping review.
Memar Montazerin S et al.·J Cardiovasc Med (Hagerstown)
2024Review
Identification of anoikis-related genes in heart failure: bioinformatics and experimental validation.
Zhang L et al.·Hereditas
2025
Non-allergic eye rubbing is a major behavioral risk factor for keratoconus.
Jaskiewicz K et al.·PLoS One
2023
Rare Missense Variants in TLN1 Are Associated With Familial and Sporadic Spontaneous Coronary Artery Dissection.
Turley TN et al.·Circ Genom Precis Med
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools