TLN2

Chr 15

talin 2

Also known as: ILWEQ

NCBI Gene: 83660 ENSG00000171914 UniProt: Q9Y4G6

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]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.28

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.992

Z-score 8.41

OE 0.20 (0.15–0.28)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.41Z-score

OE missense 0.90 (0.86–0.94)

1341 obs / 1494.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.15–0.28)

0≤0.351.4

Missense OE?0.90 (0.86–0.94)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 26 / 129.2Missense obs/exp: 1341 / 1494.5Syn Z: -2.28

Background carrier burden — how many people carry a rare variant somewhere in TLN2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 20

3,334 rare PASS variants

Rare truncating (LoF)

1 in 1,000

265 rare PASS variants

Rare synonymous (reference)

1 in 22

1,533 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TLN2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 25	1 in 970
South Asian	~43k	1 in 19	1 in 1,600
Remaining (unassigned)	~30k	1 in 18	1 in 970
European (Finnish)	~27k	1 in 57	1 in 1,100
Admixed American	~22k	1 in 19	1 in 2,800
African / African American	~21k	1 in 18	1 in 1,400
East Asian	~20k	1 in 21	1 in 1,800
Ashkenazi Jewish	~13k	1 in 54	1 in 900
Middle Eastern	~2,884	1 in 19	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 56 coding exons well covered in gnomAD exomes and genomes.? see exons ↓