TAGLN3

Chr 3

transgelin 3

Also known as: NP22, NP24, NP25

NCBI Gene: 29114 ENSG00000144834 UniProt: Q9UI15 OMIM: 607953

The protein binds actin filaments and is involved in actin filament organization, with predicted roles in transcriptional regulation and synaptic function. Mutations in this gene have not been definitively associated with human disease to date. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.72), suggesting potential intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq

Predicted to enable actin filament binding activity. Predicted to be involved in actin filament organization. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be active in actin cytoskeleton and synapse. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.71

Clinical Summary— TAGLN3

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.71LOEUF

pLI 0.185

Z-score 2.21

OE 0.28 (0.13–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.57Z-score

OE missense 0.60 (0.49–0.73)

71 obs / 119.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.13–0.71)

0≤0.351.4

Missense OE?0.60 (0.49–0.73)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 3 / 10.8Missense obs/exp: 71 / 119.2Syn Z: 0.25

This gene — mechanism propensity

0.6551th %ile

GOF

0.78top 25%

LOF

0.2289th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.