TAGLN2

Chr 1

transgelin 2

Also known as: HA1756

NCBI Gene: 8407 ENSG00000158710 UniProt: P37802 OMIM: 604634

The protein encoded by this gene is similar to the protein transgelin, which is one of the earliest markers of differentiated smooth muscle. The specific function of this protein has not yet been determined, although it is thought to be a tumor suppressor. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.93

Clinical Summary— TAGLN2

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

26 VUS of 34 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.93LOEUF

pLI 0.009

Z-score 1.73

OE 0.44 (0.23–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.71Z-score

OE missense 0.82 (0.70–0.97)

100 obs / 122.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.23–0.93)

0≤0.351.4

Missense OE?0.82 (0.70–0.97)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 5 / 11.3Missense obs/exp: 100 / 122.1Syn Z: 0.95

This gene — mechanism propensity

0.6260th %ile

GOF

0.7126th %ile

LOF

0.2386th %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.

ClinVar Variant Classifications

34 submitted variants in ClinVar

ClinVar

Classification Summary

VUS26

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	26	26
Likely Benign	0	0
Benign	0	0
Total	26	26

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap TAGLN2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →