TAGLN

Chr 11

transgelin

Also known as: SM22, SM22-alpha, SMCC, TAGLN1, TGLN, WS3-10

NCBI Gene: 6876 ENSG00000149591 UniProt: Q01995 OMIM: 600818

This gene encodes a shape change and transformation sensitive actin-binding protein which belongs to the calponin family. It is ubiquitously expressed in vascular and visceral smooth muscle, and is an early marker of smooth muscle differentiation. The encoded protein is thought to be involved in calcium-independent smooth muscle contraction. It acts as a tumor suppressor, and the loss of its expression is an early event in cell transformation and the development of some tumors, coinciding with cellular plasticity. The encoded protein has a domain architecture consisting of an N-terminal calponin homology (CH) domain and a C-terminal calponin-like (CLIK) domain. Mice with a knockout of the orthologous gene are viable and fertile but their vascular smooth muscle cells exhibit alterations in the distribution of the actin filament and changes in cytoskeletal organization. [provided by RefSeq, Aug 2017]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.91

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.085

Z-score 1.76

OE 0.35 (0.16–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.37Z-score

OE missense 0.91 (0.78–1.06)

112 obs / 123.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.16–0.91)

0≤0.351.4

Missense OE?0.91 (0.78–1.06)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 3 / 8.6Missense obs/exp: 112 / 123.5Syn Z: 0.44

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

266 rare PASS variants

Rare truncating (LoF)

1 in 3,600

47 rare PASS variants

Rare synonymous (reference)

1 in 520

98 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TAGLN. 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 210	1 in 3,700
South Asian	~43k	1 in 150	1 in 4,300
Remaining (unassigned)	~30k	1 in 140	1 in 4,300
European (Finnish)	~27k	1 in 330	≈ 1 in 8,900
Admixed American	~22k	1 in 200	≈ 1 in 4,500
African / African American	~21k	1 in 340	≈ 1 in 10,000
East Asian	~20k	1 in 220	1 in 1,600
Ashkenazi Jewish	~13k	1 in 1,600	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 260	none seen

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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓