WWTR1

Chr 3

WW domain containing transcription regulator 1

Also known as: TAZ

NCBI Gene: 25937 ENSG00000018408 UniProt: Q9GZV5 OMIM: 607392

Enables transcription coactivator activity. Involved in several processes, including intracellular signal transduction; negative regulation of canonical Wnt signaling pathway; and positive regulation of cell differentiation. Located in cytosol and nuclear body. Is active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM 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)

—

P/LP submissions

—

P/LP missense

0.36

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.36LOEUF

pLI 0.939

Z-score 3.46

OE 0.11 (0.04–0.36)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.12Z-score

OE missense 0.79 (0.70–0.90)

180 obs / 227.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.36)

0≤0.351.4

Missense OE?0.79 (0.70–0.90)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 2 / 17.7Missense obs/exp: 180 / 227.4Syn Z: -0.01

Background carrier burden — how many people carry a rare variant somewhere in WWTR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

474 rare PASS variants

Rare truncating (LoF)

1 in 12,000

34 rare PASS variants

Rare synonymous (reference)

1 in 260

243 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for WWTR1. 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 160	1 in 18,000
South Asian	~43k	1 in 130	1 in 6,900
Remaining (unassigned)	~30k	1 in 180	none seen
European (Finnish)	~27k	1 in 200	1 in 3,700
Admixed American	~22k	1 in 150	1 in 3,600
African / African American	~21k	1 in 130	1 in 2,800
East Asian	~20k	1 in 98	none seen
Ashkenazi Jewish	~13k	1 in 540	none seen
Middle Eastern	~2,884	1 in 140	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 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓