WWTR1

Chr 3

WW domain containing transcription regulator 1

Also known as: TAZ

NCBI Gene: 25937 ENSG00000018408 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…

LOFmechanismLOEUF 0.36

Clinical Summary— WWTR1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

44 VUS of 72 total submissions

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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

This gene — mechanism propensity

0.4487th %ile

GOF

0.3690th %ile

LOF

0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.36

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

72 submitted variants in ClinVar

ClinVar

Classification Summary

VUS44

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	44	0	44
Likely Benign	0	5	5
Benign	0	0	0
Total	44	5	49

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap WWTR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →