PYGO2

Chr 1

pygopus family PHD finger 2

Also known as: 1190004M21Rik

NCBI Gene: 90780 ENSG00000163348 UniProt: Q9BRQ0 OMIM: 606903

Predicted to enable several functions, including histone acetyltransferase regulator activity; histone binding activity; and zinc ion binding activity. Predicted to be involved in kidney development and spermatid nucleus differentiation. Predicted to act upstream of or within several processes, including canonical Wnt signaling pathway; lens development in camera-type eye; and regulation of mammary gland epithelial cell proliferation. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.28

Clinical Summary— PYGO2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

68 VUS of 75 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.967

Z-score 3.01

OE 0.00 (0.00–0.28)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.10Z-score

OE missense 0.78 (0.69–0.89)

161 obs / 205.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.28)

0≤0.351.4

Missense OE?0.78 (0.69–0.89)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 0 / 10.6Missense obs/exp: 161 / 205.4Syn Z: -0.86

This gene — mechanism propensity

0.2499th %ile

GOF

0.2198th %ile

LOF

0.84top 5%

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

LOFprediction above median · LOEUF 0.28

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

75 submitted variants in ClinVar

ClinVar

Classification Summary

VUS68

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	68	68
Likely Benign	0	0
Benign	0	0
Total	68	68

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap PYGO2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →