PYGO1

Chr 15

pygopus family PHD finger 1

NCBI Gene: 26108 ENSG00000171016 UniProt: Q9Y3Y4

Enables histone H3K4me3 reader activity. Predicted to be involved in kidney development and spermatid nucleus differentiation. Predicted to act upstream of or within several processes, including hematopoietic progenitor cell differentiation; positive regulation of transcription by RNA polymerase II; and spermatid development. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

Research

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

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P/LP missense

0.23

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.23LOEUF

pLI 0.987

Z-score 3.35

OE 0.00 (0.00–0.23)

Highly constrained

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

Missense Constraint?

-0.11Z-score

OE missense 1.02 (0.92–1.14)

232 obs / 227.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.23)

0≤0.351.4

Missense OE?1.02 (0.92–1.14)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 0 / 13.1Missense obs/exp: 232 / 227.4Syn Z: -0.54

Background carrier burden — how many people carry a rare variant somewhere in PYGO1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

574 rare PASS variants

Rare truncating (LoF)

1 in 7,700

33 rare PASS variants

Rare synonymous (reference)

1 in 170

205 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PYGO1. 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 170	1 in 15,000
South Asian	~43k	1 in 110	≈ 1 in 13,000
Remaining (unassigned)	~30k	1 in 180	≈ 1 in 9,100
European (Finnish)	~27k	1 in 400	1 in 4,400
Admixed American	~22k	1 in 81	1 in 2,100
African / African American	~21k	1 in 100	1 in 2,600
East Asian	~20k	1 in 130	1 in 1,600
Ashkenazi Jewish	~13k	1 in 280	none seen
Middle Eastern	~2,884	1 in 130	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): 2 of 3 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 3.? see exons ↓