POGZ

Chr 1AD

pogo transposable element derived with ZNF domain

Also known as: MRD37, WHSUS, ZNF280E, ZNF635, ZNF635m

The protein is a zinc finger transcription factor that interacts with SP1 and localizes to the nucleus. Loss-of-function mutations cause White-Sutton syndrome, an autosomal dominant neurodevelopmental disorder. The gene is highly intolerant to loss-of-function variants, supporting haploinsufficiency as the mechanism of pathogenicity.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.121 OMIM phenotype
Clinical SummaryPOGZ
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Gene-Disease Validity (ClinGen)
intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 7.15
OE 0.05 (0.020.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.51Z-score
OE missense 0.65 (0.600.70)
522 obs / 801.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.05 (0.020.12)
00.351.4
Missense OE0.65 (0.600.70)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 3 / 65.4Missense obs/exp: 522 / 801.3Syn Z: 0.40
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePOGZ-related intellectual disability (White-Sutton syndrome)LOFAD
DN
0.17100th %ile
GOF
0.1899th %ile
LOF
0.84top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.12

Literature Evidence

LOFDe novo POGZ mutations are associated with neurodevelopmental disorders and microcephalyPMID:27148570

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

POGZ · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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