POGZ

Chr 1AD

pogo transposable element derived with ZNF domain

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

NCBI Gene: 23126ENSG00000143442UniProt: Q7Z3K3

The protein encoded by this gene appears to be a zinc finger protein containing a transposase domain at the C-terminus. This protein was found to interact with the transcription factor SP1 in a yeast two-hybrid system. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Aug 2010]

Primary Disease Associations & Inheritance

White-Sutton syndromeMIM #616364
AD
380
ClinVar variants
79
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— POGZ
🧬
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.
📋
ClinVar Variants
79 Pathogenic / Likely Pathogenic· 216 VUS of 380 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.12LOEUF
pLI 1.000
Z-score 7.15
OE 0.05 (0.02–0.12)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.51Z-score
OE missense 0.65 (0.60–0.70)
522 obs / 801.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.60–0.70)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 3 / 65.4Missense obs/exp: 522 / 801.3Syn Z: 0.40

ClinVar Variant Classifications

380 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic35
VUS216
Likely Benign70
Benign2
Conflicting13
44
Pathogenic
35
Likely Pathogenic
216
VUS
70
Likely Benign
2
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
30
4
10
0
44
Likely Pathogenic
18
6
11
0
35
VUS
3
193
16
4
216
Likely Benign
0
32
7
31
70
Benign
0
1
0
1
2
Conflicting
—13
Total512364436380

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

View 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.

Gene2Phenotype Curations

POGZ-related intellectual disability (White-Sutton syndrome)

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

White-Sutton syndrome

MIM #616364

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — POGZ
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
De novo genic mutations among a Chinese autism spectrum disorder cohort.
Wang T et al.·Nat Commun
2016Cohort
New Candidates for Autism/Intellectual Disability Identified by Whole-Exome Sequencing.
Bruno LP et al.·Int J Mol Sci
2021Clinical trial
The Neurodevelopmental Protein POGZ Suppresses Metastasis in Triple-Negative Breast Cancer by Attenuating TGFβ Signaling.
Heath J et al.·Cancer Res
2024
Genotype-Phenotype Comparison in POGZ-Related Neurodevelopmental Disorders by Using Clinical Scoring.
Nagy D et al.·Genes (Basel)
2022
POGZ promotes homology-directed DNA repair in an HP1-dependent manner.
Heath J et al.·EMBO Rep
2022
POGZ-related epilepsy: Case report and review of the literature.
Ferretti A et al.·Am J Med Genet A
2019Review
POGZ de novo missense variants in neuropsychiatric disorders.
Zhao W et al.·Mol Genet Genomic Med
2019
Genetic etiology of ventriculomegaly in 73 fetuses identified by High-Throughput sequencing.
Chenyue Z et al.·Sci Rep
2025
Clinical Application of a Customized Gene Panel for Identifying Autism Spectrum Disorder-Associated Variants.
Greco V et al.·Medicina (Kaunas)
2025
Exploring the molecular pathways linking sleep phenotypes and POGZ-associated neurodevelopmental disorder.
Marquezini BP et al.·J Med Genet
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Transcriptome analysis of patients with loss-of-function POGZ variants in four unrelated Chinese families.
Wu Y et al.·Gene
2026Cohort
The Zinc-Finger Protein POGZ Associates with Polycomb Repressive Complex 1 to Regulate Bone Morphogenetic Protein Signaling During Neuronal Differentiation.
Chavez J et al.·Stem Cell Rev Rep
2026🔓 Open Access
TGM2 Regulates Radiosensitivity via POGZ-Mediated Repair of DNA Double-Strand Breaks in Cervical Cancer.
Chi Y et al.·Cancer Sci
2026🔓 Open Access
Malignant catatonia in an adolescent with pogo transposable element derived with zinc finger domain (POGZ) gene mutation: case report.
Leibovitch L et al.·BJPsych Open
2025🔓 Open AccessCase report
POGZ targeted by LINC01355/miR-27b-3p retards thyroid cancer progression via interplaying with MAD2L2.
Lu J et al.·3 Biotech
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
People With White Sutton Syndrome

Descriptive Study of Psychiatric Symptoms in White-Sutton Syndrome

RECRUITING
NCT07380594Centre Hospitalier Universitaire DijonStarted 2026-01
InterviewsQuestionnaires

External Resources

Links to major genomics databases and tools