POGZ

Chr 1AD

pogo transposable element derived with ZNF domain

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

NCBI Gene: 23126 ENSG00000143442 UniProt: Q7Z3K3 OMIM: 614787

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.121 OMIM phenotype

Clinical Summary— POGZ

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Gene-Disease Validity (ClinGen)

intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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ClinVar Variants

206 unique Pathogenic / Likely Pathogenic· 368 VUS of 857 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — POGZ

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.05 (0.02–0.12)

0≤0.351.4

Missense OE?0.65 (0.60–0.70)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

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

This gene — mechanism propensity

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 · 92% of P/LP variants are LoF · LOEUF 0.12 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFDe novo POGZ mutations are associated with neurodevelopmental disorders and microcephaly1

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

References

1.PMID 27148570 ↗

ClinVar Variant Classifications

857 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic116

Likely Pathogenic90

VUS368

Likely Benign175

Benign58

Conflicting28

116

Pathogenic

Likely Pathogenic

368

VUS

175

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	110	5	1	0	116
Likely Pathogenic	79	9	2	0	90
VUS	13	333	17	5	368
Likely Benign	0	62	32	81	175
Benign	0	2	50	6	58
Conflicting	—				28
Total	202	411	102	92	835

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap POGZ — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →