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…

Primary Disease Associations & Inheritance

White-Sutton syndromeMIM #616364

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome · AD · ClinGen 2020

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.12

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

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

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 67

1,449 rare PASS variants

Rare truncating (LoF)

1 in 7,800

42 rare PASS variants

Rare synonymous (reference)

1 in 83

746 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for POGZ. 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 76	1 in 9,400
South Asian	~43k	1 in 58	≈ 1 in 10,000
Remaining (unassigned)	~30k	1 in 61	1 in 6,000
European (Finnish)	~27k	1 in 160	1 in 3,800
Admixed American	~22k	1 in 55	≈ 1 in 6,600
African / African American	~21k	1 in 50	≈ 1 in 5,900
East Asian	~20k	1 in 66	1 in 1,900
Ashkenazi Jewish	~13k	1 in 180	none seen
Middle Eastern	~2,884	1 in 99	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.