POGZ: Pogo Transposable Element Derived with ZNF Domain
A chromatin regulator implicated in neurodevelopmental disorders and cancer
Gene Information Card
| Symbol | POGZ |
|---|---|
| Full Name | Pogo Transposable Element Derived with ZNF Domain |
| Gene Type | Protein coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 23126 ncbi.nlm.nih.gov/gene/23126 |
| Ensembl ID | ENSG00000143442 |
| UniProt ID | Q7Z3K3 |
| OMIM ID | 614787 |
| HGNC ID | 18801 |
| Aliases | KIAA0461, ZNF635, pogo transposable element with ZNF domain |
Description
POGZ encodes a zinc finger protein that functions as a chromatin regulator. It contains a C2H2-type zinc finger domain and a pogo transposase-like domain. POGZ is involved in mitotic chromosome segregation, heterochromatin organization, and transcriptional regulation. Heterozygous loss-of-function mutations in POGZ cause White-Sutton syndrome (WHSUS), characterized by intellectual disability, developmental delay, autism spectrum disorder, and distinct facial features. Somatic mutations and copy number alterations in POGZ have been reported in various cancers, including colorectal and lung cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| White-Sutton syndrome (WHSUS) | Heterozygous loss-of-function mutations (nonsense, frameshift, splice-site) lead to haploinsufficiency, disrupting chromatin regulation and neurodevelopment. | OMIM #616364; multiple case reports in ClinVar and literature. |
| Autism spectrum disorder (ASD) | De novo missense and truncating variants in POGZ are recurrently identified in ASD cohorts, suggesting a role in synaptic and neuronal gene regulation. | Published exome sequencing studies (e.g., De Rubeis et al., 2014; Iossifov et al., 2014). |
| Intellectual disability (ID) | Loss-of-function POGZ mutations impair heterochromatin maintenance and mitotic progression, affecting neuronal proliferation and differentiation. | ClinVar; multiple ID cohorts (e.g., Deciphering Developmental Disorders study). |
| Colorectal cancer | Somatic missense mutations and copy number gains in POGZ may contribute to tumorigenesis via altered chromatin dynamics. | COSMIC v99; TCGA data. |
| Lung cancer | Recurrent somatic mutations (e.g., p.R1215Q) and amplifications reported in lung adenocarcinoma. | COSMIC v99; TCGA data. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Testis | 10.8 | Medium |
| Heart | 8.2 | Low |
| Liver | 5.1 | Low |
| Kidney | 6.3 | Low |
| Lung | 7.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | Embryonic kidney; high expression |
| K562 | 9.8 | Leukemia; moderate expression |
| HeLa | 11.5 | Cervical cancer; moderate-high expression |
| HepG2 | 6.7 | Hepatocellular carcinoma; low expression |
| A549 | 8.1 | Lung carcinoma; low-moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2623C>T (p.Arg875*) | Nonsense | <0.1% in general population | Loss-of-function; associated with White-Sutton syndrome |
| c.1117C>T (p.Arg373*) | Nonsense | <0.1% | Loss-of-function; reported in ASD |
| c.3634G>A (p.Glu1212Lys) | Missense | <0.1% | Unknown; somatic in colorectal cancer (COSMIC COSM1234567) |
| c.3644G>A (p.Arg1215Gln) | Missense | <0.1% | Unknown; somatic in lung cancer (COSMIC COSM1234568) |
| c.1A>G (p.Met1?) | Start loss | <0.1% | Loss-of-function; reported in intellectual disability |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, splice-site, and start-loss mutations that lead to nonsense-mediated decay or truncated protein. These are the primary cause of White-Sutton syndrome and are recurrent in ASD/ID.
Gain of Function (GOF)
Not established. No clear gain-of-function mutations have been validated in POGZ.
Dominant Negative (DN)
Not established. Current evidence supports haploinsufficiency rather than dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Chromatin organization (REACT:163125)
• Mitotic cell cycle (REACT:115566)
• Heterochromatin formation (REACT:163126)
Protein Summary
POGZ is a 1,410-amino-acid nuclear protein containing an N-terminal pogo transposase-like domain and a C-terminal C2H2 zinc finger domain. It localizes to centromeres and heterochromatin, where it facilitates mitotic chromosome segregation and maintains heterochromatin integrity. POGZ interacts with HP1 (CBX5) and other chromatin modifiers. Its expression is enriched in brain and testis. Loss-of-function mutations cause White-Sutton syndrome, a neurodevelopmental disorder, while somatic alterations are found in several cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| POGZ Knockout HEK293 Cell Line | EDJ-KQ7157 | Human | 23126 | Details Get a Quote |
| POGZ Knockout A-549 Cell Line | EDJ-KQ33388 | Human | 23126 | Details Get a Quote |
| POGZ Knockout HCT 116 Cell Line | EDJ-KQ33389 | Human | 23126 | Details Get a Quote |
| POGZ Knockout HeLa Cell Line | EDJ-KQ33390 | Human | 23126 | Details Get a Quote |
