PAX8 Gene: Paired Box 8 – Transcription Factor in Thyroid and Kidney Development
Comprehensive genomic, functional, and clinical overview of PAX8, a master regulator of organogenesis and oncogenesis.
Gene Information Card
| Symbol | PAX8 |
|---|---|
| Full Name | Paired box 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q14.1 |
| NCBI Gene ID | 7849 ncbi.nlm.nih.gov/gene/7849 |
| Ensembl ID | ENSG00000125618 |
| UniProt ID | Q06710 |
| OMIM ID | 167415 |
| HGNC ID | 8622 |
| Aliases | PAX-8, paired domain gene 8 |
Description
PAX8 (paired box 8) is a transcription factor belonging to the paired box (PAX) family. It plays a critical role in the development of the thyroid gland, kidney, and Müllerian duct system. PAX8 regulates the expression of thyroid-specific genes such as thyroglobulin (TG), thyroid peroxidase (TPO), and the sodium/iodide symporter (SLC5A5). In the kidney, PAX8 is essential for nephron progenitor cell maintenance. PAX8 is also a lineage marker for ovarian, renal, and thyroid carcinomas. Germline mutations cause congenital hypothyroidism with thyroid dysgenesis, while somatic alterations are implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital hypothyroidism due to thyroid dysgenesis | Loss-of-function mutations impair PAX8 binding to thyroid gene promoters, leading to absent or ectopic thyroid tissue. | ClinVar, OMIM #218700 |
| Thyroid dysgenesis, non-syndromic | Heterozygous PAX8 mutations disrupt thyroid follicular cell differentiation. | OMIM #218700, NCBI GeneReviews |
| Renal hypodysplasia | PAX8 deficiency in nephron progenitors causes reduced nephron number and kidney malformations. | OMIM #167415, PubMed 19125192 |
| Ovarian carcinoma (high-grade serous) | PAX8 overexpression is a lineage-survival oncogene; promotes proliferation and invasion. | COSMIC, PubMed 25722326 |
| Thyroid carcinoma (papillary and follicular) | PAX8-PPARγ fusion (t(2;3)(q13;p25)) drives follicular thyroid carcinoma. | COSMIC, PubMed 10802655 |
| Renal cell carcinoma (clear cell) | PAX8 is a diagnostic immunohistochemical marker; role in tumorigenesis under study. | ClinVar, PubMed 24052663 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Thyroid | 89.2 | High |
| Kidney | 42.5 | Medium |
| Fallopian tube | 38.1 | Medium |
| Ovary | 25.3 | Medium |
| Endometrium | 18.7 | Low |
| Lung | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 0.2 | Not detected |
| A549 (lung carcinoma) | 0.1 | Not detected |
| HEK 293 (embryonic kidney) | 15.3 | Low (endogenous) – note: often used as PAX8-negative control |
| OVCAR-3 (ovarian carcinoma) | 45.6 | Medium – PAX8 positive |
| K1 (papillary thyroid carcinoma) | 92.1 | High – PAX8 positive |
| MCF7 (breast carcinoma) | 0.3 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.71C>T (p.Pro24Leu) | Missense | Germline (rare) | Reduced DNA binding; associated with thyroid dysgenesis |
| c.100G>A (p.Gly34Arg) | Missense | Germline (rare) | Impaired paired domain function; congenital hypothyroidism |
| c.289C>T (p.Arg97*) | Nonsense | Germline (rare) | Premature truncation; loss of function |
| PAX8-PPARγ fusion | Gene fusion | Somatic (5-10% of follicular thyroid carcinoma) | Oncogenic; constitutive PPARγ activation |
| c.404G>A (p.Arg135Gln) | Missense | Somatic (rare in cancer) | Altered transactivation; reported in ovarian cancer |
Mutation functional classification
Loss of Function (LOF)
Germline missense, nonsense, and frameshift mutations in the paired domain or transactivation domain reduce or abolish DNA binding and transcriptional activation of thyroid-specific genes, leading to thyroid dysgenesis and congenital hypothyroidism.
Gain of Function (GOF)
PAX8-PPARγ fusion in follicular thyroid carcinoma results in a chimeric protein with constitutive PPARγ activity and altered PAX8 target gene regulation, promoting cell proliferation and tumorigenesis.
Dominant Negative (DN)
Some PAX8 missense mutants (e.g., p.Pro24Leu) retain partial dimerization capacity but fail to bind DNA, interfering with wild-type PAX8 function in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Thyroid hormone synthesis (Reactome R-HSA-209968)
• Transcriptional regulation by PAX8 (Reactome R-HSA-9619483)
• Development of the urogenital system (KEGG hsa05200)
• PPAR signaling pathway (KEGG hsa03320) – via PAX8-PPARγ fusion
Protein Summary
PAX8 is a 451-amino acid transcription factor containing an N-terminal paired domain (DNA-binding), a partial homeodomain, and a C-terminal transactivation domain. It forms homodimers and heterodimers with other PAX family members. PAX8 binds to specific DNA sequences in the promoters of thyroid-specific genes (TG, TPO, SLC5A5) and is essential for thyroid follicular cell differentiation and survival. In the kidney, PAX8 maintains nephron progenitor cells. The protein is also expressed in the Müllerian duct and its derivatives (fallopian tube, endometrium, ovary). Post-translational modifications include phosphorylation and sumoylation, which modulate its transcriptional activity. PAX8 is a reliable immunohistochemical marker for tumors of thyroid, renal, and Müllerian origin.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PAX8 Knockout HEK293 Cell Line | EDJ-KQ5430 | Human | 7849 | Details Get a Quote |
| PAX8 Knockout HCT 116 Cell Line | EDJ-KQ29908 | Human | 7849 | Details Get a Quote |
| PAX8 Knockout HeLa Cell Line | EDJ-KQ54800 | Human | 7849 | Details Get a Quote |
| PAX8 Knockout A-549 Cell Line | EDJ-KQ63292 | Human | 7849 | Details Get a Quote |
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