PAX8 paired box 8 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: PAX8provided by HGNC
Official Full Name: paired box 8provided by HGNC
Primary source: HGNC:8622
See related: Ensembl:ENSG00000125618; HPRD:01335; MIM:167415; Vega:OTTHUMG00000128529
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: This gene encodes a member of the paired box (PAX) family of transcription factors. Members of this gene family typically encode proteins that contain a paired box domain, an octapeptide, and a paired-type homeodomain. This nuclear protein is involved in thyroid follicular cell development and expression of thyroid-specific genes. Mutations in this gene have been associated with thyroid dysgenesis, thyroid follicular carcinomas and atypical follicular thyroid adenomas. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2010]

Genomic context

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Location :: 2q13

Sequence :: Chromosome: 2; NC_000002.11 (113973574..114036498, complement)

See PAX8 in Epigenomics, MapViewer

Chromosome 2 - NC_000002.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

PAX8 was expressed in 61% of cases. There was no association between PAX8 and tumor stage, optimal debulking and disease recurrence for ovarian serous carcinoma.
Title: Pair Box 8 (PAX8) protein expression in high grade, late stage (stages III and IV) ovarian serous carcinoma.
investigation of expression of PAX2 and PAX8 in renal biopsy samples as diagnostic markers in the differential diagnosis of various types of primary and secondary renal cell carcinomas
Title: PAX2 and PAX8 expression in primary and metastatic renal tumors: a comprehensive comparison.
clinical and molecular findings of 4 novel PAX8 mutations, including 3 missense mutations outside the previously recognized mutational hotspot and the first experimentally confirmed mutation with protein instability (D46fs); data imply PAX8 haploinsufficiency is enough to cause congenital hypothyroidism
Title: Functional characterization of four novel PAX8 mutations causing congenital hypothyroidism: new evidence for haploinsufficiency as a disease mechanism.
PAX-2, PAX-8, and hKIM-1 should be used cautiously in distinguishing renal cell carcinoma from nonseminomatous germ cell neoplasia and also adds to the growing list of nonrenal tumors that express these 3 markers.
Title: Evaluation of putative renal cell carcinoma markers PAX-2, PAX-8, and hKIM-1 in germ cell tumors: a tissue microarray study of 100 cases.
Absence of mutations in PAX8, NKX2.5, and TSH receptor genes demonstrate the rare genetic etiology in sporadic cases of thyroid dysgenesis.
Title: Absence of mutations in PAX8, NKX2.5, and TSH receptor genes in patients with thyroid dysgenesis.
A positive association of Pax8(+) expression was found with high tumour grade (P=0.002), LVI+(P=0.0186), and type II tumour subtype (P<0.0001) in univariate analysis.
Title: Pair-Box (PAX8) protein-positive expression is associated with poor disease outcome in women with endometrial cancer.
PAX8 and PAX2 are diagnostically useful adjuncts in confirming the diagnosis of renal cell carcinoma in cytology specimens.
Title: Utility of PAX8 and PAX2 immunohistochemistry in the identification of renal cell carcinoma in diagnostic cytology.
Both Islet 1 and PAX8 are reliable immunohistochemical markers for identifying metastatic neuroendocrine tumors of pancreatic origin.
Title: Value of Islet 1 and PAX8 in identifying metastatic neuroendocrine tumors of pancreatic origin.
The relationship between mutations of PAX8 and congenital hypothyroidism in the Mexican population is studied.
Title: Molecular analysis of the PAX8 gene in a sample of Mexican patients with primary congenital hypothyroidism: identification of the recurrent p.Arg31His mutation.
The Pax-8 gene may play a crucial role in heart development and regulating cardiocyte apoptosis and knockout of Pax-8 may exert a similar effect on myocardial morphology and apoptosis as those seen in ALK3 knockouts.
Title: The defects in development and apoptosis of cardiomyocytes in mice lacking the transcriptional factor Pax-8.

Submit: New GeneRIF Correction See all (76)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
Q06710	Q09472	EP300	HPRD	PubMed
Q06710	Q02363	ID2	HPRD	PubMed
Q06710	P43699	NKX2-1	HPRD	PubMed
Q06710	P84022	SMAD3	HPRD	PubMed
Q06710	Q969T9	WBP2	HPRD	PubMed
BioGRID:113604	BioGRID:107569	CHUK	BioGRID	PubMed	Two-hybrid
BioGRID:113604	BioGRID:110429	CXCL9	BioGRID	PubMed	Two-hybrid
BioGRID:113604	BioGRID:112936	NKX2-1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:113604	BioGRID:111332	PKM	BioGRID	PubMed	Two-hybrid
BioGRID:113604	BioGRID:111446	POU2AF1	BioGRID	PubMed	Two-hybrid
BioGRID:113604	BioGRID:121579	SERINC1	BioGRID	PubMed	Affinity Capture-Western

Pathways from BioSystems

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Id Signaling Pathway, organism-specific biosystem (from WikiPathways)
Id Signaling Pathway, organism-specific biosystemInhibitor of DNA binding (ID) proteins are members of the helix-loop-helix (HLH) family of proteins which lack a DNA binding domain themselves but bind to other family members inhibiting their DNA bi...
Pathways in cancer, organism-specific biosystem (from KEGG)
Pathways in cancer, organism-specific biosystem
Pathways in cancer
TSH signaling pathway, organism-specific biosystem (from WikiPathways)
TSH signaling pathway, organism-specific biosystemHuman thyroid stimulating hormone (TSH) is a glycoprotein secreted by the anterior part of the pituitary gland (1). TSH plays an important physiological role in the regulation of the hypothalamic-pit...
Thyroid cancer, organism-specific biosystem (from KEGG)
Thyroid cancer, organism-specific biosystemThyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer- related deaths each year. More than 95% of thyroid carcinomas are derived from follicular cel...
Thyroid cancer, conserved biosystem (from KEGG)
Thyroid cancer, conserved biosystemThyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer- related deaths each year. More than 95% of thyroid carcinomas are derived from follicular cel...
Transcriptional misregulation in cancer, organism-specific biosystem (from KEGG)
Transcriptional misregulation in cancer, organism-specific biosystem
Transcriptional misregulation in cancer
Transcriptional misregulation in cancer, conserved biosystem (from KEGG)
Transcriptional misregulation in cancer, conserved biosystem
Transcriptional misregulation in cancer

General gene information

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Markers

RH45733 (e-PCR)
- UniSTS:79616

PAX8__1200 (e-PCR)
- UniSTS:277556

PAX8__v328 (e-PCR)
- UniSTS:277556

WI-19770 (e-PCR)
- UniSTS:28488

RH94024 (e-PCR)
- UniSTS:89437

RH79182 (e-PCR)
- UniSTS:31336

D11Bir2 (e-PCR), detects polymorphism
- UniSTS:141710

RH80705 (e-PCR)
- UniSTS:85135

SHGC-52928 (e-PCR)
- UniSTS:64915

D2S1597E (e-PCR)
- UniSTS:150681

D2S1963 (e-PCR)
- UniSTS:67546

Genotypes

See PAX8 SNP Geneview Report
See PAX8 SNP Genotype Report
See PAX8 SNP Variation Viewer Report

Homology

Homologs of the PAX8 gene: The PAX8 gene is conserved in chimpanzee, Rhesus monkey, cow, mouse, rat, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding	IDA Inferred from Direct Assay more info	PubMed
DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
RNA polymerase II core promoter sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
sequence-specific DNA binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
thyroid-stimulating hormone receptor activity	TAS Traceable Author Statement more info	PubMed
transcription regulatory region DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
anatomical structure morphogenesis	TAS Traceable Author Statement more info	PubMed
branching involved in ureteric bud morphogenesis	IEP Inferred from Expression Pattern more info	PubMed
cellular response to gonadotropin stimulus	IDA Inferred from Direct Assay more info	PubMed
central nervous system development	IEP Inferred from Expression Pattern more info	PubMed
inner ear morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
kidney development	IEP Inferred from Expression Pattern more info	PubMed
mesenchymal to epithelial transition involved in metanephros morphogenesis	IEP Inferred from Expression Pattern more info	PubMed
mesonephric tubule development	IEA Inferred from Electronic Annotation more info
mesonephros development	ISS Inferred from Sequence or Structural Similarity more info
metanephric S-shaped body morphogenesis	IEP Inferred from Expression Pattern more info	PubMed
metanephric comma-shaped body morphogenesis	IEP Inferred from Expression Pattern more info	PubMed
metanephric distal convoluted tubule development	ISS Inferred from Sequence or Structural Similarity more info
metanephric epithelium development	IEP Inferred from Expression Pattern more info	PubMed
metanephric nephron tubule formation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of apoptotic process involved in metanephric collecting duct development	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of apoptotic process involved in metanephric nephron tubule development	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of mesenchymal cell apoptotic process involved in metanephros development	ISS Inferred from Sequence or Structural Similarity more info
otic vesicle development	IEP Inferred from Expression Pattern more info	PubMed
positive regulation of branching involved in ureteric bud morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of metanephric DCT cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of thyroid hormone generation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-dependent	ISS Inferred from Sequence or Structural Similarity more info
pronephric field specification	ISS Inferred from Sequence or Structural Similarity more info
pronephros development	ISS Inferred from Sequence or Structural Similarity more info
regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
regulation of metanephric nephron tubule epithelial cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
regulation of thyroid-stimulating hormone secretion	IMP Inferred from Mutant Phenotype more info	PubMed
thyroid gland development	IEP Inferred from Expression Pattern more info	PubMed
thyroid gland development	IMP Inferred from Mutant Phenotype more info	PubMed
transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
urogenital system development	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
NOT nucleolus	IDA Inferred from Direct Assay more info
nucleoplasm	ISS Inferred from Sequence or Structural Similarity more info
nucleus	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: paired box protein Pax-8

Names: paired box protein Pax-8; paired domain gene 8

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012384.1 RefSeqGene

Range

5001..67925

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003466.3 → NP_003457.1 paired box protein Pax-8 isoform PAX8A

Status: REVIEWED

Description

Transcript Variant: This variant (PAX8A) represents the longest transcript and encodes the longest isoform (PAX8A).

Source sequence(s)

AC016683, AU141429, BC001060, BM726535

Consensus CDS

CCDS46398.1

UniProtKB/Swiss-Prot

Q06710

Related

ENSP00000395498, OTTHUMP00000203723, ENST00000429538, OTTHUMT00000250353

Conserved Domains (3) summary

cd00131
Location:9 – 135
Blast Score: 590

PAX; Paired Box domain

smart00351
Location:9 – 133
Blast Score: 646

PAX; Paired Box domain

pfam12403
Location:334 – 421
Blast Score: 338

Pax2_C; Paired-box protein 2 C terminal
NM_013952.3 → NP_039246.1 paired box protein Pax-8 isoform PAX8C

Status: REVIEWED

Description

Transcript Variant: This variant (PAX8C) uses an alternate splice site in the 3' coding region, compared to variant PAX8A, that results in a frameshift and an early stop codon. It encodes isoform PAX8C which has a shorter and distinct C-terminus compared to isoform PAX8A.

Source sequence(s)

AC016683, AU141429, BC001060, BM726535, S77904

Consensus CDS

CCDS46399.1

UniProtKB/Swiss-Prot

Q06710

Related

ENSP00000314750, OTTHUMP00000203724, ENST00000348715, OTTHUMT00000250356

Conserved Domains (2) summary

cd00131
Location:9 – 135
Blast Score: 576

PAX; Paired Box domain

smart00351
Location:9 – 133
Blast Score: 631

PAX; Paired Box domain
NM_013953.3 → NP_039247.1 paired box protein Pax-8 isoform PAX8D

Status: REVIEWED

Description

Transcript Variant: This variant (PAX8D) lacks two alternate exons, compared to variant PAX8A, that results in a frameshift and an early stop codon. The encoded isoform (PAX8D) is shorter and has a distinct C-terminus compared to isoform PAX8A.

Source sequence(s)

AC016683, AU141429, BC001060, BM726535, S77905

Consensus CDS

CCDS42736.1

UniProtKB/Swiss-Prot

Q06710

Related

ENSP00000263335, OTTHUMP00000158659, ENST00000263335, OTTHUMT00000250354

Conserved Domains (2) summary

cd00131
Location:9 – 135
Blast Score: 574

PAX; Paired Box domain

smart00351
Location:9 – 133
Blast Score: 628

PAX; Paired Box domain
NM_013992.3 → NP_054698.1 paired box protein Pax-8 isoform PAX8E

Status: REVIEWED

Description

Transcript Variant: This variant (PAX8E) lacks three alternate exons, compared to variant PAX8A, that results in a frameshift and an early stop codon. The encoded isoform (PAX8E) is shorter and has a distinct C-terminus compared to isoform PAX8A.

Source sequence(s)

AC016683, AU141429, BC001060, BM726535, S77906

Consensus CDS

CCDS42735.1

UniProtKB/Swiss-Prot

Q06710

Related

ENSP00000380768, OTTHUMP00000158660, ENST00000397647, OTTHUMT00000250355

Conserved Domains (2) summary

cd00131
Location:9 – 135
Blast Score: 572

PAX; Paired Box domain

smart00351
Location:9 – 133
Blast Score: 623

PAX; Paired Box domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000002.11 Reference GRCh37.p10 Primary Assembly

Range

113973574..114036498, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000134.1 Alternate HuRef

Range

106427614..106522962, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018913.1 Alternate CHM1_1.0

Range

113487206..113549755, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_013951.3: Suppressed sequence

Description

NM_013951.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01074238.1 (16283..39905)	None
genomic	ABBA01074239.1	None
genomic	ABBA01074240.1	None
genomic	ABBA01074241.1	None
genomic	AC016683.7	AAX88880.1
genomic	AMYH01010967.1 (327026..389575)	None
genomic	CH471217.1	EAW73629.1
		EAW73630.1
		EAW73631.1
		EAW73632.1
		EAW73633.1
		EAW73634.1
		EAW73635.1
		EAW73636.1
		EAW73637.1
		EAW73638.1
		EAW73639.1
genomic	FJ695202.1	None
genomic	X99590.1	CAA67903.1
mRNA	AK023855.1	None
mRNA	AK225538.1	None
mRNA	AK292191.1	BAF84880.1
mRNA	AK307173.1	None
mRNA	AK309154.1	None
mRNA	AU141429.1	None
mRNA	BC001060.2	AAH01060.1
mRNA	BG398792.1	None
mRNA	BM726535.1	None
mRNA	CR936798.1	None
mRNA	L19606.1	AAA03539.1
mRNA	S77904.1	AAB34216.1
mRNA	S77905.1	AAB34217.2
mRNA	S77906.2	AAB34218.2
mRNA	X69699.1	None
other-genetic	DQ892280.2	ABM83206.1
other-genetic	DQ895480.2	ABM86406.1