PAX8

paired box 8, the group of PRD class homeoboxes and pseudogenes|Paired boxes

Basic information

Region (hg38): 2:113215996-113278921

Links

ENSG00000125618 ∙ NCBI:7849 ∙ OMIM:167415 ∙ HGNC:8622 ∙ Uniprot:Q06710 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypothyroidism, congenital, nongoitrous, 2 (Definitive), mode of inheritance: AD
• hypothyroidism, congenital, nongoitrous, 2 (Strong), mode of inheritance: AD
• athyreosis (Supportive), mode of inheritance: AD
• thyroid hypoplasia (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypothyroidism, congenital, nongoitrous 2	AD	Endocrine	The untreated condition can result in severe neurological damage, and recognition can allow early medical treatment with thyroid hormone replacement can prevent such sequelae	Endocrine; Renal	9590296; 11502839; 11232006; 15356023; 15718293; 20718765; 20857061; 21450989; 21689132; 21976720; 22898500; 23647375
Individuals with genitourinary anomalies possibly associated with the variant have been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAX8 gene.

• Hypothyroidism, congenital, nongoitrous, 2 (108 variants)
• not provided (86 variants)
• Inborn genetic diseases (20 variants)
• not specified (11 variants)
• PAX8-related condition (1 variants)
• Congenital hypothyroidism (1 variants)
• PAX8 POLYMORPHISM (1 variants)
• Obesity;Immunodeficiency;Protruding tongue;Severe T-cell immunodeficiency;Hypothyroidism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAX8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	6	3	15
missense	1	3	33	12	1	50
nonsense	1	1	2			4
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	1		3
non coding			50	4	38	92
Total	2	4	93	22	42

Highest pathogenic variant AF is 0.0000131

Variants in PAX8

This is a list of pathogenic ClinVar variants found in the PAX8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-113216006-T-C		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 12, 2018)
2-113216016-G-A		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 13, 2018)
2-113216028-T-TTA		Congenital hypothyroidism	Uncertain significance (Jun 14, 2016)
2-113216055-G-A		Hypothyroidism, congenital, nongoitrous, 2	Benign (Jan 12, 2018)
2-113216058-G-A		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 12, 2018)
2-113216124-G-A		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 13, 2018)
2-113216165-G-A		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 13, 2018)
2-113216207-T-C		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 12, 2018)
2-113216213-C-T		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 13, 2018)
2-113216221-C-T		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 13, 2018)
2-113216224-T-C		Hypothyroidism, congenital, nongoitrous, 2	Benign (Jan 12, 2018)
2-113216257-C-T		Hypothyroidism, congenital, nongoitrous, 2	Conflicting classifications of pathogenicity (Jul 01, 2022)
2-113216302-G-A		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Mar 16, 2018)
2-113216340-C-T		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 12, 2018)
2-113216341-G-A		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 13, 2018)
2-113216387-T-C		Hypothyroidism, congenital, nongoitrous, 2	Benign (Jan 13, 2018)
2-113216489-C-G		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 12, 2018)
2-113216500-G-A		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 13, 2018)
2-113216556-A-G		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 12, 2018)
2-113216591-G-A		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 12, 2018)
2-113216619-G-C		Hypothyroidism, congenital, nongoitrous, 2	Benign (Jan 13, 2018)
2-113216726-G-C		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 12, 2018)
2-113216768-C-T		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 13, 2018)
2-113217043-C-T		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 13, 2018)
2-113217076-C-T		Hypothyroidism, congenital, nongoitrous, 2	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAX8	protein_coding	protein_coding	ENST00000429538	11	62954

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00131	124862	0	4	124866	0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.785	239	276	0.867	0.0000174	2877
Missense in Polyphen		70	112.37	0.62295		1117
Synonymous	-0.834	130	118	1.10	0.00000827	914
Loss of Function	4.32	1	23.7	0.0422	0.00000138	247

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.00	0.00
Finnish	0.0000468	0.0000464
European (Non-Finnish)	0.00000900	0.00000882
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells.
• Disease: DISEASE: Hypothyroidism, congenital, non-goitrous, 2 (CHNG2) [MIM:218700]: A disease characterized by thyroid dysgenesis, the most frequent cause of congenital hypothyroidism, accounting for 85% of case. The thyroid gland can be completely absent (athyreosis), ectopically located and/or severely hypoplastic. Ectopic thyroid gland is the most frequent malformation, with thyroid tissue being found most often at the base of the tongue. {ECO:0000269|PubMed:11232006, ECO:0000269|PubMed:11502839, ECO:0000269|PubMed:9590296}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thyroid hormone synthesis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Thyroid cancer - Homo sapiens (human);Human Thyroid Stimulating Hormone (TSH) signaling pathway;ID signaling pathway (Consensus)

Recessive Scores

• pRec: 0.570

Intolerance Scores

• loftool: 0.0270
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.43

Haploinsufficiency Scores

• pHI: 0.755
• hipred: Y
• hipred_score: 0.831
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.787

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pax8
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: pax8
• Affected structure: lateral crista
• Phenotype tag: abnormal
• Phenotype quality: physical object quality

Gene ontology

• Biological process: urogenital system development;branching involved in ureteric bud morphogenesis;kidney development;mesonephros development;ventricular septum development;mesenchymal to epithelial transition involved in metanephros morphogenesis;transcription, DNA-templated;sulfur compound metabolic process;central nervous system development;anatomical structure morphogenesis;negative regulation of cardiac muscle cell apoptotic process;thyroid gland development;thyroid-stimulating hormone signaling pathway;pronephric field specification;inner ear morphogenesis;regulation of apoptotic process;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;pronephros development;cellular response to gonadotropin stimulus;otic vesicle development;positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis;metanephric epithelium development;metanephric distal convoluted tubule development;metanephric comma-shaped body morphogenesis;metanephric S-shaped body morphogenesis;metanephric nephron tubule formation;negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis;regulation of metanephric nephron tubule epithelial cell differentiation;positive regulation of branching involved in ureteric bud morphogenesis;negative regulation of mesenchymal cell apoptotic process involved in metanephros development;negative regulation of apoptotic process involved in metanephric collecting duct development;negative regulation of apoptotic process involved in metanephric nephron tubule development;positive regulation of metanephric DCT cell differentiation;positive regulation of thyroid hormone generation;regulation of thyroid-stimulating hormone secretion
• Cellular component: nucleus;nucleoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;thyroid-stimulating hormone receptor activity;protein binding;transcription regulatory region DNA binding