PAX9

paired box 9, the group of Paired boxes

Basic information

Region (hg38): 14:36657567-36679362

Links

ENSG00000198807 ∙ NCBI:5083 ∙ OMIM:167416 ∙ HGNC:8623 ∙ Uniprot:P55771 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• tooth agenesis, selective, 3 (Definitive), mode of inheritance: AD
• tooth agenesis, selective, 3 (Strong), mode of inheritance: AD
• tooth agenesis (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tooth agenesis, selective, 3	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dental	10615120; 11941488; 11827258; 14571272; 16333316; 16479262; 18701815; 19429910; 20485064; 20618716; 21098475; 21443745; 22058014; 22277187; 22747565

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAX9 gene.

• Tooth agenesis, selective, 3 (55 variants)
• Partial congenital absence of teeth (47 variants)
• not provided (25 variants)
• Inborn genetic diseases (12 variants)
• Selective tooth agenesis (3 variants)
• PAX9-related condition (3 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAX9 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			4	5	2	11
missense	3	2	35	4	1	45
nonsense	6					6
start loss	1					1
frameshift	10	3	1			14
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding			21	4	14	39
Total	20	5	62	13	17

Variants in PAX9

This is a list of pathogenic ClinVar variants found in the PAX9 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-36657575-C-T		Tooth agenesis, selective, 3	Uncertain significance (Jan 13, 2018)
14-36657638-C-G		Tooth agenesis, selective, 3	Likely benign (Jan 13, 2018)
14-36657650-G-A		Tooth agenesis, selective, 3	Uncertain significance (Jan 13, 2018)
14-36657666-A-AC		Selective tooth agenesis	Likely benign (Jun 14, 2016)
14-36657741-C-A		Tooth agenesis, selective, 3	Uncertain significance (Jan 13, 2018)
14-36657806-C-T		Tooth agenesis, selective, 3	Uncertain significance (Jan 12, 2018)
14-36657839-C-G		Tooth agenesis, selective, 3	Benign (Jan 13, 2018)
14-36657915-G-C		Tooth agenesis, selective, 3	Uncertain significance (Jan 13, 2018)
14-36659359-C-A		Partial congenital absence of teeth	Benign (Jan 08, 2024)
14-36660669-A-G			Benign (Jun 19, 2021)
14-36660725-C-G			Benign (Jun 19, 2021)
14-36660788-C-T			Benign (Jun 19, 2021)
14-36660817-C-CA		PAX9-related disorder	Likely benign (Aug 07, 2019)
14-36660959-T-C			Benign (Jun 20, 2021)
14-36661540-C-T			Benign (Jun 19, 2021)
14-36661752-C-T		Tooth agenesis, selective, 3	Uncertain significance (Jan 13, 2018)
14-36661769-C-A		Tooth agenesis, selective, 3	Uncertain significance (Jan 13, 2018)
14-36661846-G-T		Tooth agenesis, selective, 3	Uncertain significance (Jan 12, 2018)
14-36661872-G-A		Tooth agenesis, selective, 3	Uncertain significance (Jan 13, 2018)
14-36661904-C-A		Tooth agenesis, selective, 3	Uncertain significance (Jan 13, 2018)
14-36661915-G-C		Tooth agenesis, selective, 3	Likely benign (Jan 13, 2018)
14-36661971-A-T		Tooth agenesis, selective, 3	Uncertain significance (Jan 13, 2018)
14-36662023-A-G		Tooth agenesis, selective, 3	Uncertain significance (Jan 12, 2018)
14-36662025-G-A		Tooth agenesis, selective, 3	Uncertain significance (Jan 13, 2018)
14-36662090-A-G		Tooth agenesis, selective, 3	Pathogenic (Jan 01, 2005)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAX9	protein_coding	protein_coding	ENST00000361487	4	22148

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.309	0.688	125745	0	3	125748	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.619	173	197	0.876	0.00000968	2177
Missense in Polyphen		88	106.35	0.82749		1214
Synonymous	-1.12	100	86.8	1.15	0.00000459	743
Loss of Function	2.51	3	12.6	0.237	5.53e-7	138

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000884	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor required for normal development of thymus, parathyroid glands, ultimobranchial bodies, teeth, skeletal elements of skull and larynx as well as distal limbs. {ECO:0000250, ECO:0000269|PubMed:12657635}.
• Disease: DISEASE: Tooth agenesis, selective, 3 (STHAG3) [MIM:604625]: A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). {ECO:0000269|PubMed:12786960}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Endoderm Differentiation (Consensus)

Recessive Scores

• pRec: 0.240

Intolerance Scores

• loftool: 0.0763
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.53

Haploinsufficiency Scores

• pHI: 0.576
• hipred: Y
• hipred_score: 0.856
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.899

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pax9
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; hematopoietic 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); normal phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; skeleton phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: pax9
• Affected structure: neurocranium
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: endoderm development;odontogenesis;regulation of odontogenesis;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;face morphogenesis;cellular response to growth factor stimulus
• Cellular component: nucleus
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding