PAX1

paired box 1, the group of Paired boxes

Basic information

Region (hg38): 20:21705659-21718481

Links

ENSG00000125813 ∙ NCBI:5075 ∙ OMIM:167411 ∙ HGNC:8615 ∙ Uniprot:P15863 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• otofaciocervical syndrome 2 (Strong), mode of inheritance: AR
• otofaciocervical syndrome 2 (Strong), mode of inheritance: AR
• otofaciocervical syndrome 2 (Limited), mode of inheritance: AD
• otofaciocervical syndrome 1 (Strong), mode of inheritance: AR
• otofaciocervical syndrome 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Otofaciocervical syndrome 2, with T-cell deficiency	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The condition has been described as including thymic anomalies and T-cell immunodeficiency associated with severe infections, and awareness may allow preventative measures and early and aggressive management of infections	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic	23851939; 28657137; 29681087; 32111619

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAX1 gene.

• not provided (9 variants)
• Otofaciocervical syndrome 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAX1 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			8	101	4	113
missense	1		151	10	2	164
nonsense	3		1			4
start loss						0
frameshift	5	2				7
inframe indel			5			5
splice donor/acceptor (+/-2bp)						0
splice region			5	8		13
non coding			33	42	7	82
Total	9	2	198	153	13

Highest pathogenic variant AF is 0.0000198

Variants in PAX1

This is a list of pathogenic ClinVar variants found in the PAX1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-21705720-T-C		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
20-21705730-C-A			Likely benign (Jun 08, 2022)
20-21705732-TG-T			Pathogenic (Nov 27, 2023)
20-21705735-G-A			Uncertain significance (Nov 01, 2022)
20-21705741-G-A			Uncertain significance (Aug 21, 2022)
20-21705744-C-G			Uncertain significance (Mar 24, 2021)
20-21705744-C-T			Benign (Jan 25, 2024)
20-21705745-G-T			Likely benign (Nov 06, 2023)
20-21705756-C-G		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
20-21705759-G-A			Pathogenic (Dec 12, 2023)
20-21705760-G-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2021)
20-21705764-G-C			Uncertain significance (Aug 26, 2021)
20-21705765-G-C			Uncertain significance (Nov 24, 2020)
20-21705766-G-A			Likely benign (Oct 24, 2018)
20-21705767-G-A			Uncertain significance (Apr 08, 2021)
20-21705774-C-G			Uncertain significance (May 08, 2023)
20-21705775-G-A			Likely benign (Aug 03, 2022)
20-21705775-G-T		PAX1-related disorder	Likely benign (May 01, 2024)
20-21705781-G-A			Likely benign (Jul 18, 2023)
20-21705781-G-C			Likely benign (Nov 24, 2022)
20-21705784-A-C			Likely benign (Sep 14, 2023)
20-21705787-C-T			Likely benign (Jan 08, 2024)
20-21705789-C-T			Uncertain significance (Jan 29, 2021)
20-21705790-T-C			Likely benign (Jan 08, 2024)
20-21705796-G-C		PAX1-related disorder	Benign (Jan 26, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAX1	protein_coding	protein_coding	ENST00000398485	5	10324

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.700	0.299	125571	0	4	125575	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.758	305	270	1.13	0.0000129	3303
Missense in Polyphen		83	95.948	0.86505		1136
Synonymous	-2.44	154	120	1.28	0.00000593	1203
Loss of Function	2.77	2	12.6	0.158	5.51e-7	152

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000181	0.0000176
Middle Eastern	0.0000545	0.0000544
South Asian	0.00	0.00
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This protein is a transcriptional activator. It may play a role in the formation of segmented structures of the embryo. May play an important role in the normal development of the vertebral column (By similarity). {ECO:0000250}.
• Disease: DISEASE: Otofaciocervical syndrome 2 (OTFCS2) [MIM:615560]: A disorder characterized by facial dysmorphism, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability. {ECO:0000269|PubMed:23851939}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.302

Intolerance Scores

• loftool: 0.182
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.37

Haploinsufficiency Scores

• pHI: 0.802
• hipred: Y
• hipred_score: 0.659
• ghis: 0.412

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.896

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pax1
• Phenotype: muscle phenotype; craniofacial phenotype; cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; pigmentation 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); limbs/digits/tail phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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; reproductive system 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); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: pax1b
• Affected structure: fin bud
• Phenotype tag: abnormal
• Phenotype quality: hypoplastic

Gene ontology

• Biological process: skeletal system development;somitogenesis;transcription by RNA polymerase II;cell population proliferation;CD4-positive, alpha-beta T cell differentiation;CD8-positive, alpha-beta T cell differentiation;positive regulation of transcription by RNA polymerase II;thymus development;parathyroid gland development;bone morphogenesis;sclerotome development
• Cellular component: nucleus
• 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