PAX5

paired box 5, the group of PRD class homeoboxes and pseudogenes|Paired boxes|MicroRNA protein coding host genes

Basic information

Region (hg38): 9:36833269-37034268

Links

ENSG00000196092 ∙ NCBI:5079 ∙ OMIM:167414 ∙ HGNC:8619 ∙ Uniprot:Q02548 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• leukemia, acute lymphoblastic, susceptibility to, 3 (Limited), mode of inheritance: AD
• PAX5-related B lymphopenia and autism spectrum disorder (Moderate), mode of inheritance: AR
• neurodevelopmental disorder (Moderate), mode of inheritance: AD
• leukemia, acute lymphoblastic, susceptibility to, 3 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukemia, acute lymphoblastic, susceptibility to, 3	AD	Oncologic	Awareness of B-ALL risk may allow surveillance and early detection and management, which may benefit morbidity and mortality; HSCT has been described	Oncologic	24013638

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAX5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAX5 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			1	45		46
missense		6	66	15	4	91
nonsense		3	2			5
start loss						0
frameshift		6				6
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1	1			2
splice region			3	5		8
non coding			2	22	34	58
Total	0	16	73	82	38

Variants in PAX5

This is a list of pathogenic ClinVar variants found in the PAX5 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-36840330-C-T			Benign (Mar 20, 2019)
9-36840449-G-A			Likely benign (Feb 28, 2019)
9-36840544-C-T		PAX5-related disorder	Likely benign (Nov 16, 2020)
9-36840545-G-A		not specified	not provided (Sep 19, 2013)
9-36840567-C-T		Leukemia, acute lymphoblastic, susceptibility to, 3 • not specified	Uncertain significance (Jan 12, 2021)
9-36840573-T-C			Uncertain significance (Jul 13, 2022)
9-36840575-G-A		not specified	Likely benign (Jan 02, 2019)
9-36840584-G-A			Likely benign (Jan 23, 2025)
9-36840587-T-G		Inborn genetic diseases	Likely benign (Nov 17, 2024)
9-36840588-G-A			Uncertain significance (Jun 18, 2024)
9-36840599-G-A		not specified • Inborn genetic diseases	Likely benign (Nov 28, 2024)
9-36840607-G-A		Neurodevelopmental disorder	Uncertain significance (Oct 11, 2022)
9-36840607-G-T		Inborn genetic diseases	Likely benign (Nov 30, 2024)
9-36840610-C-T		not specified	Uncertain significance (Jul 09, 2024)
9-36840611-G-A		Inborn genetic diseases	Likely benign (Nov 20, 2024)
9-36840611-G-T		PAX5-related disorder	Uncertain significance (Nov 29, 2022)
9-36840617-G-A		PAX5-related disorder • Inborn genetic diseases	Likely benign (Dec 01, 2024)
9-36840620-A-G		Inborn genetic diseases	Benign/Likely benign (Dec 06, 2024)
9-36840624-T-C		Inborn genetic diseases	Uncertain significance (Dec 02, 2024)
9-36840626-G-A		not specified	Benign (Feb 03, 2025)
9-36840626-GT-AC			Uncertain significance (Feb 02, 2025)
9-36840627-T-C		Inborn genetic diseases	Uncertain significance (Nov 17, 2024)
9-36840629-G-A		PAX5-related disorder	Likely benign (Jan 06, 2024)
9-36840636-C-G		Inborn genetic diseases	Uncertain significance (Nov 30, 2024)
9-36840647-C-A			Likely benign (Mar 13, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAX5	protein_coding	protein_coding	ENST00000358127	10	200832

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00202	125509	0	10	125519	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.45	139	248	0.561	0.0000151	2484
Missense in Polyphen		39	108.85	0.35829		1066
Synonymous	-0.469	112	106	1.06	0.00000732	801
Loss of Function	3.95	0	18.1	0.00	7.69e-7	218

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000202	0.000199
East Asian	0.000112	0.000109
Finnish	0.0000488	0.0000464
European (Non-Finnish)	0.0000182	0.0000176
Middle Eastern	0.000112	0.000109
South Asian	0.0000666	0.0000654
Other	0.000169	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play an important role in B-cell differentiation as well as neural development and spermatogenesis. Involved in the regulation of the CD19 gene, a B-lymphoid-specific target gene.
• Disease: DISEASE: Note=A chromosomal aberration involving PAX5 is a cause of acute lymphoblastic leukemia. Translocation t(9;18)(p13;q11.2) with ZNF521. Translocation t(9;3)(p13;p14.1) with FOXP1. Translocation t(9;12)(p13;p13) with ETV6. {ECO:0000269|PubMed:17344859}.; DISEASE: Leukemia, acute lymphoblastic, 3 (ALL3) [MIM:613065]: A subtype of acute leukemia, a cancer of the white blood cells. Acute lymphoblastic anemia is a malignant disease of bone marrow and the most common malignancy diagnosed in children. The malignant cells are lymphoid precursor cells (lymphoblasts) that are arrested in an early stage of development. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymphnodes. {ECO:0000269|PubMed:24013638}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Transcriptional misregulation in cancer - Homo sapiens (human);Prion disease pathway;ID signaling pathway;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;RUNX1 regulates transcription of genes involved in BCR signaling;C-MYB transcription factor network;ID;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.0809

Intolerance Scores

• loftool: 0.0277
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.437
• hipred: Y
• hipred_score: 0.875
• ghis: 0.410

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pax5
• Phenotype: neoplasm; 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; immune system 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); growth/size/body region phenotype; cellular phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: pax5
• Affected structure: hair cell
• Phenotype tag: abnormal
• Phenotype quality: apoptotic

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;humoral immune response;multicellular organism development;spermatogenesis;aging;animal organ morphogenesis;lateral ventricle development;cerebral cortex development;adult behavior;skeletal muscle cell differentiation;positive regulation of transcription by RNA polymerase II;embryonic cranial skeleton morphogenesis;regulation of B cell receptor signaling pathway;negative regulation of histone H3-K9 methylation
• Cellular component: fibrillar center;nucleoplasm;cytosol;intracellular membrane-bounded organelle
• 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;protein binding