PAX2

paired box 2, the group of Paired boxes|PRD class homeoboxes and pseudogenes

Basic information

Region (hg38): 10:100735395-100829944

Links

ENSG00000075891 ∙ NCBI:5076 ∙ OMIM:167409 ∙ HGNC:8616 ∙ Uniprot:Q02962 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• renal coloboma syndrome (Moderate), mode of inheritance: AD
• renal coloboma syndrome (Definitive), mode of inheritance: AD
• renal coloboma syndrome (Strong), mode of inheritance: AD
• renal coloboma syndrome (Supportive), mode of inheritance: AD
• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
• renal coloboma syndrome (Strong), mode of inheritance: AD
• focal segmental glomerulosclerosis 7 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Isolated renal hypoplasia; Papillorenal syndrome; Focal segmental glomerulosclerosis 7	AD	Renal	The disorders may be recognizable in some individuals, but individuals are at risk of renal findings such as unrecognized vesicoureteral reflux, which can cause renal damage, and early diagnosis to allow management may be beneficial	Audiologic/Otolaryngologic; Ophthalmologic; Renal	3377002; 8589702; 7795640; 8588587; 10533062; 11093271; 11730657; 11241473;11297491; 11461952; 20301624; 20358591; 21380624; 22213154
It has been suggested that variants may result in isolated renal hypoplasia without other manifestations, though on examination, many individuals have been found to have opthalmalogic anomalies

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAX2 gene.

• Renal coloboma syndrome;Focal segmental glomerulosclerosis 7 (143 variants)
• not provided (106 variants)
• Focal segmental glomerulosclerosis 7;Renal coloboma syndrome (91 variants)
• Renal coloboma syndrome (32 variants)
• Focal segmental glomerulosclerosis 7 (20 variants)
• Inborn genetic diseases (14 variants)
• PAX2-related condition (12 variants)
• not specified (8 variants)
• PAX2-related disorder (2 variants)
• Retinal dystrophy (2 variants)
• Renal cysts and diabetes syndrome (1 variants)
• Congenital ocular coloboma (1 variants)
• Steroid-resistant nephrotic syndrome;Focal segmental glomerulosclerosis (1 variants)
• See cases (1 variants)
• Congenital anomaly of kidney and urinary tract (1 variants)
• Renal hypoplasia (1 variants)
• Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAX2 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	8	48	4	61
missense	3	11	118	2		134
nonsense	11	2				13
start loss						0
frameshift	15	7	2			24
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)	4	3				7
splice region		1	7	4	1	13
non coding	1	1	9	50	36	97
Total	34	26	139	100	40

Highest pathogenic variant AF is 0.0000132

Variants in PAX2

This is a list of pathogenic ClinVar variants found in the PAX2 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-100735721-G-A			Uncertain significance (Sep 01, 2023)
10-100735739-A-T		PAX2-related disorder	Likely benign (Jul 12, 2023)
10-100735764-A-G		Focal segmental glomerulosclerosis 7 • Renal coloboma syndrome	Benign (Sep 05, 2021)
10-100745390-A-T			Benign (Jul 17, 2019)
10-100745582-A-G			Likely benign (Sep 26, 2020)
10-100745602-C-A			Benign (Nov 12, 2018)
10-100745705-C-T			Likely benign (Mar 02, 2020)
10-100745706-G-T			Likely benign (Mar 02, 2020)
10-100745847-C-T			Likely benign (Jun 29, 2020)
10-100745886-C-A			Benign (Nov 12, 2018)
10-100746058-A-G			Benign (Nov 12, 2018)
10-100746101-G-T			Benign (Jan 25, 2019)
10-100746167-C-T			Likely benign (Apr 03, 2020)
10-100746224-G-T		PAX2-related disorder	Likely benign (Aug 28, 2019)
10-100746257-C-T		PAX2-related disorder	Likely benign (Jun 01, 2021)
10-100746261-A-G		Focal segmental glomerulosclerosis 7	Uncertain significance (Sep 17, 2018)
10-100746268-T-A		Renal coloboma syndrome;Focal segmental glomerulosclerosis 7	Uncertain significance (Sep 25, 2023)
10-100746268-T-C		Focal segmental glomerulosclerosis 7;Renal coloboma syndrome	Uncertain significance (Dec 01, 2022)
10-100746286-C-G			Uncertain significance (Feb 14, 2020)
10-100746294-GCGATGCACCGTGAGTACCGGCGCCCGGCTCCTGTC-TGT			Pathogenic (May 13, 2019)
10-100746296-G-C		Renal coloboma syndrome;Focal segmental glomerulosclerosis 7	Likely benign (Jan 19, 2024)
10-100746304-G-A		Renal coloboma syndrome;Focal segmental glomerulosclerosis 7	Pathogenic (Oct 23, 2023)
10-100746306-G-A		Focal segmental glomerulosclerosis 7;Renal coloboma syndrome	Uncertain significance (Dec 16, 2023)
10-100746308-G-A		Focal segmental glomerulosclerosis 7 • PAX2-related disorder	Conflicting classifications of pathogenicity (Nov 18, 2022)
10-100746308-G-T			Likely pathogenic (Jan 15, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAX2	protein_coding	protein_coding	ENST00000428433	11	94339

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.670	0.330	125733	0	14	125747	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.49	178	243	0.731	0.0000132	2669
Missense in Polyphen		53	100.47	0.52751		1081
Synonymous	-1.09	113	99.1	1.14	0.00000550	877
Loss of Function	3.45	4	21.1	0.190	0.00000106	234

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000869	0.0000869
Ashkenazi Jewish	0.00	0.00
East Asian	0.000445	0.000435
Finnish	0.00	0.00
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.000445	0.000435
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that may have a role in kidney cell differentiation (PubMed:24676634). Has a critical role in the development of the urogenital tract, the eyes, and the CNS. {ECO:0000269|PubMed:24676634}.
• Disease: DISEASE: Papillorenal syndrome (PAPRS) [MIM:120330]: An autosomal dominant disorder characterized by both ocular and renal anomalies, but may also include vesicoureteral reflux, high frequency hearing loss, central nervous system anomalies, and/or genital anomalies. Eye anomalies in this disorder consist of a wide and sometimes excavated dysplastic optic disk with the emergence of the retinal vessels from the periphery of the disk, designated optic nerve coloboma or 'morning glory' anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst, microphthalmia, and pigmentary macular dysplasia. The kidneys are small and abnormally formed (renal hypodysplasia), and have fewer than the normal number of glomeruli, which are enlarged (oligomeganephronia). These ocular and renal anomalies result in decreased visual acuity and retinal detachment, as well as hypertension, proteinuria, and renal insufficiency that frequently progresses to end-stage renal disease. {ECO:0000269|PubMed:11168927, ECO:0000269|PubMed:15652857, ECO:0000269|PubMed:19954729, ECO:0000269|PubMed:22213154, ECO:0000269|PubMed:24676634, ECO:0000269|PubMed:9760197}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Focal segmental glomerulosclerosis 7 (FSGS7) [MIM:616002]: A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. {ECO:0000269|PubMed:24676634}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Primary Focal Segmental Glomerulosclerosis FSGS;ID signaling pathway;Wnt (Consensus)

Recessive Scores

• pRec: 0.553

Intolerance Scores

• loftool: 0.0842
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.37

Haploinsufficiency Scores

• pHI: 0.838
• hipred: Y
• hipred_score: 0.792
• ghis: 0.416

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.961

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pax2
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; renal/urinary 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); hearing/vestibular/ear phenotype; vision/eye 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); 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); reproductive system phenotype; pigmentation phenotype; embryo phenotype

Zebrafish Information Network

• Gene name: pax2a
• Affected structure: midbrain hindbrain boundary neural keel
• Phenotype tag: abnormal
• Phenotype quality: physical object quality

Gene ontology

• Biological process: urogenital system development;branching involved in ureteric bud morphogenesis;cell fate determination;mesonephros development;neural tube closure;optic cup morphogenesis involved in camera-type eye development;mesenchymal to epithelial transition involved in metanephros morphogenesis;retinal pigment epithelium development;transcription, DNA-templated;transcription by RNA polymerase II;axonogenesis;mesodermal cell fate specification;aging;visual perception;glial cell differentiation;optic nerve development;optic nerve morphogenesis;optic nerve structural organization;vestibulocochlear nerve formation;response to nutrient levels;regulation of metanephros size;ureter maturation;pronephric field specification;inner ear morphogenesis;camera-type eye development;negative regulation of apoptotic process;negative regulation of programmed cell death;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;protein kinase B signaling;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;negative regulation of cytolysis;positive regulation of transcription by RNA polymerase II;pronephros development;brain morphogenesis;stem cell differentiation;positive regulation of epithelial cell proliferation;mesenchymal to epithelial transition;optic chiasma development;cellular response to hydrogen peroxide;cellular response to retinoic acid;cellular response to glucose stimulus;cellular response to epidermal growth factor stimulus;metanephric mesenchyme development;positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis;metanephric mesenchymal cell differentiation;nephric duct formation;ureter development;metanephric collecting duct development;metanephric epithelium development;metanephric distal convoluted tubule development;metanephric nephron tubule formation;positive regulation of metanephric glomerulus development;negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis;regulation of metanephric nephron tubule epithelial cell differentiation;reactive oxygen species metabolic process;cochlea development;cochlea morphogenesis;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;negative regulation of reactive oxygen species metabolic process;positive regulation of metanephric DCT cell differentiation;positive regulation of optic nerve formation
• Cellular component: nucleus;nucleolus;lysosome;Golgi apparatus;microtubule organizing center;protein-containing complex;protein-DNA complex;centriolar satellite
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;proximal promoter sequence-specific DNA binding;DNA binding;protein binding;transcription factor binding;transcription regulatory region DNA binding