UPK3A

uroplakin 3A

Basic information

Region (hg38): 22:45284949-45295874

Previous symbols: [ "UPK3" ]

Links

ENSG00000100373 ∙ NCBI:7380 ∙ OMIM:611559 ∙ HGNC:12580 ∙ Uniprot:O75631 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• renal agenesis, unilateral (Supportive), mode of inheritance: AD
• renal dysplasia (Limited), mode of inheritance: AD
• congenital anomaly of kidney and urinary tract (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Renal/urogenital adysplasia	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	Genitourinary; Renal	15888565
The condition has been described as involving progressive, inexorable renal failure, and renal transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UPK3A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UPK3A 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			3	6	4	13
missense			28	4	2	34
nonsense				2		2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1	1		3
splice region			1	1		2
non coding			3	2	3	8
Total	0	1	35	15	9

Variants in UPK3A

This is a list of pathogenic ClinVar variants found in the UPK3A region.

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

Position	Type	Phenotype	Significance	ClinVar
22-45284988-C-G		Renal hypodysplasia/aplasia 1	Uncertain significance (Jan 12, 2018)
22-45284989-G-C		Renal hypodysplasia/aplasia 1	Benign (Jan 12, 2018)
22-45285940-G-A			Likely pathogenic (-)
22-45285958-C-G		not specified	Uncertain significance (Oct 04, 2024)
22-45285978-C-T		Renal hypodysplasia/aplasia 1	Benign/Likely benign (Dec 31, 2019)
22-45285983-C-A		not specified	Uncertain significance (Apr 20, 2024)
22-45285997-C-G		not specified	Uncertain significance (Aug 02, 2023)
22-45286003-A-G			Uncertain significance (Sep 16, 2018)
22-45286021-C-T		not specified	Uncertain significance (Nov 13, 2024)
22-45286036-G-C		UPK3A-related disorder	Uncertain significance (Nov 16, 2022)
22-45286065-C-A		not specified	Uncertain significance (Mar 06, 2023)
22-45286090-G-A		Renal hypodysplasia/aplasia 1	Uncertain significance (May 01, 2024)
22-45286090-G-C		not specified	Uncertain significance (Jun 26, 2024)
22-45286394-G-C			Benign (Nov 12, 2018)
22-45287094-A-G			Benign (Nov 12, 2018)
22-45287161-C-T		Renal hypodysplasia/aplasia 1	Uncertain significance (Jan 13, 2018)
22-45287222-T-G		Renal hypodysplasia/aplasia 1	Benign/Likely benign (Dec 31, 2019)
22-45287223-C-A		Renal hypodysplasia/aplasia 1	Benign/Likely benign (Dec 31, 2019)
22-45287226-C-T		not specified	Uncertain significance (Apr 04, 2024)
22-45287235-A-T		Renal hypodysplasia/aplasia 1	Benign (Jan 13, 2018)
22-45287295-G-A		Renal hypodysplasia/aplasia 1 • UPK3A-related disorder	Uncertain significance (Oct 05, 2023)
22-45287298-A-C		not specified	Uncertain significance (Jan 27, 2022)
22-45287319-T-C		Renal hypodysplasia/aplasia 1 • UPK3A-related disorder	Benign/Likely benign (Dec 31, 2019)
22-45287319-T-G		UPK3A-related disorder • not specified	Uncertain significance (Oct 16, 2024)
22-45287322-G-A		Renal hypodysplasia/aplasia 1	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UPK3A	protein_coding	protein_coding	ENST00000216211	6	10893

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.08e-10	0.0253	123504	20	2224	125748	0.00896

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.411	180	165	1.09	0.00000977	1816
Missense in Polyphen		67	51.783	1.2939		647
Synonymous	0.563	70	76.3	0.918	0.00000515	619
Loss of Function	-0.610	14	11.7	1.19	6.07e-7	124

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0422	0.0421
Ashkenazi Jewish	0.00327	0.00328
East Asian	0.0274	0.0271
Finnish	0.0271	0.0270
European (Non-Finnish)	0.00189	0.00185
Middle Eastern	0.0274	0.0271
South Asian	0.00116	0.00114
Other	0.00702	0.00686

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play an important role in AUM-cytoskeleton interaction in terminally differentiated urothelial cells. It also contributes to the formation of urothelial glycocalyx which may play an important role in preventing bacterial adherence (By similarity). {ECO:0000250}.
• Pathway: Bladder cancer - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.0995

Intolerance Scores

• loftool: 0.572
• rvis_EVS: 0.89
• rvis_percentile_EVS: 89.14

Haploinsufficiency Scores

• pHI: 0.0786
• hipred: N
• hipred_score: 0.208
• ghis: 0.508

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.930

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Upk3a
• Phenotype: homeostasis/metabolism phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: cell morphogenesis;kidney development;water transport;urea transport;epithelial cell differentiation;potassium ion homeostasis;sodium ion homeostasis;urinary bladder development
• Cellular component: endoplasmic reticulum membrane;extracellular exosome;apical plasma membrane urothelial plaque
• Molecular function: protein binding