UNG

uracil DNA glycosylase, the group of DNA glycosylases

Basic information

Region (hg38): 12:109097596-109126725

Previous symbols: [ "DGU" ]

Links

ENSG00000076248 ∙ NCBI:7374 ∙ OMIM:191525 ∙ HGNC:12572 ∙ Uniprot:P13051 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyper-IgM syndrome type 5 (Strong), mode of inheritance: AR
• hyper-IgM syndrome type 5 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency with hyper-IgM, type 5	AD	Allergy/Immunology/Infectious	Due to low/absent serum IgG, IgA, and IgE, Individuals are susceptible to recurrent/severe bacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	12958596; 15358621

ClinVar

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

• Hyper-IgM syndrome type 5 (214 variants)
• not provided (26 variants)
• Inborn genetic diseases (11 variants)
• Hyperimmunoglobulin M syndrome (4 variants)
• not specified (3 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UNG 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	38	3	45
missense			82	4	1	87
nonsense	2		2			4
start loss						0
frameshift	8	1	1			10
inframe indel			3			3
splice donor/acceptor (+/-2bp)		2				2
splice region			5	1		6
non coding			30	30	17	77
Total	10	3	122	72	21

Highest pathogenic variant AF is 0.000164

Variants in UNG

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

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

Position	Type	Phenotype	Significance	ClinVar
12-109097607-C-T		Hyper-IgM syndrome type 5	Uncertain significance (Jan 13, 2018)
12-109097629-A-G		Hyper-IgM syndrome type 5	Uncertain significance (Apr 27, 2017)
12-109097629-A-T		Hyper-IgM syndrome type 5	Uncertain significance (Jan 12, 2018)
12-109097630-G-A		Hyper-IgM syndrome type 5	Uncertain significance (Jan 12, 2018)
12-109097685-C-A		Hyper-IgM syndrome type 5	Uncertain significance (Jan 12, 2018)
12-109097693-A-G		Hyper-IgM syndrome type 5	Uncertain significance (Sep 03, 2020)
12-109097695-A-G			Uncertain significance (Sep 09, 2021)
12-109097711-T-C		Hyper-IgM syndrome type 5 • not specified	Uncertain significance (Oct 26, 2022)
12-109097713-T-A		Hyper-IgM syndrome type 5	Uncertain significance (Jul 12, 2021)
12-109097713-TC-T		Hyper-IgM syndrome type 5	Pathogenic (Jan 15, 2022)
12-109097713-TCCCCCAGCCCCGCCAGGAAGCGACACG-T		Hyper-IgM syndrome type 5	Uncertain significance (Jan 06, 2021)
12-109097715-C-A		Hyper-IgM syndrome type 5	Conflicting classifications of pathogenicity (Nov 16, 2023)
12-109097715-C-T		Hyper-IgM syndrome type 5	Likely benign (Aug 04, 2023)
12-109097739-C-T		Hyper-IgM syndrome type 5	Likely benign (Nov 13, 2023)
12-109097740-G-A		Hyper-IgM syndrome type 5 • not specified	Uncertain significance (May 20, 2023)
12-109097741-C-T		Hyper-IgM syndrome type 5	Uncertain significance (Apr 08, 2021)
12-109097744-C-T		Hyper-IgM syndrome type 5	Uncertain significance (Jul 14, 2022)
12-109097755-C-T		Hyper-IgM syndrome type 5	Uncertain significance (Feb 24, 2021)
12-109097756-C-A		Hyper-IgM syndrome type 5	Uncertain significance (Mar 07, 2022)
12-109097760-C-A		Hyper-IgM syndrome type 5	Conflicting classifications of pathogenicity (Oct 06, 2023)
12-109097765-A-C		Hyper-IgM syndrome type 5	Uncertain significance (Feb 10, 2022)
12-109097769-G-A		Hyper-IgM syndrome type 5	Likely benign (Nov 28, 2023)
12-109097769-G-T		Hyper-IgM syndrome type 5	Likely benign (Oct 14, 2023)
12-109097779-G-A		Hyper-IgM syndrome type 5	Uncertain significance (Jan 12, 2018)
12-109097784-G-A		Hyper-IgM syndrome type 5	Likely benign (Dec 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UNG	protein_coding	protein_coding	ENST00000242576	7	13419

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00172	0.975	125701	0	47	125748	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0560	173	175	0.988	0.00000871	2031
Missense in Polyphen		48	54.873	0.87475		678
Synonymous	-1.69	90	71.8	1.25	0.00000379	609
Loss of Function	2.00	7	15.5	0.452	7.44e-7	178

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00105	0.000952
Ashkenazi Jewish	0.000500	0.000496
East Asian	0.000218	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000152	0.000132
Middle Eastern	0.000218	0.000217
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.
• Disease: DISEASE: Immunodeficiency with hyper-IgM 5 (HIGM5) [MIM:608106]: A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections. {ECO:0000269|PubMed:12958596, ECO:0000269|PubMed:15967827}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Primary immunodeficiency - Homo sapiens (human);Base excision repair - Homo sapiens (human);DNA Repair;Recognition and association of DNA glycosylase with site containing an affected pyrimidine;Cleavage of the damaged pyrimidine ;Depyrimidination;Base-Excision Repair, AP Site Formation;Resolution of Abasic Sites (AP sites);Base Excision Repair;Displacement of DNA glycosylase by APEX1 (Consensus)

Recessive Scores

• pRec: 0.456

Intolerance Scores

• loftool: 0.745
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.25

Haploinsufficiency Scores

• pHI: 0.569
• hipred: Y
• hipred_score: 0.682
• ghis: 0.613

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ung
• 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); 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; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: unga
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: deformed

Gene ontology

• Biological process: DNA repair;base-excision repair;viral process;somatic hypermutation of immunoglobulin genes;somatic recombination of immunoglobulin gene segments;negative regulation of apoptotic process;depyrimidination;positive regulation of isotype switching;base-excision repair, AP site formation via deaminated base removal
• Cellular component: nucleus;nucleoplasm;mitochondrion
• Molecular function: damaged DNA binding;uracil DNA N-glycosylase activity;protein binding;ribosomal small subunit binding