XDH

xanthine dehydrogenase

Basic information

Region (hg38): 2:31334321-31414742

Links

ENSG00000158125 ∙ NCBI:7498 ∙ OMIM:607633 ∙ HGNC:12805 ∙ Uniprot:P47989 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• xanthinuria type I (Moderate), mode of inheritance: AR
• xanthinuria type I (Supportive), mode of inheritance: AR
• xanthinuria type I (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Xanthinuria, type I	AR	Biochemical; Renal	Dietary measures (eg, purine restricted, increased fluid intake) and medical measures (eg, allopurinol) can be effective	Biochemical; Musculoskeletal; Renal	13118765; 861350; 3818951; 3339736; 754557; 9767921; 9153281

ClinVar

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

• Xanthinuria type II (15 variants)
• Hereditary xanthinuria type 1 (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XDH 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			7	92	7	106
missense			253	21	4	278
nonsense	6	4				10
start loss						0
frameshift	10		1			11
inframe indel			3			3
splice donor/acceptor (+/-2bp)		9				9
splice region			22	20		42
non coding			40	83	99	222
Total	16	13	304	196	110

Highest pathogenic variant AF is 0.000105

Variants in XDH

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

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

Position	Type	Phenotype	Significance	ClinVar
2-31334357-C-T		Hereditary xanthinuria type 1	Uncertain significance (Apr 28, 2017)
2-31334403-C-A		Hereditary xanthinuria type 1	Benign (Jan 12, 2018)
2-31334442-G-A		Hereditary xanthinuria type 1	Benign (Jan 13, 2018)
2-31334464-T-C		Hereditary xanthinuria type 1	Uncertain significance (Jan 13, 2018)
2-31334467-T-C		Hereditary xanthinuria type 1	Uncertain significance (Jan 12, 2018)
2-31334481-T-C		Hereditary xanthinuria type 1	Benign (Jan 13, 2018)
2-31334506-G-A		Hereditary xanthinuria type 1	Uncertain significance (Jan 12, 2018)
2-31334541-T-C		Hereditary xanthinuria type 1	Uncertain significance (Jan 13, 2018)
2-31334551-G-A		Hereditary xanthinuria type 1	Uncertain significance (Jan 12, 2018)
2-31334620-C-A		Hereditary xanthinuria type 1	Uncertain significance (Jan 13, 2018)
2-31334694-C-T		Hereditary xanthinuria type 1	Uncertain significance (Jan 13, 2018)
2-31334738-G-A		Hereditary xanthinuria type 1	Uncertain significance (Jan 13, 2018)
2-31334775-A-T		Hereditary xanthinuria type 1	Uncertain significance (Jan 13, 2018)
2-31334864-T-G		Xanthinuria	Uncertain significance (Jun 14, 2016)
2-31334877-T-C		Hereditary xanthinuria type 1	Benign (Jan 13, 2018)
2-31334896-A-G		Hereditary xanthinuria type 1	Uncertain significance (Jan 12, 2018)
2-31335013-G-T		Hereditary xanthinuria type 1	Uncertain significance (Jan 12, 2018)
2-31335020-C-A		Hereditary xanthinuria type 1	Uncertain significance (Jan 12, 2018)
2-31335045-A-T		Hereditary xanthinuria type 1	Uncertain significance (Apr 27, 2017)
2-31335046-T-A		Hereditary xanthinuria type 1	Likely benign (Apr 27, 2017)
2-31335077-C-T		Hereditary xanthinuria type 1	Uncertain significance (Jan 13, 2018)
2-31335080-A-G		Hereditary xanthinuria type 1	Likely benign (Apr 28, 2017)
2-31335129-C-T		Hereditary xanthinuria type 1	Uncertain significance (Jan 13, 2018)
2-31335135-T-C		Hereditary xanthinuria type 1	Uncertain significance (Jan 12, 2018)
2-31335226-A-G		Hereditary xanthinuria type 1	Uncertain significance (Jan 15, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XDH	protein_coding	protein_coding	ENST00000379416	36	80395

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.59e-22	0.911	125419	1	328	125748	0.00131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.45	839	729	1.15	0.0000434	8729
Missense in Polyphen		317	281.44	1.1263		3371
Synonymous	-2.25	329	281	1.17	0.0000172	2639
Loss of Function	2.52	45	67.3	0.668	0.00000350	841

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00197	0.00197
Ashkenazi Jewish	0.000794	0.000794
East Asian	0.000707	0.000707
Finnish	0.000139	0.000139
European (Non-Finnish)	0.00172	0.00171
Middle Eastern	0.000707	0.000707
South Asian	0.00157	0.00157
Other	0.000978	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro). {ECO:0000269|PubMed:17301077}.
• Disease: DISEASE: Xanthinuria 1 (XAN1) [MIM:278300]: A disorder characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. XAN1 is due to isolated xanthine dehydrogenase deficiency. Patients can metabolize allopurinol. {ECO:0000269|PubMed:10844591, ECO:0000269|PubMed:11379872, ECO:0000269|PubMed:14551354, ECO:0000269|PubMed:9153281}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Doxorubicin Pathway (Cancer Cell), Pharmacodynamics;Peroxisome - Homo sapiens (human);Drug metabolism - other enzymes - Homo sapiens (human);Doxorubicin Pathway, Pharmacokinetics;Caffeine metabolism - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Caffeine Pathway, Pharmacokinetics;Theophylline Pathway, Pharmacokinetics;Uric Acid-Lowering Drugs Pathway, Pharmacodynamics;Doxorubicin Metabolism Pathway;Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Caffeine Metabolism;Adenosine Deaminase Deficiency;Mercaptopurine Metabolism Pathway;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Selenium Micronutrient Network;Effects of Nitric Oxide;Caffeine and Theobromine metabolism;Oxidative Stress;Nucleobase catabolism;Metabolism of nucleotides;Butyrophilin (BTN) family interactions;guanosine nucleotides degradation;Purine metabolism;urate biosynthesis/inosine 5,-phosphate degradation;adenosine nucleotides degradation;purine nucleotides degradation;Immune System;Metabolism;Adaptive Immune System;retinoate biosynthesis II;Purine nucleotides nucleosides metabolism;Purine catabolism (Consensus)

Recessive Scores

• pRec: 0.0937

Intolerance Scores

• loftool: 0.922
• rvis_EVS: 1.29
• rvis_percentile_EVS: 93.81

Haploinsufficiency Scores

• pHI: 0.309
• hipred: N
• hipred_score: 0.492
• ghis: 0.410

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.901

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xdh
• 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); immune system phenotype; renal/urinary system 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; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype

Gene ontology

• Biological process: negative regulation of protein phosphorylation;negative regulation of endothelial cell proliferation;purine nucleotide catabolic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;lactation;xanthine catabolic process;negative regulation of gene expression;electron transport chain;negative regulation of endothelial cell differentiation;negative regulation of protein kinase B signaling;positive regulation of p38MAPK cascade;negative regulation of vascular endothelial growth factor signaling pathway;positive regulation of reactive oxygen species metabolic process;negative regulation of vasculogenesis
• Cellular component: extracellular space;peroxisome;cytosol;sarcoplasmic reticulum
• Molecular function: xanthine dehydrogenase activity;xanthine oxidase activity;iron ion binding;electron transfer activity;protein homodimerization activity;molybdopterin cofactor binding;flavin adenine dinucleotide binding;2 iron, 2 sulfur cluster binding;FAD binding