XAN2
MCID: XNT011
MIFTS: 37

Xanthinuria, Type Ii (XAN2)

Categories: Genetic diseases, Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Xanthinuria, Type Ii

MalaCards integrated aliases for Xanthinuria, Type Ii:

Name: Xanthinuria, Type Ii 56 54 71
Xanthinuria Type Ii 58 29 6
Xdh and Aox Dual Deficiency 52 58
Xan2 56 73
Xanthine Dehydrogenase and Xanthine Aldehyde Oxidase Dual Deficiency 58
Xanthine Dehydrogenase and Aldehyde Oxidase, Combined Deficiency of 56
Xanthine Dehydrogenase and Aldehyde Oxidase Combined Deficiency of 52
Combined Deficiency of Xanthine Dehydrogenase and Aldehyde Oxidase 73
Xanthic Urolithiasis 73
Type Ii Xanthinuria 52
Xanthinuria Type 2 52
Type 2 Xanthinuria 52
Xanthinuria 2 73

Characteristics:

Orphanet epidemiological data:

58
xanthinuria type ii
Inheritance: Autosomal recessive;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
variable age at onset
some patients may be asymptomatic
cannot metabolize allopurinol
one patient with a heterozygous mutation has been reported (last curated july 2016)


HPO:

31
xanthinuria, type ii:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare renal diseases
Inborn errors of metabolism


External Ids:

OMIM 56 603592
OMIM Phenotypic Series 56 PS278300
ICD10 via Orphanet 33 E79.8
UMLS via Orphanet 72 C1863688
Orphanet 58 ORPHA93602
MedGen 41 C1863688
UMLS 71 C1863688

Summaries for Xanthinuria, Type Ii

OMIM : 56 Xanthinuria type II is an autosomal recessive inborn error of metabolism resulting from a defect in the synthesis of the molybdenum cofactor, which is necessary for the 2 enzymes that degrade xanthine: XDH (607633) and AOX1 (602841). Most individuals with type II xanthinuria are asymptomatic, but some develop urinary tract calculi, acute renal failure, or myositis due to tissue deposition of xanthine. Laboratory studies show increased serum and urinary hypoxanthine and xanthine and decreased serum and urinary uric acid (summary by Ichida et al., 2001). Two clinically similar but distinct forms of xanthinuria are recognized. In type I xanthinuria (XAN1; 278300), there is an isolated deficiency of xanthine dehydrogenase resulting from mutation in the XDH gene; in type II, there is a dual deficiency of xanthine dehydrogenase and aldehyde oxidase. Type I patients can metabolize allopurinol, whereas type II patients cannot (Simmonds et al., 1995). (603592)

MalaCards based summary : Xanthinuria, Type Ii, also known as xanthinuria type ii, is related to molybdenum cofactor deficiency and molybdenum cofactor deficiency, complementation group a. An important gene associated with Xanthinuria, Type Ii is MOCOS (Molybdenum Cofactor Sulfurase), and among its related pathways/superpathways are Drug metabolism - cytochrome P450 and Metabolism of water-soluble vitamins and cofactors. Affiliated tissues include kidney, and related phenotypes are renal insufficiency and nephrolithiasis

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 93602 Definition Type II xanthinuria, a type of classical xanthinuria (see this term), is a rare autosomal recessive disorder of purine metabolism (see this term) characterized by the deficiency of both xanthine dehydrogenase and aldehyde oxidase, leading to the formation of urinary xanthine urolithiasis and leading, in some patients, to kidney failure. Other less common manifestations include arthropathy, myopathy and duodenal ulcer, while some patients remain asymptomatic. Visit the Orphanet disease page for more resources.

UniProtKB/Swiss-Prot : 73 Xanthinuria 2: 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. In addition, XAN2 patients cannot metabolize allopurinol into oxypurinol due to dual deficiency of xanthine dehydrogenase and aldehyde oxidase.

Related Diseases for Xanthinuria, Type Ii

Diseases in the Xanthinuria family:

Xanthinuria, Type I Xanthinuria, Type Ii
Hereditary Xanthinuria

Diseases related to Xanthinuria, Type Ii via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 molybdenum cofactor deficiency 31.8 XDH AOX1
2 molybdenum cofactor deficiency, complementation group a 31.7 XDH MOCOS
3 xanthinuria 31.2 XDH MOCOS AOX1
4 hereditary xanthinuria 30.1 XDH AOX1
5 xanthinuria, type i 29.7 XDH AOX1
6 autism 10.0
7 autosomal recessive disease 10.0
8 urolithiasis 10.0
9 pancytopenia 10.0
10 nephrocalcinosis 10.0
11 vasculitis 10.0
12 purine-pyrimidine metabolic disorder 9.0 XDH MOCOS AOX1

Graphical network of the top 20 diseases related to Xanthinuria, Type Ii:



Diseases related to Xanthinuria, Type Ii

Symptoms & Phenotypes for Xanthinuria, Type Ii

Human phenotypes related to Xanthinuria, Type Ii:

31
# Description HPO Frequency HPO Source Accession
1 renal insufficiency 31 occasional (7.5%) HP:0000083
2 nephrolithiasis 31 occasional (7.5%) HP:0000787
3 hypouricemia 31 HP:0003537

Symptoms via clinical synopsis from OMIM:

56
Laboratory Abnormalities:
hypouricemia
increased serum and urinary hypoxanthine
increased serum and urinary xanthine
decreased or absent urinary uric acid
decreased activities of xanthine dehydrogenase and xanthine oxidase

Muscle Soft Tissue:
myopathy due to xanthine accumulation (in some patients)

Genitourinary Kidneys:
renal failure (in some patients)
renal stones (in some patients)

Clinical features from OMIM:

603592

Drugs & Therapeutics for Xanthinuria, Type Ii

Search Clinical Trials , NIH Clinical Center for Xanthinuria, Type Ii

Genetic Tests for Xanthinuria, Type Ii

Genetic tests related to Xanthinuria, Type Ii:

# Genetic test Affiliating Genes
1 Xanthinuria Type Ii 29 MOCOS

Anatomical Context for Xanthinuria, Type Ii

MalaCards organs/tissues related to Xanthinuria, Type Ii:

40
Kidney

Publications for Xanthinuria, Type Ii

Articles related to Xanthinuria, Type Ii:

# Title Authors PMID Year
1
Identification and characterization of the first mutation (Arg776Cys) in the C-terminal domain of the Human Molybdenum Cofactor Sulfurase (HMCS) associated with type II classical xanthinuria. 6 61 54 56
17368066 2007
2
Mutation of human molybdenum cofactor sulfurase gene is responsible for classical xanthinuria type II. 61 56 6 54
11302742 2001
3
Identification of a new point mutation in the human molybdenum cofactor sulferase gene that is responsible for xanthinuria type II. 56 61 6
14624414 2003
4
Using Next-Generation Sequencing to Identify a Mutation in Human MCSU that is Responsible for Type II Xanthinuria. 56 6
25967871 2015
5
Urolithiasis due to Hereditary Xanthinuria Type II: A Long-term Follow-up report. 61
32444521 2020
6
Thiopurine-induced toxicity is associated with dysfunction variant of the human molybdenum cofactor sulfurase gene (xanthinuria type II). 61
29935280 2018
7
A case of xanthinuria type I with a novel mutation in xanthine dehydrogenase. 61
28508967 2016
8
Hereditary xanthinuria type II associated with mental delay, autism, cortical renal cysts, nephrocalcinosis, osteopenia, and hair and teeth defects. 61
14627688 2003
9
Deletion mutation in Drosophila ma-l homologous, putative molybdopterin cofactor sulfurase gene is associated with bovine xanthinuria type II. 61
10801779 2000

Variations for Xanthinuria, Type Ii

ClinVar genetic disease variations for Xanthinuria, Type Ii:

6 (show top 50) (show all 109) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 XDH NM_000379.4(XDH):c.2274del (p.Glu760fs)deletion Pathogenic 579351 rs760186813 2:31589784-31589784 2:31366918-31366918
2 XDH NM_000379.4(XDH):c.3507del (p.Gly1170fs)deletion Pathogenic 570826 rs1558674294 2:31565061-31565061 2:31342195-31342195
3 XDH NM_000379.4(XDH):c.140dup (p.Cys48fs)duplication Pathogenic 641114 2:31625970-31625971 2:31403104-31403105
4 MOCOS NM_017947.4(MOCOS):c.169G>C (p.Ala57Pro)SNV Pathogenic 253161 rs886037854 18:33775246-33775246 18:36195283-36195283
5 MOCOS NM_017947.4(MOCOS):c.2326C>T (p.Arg776Cys)SNV Pathogenic 253162 rs750896617 18:33840055-33840055 18:36260092-36260092
6 MOCOS NM_017947.4(MOCOS):c.1037dup (p.Gln347fs)duplication Pathogenic 253163 rs886037855 18:33785055-33785056 18:36205092-36205093
7 XDH NM_000379.4(XDH):c.1602+1G>ASNV Likely pathogenic 566280 rs376882470 2:31598245-31598245 2:31375379-31375379
8 XDH NM_000379.4(XDH):c.2634T>C (p.Ile878=)SNV Conflicting interpretations of pathogenicity 335770 rs146994573 2:31573087-31573087 2:31350221-31350221
9 XDH NM_000379.4(XDH):c.1037C>T (p.Ala346Val)SNV Conflicting interpretations of pathogenicity 800266 2:31605868-31605868 2:31383002-31383002
10 XDH NM_000379.4(XDH):c.405C>T (p.Thr135=)SNV Conflicting interpretations of pathogenicity 335800 rs72549370 2:31621467-31621467 2:31398601-31398601
11 XDH NM_000379.4(XDH):c.3930C>T (p.Cys1310=)SNV Conflicting interpretations of pathogenicity 335756 rs138936101 2:31560528-31560528 2:31337662-31337662
12 XDH NM_000379.4(XDH):c.3052-4C>TSNV Conflicting interpretations of pathogenicity 335767 rs370085305 2:31571233-31571233 2:31348367-31348367
13 XDH NM_000379.4(XDH):c.1856+7G>ASNV Conflicting interpretations of pathogenicity 335780 rs184028774 2:31595087-31595087 2:31372221-31372221
14 XDH NM_000379.4(XDH):c.1274C>G (p.Ser425Cys)SNV Conflicting interpretations of pathogenicity 335788 rs138649664 2:31600072-31600072 2:31377206-31377206
15 XDH NM_000379.4(XDH):c.825T>C (p.Phe275=)SNV Conflicting interpretations of pathogenicity 335794 rs145596057 2:31606682-31606682 2:31383816-31383816
16 XDH NM_000379.4(XDH):c.1686+1G>CSNV Conflicting interpretations of pathogenicity 505602 rs148412639 2:31596738-31596738 2:31373872-31373872
17 XDH NM_000379.4(XDH):c.3864T>C (p.Gly1288=)SNV Conflicting interpretations of pathogenicity 791699 2:31560594-31560594 2:31337728-31337728
18 XDH NM_000379.4(XDH):c.3536T>C (p.Ile1179Thr)SNV Conflicting interpretations of pathogenicity 790908 2:31564244-31564244 2:31341378-31341378
19 XDH NM_000379.4(XDH):c.1663C>T (p.Pro555Ser)SNV Conflicting interpretations of pathogenicity 788393 2:31596762-31596762 2:31373896-31373896
20 XDH NM_000379.4(XDH):c.882C>T (p.Pro294=)SNV Conflicting interpretations of pathogenicity 786264 2:31606625-31606625 2:31383759-31383759
21 XDH NM_000379.4(XDH):c.3018T>C (p.Phe1006=)SNV Conflicting interpretations of pathogenicity 711191 2:31571798-31571798 2:31348932-31348932
22 XDH NM_000379.4(XDH):c.2037A>C (p.Thr679=)SNV Conflicting interpretations of pathogenicity 716067 2:31591470-31591470 2:31368604-31368604
23 XDH NM_000379.4(XDH):c.1868C>T (p.Thr623Ile)SNV Conflicting interpretations of pathogenicity 790933 2:31593333-31593333 2:31370467-31370467
24 XDH NM_000379.4(XDH):c.822G>A (p.Leu274=)SNV Conflicting interpretations of pathogenicity 715344 2:31606685-31606685 2:31383819-31383819
25 XDH NC_000002.12:g.(?_31375360)_(31414686_?)dupduplication Uncertain significance 831254 2:31598226-31637552
26 XDH NM_000379.4(XDH):c.3871G>A (p.Val1291Met)SNV Uncertain significance 858637 2:31560587-31560587 2:31337721-31337721
27 XDH NM_000379.4(XDH):c.2360G>A (p.Arg787Gln)SNV Uncertain significance 850229 2:31588938-31588938 2:31366072-31366072
28 XDH NM_000379.4(XDH):c.1896T>G (p.Phe632Leu)SNV Uncertain significance 851652 2:31593305-31593305 2:31370439-31370439
29 XDH NM_000379.4(XDH):c.988G>A (p.Val330Ile)SNV Uncertain significance 856017 2:31605917-31605917 2:31383051-31383051
30 XDH NM_000379.4(XDH):c.977T>G (p.Val326Gly)SNV Uncertain significance 849563 2:31605928-31605928 2:31383062-31383062
31 MOCOS NM_017947.4(MOCOS):c.686C>T (p.Thr229Met)SNV Uncertain significance 850529 18:33780032-33780032 18:36200069-36200069
32 MOCOS NM_017947.4(MOCOS):c.2327G>A (p.Arg776His)SNV Uncertain significance 860197 18:33840056-33840056 18:36260093-36260093
33 MOCOS NM_017947.4(MOCOS):c.2528T>C (p.Met843Thr)SNV Uncertain significance 856219 18:33848509-33848509 18:36268546-36268546
34 XDH NM_000379.4(XDH):c.3277-3deldeletion Uncertain significance 860457 2:31569712-31569712 2:31346846-31346846
35 XDH NM_000379.4(XDH):c.3736C>T (p.Arg1246Cys)SNV Uncertain significance 572582 rs142329784 2:31562393-31562393 2:31339527-31339527
36 XDH NM_000379.4(XDH):c.361G>A (p.Val121Ile)SNV Uncertain significance 576475 rs751332444 2:31621511-31621511 2:31398645-31398645
37 MOCOS NM_017947.4(MOCOS):c.14C>T (p.Ala5Val)SNV Uncertain significance 654063 18:33767516-33767516 18:36187553-36187553
38 MOCOS NM_017947.4(MOCOS):c.277A>G (p.Thr93Ala)SNV Uncertain significance 644865 18:33778697-33778697 18:36198734-36198734
39 MOCOS NM_017947.4(MOCOS):c.512C>T (p.Pro171Leu)SNV Uncertain significance 639841 18:33779858-33779858 18:36199895-36199895
40 MOCOS NM_017947.4(MOCOS):c.541G>A (p.Glu181Lys)SNV Uncertain significance 654879 18:33779887-33779887 18:36199924-36199924
41 MOCOS NM_017947.4(MOCOS):c.790A>G (p.Lys264Glu)SNV Uncertain significance 656034 18:33780136-33780136 18:36200173-36200173
42 MOCOS NM_017947.4(MOCOS):c.1358A>G (p.Asn453Ser)SNV Uncertain significance 651388 18:33795501-33795501 18:36215538-36215538
43 MOCOS NM_017947.4(MOCOS):c.1718G>A (p.Gly573Glu)SNV Uncertain significance 654064 18:33795861-33795861 18:36215898-36215898
44 MOCOS NM_017947.4(MOCOS):c.1849A>G (p.Met617Val)SNV Uncertain significance 657364 18:33800069-33800069 18:36220106-36220106
45 MOCOS NM_017947.4(MOCOS):c.1893A>C (p.Glu631Asp)SNV Uncertain significance 651732 18:33800113-33800113 18:36220150-36220150
46 XDH NM_000379.4(XDH):c.3488T>C (p.Val1163Ala)SNV Uncertain significance 576949 rs142988357 2:31565080-31565080 2:31342214-31342214
47 XDH NM_000379.4(XDH):c.2437G>C (p.Val813Leu)SNV Uncertain significance 574241 rs142951412 2:31588861-31588861 2:31365995-31365995
48 XDH NM_000379.4(XDH):c.1885G>T (p.Val629Phe)SNV Uncertain significance 571131 rs148464316 2:31593316-31593316 2:31370450-31370450
49 MOCOS NM_017947.4(MOCOS):c.1616C>T (p.Ser539Phe)SNV Uncertain significance 571788 rs150119583 18:33795759-33795759 18:36215796-36215796
50 MOCOS NM_017947.4(MOCOS):c.1850T>C (p.Met617Thr)SNV Uncertain significance 572695 rs368198282 18:33800070-33800070 18:36220107-36220107

UniProtKB/Swiss-Prot genetic disease variations for Xanthinuria, Type Ii:

73
# Symbol AA change Variation ID SNP ID
1 MOCOS p.Ala57Pro VAR_027528 rs886037854
2 MOCOS p.Thr294Ile VAR_027533 rs577279030
3 MOCOS p.Arg776Cys VAR_045899 rs750896617

Expression for Xanthinuria, Type Ii

Search GEO for disease gene expression data for Xanthinuria, Type Ii.

Pathways for Xanthinuria, Type Ii

Pathways related to Xanthinuria, Type Ii according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.99 XDH AOX1
2
Show member pathways
11.76 MOCOS AOX1
3 10.39 XDH AOX1
4 9.53 XDH AOX1

GO Terms for Xanthinuria, Type Ii

Biological processes related to Xanthinuria, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 electron transport chain GO:0022900 8.96 XDH AOX1
2 xanthine catabolic process GO:0009115 8.62 XDH AOX1

Molecular functions related to Xanthinuria, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 iron ion binding GO:0005506 9.43 XDH AOX1
2 electron transfer activity GO:0009055 9.4 XDH AOX1
3 flavin adenine dinucleotide binding GO:0050660 9.37 XDH AOX1
4 iron-sulfur cluster binding GO:0051536 9.32 XDH AOX1
5 FAD binding GO:0071949 9.26 XDH AOX1
6 2 iron, 2 sulfur cluster binding GO:0051537 9.16 XDH AOX1
7 molybdopterin cofactor binding GO:0043546 8.96 XDH AOX1
8 xanthine dehydrogenase activity GO:0004854 8.62 XDH AOX1

Sources for Xanthinuria, Type Ii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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