MOCOS

molybdenum cofactor sulfurase

Basic information

Region (hg38): 18:36187496-36272157

Links

ENSG00000075643 ∙ NCBI:55034 ∙ OMIM:613274 ∙ HGNC:18234 ∙ Uniprot:Q96EN8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• xanthinuria type II (Strong), mode of inheritance: AR
• xanthinuria type II (Supportive), mode of inheritance: AR
• xanthinuria type II (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Xanthinuria, type II	AR	Biochemical; Renal	Most individuals are described as asymptomatic, but xanthine deposition can lead to myositis, urinary tract calculi, and acute renal failure and dietary measures (eg, purine restricted, increased fluid intake) and medical measures (eg, allopurinol) may be beneficial	Biochemical; Musculoskeletal; Renal	11302742; 14624414; 17368066; 25967871

ClinVar

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

• Xanthinuria type II (234 variants)
• not provided (71 variants)
• Inborn genetic diseases (42 variants)
• MOCOS-related condition (2 variants)
• Primary hyperoxaluria (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MOCOS 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				53	7	60
missense			129	13	11	153
nonsense	3	1	1			5
start loss						0
frameshift	3	2	1			6
inframe indel						0
splice donor/acceptor (+/-2bp)		5	1			6
splice region			5	4		9
non coding				27	47	74
Total	6	8	132	93	65

Highest pathogenic variant AF is 0.0000985

Variants in MOCOS

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

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

Position	Type	Phenotype	Significance	ClinVar
18-36187497-G-T			Likely benign (Dec 22, 2020)
18-36187516-G-A			Benign (Nov 12, 2018)
18-36187535-G-A		MOCOS-related disorder	Benign (Dec 05, 2019)
18-36187543-G-A		Xanthinuria type II	Uncertain significance (Jan 28, 2022)
18-36187546-G-C		Xanthinuria type II • not specified	Uncertain significance (Nov 10, 2022)
18-36187547-G-C		Xanthinuria type II	Uncertain significance (Oct 09, 2022)
18-36187553-C-T		Xanthinuria type II	Uncertain significance (Feb 09, 2022)
18-36187554-G-A		Xanthinuria type II	Benign/Likely benign (Jan 25, 2024)
18-36187579-A-T		Xanthinuria type II	Uncertain significance (Nov 27, 2023)
18-36187579-AC-A		Xanthinuria type II	Pathogenic (Aug 01, 2023)
18-36187586-C-T		Xanthinuria type II	Uncertain significance (Oct 07, 2022)
18-36187588-G-T		Xanthinuria type II	Uncertain significance (Apr 18, 2020)
18-36187593-C-T		Xanthinuria type II	Likely benign (Jul 13, 2021)
18-36187600-C-T		Xanthinuria type II	Uncertain significance (Nov 03, 2021)
18-36187605-C-A		Xanthinuria type II	Benign (Jan 31, 2024)
18-36187628-A-G		Xanthinuria type II	Uncertain significance (Aug 21, 2022)
18-36187630-G-C		not specified	Uncertain significance (Nov 05, 2021)
18-36187630-G-T		Xanthinuria type II	Uncertain significance (Aug 17, 2021)
18-36187637-G-A		not specified	Uncertain significance (Aug 14, 2023)
18-36187672-C-T		Xanthinuria type II	Uncertain significance (Sep 13, 2022)
18-36187673-G-A		Xanthinuria type II	Uncertain significance (Sep 06, 2022)
18-36187692-C-A		Xanthinuria type II	Benign/Likely benign (Jan 25, 2024)
18-36187693-G-GGGCA		Xanthinuria type II	Benign/Likely benign (Jan 08, 2024)
18-36187701-T-C		Xanthinuria type II	Benign (Dec 20, 2023)
18-36187786-G-A			Benign (Jan 23, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MOCOS	protein_coding	protein_coding	ENST00000261326	15	84639

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.62e-19	0.0214	125434	0	314	125748	0.00125

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.450	503	475	1.06	0.0000276	5797
Missense in Polyphen		178	175.36	1.015		2170
Synonymous	-0.170	191	188	1.02	0.0000111	1784
Loss of Function	0.795	32	37.2	0.859	0.00000181	447

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00184	0.00184
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000381	0.000381
Finnish	0.000277	0.000277
European (Non-Finnish)	0.00137	0.00137
Middle Eastern	0.000381	0.000381
South Asian	0.00307	0.00298
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sulfurates the molybdenum cofactor. Sulfation of molybdenum is essential for xanthine dehydrogenase (XDH) and aldehyde oxidase (ADO) enzymes in which molybdenum cofactor is liganded by 1 oxygen and 1 sulfur atom in active form. In vitro, the C-terminal domain is able to reduce N-hydroxylated prodrugs, such as benzamidoxime. {ECO:0000255|HAMAP-Rule:MF_03050, ECO:0000269|PubMed:16973608}.
• Disease: DISEASE: Xanthinuria 2 (XAN2) [MIM:603592]: 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. {ECO:0000269|PubMed:11302742, ECO:0000269|PubMed:14624414, ECO:0000269|PubMed:17368066, ECO:0000269|Ref.12}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Folate biosynthesis - Homo sapiens (human);Metabolism;Molybdenum cofactor biosynthesis;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;thio-molybdenum cofactor biosynthesis (Consensus)

Recessive Scores

• pRec: 0.151

Intolerance Scores

• loftool: 0.337
• rvis_EVS: 1.72
• rvis_percentile_EVS: 96.49

Haploinsufficiency Scores

• pHI: 0.125
• hipred: N
• hipred_score: 0.243
• ghis: 0.414

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.201

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mocos

Gene ontology

• Biological process: Mo-molybdopterin cofactor biosynthetic process;molybdopterin cofactor biosynthetic process;molybdopterin cofactor metabolic process
• Cellular component: cellular_component;cytosol
• Molecular function: protein binding;Mo-molybdopterin cofactor sulfurase activity;lyase activity;molybdenum ion binding;pyridoxal phosphate binding;molybdenum cofactor sulfurtransferase activity