MOCS2

molybdenum cofactor synthesis 2

Basic information

Region (hg38): 5:53095679-53110063

Links

ENSG00000164172 ∙ NCBI:4338 ∙ OMIM:603708 ∙ HGNC:7193 ∙ Uniprot:O96007, O96033 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 26.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_004531.5	NP_004522.1	5	yes	-
ENST00000396954.8	ENSP00000380157.3	5	yes	-
NM_176806.4	NP_789776.1	3	-	yes
ENST00000450852.8	ENSP00000411022.3	3	-	yes

Phenotypes

GenCC

Source: genCC

• sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1 (Moderate), mode of inheritance: AR
• sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1 (Definitive), mode of inheritance: AR
• sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1 (Strong), mode of inheritance: AR
• sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Molybdenum cofactor deficiency, type B	AR	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	Biochemical; Neurologic	11746050; 16021469; 16429380; 19544009; 21031595

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MOCS2 gene.

• not_provided (245 variants)
• Sulfite_oxidase_deficiency_due_to_molybdenum_cofactor_deficiency_type_B1 (54 variants)
• Inborn_genetic_diseases (17 variants)
• MOCS2-related_disorder (5 variants)
• not_specified (4 variants)
• Combined_molybdoflavoprotein_enzyme_deficiency (3 variants)
• Abnormality_of_metabolism/homeostasis (1 variants)
• MOCS2-related_molybdenum_cofactor_deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MOCS2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_004531.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		2	4	51		57
missense	1	2	69	13	3	88
nonsense	3	1	2			6
start loss	2			1		3
frameshift	15	6	1			22
splice donor/acceptor (+/-2bp)		4				4
Total	21	15	76	65	3

Highest pathogenic variant AF is 0.00010658232

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MOCS2	protein_coding	protein_coding	ENST00000396954	5	14385

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125712	0	34	125746	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0788	101	98.8	1.02	0.00000482	1229
Missense in Polyphen		21	26.575	0.79021		322
Synonymous	0.710	34	39.7	0.857	0.00000241	340
Loss of Function	0.793	6	8.49	0.707	3.54e-7	120

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000838	0.000832
European (Non-Finnish)	0.0000707	0.0000703
Middle Eastern	0.0000544	0.0000544
South Asian	0.000164	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of the molybdopterin synthase complex, a complex that catalyzes the conversion of precursor Z into molybdopterin. Acts by mediating the incorporation of 2 sulfur atoms from thiocarboxylated MOCS2A into precursor Z to generate a dithiolene group. {ECO:0000255|HAMAP-Rule:MF_03052, ECO:0000269|PubMed:12732628, ECO:0000269|PubMed:15073332}.
• Pathway: Folate biosynthesis - Homo sapiens (human);Sulfur relay system - Homo sapiens (human);Metabolism;Molybdenum cofactor biosynthesis;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;molybdenum cofactor biosynthesis (Consensus)

Recessive Scores

• pRec: 0.175

Intolerance Scores

• loftool: 0.860
• rvis_EVS: 0.53
• rvis_percentile_EVS: 80.73

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.141

Gene Damage Prediction

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

Gene ontology

• Biological process: Mo-molybdopterin cofactor biosynthetic process;molybdopterin cofactor biosynthetic process
• Cellular component: nucleus;cytosol;nuclear speck;molybdopterin synthase complex
• Molecular function: molybdopterin synthase activity