MOCS2

molybdenum cofactor synthesis 2

Basic information

Region (hg38): 5:53095678-53110063

Links

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

Phenotypes

GenCC

Source: genCC

• sulfite oxidase deficiency due to molybdenum cofactor deficiency type B (Moderate), mode of inheritance: AR
• sulfite oxidase deficiency due to molybdenum cofactor deficiency type B (Strong), mode of inheritance: AR
• sulfite oxidase deficiency due to molybdenum cofactor deficiency type B (Definitive), mode of inheritance: AR
• sulfite oxidase deficiency due to molybdenum cofactor deficiency type B (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 (234 variants)
• Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B (74 variants)
• Platelet-type bleeding disorder 9 (11 variants)
• Combined molybdoflavoprotein enzyme deficiency (8 variants)
• Inborn genetic diseases (7 variants)
• not specified (2 variants)
• Abnormality of metabolism/homeostasis (1 variants)
• Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A (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.

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			1	39		40
missense			82	13	2	97
nonsense	7	1				8
start loss	1	2		1		4
frameshift	10	3	1			14
inframe indel			1			1
splice donor/acceptor (+/-2bp)		4				4
splice region			4	9	1	14
non coding		3	31	30	24	88
Total	18	13	116	83	26

Highest pathogenic variant AF is 0.000112

Variants in MOCS2

This is a list of pathogenic ClinVar variants found in the MOCS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-53095702-T-C		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Likely benign (Jan 13, 2018)
5-53095725-C-A		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Jan 12, 2018)
5-53095927-T-G		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Jan 13, 2018)
5-53095930-C-G		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Jan 13, 2018)
5-53095951-C-A		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Benign (Jan 13, 2018)
5-53095993-C-G		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Jan 12, 2018)
5-53096020-T-G		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B • Platelet-type bleeding disorder 9	Benign (Jan 13, 2018)
5-53096187-G-A		Platelet-type bleeding disorder 9 • Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Benign (Jan 13, 2018)
5-53096245-A-G		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Likely benign (Jan 13, 2018)
5-53096444-G-A		Platelet-type bleeding disorder 9 • Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Benign (Jan 13, 2018)
5-53096557-C-T		Platelet-type bleeding disorder 9 • Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Conflicting classifications of pathogenicity (Jan 13, 2018)
5-53096570-C-T		Platelet-type bleeding disorder 9 • Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Benign (Jan 13, 2018)
5-53096684-T-C		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Mar 16, 2018)
5-53096689-C-T		Platelet-type bleeding disorder 9 • Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Benign/Likely benign (Apr 01, 2023)
5-53096730-G-A		Platelet-type bleeding disorder 9 • Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Benign (Jan 13, 2018)
5-53096929-A-G		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Benign (Jan 12, 2018)
5-53096944-C-T		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Jan 13, 2018)
5-53097057-C-T		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Jan 13, 2018)
5-53097058-G-T		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Benign (Jan 12, 2018)
5-53097119-G-A		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Jan 13, 2018)
5-53097178-C-T		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Jan 13, 2018)
5-53097318-G-C		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Jan 13, 2018)
5-53097435-C-T		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Jan 12, 2018)
5-53097591-C-T		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Benign (Jan 13, 2018)
5-53097726-A-G		Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Uncertain significance (Jan 13, 2018)

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
0.000461	0.682	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

Haploinsufficiency Scores

• pHI: 0.0696
• hipred: N
• hipred_score: 0.253
• ghis: 0.443

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

Mouse Genome Informatics

• Gene name: Mocs2
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism 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); 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; hearing/vestibular/ear 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); renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

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