MOCS3

molybdenum cofactor synthesis 3, the group of Ubiquitin like modifier activating enzymes

Basic information

Region (hg38): 20:50958818-50963929

Links

ENSG00000124217 ∙ NCBI:27304 ∙ OMIM:609277 ∙ HGNC:15765 ∙ Uniprot:O95396 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MOCS3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MOCS3 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	64	4	75
missense			139	2	3	144
nonsense			7			7
start loss			3			3
frameshift			7			7
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	164	67	7

Variants in MOCS3

This is a list of pathogenic ClinVar variants found in the MOCS3 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-50958843-A-C			Uncertain significance (Sep 08, 2023)
20-50958843-A-G			Uncertain significance (Sep 08, 2023)
20-50958844-T-C			Uncertain significance (Aug 16, 2022)
20-50958846-G-T			Uncertain significance (Aug 15, 2022)
20-50958848-T-C			Likely benign (Jun 26, 2022)
20-50958850-C-G			Uncertain significance (Mar 18, 2023)
20-50958850-C-T			Uncertain significance (Jan 28, 2024)
20-50958853-G-A			Uncertain significance (May 18, 2023)
20-50958863-A-C		MOCS3-related disorder	Likely benign (Feb 01, 2024)
20-50958869-C-T			Likely benign (May 30, 2023)
20-50958874-A-G			Uncertain significance (Nov 24, 2023)
20-50958889-A-G			Uncertain significance (Dec 28, 2023)
20-50958890-A-C			Uncertain significance (Mar 24, 2021)
20-50958896-G-A			Uncertain significance (Dec 12, 2023)
20-50958900-G-A			Uncertain significance (Apr 12, 2022)
20-50958911-G-T			Likely benign (Jul 07, 2023)
20-50958918-C-T			Uncertain significance (Nov 08, 2022)
20-50958923-G-A			Likely benign (Jul 12, 2022)
20-50958924-C-T			Likely benign (Aug 31, 2022)
20-50958927-G-A		not specified	Uncertain significance (Dec 30, 2023)
20-50958927-G-T			Uncertain significance (Aug 02, 2021)
20-50958928-C-G			Uncertain significance (Nov 22, 2022)
20-50958932-G-C			Uncertain significance (Nov 02, 2023)
20-50958936-C-G			Uncertain significance (Jan 01, 2024)
20-50958951-G-C			Uncertain significance (May 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MOCS3	protein_coding	protein_coding	ENST00000244051	1	2458

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000184	0.453	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.671	246	277	0.887	0.0000154	2880
Missense in Polyphen		63	81.343	0.77449		880
Synonymous	0.00706	129	129	0.999	0.00000681	1072
Loss of Function	0.644	10	12.5	0.803	6.76e-7	136

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Also essential during biosynthesis of the molybdenum cofactor. Acts by mediating the C-terminal thiocarboxylation of sulfur carriers URM1 and MOCS2A. Its N-terminus first activates URM1 and MOCS2A as acyl-adenylates (-COAMP), then the persulfide sulfur on the catalytic cysteine is transferred to URM1 and MOCS2A to form thiocarboxylation (-COSH) of their C-terminus. The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as nucleophile towards URM1 and MOCS2A. Subsequently, a transient disulfide bond is formed. Does not use thiosulfate as sulfur donor; NFS1 probably acting as a sulfur donor for thiocarboxylation reactions. {ECO:0000255|HAMAP-Rule:MF_03049, ECO:0000269|PubMed:15073332, ECO:0000269|PubMed:19017811}.
• Pathway: 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: 0.196

Intolerance Scores

• loftool: 0.641
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.16

Haploinsufficiency Scores

• pHI: 0.188
• hipred: N
• hipred_score: 0.309
• ghis: 0.563

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.918

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mocs3

Gene ontology

• Biological process: tRNA wobble uridine modification;tRNA wobble position uridine thiolation;Mo-molybdopterin cofactor biosynthetic process;enzyme active site formation via cysteine modification to L-cysteine persulfide;molybdopterin cofactor biosynthetic process;protein urmylation;tRNA thio-modification
• Cellular component: cytoplasm;cytosol
• Molecular function: thiosulfate sulfurtransferase activity;protein binding;ATP binding;nucleotidyltransferase activity;sulfurtransferase activity;URM1 activating enzyme activity;metal ion binding;molybdopterin-synthase sulfurtransferase activity;molybdopterin-synthase adenylyltransferase activity