MOCS1

molybdenum cofactor synthesis 1, the group of Radical S-adenosylmethionine domain containing

Basic information

Region (hg38): 6:39899577-39934551

Links

ENSG00000124615 ∙ NCBI:4337 ∙ OMIM:603707 ∙ HGNC:7190 ∙ Uniprot:Q9NZB8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Molybdenum cofactor deficiency, type A	AR	Biochemical	The disorder can have severe neurologic sequelae, and the use of substitution therapy (with IV-administered purified cyclic pyranopterin monophosphate) has been reported as showing benefit in biochemical parameters as well as clinical/neurologic manifestations	Biochemical; Neurologic; Ophthalmologic	9731530; 10053004; 10327149; 16021469; 20385644; 21031595

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MOCS1 gene.

• Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A (576 variants)
• not provided (51 variants)
• Inborn genetic diseases (49 variants)
• Combined molybdoflavoprotein enzyme deficiency (16 variants)
• not specified (7 variants)
• Intellectual disability (5 variants)
• MOCS1-related condition (4 variants)
• Nephrotic syndrome, type 24 (1 variants)
• DAAM2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MOCS1 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			31	72	3	106
missense	1	4	222	4	5	236
nonsense	6	3	2			11
start loss			2			2
frameshift	15	6	4			25
inframe indel	1		3			4
splice donor/acceptor (+/-2bp)	2	7	1			10
splice region			18	18	1	37
non coding	1	2	90	54	32	179
Total	26	22	355	130	40

Highest pathogenic variant AF is 0.000598

Variants in MOCS1

This is a list of pathogenic ClinVar variants found in the MOCS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-39900079-G-A		Inborn genetic diseases	Likely benign (Feb 06, 2024)
6-39900095-C-T		Inborn genetic diseases	Uncertain significance (Oct 20, 2021)
6-39900139-C-T		DAAM2-related disorder	Likely benign (Dec 13, 2021)
6-39900150-C-T		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
6-39900172-C-T		DAAM2-related disorder	Likely benign (Apr 08, 2019)
6-39900192-A-G		DAAM2-related disorder	Benign (Apr 08, 2019)
6-39900206-A-G		Inborn genetic diseases	Uncertain significance (Dec 13, 2022)
6-39901304-C-T		DAAM2-related disorder	Likely benign (Dec 19, 2022)
6-39901326-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
6-39901332-C-A		Inborn genetic diseases	Uncertain significance (Jun 28, 2022)
6-39901356-G-A		DAAM2-related disorder • Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
6-39901366-G-C		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
6-39901374-G-C		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
6-39901378-C-A		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
6-39901405-G-A		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
6-39901432-G-A		Inborn genetic diseases	Uncertain significance (May 26, 2022)
6-39901434-A-G		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
6-39901450-G-A		Inborn genetic diseases	Uncertain significance (Feb 17, 2022)
6-39901452-C-T		Inborn genetic diseases	Uncertain significance (Nov 07, 2023)
6-39901456-C-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2021)
6-39901459-G-A		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
6-39901459-G-T		DAAM2-related disorder	Likely benign (May 24, 2022)
6-39901462-T-C		Inborn genetic diseases	Uncertain significance (Oct 05, 2022)
6-39901481-CAGTGCCAGGCCTGGGACTGAGGGGA-C		DAAM2-related disorder	Likely benign (Jun 06, 2019)
6-39901804-C-T		DAAM2-related disorder	Benign (Aug 16, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MOCS1	protein_coding	protein_coding	ENST00000373186	9	34937

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.12e-7	0.774	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.621	257	230	1.12	0.0000146	2501
Missense in Polyphen		96	95.424	1.006		1020
Synonymous	-0.133	96	94.4	1.02	0.00000552	791
Loss of Function	1.30	12	18.0	0.668	0.00000106	200

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000675	0.000670
Ashkenazi Jewish	0.000807	0.000794
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000205	0.000202
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform MOCS1A and isoform MOCS1B probably form a complex that catalyzes the conversion of 5'-GTP to cyclic pyranopterin monophosphate (cPMP). MOCS1A catalyzes the cyclization of GTP to (8S)-3',8-cyclo-7,8-dihydroguanosine 5'- triphosphate and MOCS1B catalyzes the subsequent conversion of (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate to cPMP. {ECO:0000269|PubMed:11891227}.
• Pathway: Folate biosynthesis - Homo sapiens (human);Metabolism;Molybdenum cofactor biosynthesis;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.144
• rvis_EVS: 0.11
• rvis_percentile_EVS: 62.1

Haploinsufficiency Scores

• pHI: 0.0524
• hipred: N
• hipred_score: 0.267
• ghis: 0.506

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.168

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mocs1
• Phenotype: renal/urinary system 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); homeostasis/metabolism phenotype; 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

Gene ontology

• Biological process: Mo-molybdopterin cofactor biosynthetic process;molybdopterin cofactor biosynthetic process
• Cellular component: nucleus;cytosol;molybdopterin synthase complex
• Molecular function: GTP binding;metal ion binding;4 iron, 4 sulfur cluster binding;GTP 3',8'-cyclase activity;cyclic pyranopterin monophosphate synthase activity