MOCS2

Chr 5AR

molybdenum cofactor synthesis 2

Also known as: MCBPE, MOCO1, MOCODB, MOCODB1, MPTS

NCBI Gene: 4338 ENSG00000164172 UniProt: O96007 OMIM: 603708

The MOCS2 protein serves as the catalytic subunit of molybdopterin synthase, which converts precursor Z into molybdopterin by incorporating sulfur atoms to form the molybdenum cofactor essential for molybdoenzyme function. Autosomal recessive mutations cause molybdenum cofactor deficiency type B, a severe neurometabolic disorder resulting from defective molybdenum cofactor biosynthesis that impairs sulfite oxidase and other molybdoenzymes.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Eukaryotic molybdoenzymes use a unique molybdenum cofactor (MoCo) consisting of a pterin, termed molybdopterin, and the catalytically active metal molybdenum. MoCo is synthesized from precursor Z by the heterodimeric enzyme molybdopterin synthase. The large and small subunits of molybdopterin synthase are both encoded from this gene by overlapping open reading frames. The proteins were initially thought to be encoded from a bicistronic transcript. They are now thought to be encoded from monocistronic transcripts. Alternatively spliced transcripts have been found for this locus that encode the large and small subunits. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.391 OMIM phenotype

Clinical Summary— MOCS2

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Gene-Disease Validity (ClinGen)

sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

53 unique Pathogenic / Likely Pathogenic· 140 VUS of 407 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MOCS2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.39LOEUF

pLI 0.000

Z-score 0.79

OE 0.71 (0.39–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.08Z-score

OE missense 1.02 (0.87–1.21)

101 obs / 98.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.71 (0.39–1.39)

0≤0.351.4

Missense OE?1.02 (0.87–1.21)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 6 / 8.5Missense obs/exp: 101 / 98.8Syn Z: 0.71

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveMOCS2-related molybdenum cofactor deficiencyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.76top 25%

GOF

0.6737th %ile

LOF

0.3164th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

407 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34

Likely Pathogenic19

VUS140

Likely Benign155

Benign30

Conflicting20

Pathogenic

Likely Pathogenic

140

VUS

155

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	26	5	3	0	34
Likely Pathogenic	17	1	1	0	19
VUS	3	101	34	2	140
Likely Benign	0	14	75	66	155
Benign	0	2	28	0	30
Conflicting	—				20
Total	46	123	141	68	398

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

10 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap MOCS2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →