MOCS1

Chr 6AR

molybdenum cofactor synthesis 1

Also known as: MIG11, MOCOD, MOCS1A, MOCS1B

NCBI Gene: 4337 ENSG00000124615 UniProt: Q9NZB8 OMIM: 603707

The protein catalyzes the conversion of GTP to cyclic pyranopterin monophosphate, the first step in molybdenum cofactor biosynthesis, with isoform MOCS1A performing GTP cyclization and isoform MOCS1B converting the intermediate to cyclic pyranopterin monophosphate. Biallelic mutations cause molybdenum cofactor deficiency type A, inherited in an autosomal recessive pattern. Loss-of-function mutations disrupt this essential cofactor synthesis pathway required for multiple molybdenum-dependent enzymes.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Molybdenum cofactor biosynthesis is a conserved pathway leading to the biological activation of molybdenum. The protein encoded by this gene is involved in this pathway. This gene was originally thought to produce a bicistronic mRNA with the potential to produce two proteins (MOCS1A and MOCS1B) from adjacent open reading frames. However, only the first open reading frame (MOCS1A) has been found to encode a protein from the putative bicistronic mRNA, whereas additional splice variants are likely to produce a fusion between the two open reading frames. This gene is defective in patients with molybdenum cofactor deficiency, type A. A related pseudogene has been identified on chromosome 16. [provided by RefSeq, Nov 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.081 OMIM phenotype

Clinical Summary— MOCS1

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Gene-Disease Validity (ClinGen)

sulfite oxidase deficiency due to molybdenum cofactor deficiency type A · 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

96 unique Pathogenic / Likely Pathogenic· 381 VUS of 827 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MOCS1

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?

1.08LOEUF

pLI 0.000

Z-score 1.30

OE 0.67 (0.43–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.62Z-score

OE missense 1.12 (1.01–1.24)

257 obs / 230.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.67 (0.43–1.08)

0≤0.351.4

Missense OE?1.12 (1.01–1.24)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 12 / 18.0Missense obs/exp: 257 / 230.5Syn Z: -0.13

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveMOCS1-related molybdenum cofactor deficiencyLOFAR

This gene — mechanism propensity

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

0.7132th %ile

GOF

0.5170th %ile

LOF

0.4038th %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

827 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48

Likely Pathogenic48

VUS381

Likely Benign258

Benign40

Conflicting43

Pathogenic

Likely Pathogenic

381

VUS

258

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	42	2	4	0	48
Likely Pathogenic	40	3	5	0	48
VUS	8	289	71	13	381
Likely Benign	0	8	90	160	258
Benign	0	5	32	3	40
Conflicting	—				43
Total	90	307	202	176	818

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap MOCS1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →