MOCS1

Chr 6AR

molybdenum cofactor synthesis 1

Also known as: MIG11, MOCOD, MOCS1A, MOCS1B

NCBI Gene: 4337ENSG00000124615UniProt: Q9NZB8

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]

Primary Disease Associations & Inheritance

Molybdenum cofactor deficiency AMIM #252150
AR
625
ClinVar variants
91
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MOCS1
🧬
Gene-Disease Validity (ClinGen)
sulfite oxidase deficiency due to molybdenum cofactor deficiency type A · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
91 Pathogenic / Likely Pathogenic· 268 VUS of 625 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.62Z-score
OE missense 1.12 (1.01–1.24)
257 obs / 230.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.67 (0.43–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (1.01–1.24)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 12 / 18.0Missense obs/exp: 257 / 230.5Syn Z: -0.13

ClinVar Variant Classifications

625 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic42
VUS268
Likely Benign236
Benign21
Conflicting9
49
Pathogenic
42
Likely Pathogenic
268
VUS
236
Likely Benign
21
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
27
2
20
0
49
Likely Pathogenic
30
1
11
0
42
VUS
6
211
39
12
268
Likely Benign
0
6
83
147
236
Benign
0
0
21
0
21
Conflicting
—9
Total63220174159625

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

View in ClinVar →

Protein Context — Lollipop Plot

MOCS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MOCS1-related molybdenum cofactor deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Molybdenum cofactor deficiency A

MIM #252150

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MOCS1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH.
Reiss J et al.·Hum Mutat
2003Review
Molybdenum Cofactor Deficiency in Humans.
Johannes L et al.·Molecules
2022Review
Genetics of molybdenum cofactor deficiency.
Reiss J·Hum Genet
2000Review
Ten novel mutations in the molybdenum cofactor genes MOCS1 and MOCS2 and in vitro characterization of a MOCS2 mutation that abolishes the binding ability of molybdopterin synthase.
Leimkühler S et al.·Hum Genet
2005
A prevalent MOCS2 variant in the Roma population is associated with a novel mild form of molybdenum cofactor deficiency.
Cho SK et al.·Eur J Pediatr
2025
An unusual genetic variant in the MOCS1 gene leads to complete missplicing of an alternatively spliced exon in a patient with molybdenum cofactor deficiency.
Arenas M et al.·J Inherit Metab Dis
2009Case report
Novel pathogenic variant in a mild case of type B molybdenum cofactor deficiency: case report and literature review.
Kinsinger M et al.·BMC Med Genomics
2024Review
Molybdenum cofactor and isolated sulphite oxidase deficiencies: Clinical and molecular spectrum among Egyptian patients.
Zaki MS et al.·Eur J Paediatr Neurol
2016Cohort
A mild case of molybdenum cofactor deficiency defines an alternative route of MOCS1 protein maturation.
Mayr SJ et al.·J Inherit Metab Dis
2018Case report
Mitochondrial genetic landscape and its correlation with immune cell infiltration in preeclampsia: Insights from bioinformatics.
Ye X et al.·J Reprod Immunol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant.
Schwahn BC et al.·Mol Genet Metab
2024
Mocs1 (Molybdenum cofactor synthesis 1) may contribute to lifespan extension in Drosophila.
Lamont EI et al.·MicroPubl Biol
2022🔓 Open Access
[Molybdenum cofactor deficiency caused by MOCS1 gene mutation: a case report].
Wu LH et al.·Zhongguo Dang Dai Er Ke Za Zhi
2021Case report
The effect of dietary protein restriction in a case of molybdenum cofactor deficiency with MOCS1 mutation.
Abe Y et al.·Mol Genet Metab Rep
2021🔓 Open Access
Alternative splicing of the bicistronic gene molybdenum cofactor synthesis 1 (MOCS1) uncovers a novel mitochondrial protein maturation mechanism.
Mayr SJ et al.·J Biol Chem
2020Functional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools