MOCS2

Chr 5AR

molybdenum cofactor synthesis 2

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

NCBI Gene: 4338ENSG00000164172UniProt: O96007

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]

Primary Disease Associations & Inheritance

Molybdenum cofactor deficiency B1MIM #252160
AR
414
ClinVar variants
63
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MOCS2
🧬
Gene-Disease Validity (ClinGen)
sulfite oxidase deficiency due to molybdenum cofactor deficiency type B · 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
63 Pathogenic / Likely Pathogenic· 146 VUS of 414 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.
1.39LOEUF
pLI 0.000
Z-score 0.79
OE 0.71 (0.39–1.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?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.
-0.08Z-score
OE missense 1.02 (0.87–1.21)
101 obs / 98.8 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.0.71 (0.39–1.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.87–1.21)
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.0.86
0≤1.21.6
LoF obs/exp: 6 / 8.5Missense obs/exp: 101 / 98.8Syn Z: 0.71

ClinVar Variant Classifications

414 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic20
VUS146
Likely Benign155
Benign30
Conflicting20
43
Pathogenic
20
Likely Pathogenic
146
VUS
155
Likely Benign
30
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
6
21
0
43
Likely Pathogenic
15
1
4
0
20
VUS
2
100
42
2
146
Likely Benign
0
14
75
66
155
Benign
0
2
28
0
30
Conflicting
—20
Total3312317068414

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

View in ClinVar →

Protein Context — Lollipop Plot

MOCS2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MOCS2-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 B1

MIM #252160

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MOCS2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Clinical and Molecular Characteristics of Molybdenum Cofactor Deficiency Due to MOCS2 Mutations.
Arican P et al.·Pediatr Neurol
2019Review
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
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
Genetics of molybdenum cofactor deficiency.
Reiss J·Hum Genet
2000Review
Live Birth of a Healthy Child in a Couple with Identical mtDNA Carrying a Pathogenic c.471_477delTTTAAAAinsG Variant in the MOCS2 Gene.
Tofilo M et al.·Genes (Basel)
2023Case 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
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
Genotype-Phenotype Dissociation in Two Taiwanese Children with Molybdenum Cofactor Deficiency Caused by MOCS2 Mutation.
Lee HF et al.·Neuropediatrics
2022Case report
Molybdenum cofactor and isolated sulphite oxidase deficiencies: Clinical and molecular spectrum among Egyptian patients.
Zaki MS et al.·Eur J Paediatr Neurol
2016Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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