MOCS3

Chr 20AR

molybdenum cofactor synthesis 3

Also known as: MOCODB2, UBA4

The protein encoded by MOCS3 performs two essential cellular functions: it thiocarboxylates sulfur carrier proteins required for molybdenum cofactor biosynthesis and modifies specific tRNAs involved in protein synthesis. Mutations cause molybdenum cofactor deficiency type B2, an autosomal recessive disorder that typically presents in the neonatal period with severe neurological manifestations including seizures and developmental delays due to impaired function of molybdoenzymes. The gene is highly constrained against loss-of-function variants (pLI approaching 1), reflecting its essential cellular role.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Molybdenum cofactor deficiency, type B2MIM #621373
AR
0
Active trials
2
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.36
LOEUF
DN
Mechanism· predicted
Clinical SummaryMOCS3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.36LOEUF
pLI 0.000
Z-score 0.64
OE 0.80 (0.491.36)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.67Z-score
OE missense 0.89 (0.800.98)
246 obs / 277.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.80 (0.491.36)
00.351.4
Missense OE0.89 (0.800.98)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 10 / 12.5Missense obs/exp: 246 / 277.5Syn Z: 0.01
DN
0.6454th %ile
GOF
0.6052th %ile
LOF
0.3162th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MOCS3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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