MOCS3

Chr 20AR

molybdenum cofactor synthesis 3

Also known as: MOCODB2, UBA4

NCBI Gene: 27304 ENSG00000124217 UniProt: O95396 OMIM: 609277

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Molybdenum cofactor (MoCo) is necessary for the function of all molybdoenzymes. The protein encoded by this gene adenylates and activates molybdopterin synthase, an enzyme required for biosynthesis of MoCo. This gene contains no introns. A pseudogene of this gene is present on chromosome 14. [provided by RefSeq, Nov 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Molybdenum cofactor deficiency, type B2MIM #621373

Clinical highlights

Gene–disease validity (ClinGen)

Limited · sulfite oxidase deficiency due to molybdenum cofactor deficiency type B2 · AR · ClinGen 2026

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.36

LOEUF

Mechanism· predicted

📖

GeneReview available — MOCS3

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?

1.36LOEUF

pLI 0.000

Z-score 0.64

OE 0.80 (0.49–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.67Z-score

OE missense 0.89 (0.80–0.98)

246 obs / 277.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.80 (0.49–1.36)

0≤0.351.4

Missense OE?0.89 (0.80–0.98)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 10 / 12.5Missense obs/exp: 246 / 277.5Syn Z: 0.01

Background carrier burden — how many people carry a rare variant somewhere in MOCS3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 82

630 rare PASS variants

Rare truncating (LoF)

1 in 1,700

101 rare PASS variants

Rare synonymous (reference)

1 in 190

318 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MOCS3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 1,700
South Asian	~43k	1 in 130	1 in 1,200
Remaining (unassigned)	~30k	1 in 99	1 in 1,800
European (Finnish)	~27k	1 in 370	1 in 3,800
Admixed American	~22k	1 in 160	1 in 2,200
African / African American	~21k	1 in 120	1 in 770
East Asian	~20k	1 in 120	1 in 2,000
Ashkenazi Jewish	~13k	1 in 1,000	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 96	≈ 1 in 950

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓