sulfite oxidase deficiency due to molybdenum cofactor deficiency type B2

Summary

sulfite oxidase deficiency due to molybdenum cofactor deficiency type B2 (MONDO:0980701) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	sulfite oxidase deficiency due to molybdenum cofactor deficiency type B2
Mondo ID	MONDO:0980701
OMIM	621373
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn metal metabolism disorder › sulfite oxidase deficiency due to molybdenum cofactor deficiency › sulfite oxidase deficiency due to molybdenum cofactor deficiency type B2

Related subtypes (3): sulfite oxidase deficiency due to molybdenum cofactor deficiency type A, sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1, sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4278931	A257T	MOCS3	Pathogenic	no assertion criteria provided
4278932	MCOS3, GLN459TER	MOCS3	Pathogenic	no assertion criteria provided
4278933	L109V	MOCS3	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MOCS3	HGNC:15765	ENSG00000124217	O95396	Adenylyltransferase and sulfurtransferase MOCS3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MOCS3	Adenylyltransferase and sulfurtransferase MOCS3	Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MOCS3	Enzyme (other)	yes	2.7.7.80	ThiF_NAD_FAD-bd, Rhodanese-like_dom, MOCS3/Uba4

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MOCS3	188	ubiquitous	yes	sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MOCS3	2,263

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MOCS3	O95396	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Molybdenum cofactor biosynthesis	1	1631.4×	0.002	MOCS3
Metabolism of water-soluble vitamins and cofactors	1	181.3×	0.011	MOCS3
Metabolism of vitamins and cofactors	1	116.5×	0.011	MOCS3
Metabolism	1	11.6×	0.086	MOCS3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tRNA wobble position uridine thiolation	1	4213.0×	4e-04	MOCS3
protein urmylation	1	4213.0×	4e-04	MOCS3
tRNA thio-modification	1	4213.0×	4e-04	MOCS3
Mo-molybdopterin cofactor biosynthetic process	1	2407.4×	5e-04	MOCS3
tRNA wobble uridine modification	1	1203.7×	8e-04	MOCS3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MOCS3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MOCS3	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MOCS3	2.7.7.80, 2.8.1.11	molybdopterin-synthase adenylyltransferase, molybdopterin synthase sulfurtransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	MOCS3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MOCS3	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.