Sulfite oxidase deficiency due to molybdenum cofactor deficiency

Summary

Sulfite oxidase deficiency due to molybdenum cofactor deficiency (MONDO:0020480) is a disease with 3 cohort genes. The dominant Reactome pathway is Molybdenum cofactor biosynthesis (3 cohort genes).

At a glance

• Cohort genes: 3
• ClinVar variants: 9

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
Mondo ID	MONDO:0020480
OMIM	252150
Orphanet	99732
DOID	DOID:0111165
ICD-11	819219337
UMLS	C0268119
MedGen	75652
GARD	0003705
Is cancer (heuristic)	no

Also known as: combined deficiency of sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase · combined deficiency of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase · MOCOD

Data availability: 9 ClinVar variants · 1 GenCC gene-disease record · 1 cell line.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

Related subtypes (8): familial periodic paralysis, hereditary hemochromatosis, acrodermatitis enteropathica, atransferrinemia, Wilson disease, Menkes disease, familial primary hypomagnesemia, pseudohypoparathyroidism

Subtypes (4): 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, sulfite oxidase deficiency due to molybdenum cofactor deficiency type B2

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

9 retrieved; paginated sample, class counts are floors:

5 pathogenic, 2 conflicting classifications of pathogenicity, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3339319	NM_001358530.2(MOCS1):c.502C>T (p.Gln168Ter)	MOCS1	Pathogenic	criteria provided, single submitter
1236175	NM_176806.4(MOCS2):c.33T>G (p.Tyr11Ter)	MOCS2	Pathogenic	criteria provided, multiple submitters, no conflicts
2153568	NM_176806.4(MOCS2):c.88C>T (p.Gln30Ter)	MOCS2	Pathogenic	criteria provided, multiple submitters, no conflicts
2902469	NM_004531.5(MOCS2):c.304G>T (p.Glu102Ter)	MOCS2	Pathogenic	criteria provided, multiple submitters, no conflicts
4535652	NC_000005.9:g.(?52391508)(52403052_52404351)del	MOCS2	Pathogenic	criteria provided, single submitter
6118	NM_001358530.2(MOCS1):c.1508_1509del (p.Glu503fs)	MOCS1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2101843	NM_004531.5(MOCS2):c.99-2A>G	MOCS2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2676650	NM_001358530.2(MOCS1):c.949C>T (p.Arg317Cys)	MOCS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1404818	NM_004531.5(MOCS2):c.419C>T (p.Ser140Phe)	MOCS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MOCS3	Moderate	Autosomal recessive	sulfite oxidase deficiency due to molybdenum cofactor deficiency

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MOCS1	Orphanet:308386	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A
MOCS2	Orphanet:308393	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MOCS3	HGNC:15765	ENSG00000124217	O95396	Adenylyltransferase and sulfurtransferase MOCS3	gencc
MOCS1	HGNC:7190	ENSG00000124615	Q9NZB8	Molybdenum cofactor biosynthesis protein 1	clinvar
MOCS2	HGNC:7193	ENSG00000164172	O96007	Molybdopterin synthase catalytic subunit	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).
MOCS1	Molybdenum cofactor biosynthesis protein 1	Isoform MOCS1A and isoform MOCS1B probably form a complex that catalyzes the conversion of 5’-GTP to cyclic pyranopterin monophosphate (cPMP).
MOCS2	Molybdopterin synthase catalytic subunit	Catalytic subunit of the molybdopterin synthase complex, a complex that catalyzes the conversion of precursor Z into molybdopterin.

Protein-family classification

Druggable: 3 · 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)	3	12.0×	6e-04

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
MOCS1	Enzyme (other)	yes	4.1.99.22	MoaA_NifB_PqqE_Fe-S-bd_CS, Mopterin_CF_biosynth-C_dom, Elp3/MiaA/NifB-like_rSAM
MOCS2	Enzyme (other)	yes	2.8.1.12	Mopterin_biosynth_MoaE, MOCS2B_euk, MoaE_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
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
apex of heart	1
popliteal artery	1
tibial artery	1
anterior cingulate cortex	1
prefrontal cortex	1
right adrenal gland	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
MOCS1	245	ubiquitous	marker	apex of heart, popliteal artery, tibial artery
MOCS2	282	ubiquitous	marker	right adrenal gland, anterior cingulate cortex, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MOCS3	2,263
MOCS1	1,494
MOCS2	1,345

Intra-cohort edges

A	B	Sources
MOCS1	MOCS2	string_interaction
MOCS1	MOCS3	string_interaction
MOCS2	MOCS3	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MOCS2	O96007	2
MOCS3	O95396	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MOCS1	Q9NZB8	79.87

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 3 evidence-associated genes (3 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 3 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	3	1631.4×	6e-10	MOCS3, MOCS1, MOCS2
Metabolism of water-soluble vitamins and cofactors	2	120.8×	2e-04	MOCS3, MOCS2
Metabolism of vitamins and cofactors	2	77.7×	3e-04	MOCS3, MOCS2
Metabolism	2	7.7×	0.021	MOCS3, MOCS2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Mo-molybdopterin cofactor biosynthetic process	3	2407.4×	3e-10	MOCS3, MOCS1, MOCS2
molybdopterin cofactor biosynthetic process	1	1872.4×	9e-04	MOCS2
tRNA wobble position uridine thiolation	1	1404.3×	9e-04	MOCS3
protein urmylation	1	1404.3×	9e-04	MOCS3
tRNA thio-modification	1	1404.3×	9e-04	MOCS3
tRNA wobble uridine modification	1	401.2×	0.002	MOCS3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
MOCS1	0	0
MOCS2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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
MOCS1	4.1.99.22, 4.6.1.17	GTP 3’,8-cyclase, cyclic pyranopterin monophosphate synthase
MOCS2	2.8.1.12	molybdopterin synthase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	2	MOCS3, MOCS2
D	Druggable family + AlphaFold only, no drug	1	MOCS1
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MOCS3	2	—
MOCS1	0	—
MOCS2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.