sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1

Summary

sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1 (MONDO:0009644) is a disease caused by MOCS2 (GenCC Definitive), with 5 cohort genes.

At a glance

• Causal gene: MOCS2 (GenCC Definitive)
• Cohort genes: 5
• ClinVar variants: 122

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 B1
Mondo ID	MONDO:0009644
MeSH	C565373
OMIM	252160
Orphanet	308393
DOID	DOID:0111163
UMLS	C1854989
MedGen	340760
GARD	0017387
Is cancer (heuristic)	no

Also known as: combined deficiency of sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase type B · MOCOD type B · MOCODB · molybdenum cofactor deficiency B · molybdenum cofactor deficiency, complementation group B · molybdenum cofactor deficiency, complementation group type B · sulfite oxidase deficiency due to molybdenum cofactor deficiency type B

Data availability: 122 ClinVar variants · 4 GenCC gene-disease records.

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 B1

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

122 retrieved; paginated sample, class counts are floors:

64 uncertain significance, 15 conflicting classifications of pathogenicity, 13 benign, 12 pathogenic, 7 pathogenic/likely pathogenic, 7 likely pathogenic, 2 likely benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1456543	NM_176806.4(MOCS2):c.1A>G (p.Met1Val)	LOC129993881	Pathogenic	criteria provided, multiple submitters, no conflicts
6113	NM_176806.4(MOCS2):c.16C>T (p.Gln6Ter)	LOC129993881	Pathogenic	criteria provided, multiple submitters, no conflicts
813890	NM_176806.4(MOCS2):c.3G>A (p.Met1Ile)	LOC129993881	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1211302	NM_004531.5(MOCS2):c.377+1G>A	MOCS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1236175	NM_176806.4(MOCS2):c.33T>G (p.Tyr11Ter)	MOCS2	Pathogenic	criteria provided, multiple submitters, no conflicts
1236176	NM_004531.5(MOCS2):c.24del (p.Ser9fs)	MOCS2	Pathogenic	criteria provided, single submitter
2153568	NM_176806.4(MOCS2):c.88C>T (p.Gln30Ter)	MOCS2	Pathogenic	criteria provided, multiple submitters, no conflicts
2177297	NM_004531.5(MOCS2):c.118G>T (p.Glu40Ter)	MOCS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2829748	NM_004531.5(MOCS2):c.469dup (p.Thr157fs)	MOCS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2998110	NM_004531.5(MOCS2):c.106_107del (p.Met36fs)	MOCS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3592706	NM_004531.5(MOCS2):c.182_185del (p.Gln61fs)	MOCS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
587508	NM_004531.5(MOCS2):c.2T>G (p.Met1Arg)	MOCS2	Pathogenic	criteria provided, single submitter
6109	NM_004531.5(MOCS2):c.502G>A (p.Glu168Lys)	MOCS2	Pathogenic	no assertion criteria provided
6110	NM_004531.5(MOCS2):c.346_349del (p.Val116fs)	MOCS2	Pathogenic	criteria provided, multiple submitters, no conflicts
6111	NM_004531.5(MOCS2):c.65dup (p.Leu23fs)	MOCS2	Pathogenic	criteria provided, multiple submitters, no conflicts
6112	NM_004531.5(MOCS2):c.3G>A (p.Met1Ile)	MOCS2	Pathogenic	no assertion criteria provided
6114	NM_176806.4(MOCS2):c.19G>T (p.Val7Phe)	MOCS2	Pathogenic	no assertion criteria provided
6115	NM_004531.5(MOCS2):c.567A>C (p.Ter189Tyr)	MOCS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2788808	NM_025215.6(PUS1):c.930del (p.Glu311fs)	PUS1	Pathogenic	criteria provided, multiple submitters, no conflicts
2582660	NM_176806.4(MOCS2):c.18+1G>C	LOC129993881	Likely pathogenic	criteria provided, single submitter
6116	NM_176806.4(MOCS2):c.-8_15del (p.Met1fs)	LOC129993881	Likely pathogenic	criteria provided, single submitter
4845352	NM_032793.5(MFSD2A):c.432_437del (p.Trp146_Tyr147del)	MFSD2A	Likely pathogenic	criteria provided, single submitter
2441783	NM_004531.5(MOCS2):c.58del (p.Ser20fs)	MOCS2	Likely pathogenic	criteria provided, single submitter
452473	NM_176806.4(MOCS2):c.114G>A (p.Trp38Ter)	MOCS2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
6108	NM_004531.5(MOCS2):c.539_540del (p.Lys180fs)	MOCS2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
930940	NM_176806.4(MOCS2):c.30_34del (p.Leu10fs)	MOCS2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
903790	NM_004531.5(MOCS2):c.*2045G>A	ITGA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
353883	NM_004531.5(MOCS2):c.-622G>A	LOC129993881	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
353884	NM_176806.4(MOCS2):c.14G>A (p.Cys5Tyr)	LOC129993881	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1043881	NM_004531.5(MOCS2):c.45G>A (p.Thr15=)	MOCS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 5 · 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
MOCS2	Definitive	Autosomal recessive	sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MOCS2	Orphanet:308393	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B
PUS1	Orphanet:2598	Mitochondrial myopathy and sideroblastic anemia
MFSD2A	Orphanet:2512	Autosomal recessive primary microcephaly
ITGA2	Orphanet:853	Fetal and neonatal alloimmune thrombocytopenia
MOCS1	Orphanet:308386	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MOCS2	HGNC:7193	ENSG00000164172	O96007	Molybdopterin synthase catalytic subunit	gencc,clinvar
PUS1	HGNC:15508	ENSG00000177192	Q9Y606	Pseudouridylate synthase 1 homolog	clinvar
MFSD2A	HGNC:25897	ENSG00000168389	Q8NA29	Sodium-dependent lysophosphatidylcholine symporter 1	clinvar
ITGA2	HGNC:6137	ENSG00000164171	P17301	Integrin alpha-2	clinvar
MOCS1	HGNC:7190	ENSG00000124615	Q9NZB8	Molybdenum cofactor biosynthesis protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MOCS2	Molybdopterin synthase catalytic subunit	Catalytic subunit of the molybdopterin synthase complex, a complex that catalyzes the conversion of precursor Z into molybdopterin.
PUS1	Pseudouridylate synthase 1 homolog	Pseudouridylate synthase that catalyzes pseudouridylation of tRNAs and mRNAs.
MFSD2A	Sodium-dependent lysophosphatidylcholine symporter 1	Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function.
ITGA2	Integrin alpha-2	Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin.
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).

Protein-family classification

Druggable: 5 · 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	7.2×	0.015
Transporter	1	15.6×	0.094
Antibody/Immunoglobulin	1	5.8×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MOCS2	Enzyme (other)	yes	2.8.1.12	Mopterin_biosynth_MoaE, MOCS2B_euk, MoaE_sf
PUS1	Enzyme (other)	yes	5.4.99.B22	PsdUridine_synth_TruA, TruA/RsuA/RluB/E/F_N, PsdUridine_synth_TruA_C
MFSD2A	Transporter	yes		MFS_trans_sf, MFS_2
ITGA2	Antibody/Immunoglobulin	yes		Integrin_alpha, VWF_A, FG-GAP
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

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
anterior cingulate cortex	1
prefrontal cortex	1
right adrenal gland	1
granulocyte	1
lower esophagus mucosa	1
mucosa of transverse colon	1
ileal mucosa	1
right lobe of liver	1
skin of abdomen	1
epithelium of nasopharynx	1
nasopharynx	1
ventricular zone	1
apex of heart	1
popliteal artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MOCS2	282	ubiquitous	marker	right adrenal gland, anterior cingulate cortex, prefrontal cortex
PUS1	229	ubiquitous	marker	granulocyte, mucosa of transverse colon, lower esophagus mucosa
MFSD2A	220	ubiquitous	marker	right lobe of liver, skin of abdomen, ileal mucosa
ITGA2	240	ubiquitous	marker	ventricular zone, epithelium of nasopharynx, nasopharynx
MOCS1	245	ubiquitous	marker	apex of heart, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PUS1	2,688
ITGA2	2,578
MOCS1	1,494
MOCS2	1,345
MFSD2A	1,054

Intra-cohort edges

A	B	Sources
MOCS1	MOCS2	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGA2	P17301	17
PUS1	Q9Y606	6
MOCS2	O96007	2
MFSD2A	Q8NA29	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: 28. Enrichment computed across 5 evidence-associated genes (5 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 5 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	2	652.6×	9e-05	MOCS2, MOCS1
CHL1 interactions	1	253.8×	0.037	ITGA2
tRNA modification in the mitochondrion	1	207.6×	0.037	PUS1
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	1	175.7×	0.037	ITGA2
Platelet Adhesion to exposed collagen	1	134.3×	0.037	ITGA2
MET promotes cell motility	1	120.2×	0.037	ITGA2
Syndecan interactions	1	84.6×	0.037	ITGA2
Synthesis of PC	1	81.6×	0.037	MFSD2A
Laminin interactions	1	76.1×	0.037	ITGA2
MET activates PTK2 signaling	1	76.1×	0.037	ITGA2
Signaling by MET	1	63.4×	0.040	ITGA2
tRNA modification in the nucleus and cytosol	1	58.6×	0.040	PUS1
Metabolism of water-soluble vitamins and cofactors	1	36.2×	0.055	MOCS2
MITF-M-dependent gene expression	1	36.2×	0.055	ITGA2
Non-integrin membrane-ECM interactions	1	30.9×	0.057	ITGA2
ECM proteoglycans	1	30.1×	0.057	ITGA2
Integrin cell surface interactions	1	26.9×	0.060	ITGA2
L1CAM interactions	1	24.0×	0.060	ITGA2
Metabolism of vitamins and cofactors	1	23.3×	0.060	MOCS2
MITF-M-regulated melanocyte development	1	22.8×	0.060	ITGA2
Extracellular matrix organization	1	12.6×	0.102	ITGA2
Signaling by Receptor Tyrosine Kinases	1	10.3×	0.118	ITGA2
Axon guidance	1	9.0×	0.129	ITGA2
Nervous system development	1	8.6×	0.130	ITGA2
Hemostasis	1	7.2×	0.147	ITGA2
Developmental Biology	1	2.9×	0.324	ITGA2
Metabolism	1	2.3×	0.376	MOCS2
Signal Transduction	1	2.0×	0.404	ITGA2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 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	2	963.0×	1e-04	MOCS2, MOCS1
lysophospholipid translocation	1	3370.4×	0.006	MFSD2A
regulation of phosphatidylethanolamine metabolic process	1	3370.4×	0.006	MFSD2A
obsolete regulation of phosphatidylserine metabolic process	1	3370.4×	0.006	MFSD2A
hypotonic response	1	1685.2×	0.007	ITGA2
regulation of phosphatidylcholine metabolic process	1	1685.2×	0.007	MFSD2A
molybdopterin cofactor biosynthetic process	1	1123.5×	0.007	MOCS2
mitochondrial tRNA pseudouridine synthesis	1	1123.5×	0.007	PUS1
carbohydrate transport	1	842.6×	0.007	MFSD2A
negative regulation of fatty acid beta-oxidation	1	842.6×	0.007	MFSD2A
response to L-ascorbic acid	1	842.6×	0.007	ITGA2
collagen-activated signaling pathway	1	842.6×	0.007	ITGA2
response to parathyroid hormone	1	842.6×	0.007	ITGA2
positive regulation of cell projection organization	1	674.1×	0.007	ITGA2
lysophospholipid transport	1	674.1×	0.007	MFSD2A
lipid transport across blood-brain barrier	1	674.1×	0.007	MFSD2A
photoreceptor cell morphogenesis	1	561.7×	0.007	MFSD2A
tRNA pseudouridine synthesis	1	561.7×	0.007	PUS1
regulation of neuron projection arborization	1	561.7×	0.007	MFSD2A
substrate-dependent cell migration	1	481.5×	0.008	ITGA2
positive regulation of transmission of nerve impulse	1	481.5×	0.008	ITGA2
response to amine	1	374.5×	0.009	ITGA2
retina morphogenesis in camera-type eye	1	374.5×	0.009	MFSD2A
retinal pigment epithelium development	1	337.0×	0.009	MFSD2A
transcytosis	1	337.0×	0.009	MFSD2A
mRNA pseudouridine synthesis	1	337.0×	0.009	PUS1
mesodermal cell differentiation	1	306.4×	0.009	ITGA2
skin morphogenesis	1	280.9×	0.009	ITGA2
positive regulation of positive chemotaxis	1	280.9×	0.009	ITGA2
establishment of blood-brain barrier	1	280.9×	0.009	MFSD2A

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 2 of 5 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MOCS2	0	0
PUS1	0	0
MFSD2A	0	0
ITGA2	0	0
MOCS1	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
ITGA2	21	Binding:20, Functional:1
PUS1	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MOCS2	2.8.1.12	molybdopterin synthase
PUS1	5.4.99.B22
MOCS1	4.1.99.22, 4.6.1.17	GTP 3’,8-cyclase, cyclic pyranopterin monophosphate synthase

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	4	MOCS2, PUS1, MFSD2A, ITGA2
D	Druggable family + AlphaFold only, no drug	1	MOCS1
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MOCS2	0	—
PUS1	6	—
MFSD2A	0	—
ITGA2	21	—
MOCS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.