sulfite oxidase deficiency due to molybdenum cofactor deficiency type A

Summary

sulfite oxidase deficiency due to molybdenum cofactor deficiency type A (MONDO:0009643) is a disease caused by MOCS1 (GenCC Definitive), with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: MOCS1 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 763

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	sulfite oxidase deficiency due to molybdenum cofactor deficiency type A
Mondo ID	MONDO:0009643
MeSH	C565372
OMIM	252150
Orphanet	308386
DOID	DOID:0111164
UMLS	C1854988
MedGen	381530
GARD	0017386
Is cancer (heuristic)	no

Also known as: combined deficiency of sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase type A · MOCOD type A · MOCODA · molybdenum cofactor deficiency A · molybdenum cofactor deficiency, complementation group A · molybdenum cofactor deficiency, complementation group type a

Data availability: 763 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 A

Related subtypes (3): 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

600 retrieved; paginated sample, class counts are floors:

288 uncertain significance, 183 likely benign, 39 pathogenic, 29 likely pathogenic, 29 benign, 21 conflicting classifications of pathogenicity, 8 pathogenic/likely pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1071304	NM_001358530.2(MOCS1):c.291del (p.Ala99fs)	MOCS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1362490	NM_001358530.2(MOCS1):c.1001_1002del (p.Asn333_Ser334insTer)	MOCS1	Pathogenic	criteria provided, single submitter
1388733	NM_001358530.2(MOCS1):c.1150+1G>T	MOCS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1420113	NM_001358530.2(MOCS1):c.1222C>T (p.Gln408Ter)	MOCS1	Pathogenic	criteria provided, single submitter
1433315	NM_001358530.2(MOCS1):c.721del (p.Leu241fs)	MOCS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1448612	NM_001358530.2(MOCS1):c.343del (p.Phe114_Val115insTer)	MOCS1	Pathogenic	criteria provided, single submitter
1453244	NM_001358530.2(MOCS1):c.268G>T (p.Glu90Ter)	MOCS1	Pathogenic	criteria provided, single submitter
1456535	NM_001358530.2(MOCS1):c.48del (p.Ser17fs)	MOCS1	Pathogenic	criteria provided, single submitter
1457660	NM_001358530.2(MOCS1):c.271del (p.Glu91fs)	MOCS1	Pathogenic	criteria provided, single submitter
1459223	NM_001358530.2(MOCS1):c.955C>T (p.Arg319Ter)	MOCS1	Pathogenic	criteria provided, multiple submitters, no conflicts
1511609	NM_001358530.2(MOCS1):c.1102+2T>C	MOCS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2005863	NM_001358530.2(MOCS1):c.1150G>T (p.Glu384Ter)	MOCS1	Pathogenic	criteria provided, single submitter
2017259	NM_001358530.2(MOCS1):c.1332del (p.Gln446fs)	MOCS1	Pathogenic	criteria provided, single submitter
2022501	NM_001358530.2(MOCS1):c.109C>T (p.Arg37Ter)	MOCS1	Pathogenic	criteria provided, single submitter
2027093	NM_001358530.2(MOCS1):c.1160dup (p.Leu387fs)	MOCS1	Pathogenic	criteria provided, single submitter
2045609	NM_001358530.2(MOCS1):c.486del (p.Leu163fs)	MOCS1	Pathogenic	criteria provided, single submitter
2045610	NM_001358530.2(MOCS1):c.484del (p.Arg162fs)	MOCS1	Pathogenic	criteria provided, single submitter
2110087	NM_001358530.2(MOCS1):c.1446_1449dup (p.His484fs)	MOCS1	Pathogenic	criteria provided, single submitter
2424131	NC_000006.11:g.(?39874133)(39902156_?)del	MOCS1	Pathogenic	criteria provided, single submitter
2633148	NM_001358530.2(MOCS1):c.306_309dup (p.Thr104fs)	MOCS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265444	NM_001358530.2(MOCS1):c.1102+1G>A	MOCS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2676644	NM_001358530.2(MOCS1):c.664C>T (p.Arg222Ter)	MOCS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2705520	NM_001358530.2(MOCS1):c.925G>T (p.Glu309Ter)	MOCS1	Pathogenic	criteria provided, single submitter
2709895	NM_001358530.2(MOCS1):c.455del (p.Gly152fs)	MOCS1	Pathogenic	criteria provided, single submitter
2739380	NM_001358530.2(MOCS1):c.1451_1452del (p.His484fs)	MOCS1	Pathogenic	criteria provided, single submitter
2760273	NM_001358530.2(MOCS1):c.1338_1341dup (p.His448fs)	MOCS1	Pathogenic	criteria provided, single submitter
2791335	NM_001358530.2(MOCS1):c.544del (p.Leu182fs)	MOCS1	Pathogenic	criteria provided, single submitter
2798857	NM_001358530.2(MOCS1):c.1501_1504del (p.Asp501fs)	MOCS1	Pathogenic	criteria provided, single submitter
2827183	NM_001358530.2(MOCS1):c.993del (p.Phe331fs)	MOCS1	Pathogenic	criteria provided, single submitter
2833976	NM_001358530.2(MOCS1):c.421C>T (p.Gln141Ter)	MOCS1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 4 · 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
MOCS1	Definitive	Autosomal recessive	sulfite oxidase deficiency due to molybdenum cofactor deficiency type A	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MOCS1	Orphanet:308386	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A
GPHN	Orphanet:308400	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C
GPHN	Orphanet:3197	Hereditary hyperekplexia
DAAM2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome

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
MOCS1	HGNC:7190	ENSG00000124615	Q9NZB8	Molybdenum cofactor biosynthesis protein 1	gencc,clinvar
GPHN	HGNC:15465	ENSG00000171723	Q9NQX3	Gephyrin	clinvar
DAAM2	HGNC:18143	ENSG00000146122	Q86T65	Disheveled-associated activator of morphogenesis 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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).
GPHN	Gephyrin	Microtubule-associated protein involved in membrane protein-cytoskeleton interactions.
DAAM2	Disheveled-associated activator of morphogenesis 2	Key regulator of the Wnt signaling pathway, which is required for various processes during development, such as dorsal patterning, determination of left/right symmetry or myelination in the central nervous system.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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
GPHN	Other/Unknown	no		MoaB/Mog_dom, MoeA_linker/N, MoeA_C_domain_IV
DAAM2	Other/Unknown	no		FH3_dom, GTPase-bd, ARM-like

Expression context

Cohort genes with no expression data: 0.

3 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
apex of heart	1
popliteal artery	1
tibial artery	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
corpus callosum	1
inferior vagus X ganglion	1
middle frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MOCS1	245	ubiquitous	marker	apex of heart, popliteal artery, tibial artery
GPHN	270	ubiquitous	marker	cerebellar cortex, cerebellar hemisphere, right hemisphere of cerebellum
DAAM2	276	ubiquitous	marker	corpus callosum, middle frontal gyrus, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GPHN	2,500
DAAM2	2,071
MOCS1	1,494

Intra-cohort edges

A	B	Sources
GPHN	MOCS1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GPHN	Q9NQX3	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DAAM2	Q86T65	80.02
MOCS1	Q9NZB8	79.87

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 3 evidence-associated genes (2 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 2 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	1631.4×	3e-07	MOCS1, GPHN

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	2	1605.0×	9e-06	MOCS1, GPHN
glycine receptor clustering	1	5617.3×	0.002	GPHN
establishment of synaptic specificity at neuromuscular junction	1	2808.7×	0.002	GPHN
regulation of non-canonical Wnt signaling pathway	1	2808.7×	0.002	DAAM2
gamma-aminobutyric acid receptor clustering	1	1123.5×	0.004	GPHN
podocyte cell migration	1	802.5×	0.004	DAAM2
dorsal spinal cord development	1	561.7×	0.005	DAAM2
response to metal ion	1	510.7×	0.005	GPHN
negative regulation of oligodendrocyte differentiation	1	374.5×	0.006	DAAM2
regulation of filopodium assembly	1	351.1×	0.006	DAAM2
neurotransmitter receptor localization to postsynaptic specialization membrane	1	267.5×	0.007	GPHN
regulation of actin filament polymerization	1	193.7×	0.009	DAAM2
regulation of canonical Wnt signaling pathway	1	181.2×	0.009	DAAM2
establishment of protein localization	1	144.0×	0.010	GPHN
determination of left/right symmetry	1	85.1×	0.016	DAAM2
synapse assembly	1	77.0×	0.017	GPHN
regulation of actin cytoskeleton organization	1	52.5×	0.022	DAAM2
positive regulation of canonical Wnt signaling pathway	1	51.5×	0.022	DAAM2
Wnt signaling pathway	1	33.2×	0.033	DAAM2
actin cytoskeleton organization	1	26.4×	0.039	DAAM2
positive regulation of cell migration	1	20.6×	0.048	DAAM2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MOCS1	0	0
GPHN	0	0
DAAM2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MOCS1	4.1.99.22, 4.6.1.17	GTP 3’,8-cyclase, cyclic pyranopterin monophosphate 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	0
D	Druggable family + AlphaFold only, no drug	1	MOCS1
E	Difficult family or no structure, no drug	2	GPHN, DAAM2

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)
MOCS1	0	—
GPHN	0	—
DAAM2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.