Isolated sulfite oxidase deficiency

Summary

Isolated sulfite oxidase deficiency (MONDO:0010089) is a disease caused by SUOX (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SUOX (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 484
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated sulfite oxidase deficiency
Mondo ID	MONDO:0010089
MeSH	C538141
OMIM	272300
Orphanet	99731
DOID	DOID:0111270
ICD-11	963607692
SNOMED CT	367368009
UMLS	C0268624
MedGen	78695
GARD	0005062
Is cancer (heuristic)	no

Also known as: ISOD · isolated sulfite oxidase deficiency · sulfite oxidase deficiency · sulfite oxidase deficiency, isolated · Sulfocysteinuria · sulfocysteinuria

Data availability: 484 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › lens disorder › encephalopathy due to sulfite oxidase deficiency › isolated sulfite oxidase deficiency

Related subtypes (1): sulfite oxidase deficiency due to molybdenum cofactor deficiency

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

484 retrieved; paginated sample, class counts are floors:

192 likely benign, 180 uncertain significance, 55 pathogenic, 24 conflicting classifications of pathogenicity, 16 likely pathogenic, 8 pathogenic/likely pathogenic, 5 benign, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068910	NM_001032386.2(SUOX):c.115C>T (p.Gln39Ter)	SUOX	Pathogenic	criteria provided, single submitter
1071284	NM_001032386.2(SUOX):c.621C>G (p.Tyr207Ter)	SUOX	Pathogenic	criteria provided, single submitter
1344577	NM_001032386.2(SUOX):c.1096dup (p.Arg366fs)	SUOX	Pathogenic	criteria provided, single submitter
1383872	NM_001032386.2(SUOX):c.142_145dup (p.Asn49delinsArgTer)	SUOX	Pathogenic	criteria provided, multiple submitters, no conflicts
1401523	NM_001032386.2(SUOX):c.1312_1318del (p.Val438fs)	SUOX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1401552	NM_001032386.2(SUOX):c.802C>T (p.Arg268Ter)	SUOX	Pathogenic	criteria provided, single submitter
1408706	NM_001032386.2(SUOX):c.917del (p.Gly306fs)	SUOX	Pathogenic	criteria provided, single submitter
1410729	NM_001032386.2(SUOX):c.215_222del (p.Asp72fs)	SUOX	Pathogenic	criteria provided, single submitter
1414343	NM_001032386.2(SUOX):c.90C>A (p.Cys30Ter)	SUOX	Pathogenic	criteria provided, single submitter
1420277	NM_001032386.2(SUOX):c.1312_1313del (p.Val438fs)	SUOX	Pathogenic	criteria provided, single submitter
1465250	NM_001032386.2(SUOX):c.1349G>A (p.Trp450Ter)	SUOX	Pathogenic	criteria provided, single submitter
1687733	NM_001032386.2(SUOX):c.905T>G (p.Leu302Ter)	SUOX	Pathogenic	no assertion criteria provided
2124058	NM_001032386.2(SUOX):c.141dup (p.Asp48Ter)	SUOX	Pathogenic	criteria provided, single submitter
2132887	NM_001032386.2(SUOX):c.849G>A (p.Trp283Ter)	SUOX	Pathogenic	criteria provided, single submitter
2164571	NM_001032386.2(SUOX):c.1109del (p.Pro370fs)	SUOX	Pathogenic	criteria provided, single submitter
2189731	NM_001032386.2(SUOX):c.599_600del (p.Pro200fs)	SUOX	Pathogenic	criteria provided, single submitter
2195828	NM_001032386.2(SUOX):c.571del (p.Gln191fs)	SUOX	Pathogenic	criteria provided, single submitter
2412504	NM_001032386.2(SUOX):c.423del (p.Val142fs)	SUOX	Pathogenic	criteria provided, multiple submitters, no conflicts
2423120	NC_000012.11:g.(?56396006)(56396524_?)del	SUOX	Pathogenic	criteria provided, single submitter
2635515	NM_001032386.2(SUOX):c.1276C>T (p.Gln426Ter)	SUOX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2708487	NM_001032386.2(SUOX):c.544del (p.Arg182fs)	SUOX	Pathogenic	criteria provided, single submitter
2711061	NM_001032386.2(SUOX):c.452T>A (p.Leu151Ter)	SUOX	Pathogenic	criteria provided, single submitter
2718184	NM_001032386.2(SUOX):c.207dup (p.Tyr70fs)	SUOX	Pathogenic	criteria provided, single submitter
2741574	NM_001032386.2(SUOX):c.1071del (p.Pro358fs)	SUOX	Pathogenic	criteria provided, single submitter
2745311	NM_001032386.2(SUOX):c.466A>T (p.Lys156Ter)	SUOX	Pathogenic	criteria provided, single submitter
2760559	NM_001032386.2(SUOX):c.1578G>A (p.Trp526Ter)	SUOX	Pathogenic	criteria provided, single submitter
2763256	NM_001032386.2(SUOX):c.1464G>A (p.Trp488Ter)	SUOX	Pathogenic	criteria provided, single submitter
2771542	NM_001032386.2(SUOX):c.1545C>G (p.Tyr515Ter)	SUOX	Pathogenic	criteria provided, single submitter
2779253	NM_001032386.2(SUOX):c.1121del (p.Gly374fs)	SUOX	Pathogenic	criteria provided, single submitter
2783390	NM_001032386.2(SUOX):c.1049_1052del (p.Ala349_Tyr350insTer)	SUOX	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
SUOX	Definitive	Autosomal recessive	isolated sulfite oxidase deficiency	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SUOX	Orphanet:99731	Isolated sulfite oxidase deficiency

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
SUOX	HGNC:11460	ENSG00000139531	P51687	Sulfite oxidase, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SUOX	Sulfite oxidase, mitochondrial	Catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.

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)
SUOX	Enzyme (other)	yes	1.8.3.1	OxRdtase_Mopterin-bd_dom, Cyt_B5-like_heme/steroid-bd, MoCF_OxRdtse_dimer

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right adrenal gland	1
right adrenal gland cortex	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SUOX	267	ubiquitous	marker	right lobe of liver, right adrenal gland, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SUOX	3,449

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SUOX	P51687	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Sulfide oxidation to sulfate	1	1903.3×	0.003	SUOX
Degradation of cysteine and homocysteine	1	951.7×	0.003	SUOX
Sulfur amino acid metabolism	1	571.0×	0.003	SUOX
Metabolism of amino acids and derivatives	1	67.6×	0.018	SUOX
Metabolism	1	11.6×	0.086	SUOX

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
sulfur compound metabolic process	1	1123.5×	9e-04	SUOX

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
SUOX	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SUOX	1.8.3.1	sulfite oxidase

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	SUOX
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)
SUOX	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01735188	Not specified	COMPLETED	A Natural History Study of Molybdenum Cofactor and Isolated Sulfite Oxidase Deficiencies