SUOX

Summary

SUOX (sulfite oxidase, HGNC:11460) is a protein-coding gene on chromosome 12q13.2, encoding Sulfite oxidase, mitochondrial (P51687). Catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.

Sulfite oxidase is a homodimeric protein localized to the intermembrane space of mitochondria. Each subunit contains a heme domain and a molybdopterin-binding domain. The enzyme catalyzes the oxidation of sulfite to sulfate, the final reaction in the oxidative degradation of the sulfur amino acids cysteine and methionine. Sulfite oxidase deficiency results in neurological abnormalities which are often fatal at an early age. Alternative splicing results in multiple transcript variants encoding identical proteins.

Source: NCBI Gene 6821 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated sulfite oxidase deficiency (Definitive, ClinGen)
• GWAS associations: 22
• Clinical variants (ClinVar): 517 total — 55 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 37
• MANE Select transcript: NM_001032386

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11460
Approved symbol	SUOX
Name	sulfite oxidase
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000139531
Ensembl biotype	protein_coding
OMIM	606887
Entrez	6821

Gene structure

Transcript identifiers

Ensembl transcripts: 58 — 50 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000266971, ENST00000356124, ENST00000394109, ENST00000394115, ENST00000546712, ENST00000546833, ENST00000547586, ENST00000548274, ENST00000550065, ENST00000550121, ENST00000550340, ENST00000550478, ENST00000551698, ENST00000551841, ENST00000552258, ENST00000552363, ENST00000552813, ENST00000886412, ENST00000886413, ENST00000886414, ENST00000886415, ENST00000886416, ENST00000886417, ENST00000886418, ENST00000886419, ENST00000886420, ENST00000886421, ENST00000886422, ENST00000886423, ENST00000886424, ENST00000886425, ENST00000886426, ENST00000886427, ENST00000886428, ENST00000886429, ENST00000886430, ENST00000886431, ENST00000886432, ENST00000886433, ENST00000886434, ENST00000886435, ENST00000886436, ENST00000886437, ENST00000886438, ENST00000886439, ENST00000886440, ENST00000886441, ENST00000886442, ENST00000930303, ENST00000930304, ENST00000930305, ENST00000930306, ENST00000930307, ENST00000930308, ENST00000954614, ENST00000954615, ENST00000954616, ENST00000954617

RefSeq mRNA: 3 — MANE Select: NM_001032386 NM_000456, NM_001032386, NM_001032387

CCDS: CCDS8901

Canonical transcript exons

ENST00000266971 — 5 exons

Exon	Start	End
ENSE00001401006	55997615	55997723
ENSE00001481715	56002543	56002720
ENSE00001839375	56003618	56005525
ENSE00002376865	55997276	55997339
ENSE00003482541	56002212	56002271

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 94.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.8645 / max 97.5973, expressed in 1744 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126037	10.8645	1744

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	94.43	gold quality
right adrenal gland	UBERON:0001233	93.30	gold quality
right adrenal gland cortex	UBERON:0035827	93.12	gold quality
adult mammalian kidney	UBERON:0000082	92.59	gold quality
left adrenal gland	UBERON:0001234	92.14	gold quality
metanephros cortex	UBERON:0010533	92.01	gold quality
left adrenal gland cortex	UBERON:0035825	91.72	gold quality
adrenal cortex	UBERON:0001235	91.55	gold quality
liver	UBERON:0002107	91.46	gold quality
mucosa of transverse colon	UBERON:0004991	91.29	gold quality
adrenal gland	UBERON:0002369	91.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.04	gold quality
apex of heart	UBERON:0002098	90.58	gold quality
renal medulla	UBERON:0000362	90.35	gold quality
kidney	UBERON:0002113	90.23	gold quality
heart left ventricle	UBERON:0002084	90.19	gold quality
cardiac ventricle	UBERON:0002082	90.04	gold quality
heart	UBERON:0000948	88.37	gold quality
body of stomach	UBERON:0001161	88.32	gold quality
muscle of leg	UBERON:0001383	88.30	gold quality
transverse colon	UBERON:0001157	88.29	gold quality
lower esophagus mucosa	UBERON:0035834	88.28	gold quality
islet of Langerhans	UBERON:0000006	88.21	gold quality
gastrocnemius	UBERON:0001388	88.17	gold quality
cortex of kidney	UBERON:0001225	88.15	gold quality
right atrium auricular region	UBERON:0006631	88.13	gold quality
pancreatic ductal cell	CL:0002079	87.97	silver quality
right lobe of thyroid gland	UBERON:0001119	87.81	gold quality
nephron tubule	UBERON:0001231	87.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

40 targeting SUOX, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-4254	99.11	65.15	1315

Literature-anchored findings (GeneRIF, showing 30)

• role of conserved tyrosine 343 in intramolecular electron transfer in this enzyme (PMID:12424234)
• Sulfite oxidase gene expression in brain and in other tissues. (PMID:12763039)
• comparison of this structure with other b(5)-type cytochromes reveals distinct structural features present in the sulfite oxidase b(5) domain which promote optimal electron transport between the Moco of sulfite oxidase and the heme of cytochrome c (PMID:12832761)
• To further assess the role of Arg 160 in human SO, intramolecular electron transfer rates between the reduced heme and oxidized molybdenum centers in the wild type, R160Q, and R160K human SO forms were investigated by laser flash photolysis (PMID:14567685)
• the Tyr(343) residue is important for both substrate binding and oxidation of sulfite by sulfite oxidase (PMID:14729666)
• mutation in SUOX gene in sulfite oxidase deficiency (PMID:16140720)
• mutations to charged residues at the equivalent sites most likely cause crucial global or localized structural changes, and expose an alternative docking site that may compete with the Mo domain for docking of the heme (PMID:16229463)
• Analysis of recombinant G473D sulfite oxidase indicated that it is severely impaired both in the ability to bind sulfite and in catalysis, with a second-order rate constant 5 orders of magnitude lower than that of the wild type. (PMID:16475804)
• Magnetic resonance imaging and MR spectroscopy measurements may help differentiate isolated sulfite oxidase deficiency from hypoxic-ischemic condition in patients in whom this diagnosis is not clinically suspected. (PMID:17940249)
• analysis of protein-protein interaction of sulfite oxidase and cytochrome c catalyzing oxidation of sulfite (PMID:18177044)
• EPR study of the Mo(V) center of the pathogenic R160Q mutant confirms the presence of three distinct species whose relative abundances depend upon pH. (PMID:18529001)
• the activity of molybdoenzymes, such as sulfite oxidase, is inhibited by high concentrations of heavy metals in the cell (PMID:18959753)
• Experimental deletions of nonconserved amino acids in the 14-residue interdomain polypeptide tether of sulfite oxidase shorten its length and result in more drastically reduced intramolecular electron transfer rate constants. (PMID:20063894)
• prepared and purified samples of the wild type and various mutants of human SO that are depleted of chloride. These samples do not exhibit the typical lpH EPR spectrum at low pH but rather exhibit spectra that are characteristic of the blocked species (PMID:20491442)
• In this study a human sulfite oxidase variant, in which the active site has been modified to alter substrate specificity and activity from sulfite oxidation to nitrate reduction, is compared to chicken sulfite oxidase. (PMID:22263579)
• effect of mutation of surface residues on the heme domain on intramolecular electron transfer, and steady-state kinetics (PMID:22975842)
• SUOX was decreased and AKR1B10 and CD34 were increased with the stepwise progression of hepatocarcinogenesis. (PMID:23665285)
• combined genetic association studies in women from China/Netherlands/United States: Data suggest that an SNP in SUOX locus (rs705702) and SNPs in other proteins are associated with polycystic ovary syndrome across ethnic differences. [META-ANALYSIS] (PMID:24106282)
• Several mutants of H304 and R309 of SUOX were investigated by steady-state kinetics, laser flash photolysis studies of intramolecular electron transfer (IET), and spectroelectrochemistry. (PMID:24968320)
• Nitrite binds and reduces at the molybdenum site of mammalian sulfite oxidase, which may be allosterically regulated by heme and molybdenum domain interactions, and contributes to the mammalian nitrate-nitrite-NO signaling pathway in human fibroblasts. (PMID:25314640)
• This finding suggests the possibility to use oxygen-reactive SO variants in sulfite detoxification, as the loss of SO activity is causing severe neurodegeneration (PMID:26171830)
• Novel SUOX mutations were detected in 3 Sulfite oxidase deficiency cases (PMID:27289259)
• This is the first description of the prenatal neurodevelopment of brain disruption in isolated sulfite oxidase deficiency. (PMID:28629418)
• SUOX is negatively associated with the progression and proliferation of oral squamous cell carcinoma. (PMID:29280012)
• High SUOX expression could predict postoperative biochemical recurrence in patients with prostate cancer after total prostatectomy. (PMID:30631948)
• this study demonstrates the importance of the orchestrated maturation of SO and provides a first case of Moco-responsive iSOD. (PMID:31127934)
• Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency. (PMID:34117075)
• Predictive and Prognostic Value of SUOX Expression in Pancreatic Ductal Adenocarcinoma. (PMID:35896256)
• Epilepsy in sulfite oxidase deficiency and related disorders: insights from neuroimaging and genetics. (PMID:37187015)
• Mechanistic complexities of sulfite oxidase: An enzyme with multiple domains, subunits, and cofactors. (PMID:37441922)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	suox	ENSDARG00000091574
mus_musculus	Suox	ENSMUSG00000049858
rattus_norvegicus	Suox	ENSRNOG00000005987
drosophila_melanogaster	shop	FBGN0030966
caenorhabditis_elegans		WBGENE00010397

Protein

Protein identifiers

Sulfite oxidase, mitochondrial — P51687 (reviewed: P51687)

All UniProt accessions (5): P51687, F8VPA2, F8VRK9, F8VVW9, F8VX56

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.

Subunit / interactions. Homodimer.

Subcellular location. Mitochondrion intermembrane space.

Disease relevance. Sulfite oxidase deficiency, isolated (ISOD) [MIM:272300] A life-threatening, autosomal recessive neurometabolic disorder characterized by severe neurological impairment. Classic ISOD manifests in the first few hours to days of life and is characterized by intractable seizures, feeding difficulties, rapidly progressive encephalopathy, microcephaly, and profound intellectual disability. Children usually die during the first few months of life. Mild ISOD manifests in infancy or early childhood and is characterized by ectopia lentis that is variably present, developmental delay and regression, movement disorder characterized by dystonia and choreoathetosis, ataxia, and rarely acute hemiplegia due to metabolic stroke. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 heme b (iron(II)-protoporphyrin IX) group non-covalently per subunit. Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.

Pathway. Energy metabolism; sulfur metabolism.

RefSeq proteins (3): NP_000447, NP_001027558, NP_001027559 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000572	OxRdtase_Mopterin-bd_dom	Domain
IPR001199	Cyt_B5-like_heme/steroid-bd	Domain
IPR005066	MoCF_OxRdtse_dimer	Domain
IPR008335	Mopterin_OxRdtase_euk	Family
IPR014756	Ig_E-set	Homologous_superfamily
IPR018506	Cyt_B5_heme-BS	Binding_site
IPR022407	OxRdtase_Mopterin_BS	Binding_site
IPR036374	OxRdtase_Mopterin-bd_sf	Homologous_superfamily
IPR036400	Cyt_B5-like_heme/steroid_sf	Homologous_superfamily

Pfam: PF00173, PF00174, PF03404

Enzyme classification (BRENDA):

• EC 1.8.3.1 — sulfite oxidase (BRENDA: 53 organisms, 56 substrates, 63 inhibitors, 200 Km, 180 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SULFITE	0.0005–418	172
CYTOCHROME C	0.0004–0.107	18
FERRICYANIDE	0.698	1
O2	0.015	1

Catalyzed reactions (Rhea), 1 shown:

• sulfite + O2 + H2O = sulfate + H2O2 (RHEA:24600)

UniProt features (41 total): sequence variant 12, binding site 10, helix 5, strand 4, turn 3, region of interest 3, transit peptide 1, chain 1, modified residue 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1MJ4	X-RAY DIFFRACTION	1.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51687-F1	84.99	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (10): 215–219; 264; 322; 361; 366; 377–379; 118 (axial binding residue); 143 (axial binding residue); 145; 147

Post-translational modifications (1): 123

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1614517	Sulfide oxidation to sulfate
R-HSA-1430728	Metabolism
R-HSA-1614558	Degradation of cysteine and homocysteine
R-HSA-1614635	Sulfur amino acid metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 265 (showing top): PAX4_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, KYNG_DNA_DAMAGE_DN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOCC_MITOCHONDRIAL_ENVELOPE, TGANTCA_AP1_C, LEF1_Q6, MODULE_568, MODULE_491, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, GOCC_MITOCHONDRIAL_MATRIX, GOCC_ORGANELLE_ENVELOPE_LUMEN

GO Biological Process (1): sulfur compound metabolic process (GO:0006790)

GO Molecular Function (7): sulfite oxidase activity (GO:0008482), heme binding (GO:0020037), molybdenum ion binding (GO:0030151), molybdopterin cofactor binding (GO:0043546), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Degradation of cysteine and homocysteine	1
Sulfur amino acid metabolism	1
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
metabolic process	1
oxidoreductase activity, acting on a sulfur group of donors, oxygen as acceptor	1
tetrapyrrole binding	1
transition metal ion binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial envelope	1
organelle envelope lumen	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

3066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SUOX	MOCS1	Q9NZB8	972
SUOX	AOX1	Q06278	966
SUOX	MOCS2	O96007	962
SUOX	GPHN	Q9NQX3	878
SUOX	ETHE1	O95571	853
SUOX	SQOR	Q9Y6N5	845
SUOX	TST	Q16762	811
SUOX	MPST	P25325	764
SUOX	CYCS	P00001	755
SUOX	XDH	P47989	726
SUOX	CTH	P32929	717
SUOX	MOCS3	O95396	715
SUOX	CDO1	P78513	711
SUOX	DENND1A	Q8TEH3	669
SUOX	MTARC1	Q5VT66	664

IntAct

279 interactions, top by confidence:

A	B	Type	Score
SUOX	NUP62	psi-mi:“MI:0915”(physical association)	0.720
NUP62	SUOX	psi-mi:“MI:0915”(physical association)	0.720
SPANXN3	SUOX	psi-mi:“MI:0914”(association)	0.640
SUOX	RCN1	psi-mi:“MI:0915”(physical association)	0.560
SUOX	FANCG	psi-mi:“MI:0915”(physical association)	0.560
SUOX	ZFP90	psi-mi:“MI:0915”(physical association)	0.560
SUOX	TRIM74	psi-mi:“MI:0915”(physical association)	0.560
SUOX	ZNF710	psi-mi:“MI:0915”(physical association)	0.560
SUOX	RHOH	psi-mi:“MI:0915”(physical association)	0.560
SUOX	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
SUOX	STN1	psi-mi:“MI:0915”(physical association)	0.560
SUOX	PTTG2	psi-mi:“MI:0915”(physical association)	0.560
SUOX	MYL7	psi-mi:“MI:0915”(physical association)	0.560
SUOX	RELA	psi-mi:“MI:0915”(physical association)	0.560
SUOX	SERTAD3	psi-mi:“MI:0915”(physical association)	0.560
SUOX	PIH1D2	psi-mi:“MI:0915”(physical association)	0.560
FANCG	SUOX	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (104): SUOX (Affinity Capture-MS), NUP62 (Two-hybrid), CES3 (Affinity Capture-MS), SUOX (Affinity Capture-MS), FHOD1 (Affinity Capture-MS), DNAJC11 (Affinity Capture-MS), SUOX (Affinity Capture-MS), SUOX (Affinity Capture-MS), SUOX (Two-hybrid), SUOX (Two-hybrid), SUOX (Two-hybrid), SUOX (Two-hybrid), SUOX (Two-hybrid), SUOX (Two-hybrid), SUOX (Two-hybrid)

ESM2 similar proteins: A0JNU3, A2RRV9, A4FV58, A7SDA8, A8WH18, B0WU52, B3N018, B3NKH7, B4GXC8, B4IMH3, B4ISL0, B4JBE6, B4KFU7, B4LQR5, B4MUM8, B4NSS7, B5DK31, D3ZX08, O88202, O93610, P51178, P51687, Q16ML2, Q2YDU6, Q3UQ84, Q58DG1, Q5BK18, Q5JTZ9, Q5RCH4, Q5RF36, Q5ZKI2, Q641W2, Q68FW7, Q6DE00, Q6DHP6, Q6GP25, Q75E78, Q7PWB8, Q7TMW6, Q86U10

Diamond homologs: A0A286R227, A1C7E9, A1DHW1, A2QCV4, A3GF86, A3LT66, A4QR21, A4R935, A5DQ25, A5E7U2, A6R2K7, A6ZVM6, A7TNL7, B0CQN7, O74557, P00387, P07514, P07850, P08509, P08619, P0CP14, P0CP15, P11035, P11605, P11832, P16081, P17569, P17570, P17571, P20070, P22945, P23312, P27783, P27967, P27968, P27969, P36841, P36842, P36858, P36859

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

517 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	55
Likely pathogenic	18
Uncertain significance	204
Likely benign	194
Benign	6

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068910	NM_001032386.2(SUOX):c.115C>T (p.Gln39Ter)	Pathogenic
1071284	NM_001032386.2(SUOX):c.621C>G (p.Tyr207Ter)	Pathogenic
1344577	NM_001032386.2(SUOX):c.1096dup (p.Arg366fs)	Pathogenic
1383872	NM_001032386.2(SUOX):c.142_145dup (p.Asn49delinsArgTer)	Pathogenic
1401552	NM_001032386.2(SUOX):c.802C>T (p.Arg268Ter)	Pathogenic
1408706	NM_001032386.2(SUOX):c.917del (p.Gly306fs)	Pathogenic
1410729	NM_001032386.2(SUOX):c.215_222del (p.Asp72fs)	Pathogenic
1414343	NM_001032386.2(SUOX):c.90C>A (p.Cys30Ter)	Pathogenic
1420277	NM_001032386.2(SUOX):c.1312_1313del (p.Val438fs)	Pathogenic
1465250	NM_001032386.2(SUOX):c.1349G>A (p.Trp450Ter)	Pathogenic
1687733	NM_001032386.2(SUOX):c.905T>G (p.Leu302Ter)	Pathogenic
2124058	NM_001032386.2(SUOX):c.141dup (p.Asp48Ter)	Pathogenic
2132887	NM_001032386.2(SUOX):c.849G>A (p.Trp283Ter)	Pathogenic
2164571	NM_001032386.2(SUOX):c.1109del (p.Pro370fs)	Pathogenic
2189731	NM_001032386.2(SUOX):c.599_600del (p.Pro200fs)	Pathogenic
2195828	NM_001032386.2(SUOX):c.571del (p.Gln191fs)	Pathogenic
2412504	NM_001032386.2(SUOX):c.423del (p.Val142fs)	Pathogenic
2423120	NC_000012.11:g.(?56396006)(56396524_?)del	Pathogenic
2708487	NM_001032386.2(SUOX):c.544del (p.Arg182fs)	Pathogenic
2711061	NM_001032386.2(SUOX):c.452T>A (p.Leu151Ter)	Pathogenic
2718184	NM_001032386.2(SUOX):c.207dup (p.Tyr70fs)	Pathogenic
2741574	NM_001032386.2(SUOX):c.1071del (p.Pro358fs)	Pathogenic
2745311	NM_001032386.2(SUOX):c.466A>T (p.Lys156Ter)	Pathogenic
2760559	NM_001032386.2(SUOX):c.1578G>A (p.Trp526Ter)	Pathogenic
2763256	NM_001032386.2(SUOX):c.1464G>A (p.Trp488Ter)	Pathogenic
2771542	NM_001032386.2(SUOX):c.1545C>G (p.Tyr515Ter)	Pathogenic
2779253	NM_001032386.2(SUOX):c.1121del (p.Gly374fs)	Pathogenic
2783390	NM_001032386.2(SUOX):c.1049_1052del (p.Ala349_Tyr350insTer)	Pathogenic
2817463	NM_001032386.2(SUOX):c.1406_1421del (p.Thr469fs)	Pathogenic
2824409	NM_001032386.2(SUOX):c.37C>T (p.Gln13Ter)	Pathogenic

SpliceAI

797 predictions. Top by Δscore:

Variant	Effect	Δscore
12:55997340:G:GG	donor_gain	1.0000
12:55997341:T:A	donor_loss	1.0000
12:55997336:CCCG:C	donor_gain	0.9700
12:55997337:CCG:C	donor_gain	0.9700
12:56002635:A:AG	donor_gain	0.9700
12:55997338:CG:C	donor_gain	0.9600
12:55997339:GG:G	donor_gain	0.9600
12:56002206:CTACA:C	acceptor_loss	0.9600
12:56002207:TACAG:T	acceptor_loss	0.9600
12:56002208:ACAG:A	acceptor_loss	0.9600
12:56002209:CA:C	acceptor_loss	0.9600
12:56002210:A:C	acceptor_loss	0.9600
12:56002211:G:A	acceptor_loss	0.9600
12:56002719:GG:G	donor_gain	0.9600
12:56002720:GG:G	donor_gain	0.9600
12:55997335:ACCCG:A	donor_gain	0.9500
12:56003599:A:AG	acceptor_gain	0.9400
12:56002541:A:AG	acceptor_gain	0.9300
12:56002542:G:GG	acceptor_gain	0.9300
12:56002688:GC:G	donor_gain	0.9300
12:56003616:A:AT	acceptor_loss	0.9300
12:56002210:A:AG	acceptor_gain	0.9200
12:56002211:G:GG	acceptor_gain	0.9200
12:56002267:TGCAG:T	donor_loss	0.9200
12:56002268:GCAGG:G	donor_loss	0.9200
12:56002269:CAGGT:C	donor_loss	0.9200
12:56002270:AGGTA:A	donor_loss	0.9200
12:56002271:G:GC	donor_loss	0.9200
12:56002272:G:GA	donor_loss	0.9200
12:56002273:T:G	donor_loss	0.9200

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000071886 (12:56003480 T>C,G), RS1000141831 (12:55998541 C>G), RS1000226340 (12:55999288 C>T), RS1000429845 (12:55998796 G>A), RS1000677563 (12:56005158 G>A), RS1001095377 (12:55999681 C>A,T), RS1001546702 (12:56000023 C>A), RS1002387437 (12:55999575 G>A), RS1002492383 (12:56005956 A>C,G,T), RS1002584037 (12:55996661 G>A,T), RS1003106003 (12:56002387 G>A,C), RS1003125889 (12:56000520 C>T), RS1003646622 (12:55998123 G>A,T), RS1004461342 (12:55998902 C>T), RS1004839389 (12:56000494 G>A)

Disease associations

OMIM: gene MIM:606887 | disease phenotypes: MIM:272300

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated sulfite oxidase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
isolated sulfite oxidase deficiency	Definitive	AR

Mondo (1): isolated sulfite oxidase deficiency (MONDO:0010089)

Orphanet (2): Encephalopathy due to sulfite oxidase deficiency (Orphanet:833), Isolated sulfite oxidase deficiency (Orphanet:99731)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000341	Narrow forehead
HP:0000400	Macrotia
HP:0000490	Deeply set eye
HP:0000684	Delayed eruption of teeth
HP:0000713	Agitation
HP:0000964	Eczematoid dermatitis
HP:0001083	Ectopia lentis
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001276	Hypertonia
HP:0001290	Generalized hypotonia
HP:0001321	Cerebellar hypoplasia
HP:0001344	Absent speech
HP:0001522	Death in infancy
HP:0001942	Metabolic acidosis
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure
HP:0002213	Fine hair
HP:0002301	Hemiplegia
HP:0002572	Episodic vomiting
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003359	Decreased urinary sulfate
HP:0003623	Neonatal onset
HP:0003643	Sulfite oxidase deficiency
HP:0007325	Generalized dystonia
HP:0008936	Axial hypotonia
HP:0008947	Floppy infant

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST000141_1	Type 1 diabetes	9.000000e-10
GCST001634_7	Polycystic ovary syndrome	9.000000e-26
GCST001670_1	Vitiligo	8.000000e-12
GCST002774_24	Cognitive function	3.000000e-07
GCST003097_25	Pediatric autoimmune diseases	4.000000e-09
GCST004367_1	Anorexia nervosa	4.000000e-09
GCST005038_78	Allergic disease (asthma, hay fever or eczema)	1.000000e-19
GCST005316_372	Intelligence (MTAG)	2.000000e-12
GCST007563_23	Allergic disease (asthma, hay fever or eczema)	4.000000e-10
GCST007564_9	Asthma or allergic disease (pleiotropy)	1.000000e-13
GCST007942_9	Medication use (glucocorticoids)	1.000000e-11
GCST007993_28	Asthma (adult onset)	6.000000e-07
GCST007995_39	Asthma (childhood onset)	1.000000e-11
GCST008377_5	Type 1 diabetes	7.000000e-20
GCST008832_15	Gastroesophageal reflux disease	1.000000e-08
GCST008916_124	Asthma	1.000000e-16
GCST009798_45	Asthma	1.000000e-15
GCST010002_217	Refractive error	6.000000e-174
GCST010043_57	Asthma	2.000000e-31
GCST010703_297	Brain morphology (MOSTest)	4.000000e-10
GCST90002381_491	Eosinophil count	1.000000e-31
GCST90002382_312	Eosinophil percentage of white cells	1.000000e-35

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0009942	Glucocorticoid use measurement
EFO:1002011	adult onset asthma
EFO:0004346	neuroimaging measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538141	Sulfite oxidase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	3
sodium arsenite	affects cotreatment, increases abundance, decreases expression	2
perfluoro-n-nonanoic acid	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Tretinoin	increases expression	2
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
diisodecyl phthalate	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
avobenzone	decreases expression	1
4-octylphenol	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cannabidiol	decreases expression	1
Diazinon	increases methylation	1

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

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