MOCS2

Summary

MOCS2 (molybdenum cofactor synthesis 2, HGNC:7193) is a protein-coding gene on chromosome 5q11.2, encoding Molybdopterin synthase catalytic subunit (O96007). Catalytic subunit of the molybdopterin synthase complex, a complex that catalyzes the conversion of precursor Z into molybdopterin.

Eukaryotic molybdoenzymes use a unique molybdenum cofactor (MoCo) consisting of a pterin, termed molybdopterin, and the catalytically active metal molybdenum. MoCo is synthesized from precursor Z by the heterodimeric enzyme molybdopterin synthase. The large and small subunits of molybdopterin synthase are both encoded from this gene by overlapping open reading frames. The proteins were initially thought to be encoded from a bicistronic transcript. They are now thought to be encoded from monocistronic transcripts. Alternatively spliced transcripts have been found for this locus that encode the large and small subunits.

Source: NCBI Gene 4338 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1 (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 366 total — 30 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 43
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004531

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7193
Approved symbol	MOCS2
Name	molybdenum cofactor synthesis 2
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MOCO1, MOCS2A, MOCS2B
Ensembl gene	ENSG00000164172
Ensembl biotype	protein_coding
OMIM	603708
Entrez	4338

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 24 protein_coding, 2 retained_intron

ENST00000361377, ENST00000396954, ENST00000450852, ENST00000502402, ENST00000508922, ENST00000510818, ENST00000514553, ENST00000527216, ENST00000582677, ENST00000584946, ENST00000855413, ENST00000855414, ENST00000855415, ENST00000855416, ENST00000855417, ENST00000855418, ENST00000855419, ENST00000855420, ENST00000855421, ENST00000855422, ENST00000855423, ENST00000855424, ENST00000855425, ENST00000855426, ENST00000855427, ENST00000929999

RefSeq mRNA: 2 — MANE Select: NM_004531 NM_004531, NM_176806

CCDS: CCDS3958, CCDS47205

Canonical transcript exons

ENST00000396954 — 7 exons

Exon	Start	End
ENSE00001434702	53109251	53109757
ENSE00002028084	53095679	53098667
ENSE00003461905	53102097	53102224
ENSE00003556306	53100411	53100534
ENSE00003570146	53107077	53107221
ENSE00003657581	53108522	53108643
ENSE00003666750	53101359	53101509

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 96.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.8430 / max 2149.5002, expressed in 1801 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61624	38.8430	1801

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	96.95	gold quality
anterior cingulate cortex	UBERON:0009835	96.95	gold quality
prefrontal cortex	UBERON:0000451	96.92	gold quality
right adrenal gland cortex	UBERON:0035827	96.91	gold quality
cingulate cortex	UBERON:0003027	96.81	gold quality
left adrenal gland	UBERON:0001234	96.68	gold quality
left adrenal gland cortex	UBERON:0035825	96.52	gold quality
caudate nucleus	UBERON:0001873	96.33	gold quality
right frontal lobe	UBERON:0002810	96.18	gold quality
right atrium auricular region	UBERON:0006631	96.17	gold quality
nucleus accumbens	UBERON:0001882	96.03	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.98	gold quality
ventricular zone	UBERON:0003053	95.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.97	gold quality
adrenal cortex	UBERON:0001235	95.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.95	gold quality
heart left ventricle	UBERON:0002084	95.75	gold quality
amygdala	UBERON:0001876	95.73	gold quality
adrenal gland	UBERON:0002369	95.63	gold quality
cardiac ventricle	UBERON:0002082	95.59	gold quality
adrenal tissue	UBERON:0018303	95.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.47	gold quality
putamen	UBERON:0001874	95.29	gold quality
metanephros cortex	UBERON:0010533	95.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.20	gold quality
lower esophagus	UBERON:0013473	95.17	gold quality
tibial artery	UBERON:0007610	95.14	gold quality
popliteal artery	UBERON:0002250	95.13	gold quality
left coronary artery	UBERON:0001626	95.12	gold quality
calcaneal tendon	UBERON:0003701	95.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 5)

• analysis of sites within MOCS2 where mutations cause molybdenum cofactor deficiency (PMID:12732628)
• Review: A total of 32 different disease-causing mutations, including several common to more than one family, have been identified in molybdenum cofactor-deficient patients and their relatives (PMID:12754701)
• There was undisturbed production of both transcripts, while Western blot analysis demonstrated that MOCS2B, the large subunit, is unstable in the absence of MOCS2A. (PMID:16737835)
• We reported here an infant with MoCD who presented with hypoxic ischaemic encephalopathy and identified a novel mutation, c.130C>T in cDNA of the MOCS2 gene from the infant. (PMID:17158010)
• Beyond Moco Biosynthesis-Moonlighting Roles of MoaE and MOCS2. (PMID:35744859)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mocs2	ENSDARG00000077202
mus_musculus	Mocs2	ENSMUSG00000015536
rattus_norvegicus	Mocs2	ENSRNOG00000056325
drosophila_melanogaster	Mocs2B	FBGN0039280
caenorhabditis_elegans	nmrk-1	WBGENE00020842

Paralogs (3): NMRK2 (ENSG00000077009), NMRK1 (ENSG00000106733), MBIP (ENSG00000151332)

Protein

Protein identifiers

Molybdopterin synthase catalytic subunit — O96007 (reviewed: O96007, O96033)

Alternative names: MOCO1-B, Molybdenum cofactor synthesis protein 2 large subunit, Molybdenum cofactor synthesis protein 2B, Molybdopterin-synthase large subunit

All UniProt accessions (3): E9PKT9, O96007, O96033

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of the molybdopterin synthase complex, a complex that catalyzes the conversion of precursor Z into molybdopterin. Acts by mediating the incorporation of 2 sulfur atoms from thiocarboxylated MOCS2A into precursor Z to generate a dithiolene group. Together with MBIP, inhibits the activity of stress kinase EIF2AK2/PKR; this may suppress JNK activation and subsequent stress-responsive transcription, or suppress eIF2a phosphorylation to favor translation.

Subunit / interactions. Heterotetramer; composed of 2 small (MOCS2A) and 2 large (MOCS2B) subunits. Component of the molybdopterin synthase complex consisting of MOCS2A and MOCS2B. Interacts with the histone acetyltransferase ATAC complex component MBIP; the interaction is direct and enhances the interaction between MBIP and protein kinase EIF2AK2/PKR. Interacts with protein kinase EIF2AK2/PKR; the interaction is direct and enhances the interaction between EIF2AK2 and MBIP.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Tissue specificity. Highest levels are found in heart and skeletal muscle. Lower levels are present in brain, kidney and pancreas. Very low levels are found in lung and peripheral blood leukocytes.

Disease relevance. Molybdenum cofactor deficiency B (MOCODB) [MIM:252160] An autosomal recessive metabolic disorder characterized by neonatal onset of intractable seizures, opisthotonus, and facial dysmorphism associated with hypouricemia and elevated urinary sulfite levels. Affected individuals show severe neurologic damage and often die in early childhood. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Cofactor biosynthesis; molybdopterin biosynthesis.

Miscellaneous. This protein is produced by a bicistronic gene which also produces the small subunit (MOCS2A) from an overlapping reading frame. Expression of these 2 proteins are related since a mutation that removes the start codon of the small subunit (MOCS2A) also impairs expression of the large subunit (MOCS2B).

Similarity. Belongs to the MoaE family. MOCS2B subfamily.

RefSeq proteins (2): NP_004522, NP_789776 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003448	Mopterin_biosynth_MoaE	Family
IPR028888	MOCS2B_euk	Family
IPR036563	MoaE_sf	Homologous_superfamily
IPR003749	ThiS/MoaD-like	Family
IPR012675	Beta-grasp_dom_sf	Homologous_superfamily
IPR016155	Mopterin_synth/thiamin_S_b	Homologous_superfamily
IPR028887	MOCS2A_euk	Family
IPR044672	MOCS2A	Family

Pfam: PF02391, PF02597

Enzyme classification (BRENDA):

• EC 2.8.1.12 — molybdopterin synthase (BRENDA: 10 organisms, 4 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• 2 [molybdopterin-synthase sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + cyclic pyranopterin phosphate + H2O = molybdopterin + 2 [molybdopterin-synthase sulfur-carrier protein]-C-terminal Gly-Gly + 2 H(+) (RHEA:26333)

UniProt features (54 total): sequence variant 22, strand 16, helix 6, binding site 3, modified residue 3, chain 2, mutagenesis site 2

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5MPO	X-RAY DIFFRACTION	2.43
4AP8	X-RAY DIFFRACTION	2.78

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O96007-F1	84.07	0.68
AF-O96033-F1	92.37	0.85

Functional residue map

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

O96007 (canonical)

Ligand- & substrate-binding residues (3): 143–144; 159; 166–168

Post-translational modifications (1): 20

O96033

Post-translational modifications (2): 88, 88

Mutagenesis-validated functional residues (2):

Position	Phenotype
88	decreases mocs3-dependent amp formation and thiocarboxylation.
88	abolishes mocs3-dependent amp formation and thiocarboxylation, and decreases nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-947581	Molybdenum cofactor biosynthesis
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 221 (showing top): TTTGTAG_MIR520D, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, DOUGLAS_BMI1_TARGETS_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, DANG_BOUND_BY_MYC, GOCC_TRANSFERASE_COMPLEX, chr5q11, BLALOCK_ALZHEIMERS_DISEASE_DN, BENPORATH_MYC_MAX_TARGETS, REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_SULPHUR_CONTAINING_GROUPS, TIEN_INTESTINE_PROBIOTICS_6HR_DN, GRYDER_PAX3FOXO1_ENHANCERS_KO_DOWN, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D

GO Biological Process (2): Mo-molybdopterin cofactor biosynthetic process (GO:0006777), molybdopterin cofactor biosynthetic process (GO:0032324)

GO Molecular Function (4): molybdopterin synthase activity (GO:0030366), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear speck (GO:0016607), molybdopterin synthase complex (GO:1990140), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
molybdenum incorporation into molybdenum-molybdopterin complex	1
Mo-molybdopterin cofactor metabolic process	1
molybdopterin cofactor biosynthetic process	1
GTP 3’,8’-cyclase activity	1
cyclic pyranopterin monophosphate synthase activity	1
molybdopterin synthase activity	1
cysteine desulfurase activity	1
molybdopterin cofactor metabolic process	1
molybdopterin adenylyltransferase activity	1
molybdopterin-synthase sulfurtransferase activity	1
molybdopterin-synthase adenylyltransferase activity	1
organophosphate biosynthetic process	1
sulfurtransferase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
nuclear lumen	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
sulfurtransferase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MOCS2	MOCS1	Q9NZB8	996
MOCS2	MOCS3	O95396	985
MOCS2	SUOX	P51687	962
MOCS2	GPHN	Q9NQX3	949
MOCS2	AOX1	Q06278	945
MOCS2	MTARC2	Q969Z3	910
MOCS2	PEX19	P40855	749
MOCS2	TST	Q16762	720
MOCS2	PEX16	Q9Y5Y5	609
MOCS2	PEX13	Q92968	571
MOCS2	PEX7	O00628	545
MOCS2	PEX3	P56589	545
MOCS2	CTU1	Q7Z7A3	544
MOCS2	NFS1	Q9Y697	539
MOCS2	COMMD5	Q9GZQ3	528

IntAct

17 interactions, top by confidence:

A	B	Type	Score
MOCS2	MOCS2	psi-mi:“MI:0407”(direct interaction)	0.620
MOCS2	MOCS2	psi-mi:“MI:0407”(direct interaction)	0.440
GSTT2	MOCS2	psi-mi:“MI:0915”(physical association)	0.400
FANCM	MOCS2	psi-mi:“MI:0914”(association)	0.350
IPO13	MOCS2	psi-mi:“MI:0914”(association)	0.350
MAP2K7	MOCS2	psi-mi:“MI:0914”(association)	0.350
WWC1	CIT	psi-mi:“MI:0914”(association)	0.350
TOP3B	PRMT5	psi-mi:“MI:0914”(association)	0.350
MOCS2	CRYBB1	psi-mi:“MI:0914”(association)	0.350
TCTE1	DVL2	psi-mi:“MI:2364”(proximity)	0.270
MOCS2		psi-mi:“MI:0915”(physical association)	0.000
ABCF3	MOCS2	psi-mi:“MI:0915”(physical association)	0.000
RPL9	MOCS2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): MOCS2 (Two-hybrid), MOCS2 (Two-hybrid), MOCS2 (Proximity Label-MS), MOCS2 (Affinity Capture-MS), MOCS2 (Affinity Capture-MS), MOCS2 (Affinity Capture-MS), MOCS2 (Proximity Label-MS), MOCS2 (Reconstituted Complex), MOCS2 (Affinity Capture-MS), MOCS2 (Affinity Capture-MS), RPP25 (Affinity Capture-MS), MOCS2 (Affinity Capture-MS), CRYBB1 (Affinity Capture-MS), MOCS2 (Affinity Capture-MS), MOCS2 (Affinity Capture-MS)

ESM2 similar proteins: A4FUY7, A6QXC6, A7EVF4, B0X1V5, B3M268, B3P6R5, B4IJG7, B4PUD1, B4QUC0, B5FXU9, F4I1L3, F4IPY2, F4JZC2, O13830, O22827, O94530, O96007, P93111, Q08C33, Q171H3, Q1DGL6, Q29RH3, Q2KF83, Q2TAF8, Q43316, Q4LB35, Q4R7L8, Q5RD76, Q655R6, Q6AY59, Q7QAD7, Q80Y20, Q86HF4, Q8GW43, Q8LGM7, Q94AC1, Q96BT7, Q9BQG2, Q9C5X8, Q9D853

Diamond homologs: A1CJM9, A1D7X4, A2QF55, A2X0R4, A4FUY7, A6R104, A7EVF4, B0X1V5, B0XYQ4, B2WBW4, B3M268, B3P6R5, B4GE20, B4IJG7, B4JHP4, B4KBH3, B4LVP8, B4NJW0, B4PUD1, B4QUC0, B5FXU9, O22827, O31705, O67928, O96007, P30749, P45308, P65396, P65397, P65398, P65399, P65400, P65401, P9WJR0, P9WJR1, P9WJR2, P9WJR3, Q0V713, Q171H3, Q1DGL6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	8
Uncertain significance	132
Likely benign	137
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1236175	NM_176806.4(MOCS2):c.33T>G (p.Tyr11Ter)	Pathogenic
1236176	NM_004531.5(MOCS2):c.24del (p.Ser9fs)	Pathogenic
1406875	NM_004531.5(MOCS2):c.109_112del (p.Asp37fs)	Pathogenic
1424517	NM_004531.5(MOCS2):c.140_141dup (p.Asn48Ter)	Pathogenic
1451432	NM_176806.4(MOCS2):c.106C>T (p.Gln36Ter)	Pathogenic
1454403	NM_176806.4(MOCS2):c.57_58del (p.Gly20fs)	Pathogenic
1458938	NM_004531.5(MOCS2):c.163dup (p.Ser55fs)	Pathogenic
1942085	NM_004531.5(MOCS2):c.164C>G (p.Ser55Ter)	Pathogenic
2021553	NM_004531.5(MOCS2):c.60_70del (p.Pro21fs)	Pathogenic
2108181	NM_004531.5(MOCS2):c.367del (p.His123fs)	Pathogenic
2153568	NM_176806.4(MOCS2):c.88C>T (p.Gln30Ter)	Pathogenic
2696333	NM_004531.5(MOCS2):c.292del (p.Met98fs)	Pathogenic
2750933	NM_004531.5(MOCS2):c.147del (p.Phe49fs)	Pathogenic
2805758	NM_004531.5(MOCS2):c.400_403dup (p.Ile135fs)	Pathogenic
2826287	NM_004531.5(MOCS2):c.217del (p.Leu73fs)	Pathogenic
2858763	NM_004531.5(MOCS2):c.134del (p.Asp45fs)	Pathogenic
2863141	NM_004531.5(MOCS2):c.271G>T (p.Glu91Ter)	Pathogenic
2875294	NM_004531.5(MOCS2):c.168del (p.Asp57fs)	Pathogenic
2902469	NM_004531.5(MOCS2):c.304G>T (p.Glu102Ter)	Pathogenic
3246510	NC_000005.9:g.(?52394432)(52404493_?)del	Pathogenic
3246573	NC_000005.9:g.(?52394432)(52405559_?)del	Pathogenic
3645068	NM_004531.5(MOCS2):c.515_516del (p.Glu172fs)	Pathogenic
4535652	NC_000005.9:g.(?52391508)(52403052_52404351)del	Pathogenic
4711719	NM_176806.4(MOCS2):c.68C>G (p.Ser23Ter)	Pathogenic
587508	NM_004531.5(MOCS2):c.2T>G (p.Met1Arg)	Pathogenic
6109	NM_004531.5(MOCS2):c.502G>A (p.Glu168Lys)	Pathogenic
6110	NM_004531.5(MOCS2):c.346_349del (p.Val116fs)	Pathogenic
6111	NM_004531.5(MOCS2):c.65dup (p.Leu23fs)	Pathogenic
6112	NM_004531.5(MOCS2):c.3G>A (p.Met1Ile)	Pathogenic
6114	NM_176806.4(MOCS2):c.19G>T (p.Val7Phe)	Pathogenic

SpliceAI

1027 predictions. Top by Δscore:

Variant	Effect	Δscore
5:53100406:CTTA:C	donor_loss	1.0000
5:53100407:TTACC:T	donor_loss	1.0000
5:53100408:TA:T	donor_loss	1.0000
5:53100409:A:AG	donor_loss	1.0000
5:53100530:CCAAG:C	acceptor_gain	1.0000
5:53100531:CAAG:C	acceptor_gain	1.0000
5:53100531:CAAGC:C	acceptor_gain	1.0000
5:53100532:AAG:A	acceptor_gain	1.0000
5:53100533:AG:A	acceptor_gain	1.0000
5:53100535:C:CC	acceptor_gain	1.0000
5:53100536:T:C	acceptor_gain	1.0000
5:53100537:T:C	acceptor_gain	1.0000
5:53100541:CAAGA:C	acceptor_gain	1.0000
5:53100542:A:T	acceptor_gain	1.0000
5:53101509:CCTT:C	acceptor_gain	1.0000
5:53101518:A:AC	acceptor_gain	1.0000
5:53102092:CTCA:C	donor_loss	1.0000
5:53102094:CA:C	donor_loss	1.0000
5:53102095:A:AC	donor_gain	1.0000
5:53102095:A:AG	donor_loss	1.0000
5:53102096:C:CC	donor_gain	1.0000
5:53102096:CCTA:C	donor_gain	1.0000
5:53102220:CTTTC:C	acceptor_gain	1.0000
5:53102221:TTTC:T	acceptor_gain	1.0000
5:53102223:TC:T	acceptor_gain	1.0000
5:53102224:CC:C	acceptor_gain	1.0000
5:53102225:C:CC	acceptor_gain	1.0000
5:53102225:CTAG:C	acceptor_loss	1.0000
5:53107073:ATACC:A	donor_loss	1.0000
5:53107074:TA:T	donor_loss	1.0000

AlphaMissense

1232 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:53100421:A:T	I164K	0.995
5:53100435:T:A	K159N	0.995
5:53100435:T:G	K159N	0.995
5:53100510:G:C	S134R	0.993
5:53100510:G:T	S134R	0.993
5:53100512:T:G	S134R	0.993
5:53100414:T:A	K166N	0.991
5:53100414:T:G	K166N	0.991
5:53100415:T:A	K166I	0.991
5:53100436:T:A	K159I	0.991
5:53101369:G:C	H123D	0.991
5:53100529:A:T	V128D	0.990
5:53101462:A:G	Y92H	0.990
5:53100421:A:C	I164R	0.989
5:53102101:A:C	F74L	0.989
5:53102101:A:T	F74L	0.989
5:53102103:A:G	F74L	0.989
5:53100499:G:T	A138D	0.987
5:53101499:T:A	R79S	0.986
5:53101499:T:G	R79S	0.986
5:53100480:T:A	R144S	0.985
5:53100480:T:G	R144S	0.985
5:53100481:C:G	R144T	0.985
5:53100419:A:G	W165R	0.984
5:53100419:A:T	W165R	0.984
5:53101467:A:G	L90S	0.983
5:53101378:C:G	A120P	0.982
5:53101456:C:G	A94P	0.982
5:53100481:C:A	R144I	0.981
5:53100500:C:G	A138P	0.981

dbSNP variants (sampled 300 via entrez): RS1000084809 (5:53096325 T>A), RS1000237662 (5:53105699 A>T), RS1000463791 (5:53099096 A>G), RS1000520021 (5:53109557 G>T), RS1000576687 (5:53104776 C>G), RS1000687386 (5:53097936 T>C), RS1000962441 (5:53104043 G>C,T), RS1000967963 (5:53110552 AG>A), RS1001115116 (5:53110093 G>A), RS1001121669 (5:53110265 G>A), RS1001454466 (5:53105766 G>A), RS1001567572 (5:53106019 T>C), RS1001853258 (5:53108766 T>A,C,G), RS1001978110 (5:53102277 C>G,T), RS1002084957 (5:53099334 A>G,T)

Disease associations

OMIM: gene MIM:603708 | disease phenotypes: MIM:252160, MIM:252150

GenCC curated gene-disease

Disease	Classification	Inheritance
sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1	Definitive	AR

Mondo (2): sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1 (MONDO:0009644), sulfite oxidase deficiency due to molybdenum cofactor deficiency (MONDO:0020480)

Orphanet (3): Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B (Orphanet:308393), Encephalopathy due to sulfite oxidase deficiency (Orphanet:833), Sulfite oxidase deficiency due to molybdenum cofactor deficiency (Orphanet:99732)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000639	Nystagmus
HP:0000737	Irritability
HP:0000804	Xanthine nephrolithiasis
HP:0001083	Ectopia lentis
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001510	Growth delay
HP:0002007	Frontal bossing
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002171	Gliosis
HP:0002179	Opisthotonus
HP:0002506	Diffuse cerebral atrophy
HP:0002510	Spastic tetraplegia
HP:0003166	Increased urinary taurine
HP:0003196	Short nose
HP:0003447	Axonal loss
HP:0003537	Hypouricemia
HP:0003570	Molybdenum cofactor deficiency

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002481_13	Acne (severe)	5.000000e-09
GCST004025_21	Systemic juvenile idiopathic arthritis	4.000000e-06
GCST005170_47	Intraocular pressure	1.000000e-16
GCST009600_3	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1.000000e-08
GCST011391_2	Corneal hysteresis	5.000000e-60
GCST90013442_6	Keratoconus	3.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0010066	corneal hysteresis

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565373	Molybdenum Cofactor Deficiency, Complementation Group B (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
trichostatin A	decreases expression	1
arsenite	affects binding, increases reaction	1
jinfukang	affects cotreatment, increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants, Occupational	affects expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	increases expression	1
Quercetin	decreases expression	1
Tretinoin	decreases expression	1
Zinc	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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