MOCS3

Summary

MOCS3 (molybdenum cofactor synthesis 3, HGNC:15765) is a protein-coding gene on chromosome 20q13.13, encoding Adenylyltransferase and sulfurtransferase MOCS3 (O95396). Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). It is a selective cancer dependency (DepMap: 89.0% of cell lines).

Molybdenum cofactor (MoCo) is necessary for the function of all molybdoenzymes. The protein encoded by this gene adenylates and activates molybdopterin synthase, an enzyme required for biosynthesis of MoCo. This gene contains no introns. A pseudogene of this gene is present on chromosome 14.

Source: NCBI Gene 27304 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sulfite oxidase deficiency due to molybdenum cofactor deficiency (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 318 total — 4 pathogenic
• Phenotypes (HPO): 43
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 89.0% of screened cell lines
• MANE Select transcript: NM_014484

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15765
Approved symbol	MOCS3
Name	molybdenum cofactor synthesis 3
Location	20q13.13
Locus type	gene with protein product
Status	Approved
Aliases	UBA4, dJ914P20.3
Ensembl gene	ENSG00000124217
Ensembl biotype	protein_coding
OMIM	609277
Entrez	27304

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000244051

RefSeq mRNA: 1 — MANE Select: NM_014484 NM_014484

CCDS: CCDS13435

Canonical transcript exons

ENST00000244051 — 1 exons

Exon	Start	End
ENSE00000845634	50958818	50963929

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 78.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.7954 / max 77.4493, expressed in 1767 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185295	10.3113	1762
185296	0.4841	234

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	78.97	gold quality
male germ cell	CL:0000015	77.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.47	silver quality
stromal cell of endometrium	CL:0002255	73.56	gold quality
cortical plate	UBERON:0005343	72.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.16	gold quality
ventricular zone	UBERON:0003053	70.89	gold quality
cervix squamous epithelium	UBERON:0006922	70.79	gold quality
cervix epithelium	UBERON:0004801	70.75	gold quality
ganglionic eminence	UBERON:0004023	70.69	gold quality
islet of Langerhans	UBERON:0000006	70.50	gold quality
gastrocnemius	UBERON:0001388	70.25	gold quality
muscle of leg	UBERON:0001383	69.95	gold quality
nasal cavity epithelium	UBERON:0005384	69.64	silver quality
prefrontal cortex	UBERON:0000451	69.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	69.12	gold quality
granulocyte	CL:0000094	68.84	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.77	gold quality
triceps brachii	UBERON:0001509	68.70	gold quality
right adrenal gland cortex	UBERON:0035827	68.70	gold quality
mucosa of transverse colon	UBERON:0004991	68.65	gold quality
gluteal muscle	UBERON:0002000	68.59	gold quality
right testis	UBERON:0004534	68.42	gold quality
right adrenal gland	UBERON:0001233	68.24	gold quality
diaphragm	UBERON:0001103	68.16	gold quality
bronchial epithelial cell	CL:0002328	68.02	gold quality
left adrenal gland	UBERON:0001234	67.89	gold quality
tongue squamous epithelium	UBERON:0006919	67.88	gold quality
muscle organ	UBERON:0001630	67.78	gold quality
epithelium of bronchus	UBERON:0002031	67.74	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting MOCS3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• MOCS3 protein is believed to catalyze both the adenylation and the subsequent generation of a thiocarboxylate group at the C terminus of the smaller subunit of molybdopterin synthase (PMID:15073332)
• Electrospray ionization mass spectrometry performed on a rhodanese-like carboxyl-terminal domain of human MOCS3 provides direct evidence for the formation of persulfide on cysteine residue 412. (PMID:15910006)
• in humans & most eukaryotes thiosulfate is not physiologic sulfur donor for MOCS3, whereas in bacterial homologs, which have arginine at last position of active site loop, thiosulfate can be used as a sulfur source for molybdenum cofactor biosynthesis. (PMID:17459099)
• The UBA4-URM1 system represents the evolutionary link between protein conjugation and protein modification by sulfur carrier proteins. (PMID:18491921)
• Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis (PMID:18650437)
• extension of the C terminus with an additional glycine of MOCS2A and URM1 altered the localization of MOCS3 from the cytosol to the nucleus. (PMID:22453920)
• ubiquitin-like Urm1.Uba4 systems are conserved and exchangeable between human and yeast cells (PMID:25747390)
• Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08x10(-6), preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56x10(-6)). (PMID:26917578)
• This observation should encourage testing of additional intellectual disability patients with mild abnormalities of sulfite metabolism for MOCS3 mutations. (PMID:28544736)
• By different methods, this study identified a MOCS3-independent novel localization of NFS1 at the centrosome. (PMID:30817134)
• Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system in tRNA thiolation and ubiquitin-like conjugation. (PMID:32901956)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mocs3	ENSDARG00000008239
mus_musculus	Mocs3	ENSMUSG00000074576
rattus_norvegicus	Mocs3	ENSRNOG00000081351
drosophila_melanogaster	Uba4	FBGN0032054
caenorhabditis_elegans		WBGENE00018357

Paralogs (9): UBA6 (ENSG00000033178), UBA5 (ENSG00000081307), UBA2 (ENSG00000126261), UBA1 (ENSG00000130985), SAE1 (ENSG00000142230), UBA3 (ENSG00000144744), NAE1 (ENSG00000159593), UBA7 (ENSG00000182179), ATG7 (ENSG00000197548)

Protein

Protein identifiers

Adenylyltransferase and sulfurtransferase MOCS3 — O95396 (reviewed: O95396)

Alternative names: Molybdenum cofactor synthesis protein 3, Molybdopterin synthase sulfurylase

All UniProt accessions (1): O95396

UniProt curated annotations — full annotation on UniProt →

Function. Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Also essential during biosynthesis of the molybdenum cofactor. Acts by mediating the C-terminal thiocarboxylation of sulfur carriers URM1 and MOCS2A. Its N-terminus first activates URM1 and MOCS2A as acyl-adenylates (-COAMP), then the persulfide sulfur on the catalytic cysteine is transferred to URM1 and MOCS2A to form thiocarboxylation (-COSH) of their C-terminus. The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as a nucleophile towards URM1 and MOCS2A. Subsequently, a transient disulfide bond is formed. Does not use thiosulfate as sulfur donor; NFS1 acting as a sulfur donor for thiocarboxylation reactions.

Subunit / interactions. Interacts with NFS1.

Subcellular location. Cytoplasm. Cytosol.

Disease relevance. Defects in MOCS3 may be the cause of a form of molybdenum cofactor deficiency. One case presented with early onset of neonatal seizures, hypertonia, feeding difficulty, global cystic encephalomalacia, cortical necrosis and severe developmental delay, and died in infancy. Another case presented with moderate abnormalities of sulfite metabolism, intellectual disability, autism, and dysmorphic features.

Cofactor. Binds 1 zinc ion per subunit.

Pathway. tRNA modification; 5-methoxycarbonylmethyl-2-thiouridine-tRNA biosynthesis. Cofactor biosynthesis; molybdopterin biosynthesis.

Similarity. In the N-terminal section; belongs to the HesA/MoeB/ThiF family. UBA4 subfamily.

RefSeq proteins (1): NP_055299* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000594	ThiF_NAD_FAD-bd	Domain
IPR001763	Rhodanese-like_dom	Domain
IPR028885	MOCS3/Uba4	Family
IPR035985	Ubiquitin-activating_enz	Homologous_superfamily
IPR036873	Rhodanese-like_dom_sf	Homologous_superfamily
IPR045886	ThiF/MoeB/HesA	Family

Pfam: PF00581, PF00899

Enzyme classification (BRENDA):

• EC 2.7.7.80 — molybdopterin-synthase adenylyltransferase (BRENDA: 2 organisms, 1 substrates, 0 inhibitors, 0 Km, 0 kcat entries)
• EC 2.8.1.11 — molybdopterin synthase sulfurtransferase (BRENDA: 3 organisms, 10 substrates, 0 inhibitors, 1 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 2 shown:

• [molybdopterin-synthase sulfur-carrier protein]-C-terminal Gly-Gly + ATP + H(+) = [molybdopterin-synthase sulfur-carrier protein]-C-terminal Gly-Gly-AMP + diphosphate (RHEA:43616)
• [molybdopterin-synthase sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 = [molybdopterin-synthase sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) (RHEA:48612)

UniProt features (45 total): mutagenesis site 13, binding site 9, helix 6, strand 6, sequence variant 4, active site 2, chain 1, domain 1, modified residue 1, disulfide bond 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3I2V	X-RAY DIFFRACTION	1.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95396-F1	91.60	0.79

Functional residue map

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

Catalytic / active sites (2): 239 (glycyl thioester intermediate; for adenylyltransferase activity); 412 (cysteine persulfide intermediate; for sulfurtransferase activity)

Ligand- & substrate-binding residues (9): 222; 225; 297; 300; 92; 113; 120–124; 137; 181–182

Post-translational modifications (1): 412

Disulfide bonds (1): 316–324

Mutagenesis-validated functional residues (13):

Position	Phenotype
239	impairs sulfurtransferase activity.
316	does not affect sulfurtransferase activity.
324	does not affect sulfurtransferase activity.
365	does not affect sulfurtransferase activity.
412	abolishes sulfurtransferase activity.
413	does not affect sulfurtransferase specificity and activity.
414	does not affect sulfurtransferase specificity and activity.
415	does not affect sulfurtransferase specificity and activity.
416	does not affect sulfurtransferase specificity and activity.
417	results in 470-fold increased activity.
417	results in 90-fold increased activity.
458	does not affect sulfurtransferase specificity and activity.
460	does not affect sulfurtransferase specificity and activity.

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: 115 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_RNA_MODIFICATION, GGAANCGGAANY_UNKNOWN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, KIM_GASTRIC_CANCER_CHEMOSENSITIVITY, DANG_BOUND_BY_MYC, GOBP_TRNA_PROCESSING, GOBP_TRNA_MODIFICATION, LIU_SOX4_TARGETS_DN, BENPORATH_MYC_MAX_TARGETS, SCGGAAGY_ELK1_02

GO Biological Process (6): tRNA wobble uridine modification (GO:0002098), tRNA wobble position uridine thiolation (GO:0002143), Mo-molybdopterin cofactor biosynthetic process (GO:0006777), protein urmylation (GO:0032447), tRNA thio-modification (GO:0034227), tRNA processing (GO:0008033)

GO Molecular Function (14): thiosulfate-cyanide sulfurtransferase activity (GO:0004792), ATP binding (GO:0005524), nucleotidyltransferase activity (GO:0016779), sulfurtransferase activity (GO:0016783), URM1 activating enzyme activity (GO:0042292), metal ion binding (GO:0046872), molybdopterin-synthase sulfurtransferase activity (GO:0061604), molybdopterin-synthase adenylyltransferase activity (GO:0061605), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), ubiquitin-like modifier activating enzyme activity (GO:0008641), transferase activity (GO:0016740), adenylyltransferase activity (GO:0070566)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

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
sulfurtransferase activity	2
cellular anatomical structure	2
tRNA wobble base modification	1
tRNA wobble uridine modification	1
tRNA thio-modification	1
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
protein modification by small protein conjugation	1
tRNA modification	1
RNA processing	1
tRNA metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transferase activity, transferring phosphorus-containing groups	1
transferase activity, transferring sulphur-containing groups	1
ubiquitin-like modifier activating enzyme activity	1
cation binding	1
adenylyltransferase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
ligase activity, forming carbon-sulfur bonds	1
catalytic activity, acting on a protein	1
ATP-dependent activity	1
catalytic activity	1
nucleotidyltransferase activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MOCS3	MOCS2	O96007	985
MOCS3	URM1	Q9BTM9	956
MOCS3	TST	Q16762	942
MOCS3	CTU1	Q7Z7A3	917
MOCS3	NFS1	Q9Y697	899
MOCS3	MPST	P25325	880
MOCS3	MOCS1	Q9NZB8	843
MOCS3	CTU2	Q2VPK5	842
MOCS3	KTI12	Q96EK9	717
MOCS3	SUOX	P51687	715
MOCS3	UFM1	P61960	710
MOCS3	MCM5	P33992	667
MOCS3	ELP3	Q9H9T3	665
MOCS3	TRMT112	Q9UI30	646
MOCS3	ELP4	Q96EB1	645

IntAct

55 interactions, top by confidence:

A	B	Type	Score
CA10	WDHD1	psi-mi:“MI:0914”(association)	0.640
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
URM1	MOCS3	psi-mi:“MI:0195”(covalent binding)	0.590
URM1	MOCS3	psi-mi:“MI:0915”(physical association)	0.590
MOCS3	ATXN1	psi-mi:“MI:0915”(physical association)	0.560
MOCS3	TARDBP	psi-mi:“MI:0915”(physical association)	0.560
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
RSPH9	EIF3H	psi-mi:“MI:0914”(association)	0.530
ALX3	CRTAP	psi-mi:“MI:0914”(association)	0.530
ISX	MOCS3	psi-mi:“MI:0914”(association)	0.530
POMK	CLGN	psi-mi:“MI:0914”(association)	0.530
URM1	OGT	psi-mi:“MI:0914”(association)	0.350
URM1	ELP1	psi-mi:“MI:0914”(association)	0.350
MOCS3	HSPA6	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
BTLA	MOCS3	psi-mi:“MI:0914”(association)	0.350
KLK15	SPINT1	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MOCS3	HSPA8	psi-mi:“MI:0914”(association)	0.350
VEGFD	RPSA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): MOCS3 (Affinity Capture-MS), MOCS3 (Affinity Capture-MS), MOCS3 (Affinity Capture-MS), MOCS3 (Affinity Capture-MS), MOCS3 (Affinity Capture-MS), MOCS3 (Affinity Capture-MS), KLC2 (Affinity Capture-MS), FBXL18 (Affinity Capture-MS), HERC4 (Affinity Capture-MS), MOCS3 (Affinity Capture-MS), MOCS3 (Affinity Capture-MS), DYNC2H1 (Affinity Capture-MS), SACS (Affinity Capture-MS), MOCS3 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS)

ESM2 similar proteins: A1A4L8, A2BDX3, A4RPM5, A5GFZ6, A6NK58, B4FAT0, B4NXF7, B6TNK6, O19179, O43323, O95396, O95571, P19971, P55203, P85971, Q02846, Q05922, Q08DH8, Q0VFH3, Q14BV6, Q17CA7, Q1WNP0, Q3KQV9, Q3TW96, Q3UQ84, Q561R2, Q58E95, Q5PQQ1, Q5ZKI2, Q61488, Q66JK4, Q6PAT0, Q7PY41, Q86U10, Q8AWD2, Q8NFV4, Q8VBZ0, Q8VDG5, Q923K4, Q96EY9

Diamond homologs: A1A4L8, A1CAZ7, A1DED8, A2BDX3, A2R3H4, A3ACF3, A3LQF9, A4RPM5, A5DMB6, A5DSR2, A5GFZ6, A6ZT19, A7F582, A7THV5, A8WRE3, B0W377, B0WQV1, B0Y0P7, B3LSM6, B3MLX7, B3NUC9, B4FAT0, B4GKQ3, B4HYP0, B4IK21, B4JBC4, B4JIY0, B4KI53, B4L1K2, B4LRB9, B4M357, B4N7R4, B4NXF7, B4PYA4, B4R345, B5DS72, B5VK45, B6TNK6, D1GY43, D4GSF3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	232
Likely benign	72
Benign	7

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2424782	NC_000020.10:g.(?49507942)(49576762_?)del	Pathogenic
4278931	A257T	Pathogenic
4278932	MCOS3, GLN459TER	Pathogenic
4278933	L109V	Pathogenic

SpliceAI

191 predictions. Top by Δscore:

Variant	Effect	Δscore
20:50960139:GA:G	donor_gain	0.9800
20:50960141:G:GG	donor_gain	0.9600
20:50960013:G:GT	donor_gain	0.9500
20:50960140:A:AG	donor_gain	0.9500
20:50960236:AT:A	donor_gain	0.9500
20:50959928:G:GA	donor_gain	0.9200
20:50960025:G:GT	donor_gain	0.9200
20:50960025:G:T	donor_gain	0.9200
20:50959927:T:TA	donor_gain	0.9100
20:50960163:G:GT	donor_gain	0.9000
20:50960145:G:GT	donor_gain	0.8600
20:50959921:TGG:T	donor_gain	0.8500
20:50960218:A:AG	donor_gain	0.8400
20:50960219:G:GG	donor_gain	0.8400
20:50959922:G:GA	donor_gain	0.8200
20:50960142:T:G	donor_gain	0.8200
20:50960143:T:A	donor_gain	0.8200
20:50960279:A:G	donor_gain	0.8200
20:50959923:GAG:G	donor_gain	0.8100
20:50960474:GATG:G	donor_gain	0.8100
20:50959923:G:GT	donor_gain	0.7900
20:50960606:T:G	donor_gain	0.7800
20:50959986:G:T	donor_gain	0.7700
20:50960232:T:A	donor_gain	0.7700
20:50960304:A:AG	donor_gain	0.7600
20:50959905:G:GT	donor_gain	0.7500
20:50960363:G:GT	donor_gain	0.7500
20:50960364:G:GT	donor_gain	0.7500
20:50959617:G:GT	donor_gain	0.7100
20:50960163:G:T	donor_gain	0.7000

AlphaMissense

2895 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:50959379:C:G	C179W	0.997
20:50959384:A:T	D181V	0.997
20:50959385:C:A	D181E	0.995
20:50959385:C:G	D181E	0.995
20:50959253:G:C	K137N	0.994
20:50959253:G:T	K137N	0.994
20:50959384:A:C	D181A	0.993
20:50959912:G:T	R357M	0.993
20:50959217:A:C	Q125H	0.991
20:50959217:A:T	Q125H	0.991
20:50959383:G:C	D181H	0.991
20:50959412:T:A	N190K	0.991
20:50959412:T:G	N190K	0.991
20:50959421:T:G	C193W	0.991
20:50959456:C:A	A205D	0.991
20:50959378:G:A	C179Y	0.990
20:50959452:A:C	S204R	0.990
20:50959454:T:A	S204R	0.990
20:50959454:T:G	S204R	0.990
20:50959912:G:C	R357T	0.990
20:50959420:G:A	C193Y	0.989
20:50959381:C:G	S180W	0.988
20:50959372:C:A	A177D	0.987
20:50959377:T:C	C179R	0.987
20:50959627:A:T	K262I	0.987
20:50959205:C:A	N121K	0.985
20:50959205:C:G	N121K	0.985
20:50959913:G:C	R357S	0.985
20:50959913:G:T	R357S	0.985
20:50960086:G:T	G415V	0.985

dbSNP variants (sampled 300 via entrez): RS1000358015 (20:50958617 C>A,G,T), RS1000726687 (20:50960069 T>C,G), RS1000986136 (20:50963229 A>G), RS1001657193 (20:50958631 C>A,G,T), RS1001747661 (20:50957853 T>C,G), RS1002184049 (20:50963084 T>A), RS1002241519 (20:50963495 AAG>A), RS1002605919 (20:50957725 G>A), RS1002858716 (20:50960433 ATT>A,AT,ATTT,ATTTT), RS1002912540 (20:50960783 G>A,C), RS1003068028 (20:50957365 T>C), RS1004801731 (20:50960837 A>G), RS1004958791 (20:50961111 T>G), RS1005380187 (20:50964017 A>T), RS1005805045 (20:50957819 C>A)

Disease associations

OMIM: gene MIM:609277 | disease phenotypes: MIM:236750, MIM:608799, MIM:621373

GenCC curated gene-disease

Disease	Classification	Inheritance
sulfite oxidase deficiency due to molybdenum cofactor deficiency	Moderate	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 B2	Limited	AR

Mondo (4): non-immune hydrops fetalis (MONDO:0009369), congenital disorder of glycosylation type 1E (MONDO:0012123), sulfite oxidase deficiency due to molybdenum cofactor deficiency type B2 (MONDO:0980701), sulfite oxidase deficiency due to molybdenum cofactor deficiency (MONDO:0020480)

Orphanet (2): Non-immune hydrops fetalis (Orphanet:363999), DPM1-CDG (Orphanet:79322)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000486	Strabismus
HP:0000689	Dental malocclusion
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0001166	Arachnodactyly
HP:0001181	Adducted thumb
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001290	Generalized hypotonia
HP:0001347	Hyperreflexia
HP:0001833	Long foot
HP:0002078	Truncal ataxia
HP:0002093	Respiratory insufficiency
HP:0002149	Hyperuricemia
HP:0002307	Drooling
HP:0002376	Developmental regression
HP:0002967	Cubitus valgus
HP:0003149	Hyperuricosuria
HP:0003487	Babinski sign
HP:0003623	Neonatal onset
HP:0003643	Sulfite oxidase deficiency
HP:0005484	Secondary microcephaly
HP:0005639	Hyperextensible hand joints
HP:0006532	Recurrent pneumonia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008103_111	Bipolar disorder	4.000000e-06
GCST008115_15	Bipolar I disorder	6.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009963	bipolar I disorder

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535743	Congenital disorder of glycosylation type 1E (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295684 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
sodium arsenite	increases expression	1
ferrous chloride	decreases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Benzo(a)pyrene	increases methylation	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118771	Binding	Binding affinity to MOCS3 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04308603	Not specified	COMPLETED	Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing
NCT05528796	Not specified	ENROLLING_BY_INVITATION	Uncovering the Etiologies of Non-immune Hydrops Fetalis