MOCS1

Summary

MOCS1 (molybdenum cofactor synthesis 1, HGNC:7190) is a protein-coding gene on chromosome 6p21.2, encoding Molybdenum cofactor biosynthesis protein 1 (Q9NZB8). Isoform MOCS1A and isoform MOCS1B probably form a complex that catalyzes the conversion of 5’-GTP to cyclic pyranopterin monophosphate (cPMP).

Molybdenum cofactor biosynthesis is a conserved pathway leading to the biological activation of molybdenum. The protein encoded by this gene is involved in this pathway. This gene was originally thought to produce a bicistronic mRNA with the potential to produce two proteins (MOCS1A and MOCS1B) from adjacent open reading frames. However, only the first open reading frame (MOCS1A) has been found to encode a protein from the putative bicistronic mRNA, whereas additional splice variants are likely to produce a fusion between the two open reading frames. This gene is defective in patients with molybdenum cofactor deficiency, type A. A related pseudogene has been identified on chromosome 16.

Source: NCBI Gene 4337 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sulfite oxidase deficiency due to molybdenum cofactor deficiency type A (Definitive, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 808 total — 48 pathogenic, 39 likely-pathogenic
• Phenotypes (HPO): 44
• MANE Select transcript: NM_001358530

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7190
Approved symbol	MOCS1
Name	molybdenum cofactor synthesis 1
Location	6p21.2
Locus type	gene with protein product
Status	Approved
Aliases	MOCOD, MOCS1A, MOCS1B
Ensembl gene	ENSG00000124615
Ensembl biotype	protein_coding
OMIM	603707
Entrez	4337

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000340692, ENST00000373181, ENST00000373188, ENST00000373195, ENST00000425303, ENST00000432280, ENST00000473742, ENST00000487924, ENST00000645522, ENST00000713661, ENST00000713662, ENST00000713663, ENST00000713664, ENST00000713665, ENST00000937948, ENST00000961859, ENST00000961860

RefSeq mRNA: 7 — MANE Select: NM_001358530 NM_001075098, NM_001358529, NM_001358530, NM_001358531, NM_001358533, NM_001358534, NM_005943

CCDS: CCDS43460, CCDS87394

Canonical transcript exons

ENST00000340692 — 11 exons

Exon	Start	End
ENSE00000849495	39912892	39913004
ENSE00000849499	39909835	39909955
ENSE00001871180	39912264	39912374
ENSE00002480849	39913774	39913835
ENSE00002505858	39913317	39913428
ENSE00003673631	39916068	39916232
ENSE00004022048	39925678	39925845
ENSE00004022049	39909055	39909102
ENSE00004022050	39927329	39927455
ENSE00004022051	39904170	39907117
ENSE00004022052	39934295	39934462

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 92.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9880 / max 178.9279, expressed in 1431 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73496	7.7672	1414
73495	1.2208	709

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	92.98	gold quality
popliteal artery	UBERON:0002250	91.21	gold quality
tibial artery	UBERON:0007610	91.21	gold quality
right lung	UBERON:0002167	91.14	gold quality
pancreatic ductal cell	CL:0002079	91.11	silver quality
right lobe of liver	UBERON:0001114	90.83	gold quality
omental fat pad	UBERON:0010414	90.83	gold quality
peritoneum	UBERON:0002358	90.75	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.61	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.31	gold quality
mucosa of transverse colon	UBERON:0004991	90.17	gold quality
aorta	UBERON:0000947	89.85	gold quality
gastrocnemius	UBERON:0001388	89.83	gold quality
tibial nerve	UBERON:0001323	89.49	gold quality
heart left ventricle	UBERON:0002084	89.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.39	gold quality
left coronary artery	UBERON:0001626	89.08	gold quality
muscle of leg	UBERON:0001383	89.04	gold quality
adipose tissue	UBERON:0001013	88.99	gold quality
cardiac ventricle	UBERON:0002082	88.85	gold quality
descending thoracic aorta	UBERON:0002345	88.73	gold quality
right adrenal gland cortex	UBERON:0035827	88.60	gold quality
upper lobe of left lung	UBERON:0008952	88.43	gold quality
thoracic aorta	UBERON:0001515	88.36	gold quality
ascending aorta	UBERON:0001496	88.35	gold quality
right atrium auricular region	UBERON:0006631	88.14	gold quality
connective tissue	UBERON:0002384	88.05	gold quality
coronary artery	UBERON:0001621	88.01	gold quality
medial globus pallidus	UBERON:0002477	87.81	gold quality
right lobe of thyroid gland	UBERON:0001119	87.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting MOCS1, 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-6740-5P	100.00	65.64	932
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-520F-5P	99.34	70.40	1632

Literature-anchored findings (GeneRIF, showing 7)

• 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)
• MOCS1A is an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis (PMID:15180982)
• genetic and protein structural analysis of MOCS1 in molybdenum cofactor deficiency [case report] (PMID:17065069)
• Case Report: in a mild case of molybdenum cofactor deficiency detected two proteins: a truncated MOCS1AB protein and a 22.4 kDa protein representing MOCS1B, demonstrating an unusual mechanism of translation re-initiation in the MOCS1 transcript, which results in trace amounts of functional MOCS1B protein being sufficient to partially protect the patient from the most severe symptoms. (PMID:29368224)
• ETHE1 and MOCS1 deficiencies: Disruption of mitochondrial bioenergetics, dynamics, redox homeostasis and endoplasmic reticulum-mitochondria crosstalk in patient fibroblasts. (PMID:31477743)
• Alternative splicing of the bicistronic gene molybdenum cofactor synthesis 1 (MOCS1) uncovers a novel mitochondrial protein maturation mechanism. (PMID:31996372)
• New Neuroimaging Findings in Patients with Molybdenum Cofactor Deficiency Type A: A Case Report and Literature Review. (PMID:38389347)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mocs1	ENSDARG00000078479
mus_musculus	Mocs1	ENSMUSG00000064120
rattus_norvegicus	Mocs1	ENSRNOG00000011784
drosophila_melanogaster	Mocs1	FBGN0263241
caenorhabditis_elegans		WBGENE00009885
caenorhabditis_elegans		WBGENE00009908

Protein

Protein identifiers

Molybdenum cofactor biosynthesis protein 1 — Q9NZB8 (reviewed: Q9NZB8)

Alternative names: Cell migration-inducing gene 11 protein, Molybdenum cofactor synthesis-step 1 protein A-B

All UniProt accessions (7): A0AAQ5BGK8, A0AAQ5BGL9, A0AAQ5BGM4, A0AAQ5BGM5, A0AAQ5BGP5, Q9NZB8, F8WCK1

UniProt curated annotations — full annotation on UniProt →

Function. Isoform MOCS1A and isoform MOCS1B probably form a complex that catalyzes the conversion of 5’-GTP to cyclic pyranopterin monophosphate (cPMP). MOCS1A catalyzes the cyclization of GTP to (8S)-3’,8-cyclo-7,8-dihydroguanosine 5’-triphosphate and MOCS1B catalyzes the subsequent conversion of (8S)-3’,8-cyclo-7,8-dihydroguanosine 5’-triphosphate to cPMP. Has very weak catalytic activity.

Subunit / interactions. Isoform MOCS1A and isoform MOCS1B probably form a heterooligomer.

Subcellular location. Mitochondrion matrix Mitochondrion matrix Mitochondrion matrix Cytoplasm. Cytosol Cytoplasm Mitochondrion matrix.

Tissue specificity. Isoform MOCS1A and isoform 2 are widely expressed.

Disease relevance. Molybdenum cofactor deficiency A (MOCODA) [MIM:252150] An autosomal recessive metabolic disorder leading to the pleiotropic loss of molybdoenzyme activities. It is clinically characterized by onset in infancy of poor feeding, intractable seizures, severe psychomotor retardation, and death in early childhood in most patients. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 [4Fe-4S] clusters. Binds 1 [4Fe-4S] cluster coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine and 1 [4Fe-4S] cluster coordinated with 3 cysteines and the GTP-derived substrate.

Pathway. Cofactor biosynthesis; molybdopterin biosynthesis.

Miscellaneous. The MOCS1 transcript is alternatively spliced resulting in production of alternative MOCS1A and MOCS1B products. Type I splicing results in bicistronic transcripts with two open reading frames, of which only the first, MOCS1A, is translated due to a stop codon in exon 9. Alternative splicing of exon 9 leads to production of type II or III transcripts (where exon 9 is partially or fully removed) and where MOCS1B is translated as a fusion protein together with catalytically inactive MOCS1A; inactive MOCS1A is subsequently proteolytically cleaved during mitochondrial import and it is not known if it has a functional role. Alternative splicing of the N-terminal exon 1 cassettes a-d appears to impart different properties to the protein; exon 1a targets MOCS1A to the mitochondrion whereas exon 1b at the N-terminus remains in the cytosol, exon 1c might stabilize MOCS1A, and exon 1d is essential for MOCS1A catalytic activity. Exon 1a seems dispensable for targeting MOCS1B to the mitochondrion due to the presence of a linker region separating MOCS1A and MOCS1B that appears to facilitate mitochondrial import. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Multidomain protein with inactive MOCS1A and active MOCS1B.

Similarity. In the C-terminal section; belongs to the MoaC family. In the N-terminal section; belongs to the radical SAM superfamily. MoaA family.

Isoforms (9)

UniProt ID	Names	Canonical?
Q9NZB8-1	MOCS1B, MOCS1B Type-II	yes
Q9NZB8-5	MOCS1A, MOCS1A Type-Iad, Larin
Q9NZB8-6	2, MOCS1A Type-Ibcd, Reiss
Q9NZB8-3	3, MOCS1A Type-Ibd, Gross-Hardt
Q9NZB8-4	4
Q9NZB8-2	6, MOCS1B Type-III
Q9NZB8-7	7
Q9NZB8-8	8, MOCS1AB-bcd
Q9NZB8-9	9, MOCS1A Type-Ia, Arenas

RefSeq proteins (7): NP_001068566, NP_001345458, NP_001345459, NP_001345460, NP_001345462, NP_001345463, NP_005934 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000385	MoaA_NifB_PqqE_Fe-S-bd_CS	Conserved_site
IPR002820	Mopterin_CF_biosynth-C_dom	Domain
IPR006638	Elp3/MiaA/NifB-like_rSAM	Domain
IPR007197	rSAM	Domain
IPR010505	MoaA_twitch	Domain
IPR013483	MoaA	Family
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR023045	MoaC	Family
IPR036522	MoaC_sf	Homologous_superfamily
IPR040064	MoaA-like	Family
IPR047594	MoaC_bact/euk	Family
IPR050105	MoCo_biosynth_MoaA/MoaC	Family
IPR058240	rSAM_sf	Homologous_superfamily

Pfam: PF01967, PF04055, PF06463

Enzyme classification (BRENDA):

• EC 4.1.99.22 — GTP 3’,8-cyclase (BRENDA: 8 organisms, 16 substrates, 0 inhibitors, 8 Km, 4 kcat entries)
• EC 4.6.1.17 — cyclic pyranopterin monophosphate synthase (BRENDA: 5 organisms, 6 substrates, 1 inhibitors, 6 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
(8S)-3’,8-CYCLO-7,8-DIHYDROGUANOSINE 5’-TRIPHOSP	0.0002–0.0043	6
(8S)-3’,8-CYCLO-7,8-DIHYDROGUANOSINE 5’-TRIPHOSP	0.0001–0.0008	2
GTP	0.0031–0.0069	2
S-ADENOSYL-L-METHIONINE	0.0051–0.036	2

Catalyzed reactions (Rhea), 2 shown:

• GTP + AH2 + S-adenosyl-L-methionine = (8S)-3’,8-cyclo-7,8-dihydroguanosine 5’-triphosphate + 5’-deoxyadenosine + L-methionine + A + H(+) (RHEA:49576)
• (8S)-3’,8-cyclo-7,8-dihydroguanosine 5’-triphosphate = cyclic pyranopterin phosphate + diphosphate (RHEA:49580)

UniProt features (77 total): sequence variant 26, binding site 17, splice variant 9, mutagenesis site 8, region of interest 5, modified residue 3, sequence conflict 3, transit peptide 1, chain 1, propeptide 1, domain 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZB8-F1	79.87	0.61

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 (1): 606 (for mocs1b activity)

Ligand- & substrate-binding residues (17): 73; 80; 84; 86; 87; 123; 127; 154; 178; 215; 249; 312 …

Post-translational modifications (3): 64, 198, 528

Mutagenesis-validated functional residues (8):

Position	Phenotype
80	impairs precursor z synthesis.
84	impairs precursor z synthesis.
87	impairs precursor z synthesis.
312	impairs precursor z synthesis.
315	impairs precursor z synthesis.
329	impairs precursor z synthesis.
431	decreases proteolytic cleavage of the protein.
436	no effect on proteolytic cleavage of the protein.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-947581	Molybdenum cofactor biosynthesis

MSigDB gene sets: 161 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, CACCAGC_MIR138, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GTGCCTT_MIR506, TCCCCAC_MIR491, TGCCTTA_MIR124A, GOCC_MITOCHONDRIAL_MATRIX, CTGAGCC_MIR24, WGTTNNNNNAAA_UNKNOWN, LINDGREN_BLADDER_CANCER_CLUSTER_1_DN, KIM_WT1_TARGETS_DN, GOMF_SULFUR_COMPOUND_BINDING, REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS

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

GO Molecular Function (10): GTP binding (GO:0005525), metal ion binding (GO:0046872), 4 iron, 4 sulfur cluster binding (GO:0051539), GTP 3’,8’-cyclase activity (GO:0061798), cyclic pyranopterin monophosphate synthase activity (GO:0061799), S-adenosyl-L-methionine binding (GO:1904047), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), lyase activity (GO:0016829), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cation binding	2
cytoplasm	2
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
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
iron-sulfur cluster binding	1
carbon-carbon lyase activity	1
phosphorus-oxygen lyase activity	1
sulfur compound binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
catalytic activity	1
metal cluster binding	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1418 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MOCS1	MOCS2	O96007	996
MOCS1	SUOX	P51687	972
MOCS1	AOX1	Q06278	961
MOCS1	GPHN	Q9NQX3	957
MOCS1	MTARC2	Q969Z3	895
MOCS1	MOCS3	O95396	843
MOCS1	TYW1	Q9NV66	622
MOCS1	MOCOS	Q96EN8	603
MOCS1	LIAS	O43766	578
MOCS1	CDK5RAP1	Q96SZ6	538
MOCS1	ETHE1	O95571	533
MOCS1	ISCA2	Q86U28	527
MOCS1	CTU1	Q7Z7A3	519
MOCS1	ISCA1	Q9BUE6	519
MOCS1	HLCS	P50747	518

IntAct

30 interactions, top by confidence:

A	B	Type	Score
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
RAB8B	BLTP3B	psi-mi:“MI:0914”(association)	0.530
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RAB17	GTPBP1	psi-mi:“MI:0914”(association)	0.530
KLHDC3	DPYSL4	psi-mi:“MI:0914”(association)	0.530
PDGFRL	ANKRD28	psi-mi:“MI:0914”(association)	0.530
Mgu	GCLM	psi-mi:“MI:0914”(association)	0.530
KLHDC3	CLUH	psi-mi:“MI:0914”(association)	0.530
MOCS1	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
PCNA	MOCS1	psi-mi:“MI:0915”(physical association)	0.370
PIN1	MOCS1	psi-mi:“MI:0915”(physical association)	0.370
RAMP2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
MALSU1	VWA8	psi-mi:“MI:0914”(association)	0.350
MFAP5	MANBA	psi-mi:“MI:0914”(association)	0.350
OXLD1	PRORP	psi-mi:“MI:0914”(association)	0.350
PRAMEF9	PRAMEF4	psi-mi:“MI:0914”(association)	0.350
TINAG	VPS26A	psi-mi:“MI:0914”(association)	0.350
HINT2	CST4	psi-mi:“MI:0914”(association)	0.350
GUCY2D	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
HDAC6	HSPA8	psi-mi:“MI:0914”(association)	0.350
FCRL4	HCCS	psi-mi:“MI:0914”(association)	0.350
MOCS1	TMF1	psi-mi:“MI:0914”(association)	0.350
SSC4D	TOP3A	psi-mi:“MI:0914”(association)	0.350
PF4	BLZF1	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350
CHCHD4	PDHX	psi-mi:“MI:0914”(association)	0.350
KLHDC3	SMAP	psi-mi:“MI:0914”(association)	0.350
HOOK2	SEC16A	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (46): MOCS1 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), MOCS1 (Synthetic Lethality), MOCS1 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), MOCS1 (Proximity Label-MS)

ESM2 similar proteins: A1A4I4, A4K436, A6QLH6, D3ZVM4, F1M5F3, F1N2W9, O00459, O08908, O43272, O60336, O95294, P0C928, P23726, P70268, Q0VGM9, Q16512, Q1JQD7, Q1PSW8, Q3KRC5, Q496Y0, Q5M9F8, Q5R812, Q5RE34, Q5RJZ1, Q5RKZ7, Q5XIS9, Q5ZIW1, Q63433, Q63788, Q6H1L8, Q6NS57, Q6NYU2, Q6PFQ7, Q8BZ03, Q8R1T1, Q91XI1, Q920N2, Q92889, Q92994, Q96G46

Diamond homologs: A0AHG0, A0L7R4, A0R443, A0RMJ2, A1U578, A1ULP7, A3Q648, A4J6S5, A4XW05, A5CYZ0, A5I365, A5VZZ2, A6Q6R2, A6TVF9, A6U9U3, A7FUZ6, A7GEQ5, A7GWA5, A7ZB87, A8ERS0, A8MLW5, A9BF51, B0CDZ6, B0JNC2, B0KST1, B0TI16, B1IN35, B1JCW0, B1KU20, B1X0G3, B1XLR4, B2GCN4, B2HFA4, B2J1M7, B3PQ08, B3QCQ7, B5YJ09, B5ZRM8, B6JM01, B7JWW6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	48
Likely pathogenic	39
Uncertain significance	372
Likely benign	251
Benign	37

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1362490	NM_001358530.2(MOCS1):c.1001_1002del (p.Asn333_Ser334insTer)	Pathogenic
1420113	NM_001358530.2(MOCS1):c.1222C>T (p.Gln408Ter)	Pathogenic
1448612	NM_001358530.2(MOCS1):c.343del (p.Phe114_Val115insTer)	Pathogenic
1453244	NM_001358530.2(MOCS1):c.268G>T (p.Glu90Ter)	Pathogenic
1456535	NM_001358530.2(MOCS1):c.48del (p.Ser17fs)	Pathogenic
1457660	NM_001358530.2(MOCS1):c.271del (p.Glu91fs)	Pathogenic
1459223	NM_001358530.2(MOCS1):c.955C>T (p.Arg319Ter)	Pathogenic
2005863	NM_001358530.2(MOCS1):c.1150G>T (p.Glu384Ter)	Pathogenic
2017259	NM_001358530.2(MOCS1):c.1332del (p.Gln446fs)	Pathogenic
2022501	NM_001358530.2(MOCS1):c.109C>T (p.Arg37Ter)	Pathogenic
2027093	NM_001358530.2(MOCS1):c.1160dup (p.Leu387fs)	Pathogenic
2045609	NM_001358530.2(MOCS1):c.486del (p.Leu163fs)	Pathogenic
2045610	NM_001358530.2(MOCS1):c.484del (p.Arg162fs)	Pathogenic
2110087	NM_001358530.2(MOCS1):c.1446_1449dup (p.His484fs)	Pathogenic
2424131	NC_000006.11:g.(?39874133)(39902156_?)del	Pathogenic
2705520	NM_001358530.2(MOCS1):c.925G>T (p.Glu309Ter)	Pathogenic
2709895	NM_001358530.2(MOCS1):c.455del (p.Gly152fs)	Pathogenic
2739380	NM_001358530.2(MOCS1):c.1451_1452del (p.His484fs)	Pathogenic
2760273	NM_001358530.2(MOCS1):c.1338_1341dup (p.His448fs)	Pathogenic
2791335	NM_001358530.2(MOCS1):c.544del (p.Leu182fs)	Pathogenic
2798857	NM_001358530.2(MOCS1):c.1501_1504del (p.Asp501fs)	Pathogenic
280910	NM_001358530.2(MOCS1):c.604_624del (p.Gly202_Glu208del)	Pathogenic
2827183	NM_001358530.2(MOCS1):c.993del (p.Phe331fs)	Pathogenic
2833976	NM_001358530.2(MOCS1):c.421C>T (p.Gln141Ter)	Pathogenic
2837772	NM_001358530.2(MOCS1):c.1340_1341del (p.Arg447fs)	Pathogenic
2838136	NM_001358530.2(MOCS1):c.1206G>A (p.Trp402Ter)	Pathogenic
2838918	NM_001358530.2(MOCS1):c.106del (p.Ala36fs)	Pathogenic
2844954	NM_001358530.2(MOCS1):c.277del (p.Val93fs)	Pathogenic
2851529	NM_001358530.2(MOCS1):c.750del (p.Phe251fs)	Pathogenic
2852183	NM_001358530.2(MOCS1):c.142C>T (p.Gln48Ter)	Pathogenic

SpliceAI

2031 predictions. Top by Δscore:

Variant	Effect	Δscore
6:39900073:TCAG:T	acceptor_loss	1.0000
6:39900075:A:AG	acceptor_gain	1.0000
6:39900075:A:T	acceptor_loss	1.0000
6:39900075:AG:A	acceptor_gain	1.0000
6:39900076:G:GT	acceptor_gain	1.0000
6:39900076:GG:G	acceptor_gain	1.0000
6:39900076:GGA:G	acceptor_gain	1.0000
6:39900076:GGAGC:G	acceptor_gain	1.0000
6:39900206:AAGG:A	donor_loss	1.0000
6:39900207:AG:A	donor_gain	1.0000
6:39900208:GG:G	donor_gain	1.0000
6:39900209:G:GA	donor_loss	1.0000
6:39900209:G:GG	donor_gain	1.0000
6:39901300:A:AG	acceptor_gain	1.0000
6:39901301:G:GC	acceptor_gain	1.0000
6:39901464:G:GT	donor_gain	1.0000
6:39901811:A:AG	acceptor_gain	1.0000
6:39901812:G:GG	acceptor_gain	1.0000
6:39909830:CTTA:C	donor_loss	1.0000
6:39909831:TTAC:T	donor_loss	1.0000
6:39909832:TA:T	donor_loss	1.0000
6:39912259:CTCA:C	donor_loss	1.0000
6:39912260:TCA:T	donor_loss	1.0000
6:39912261:CA:C	donor_loss	1.0000
6:39912262:A:C	donor_loss	1.0000
6:39912263:C:CA	donor_loss	1.0000
6:39912890:A:C	donor_gain	1.0000
6:39912890:ACC:A	donor_loss	1.0000
6:39912891:C:T	donor_loss	1.0000
6:39912911:T:TA	donor_gain	1.0000

AlphaMissense

4122 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:39912996:A:G	W256R	0.999
6:39912996:A:T	W256R	0.999
6:39916117:G:C	S178R	0.999
6:39916117:G:T	S178R	0.999
6:39916119:T:G	S178R	0.999
6:39927329:A:G	C84R	0.999
6:39913321:A:C	F251L	0.998
6:39913321:A:T	F251L	0.998
6:39913323:A:G	F251L	0.998
6:39925835:G:C	C87W	0.998
6:39925836:C:T	C87Y	0.998
6:39912994:C:A	W256C	0.997
6:39912994:C:G	W256C	0.997
6:39925836:C:G	C87S	0.997
6:39925837:A:G	C87R	0.997
6:39925837:A:T	C87S	0.997
6:39925844:A:C	C84W	0.997
6:39925845:C:G	C84S	0.997
6:39927329:A:T	C84S	0.997
6:39927341:A:G	C80R	0.997
6:39927364:A:G	L72P	0.997
6:39909944:A:C	F331L	0.996
6:39909944:A:T	F331L	0.996
6:39909946:A:G	F331L	0.996
6:39909952:A:G	C329R	0.996
6:39912268:A:G	L326P	0.996
6:39913325:G:T	P250H	0.996
6:39913334:T:A	E247V	0.996
6:39913340:A:G	F245S	0.996
6:39913343:C:G	R244P	0.996

dbSNP variants (sampled 300 via entrez): RS1000006232 (6:39912088 A>G), RS1000102217 (6:39922453 T>C), RS1000208129 (6:39927921 C>G), RS1000352469 (6:39926401 T>C), RS1000472288 (6:39933519 C>A,T), RS1000522773 (6:39909122 G>A), RS1000555897 (6:39922300 C>T), RS1000636119 (6:39921409 A>C), RS1000745697 (6:39915096 A>C,T), RS1000814819 (6:39933874 A>C), RS1000837037 (6:39931099 G>A), RS1000866524 (6:39931381 T>C), RS1000880626 (6:39917140 T>C), RS1001206381 (6:39927431 G>A), RS1001385068 (6:39932832 T>C)

Disease associations

OMIM: gene MIM:603707 | disease phenotypes: MIM:252150, MIM:252160

GenCC curated gene-disease

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

Mondo (4): sulfite oxidase deficiency due to molybdenum cofactor deficiency type A (MONDO:0009643), sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1 (MONDO:0009644), intellectual disability (MONDO:0001071), sulfite oxidase deficiency due to molybdenum cofactor deficiency (MONDO:0020480)

Orphanet (5): Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A (Orphanet:308386), Encephalopathy due to sulfite oxidase deficiency (Orphanet:833), Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B (Orphanet:308393), Sulfite oxidase deficiency due to molybdenum cofactor deficiency (Orphanet:99732), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

44 total (30 of 44 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:0000804	Xanthine nephrolithiasis
HP:0001083	Ectopia lentis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001285	Spastic tetraparesis
HP:0001510	Growth delay
HP:0002007	Frontal bossing
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002171	Gliosis
HP:0002179	Opisthotonus
HP:0002510	Spastic tetraplegia
HP:0002932	Aldehyde oxidase deficiency
HP:0003166	Increased urinary taurine
HP:0003196	Short nose
HP:0003359	Decreased urinary sulfate
HP:0003447	Axonal loss
HP:0003534	Reduced xanthine dehydrogenase level
HP:0003537	Hypouricemia
HP:0003570	Molybdenum cofactor deficiency
HP:0003606	Absent urinary urothione

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST011382_14	Systemic mastocytosis	5.000000e-08
GCST011383_13	Mastocytosis	9.000000e-08

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C565372	Molybdenum Cofactor Deficiency, Complementation Group A (supp.)
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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation, increases mutagenesis	3
Valproic Acid	decreases methylation, increases expression	2
bisphenol F	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
terbufos	increases methylation	1
sodium arsenite	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Acetaminophen	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Cadmium	decreases expression	1
Fonofos	increases methylation	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Parathion	increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders