MOCOS

Summary

MOCOS (molybdenum cofactor sulfurase, HGNC:18234) is a protein-coding gene on chromosome 18q12.2, encoding Molybdenum cofactor sulfurase (Q96EN8). Sulfurates the molybdenum cofactor.

This gene encodes an enzyme that sulfurates the molybdenum cofactor which is required for activation of the xanthine dehydrogenase (XDH) and aldehyde oxidase (AO) enzymes. XDH catalyzes the conversion of hypoxanthine to uric acid via xanthine, as well as the conversion of allopurinol to oxypurinol, and pyrazinamide to 5-hydroxy pyrazinamide. Mutations in this gene cause the metabolic disorder classical xanthinuria type II which is characterized by the loss of XDH/XO and AO enzyme activity, decreased levels of uric acid in the urine, increased levels of xanthine and hypoxanthine in the serum and urine, formation of xanthine stones in the urinary tract, and myositis due to tissue deposition of xanthine.

Source: NCBI Gene 55034 — RefSeq curated summary.

At a glance

• Gene–disease (curated): xanthinuria type II (Definitive, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 537 total — 13 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 12
• MANE Select transcript: NM_017947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18234
Approved symbol	MOCOS
Name	molybdenum cofactor sulfurase
Location	18q12.2
Locus type	gene with protein product
Status	Approved
Aliases	HMCS, FLJ20733, MOS, MCS
Ensembl gene	ENSG00000075643
Ensembl biotype	protein_coding
OMIM	613274
Entrez	55034

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000261326, ENST00000588132, ENST00000880901, ENST00000880902, ENST00000880903, ENST00000880904, ENST00000880905, ENST00000880906, ENST00000880907, ENST00000880908, ENST00000948181

RefSeq mRNA: 1 — MANE Select: NM_017947 NM_017947

CCDS: CCDS11919

Canonical transcript exons

ENST00000261326 — 15 exons

Exon	Start	End
ENSE00000668509	36220055	36220217
ENSE00000916114	36187497	36187681
ENSE00000916115	36195257	36195346
ENSE00000916116	36198690	36198756
ENSE00000916117	36199683	36200324
ENSE00001108493	36266749	36266853
ENSE00001108495	36213366	36213482
ENSE00001108500	36205077	36205276
ENSE00001108502	36248922	36249000
ENSE00001108505	36215516	36215977
ENSE00001108507	36256968	36257073
ENSE00001108514	36203113	36203189
ENSE00001197546	36251159	36251283
ENSE00001287834	36268533	36272157
ENSE00003621742	36260037	36260175

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 88.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4368 / max 159.3110, expressed in 1208 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169960	4.3337	1084
169959	2.1030	825

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	88.68	gold quality
right lobe of liver	UBERON:0001114	87.89	gold quality
liver	UBERON:0002107	87.37	gold quality
adrenal tissue	UBERON:0018303	87.12	gold quality
palpebral conjunctiva	UBERON:0001812	85.49	gold quality
oocyte	CL:0000023	85.18	gold quality
right adrenal gland	UBERON:0001233	84.93	gold quality
right adrenal gland cortex	UBERON:0035827	84.61	gold quality
jejunal mucosa	UBERON:0000399	84.49	gold quality
left adrenal gland	UBERON:0001234	84.35	gold quality
left adrenal gland cortex	UBERON:0035825	84.21	gold quality
adrenal gland	UBERON:0002369	83.66	gold quality
adrenal cortex	UBERON:0001235	83.58	gold quality
buccal mucosa cell	CL:0002336	81.40	silver quality
duodenum	UBERON:0002114	80.11	gold quality
left ovary	UBERON:0002119	79.71	gold quality
esophagus squamous epithelium	UBERON:0006920	79.14	gold quality
right ovary	UBERON:0002118	78.34	gold quality
epithelium of esophagus	UBERON:0001976	78.32	gold quality
ovary	UBERON:0000992	76.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.26	silver quality
esophagus mucosa	UBERON:0002469	75.75	gold quality
bronchial epithelial cell	CL:0002328	75.00	gold quality
mucosa of transverse colon	UBERON:0004991	74.27	gold quality
gingival epithelium	UBERON:0001949	74.17	silver quality
squamous epithelium	UBERON:0006914	73.74	gold quality
stromal cell of endometrium	CL:0002255	73.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.76	gold quality
endometrium	UBERON:0001295	72.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.34

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• Two mutations, both in the N-terminal domain of the Human Molybdenum Cofactor Sulfurase (HMCS), were reported in patients with type II xanthinuria. (PMID:17368066)
• MOCOS sulfurates the molybdenum cofactor of xanthine oxidase (XDH) and aldehyde oxidase 1 (AOX1), which is required for their activities. (PMID:22495427)
• The rs594445 in MOCOS gene is associated with risk of autism spectrum disorder. (PMID:31900757)
• Impaired expression of the COSMOC/MOCOS gene unit in ASD patient stem cells. (PMID:32327736)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mocos	ENSMUSG00000039616
rattus_norvegicus	Mocos	ENSRNOG00000015113
drosophila_melanogaster	mal	FBGN0002641
caenorhabditis_elegans		WBGENE00010983

Paralogs (2): MTARC2 (ENSG00000117791), MTARC1 (ENSG00000186205)

Protein

Protein identifiers

Molybdenum cofactor sulfurase — Q96EN8 (reviewed: Q96EN8)

Alternative names: Molybdenum cofactor sulfurtransferase

All UniProt accessions (1): Q96EN8

UniProt curated annotations — full annotation on UniProt →

Function. Sulfurates the molybdenum cofactor. Sulfation of molybdenum is essential for xanthine dehydrogenase (XDH) and aldehyde oxidase (ADO) enzymes in which molybdenum cofactor is liganded by 1 oxygen and 1 sulfur atom in active form. In vitro, the C-terminal domain is able to reduce N-hydroxylated prodrugs, such as benzamidoxime.

Disease relevance. Xanthinuria 2 (XAN2) [MIM:603592] A disorder characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. In addition, XAN2 patients cannot metabolize allopurinol into oxypurinol due to dual deficiency of xanthine dehydrogenase and aldehyde oxidase. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Cofactor biosynthesis; molybdopterin biosynthesis.

Similarity. Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. MOCOS subfamily.

RefSeq proteins (1): NP_060417* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000192	Aminotrans_V_dom	Domain
IPR005302	MoCF_Sase_C	Domain
IPR005303	MOCOS_middle	Domain
IPR011037	Pyrv_Knase-like_insert_dom_sf	Homologous_superfamily
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR028886	MoCo_sulfurase	Family

Pfam: PF00266, PF03473, PF03476

Catalyzed reactions (Rhea), 1 shown:

• Mo-molybdopterin + L-cysteine + AH2 = thio-Mo-molybdopterin + L-alanine + A + H2O (RHEA:42636)

UniProt features (24 total): sequence variant 15, modified residue 4, sequence conflict 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EN8-F1	80.88	0.59

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): 424

Post-translational modifications (4): 34, 264, 528, 530

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: 291 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WANG_CLIM2_TARGETS_UP, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_NUCLEAR_DIVISION, MODULE_255, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_SPINDLE_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_OOGENESIS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE

GO Biological Process (3): Mo-molybdopterin cofactor biosynthetic process (GO:0006777), molybdopterin cofactor biosynthetic process (GO:0032324), molybdopterin cofactor metabolic process (GO:0043545)

GO Molecular Function (7): molybdenum cofactor sulfurtransferase activity (GO:0008265), lyase activity (GO:0016829), molybdenum ion binding (GO:0030151), pyridoxal phosphate binding (GO:0030170), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (1): 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
catalytic activity	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
organophosphate metabolic process	1
prosthetic group metabolic process	1
sulfurtransferase activity	1
transition metal ion binding	1
anion binding	1
vitamin B6 binding	1
molecular_function	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1654 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MOCOS	AOX1	Q06278	969
MOCOS	SUOX	P51687	627
MOCOS	MOCS1	Q9NZB8	603
MOCOS	NFS1	Q9Y697	587
MOCOS	XDH	P47989	564
MOCOS	ELP2	Q6IA86	543
MOCOS	NUDT15	Q9NV35	488
MOCOS	RMP24	Q32NC0	483
MOCOS	MOCS2	O96007	466
MOCOS	TPMT	P51580	460
MOCOS	GPHN	Q9NQX3	437
MOCOS	ITPA	Q9BY32	412
MOCOS	FGD6	Q6ZV73	407
MOCOS	ZNF605	Q86T29	398
MOCOS	RPRD1A	Q96P16	397

IntAct

59 interactions, top by confidence:

A	B	Type	Score
MOCOS	PARVA	psi-mi:“MI:0915”(physical association)	0.800
PARVA	MOCOS	psi-mi:“MI:0915”(physical association)	0.800
TANC2	TAX1BP3	psi-mi:“MI:0914”(association)	0.690
MOCOS	ARL8A	psi-mi:“MI:0915”(physical association)	0.670
ARL8A	MOCOS	psi-mi:“MI:0915”(physical association)	0.670
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
TKT	POTEF	psi-mi:“MI:0914”(association)	0.530
PARVA	CCNB1	psi-mi:“MI:0914”(association)	0.530
RAB3A	RAB3B	psi-mi:“MI:0914”(association)	0.530
HSD17B8	MTIF2	psi-mi:“MI:0914”(association)	0.530
RIMKLA	ZNG1C	psi-mi:“MI:0914”(association)	0.530
WDR53	BLVRA	psi-mi:“MI:0914”(association)	0.530
CNTROB	CENPX	psi-mi:“MI:0914”(association)	0.350
MRPL50	MRPL43	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
APOA1	CNMD	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
NUDCD1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
KLK11	DENND11	psi-mi:“MI:0914”(association)	0.350
TSHR	POTEF	psi-mi:“MI:0914”(association)	0.350
RGS20	PGP	psi-mi:“MI:0914”(association)	0.350
TULP2	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
DOCK5	DPYSL4	psi-mi:“MI:0914”(association)	0.350

BioGRID (72): PARVA (Two-hybrid), MOCOS (Affinity Capture-MS), MOCOS (Affinity Capture-MS), MOCOS (Affinity Capture-MS), MOCOS (Affinity Capture-MS), MOCOS (Affinity Capture-MS), MOCOS (Affinity Capture-MS), MOCOS (Affinity Capture-MS), MOCOS (Affinity Capture-MS), MOCOS (Affinity Capture-MS), PSAT1 (Co-fractionation), SEPT8 (Co-fractionation), PARVA (Two-hybrid), MOCOS (Affinity Capture-MS), MOCOS (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2QC33, A0FKG7, A6H7H7, F1N9S8, O95453, P0C0T1, P42694, P50747, P69341, Q0IIH8, Q0VGM9, Q13572, Q28559, Q4R528, Q5BJZ6, Q5F480, Q5R699, Q5RC51, Q5ZIA0, Q5ZIW7, Q640G7, Q6DDJ3, Q6DFV5, Q6DG88, Q6DJB3, Q6GR37, Q6NYU2, Q6PZ02, Q6PZ03, Q6PZ05, Q7T0P6, Q80UY1, Q80YV4, Q811C2, Q8BGE6, Q8BYN3, Q8C9S8, Q8N4J0, Q8VDG3, Q8WYN0

Diamond homologs: A1CHL0, A1CX75, A2QIK9, A2VD33, A4RK48, A6SRX6, B0WSW8, B0WSX1, B0Y691, B3MZN7, B3NY19, B4H0S8, B4JXP7, B4L340, B4N1V2, B4PYH5, Q0CLW8, Q14CH1, Q16GH0, Q16P87, Q16P90, Q29GM0, Q2HE65, Q2UH11, Q4WPE6, Q655R6, Q7QFL7, Q7SE17, Q8IU29, Q8LGM7, Q96EN8, Q9C5X8, Q9N0E7, Q9UV64, Q9VRA2, Q559G8, A8X493, Q21657, Q5U534, Q9CW42

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	24
Uncertain significance	272
Likely benign	123
Benign	63

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1452243	NM_017947.4(MOCOS):c.916del (p.Ile306fs)	Pathogenic
1452480	NM_017947.4(MOCOS):c.1665dup (p.Pro556fs)	Pathogenic
1969820	NM_017947.4(MOCOS):c.1767_1768del (p.Tyr590fs)	Pathogenic
2017024	NM_017947.4(MOCOS):c.2376G>A (p.Trp792Ter)	Pathogenic
2085322	NM_017947.4(MOCOS):c.1809G>A (p.Trp603Ter)	Pathogenic
253160	NM_017947.4(MOCOS):c.1255C>T (p.Arg419Ter)	Pathogenic
253161	NM_017947.4(MOCOS):c.169G>C (p.Ala57Pro)	Pathogenic
253163	NM_017947.4(MOCOS):c.1037dup (p.Gln347fs)	Pathogenic
2835594	NM_017947.4(MOCOS):c.2268del (p.Ser757fs)	Pathogenic
3583327	NM_017947.4(MOCOS):c.2356del (p.Ala786fs)	Pathogenic
3716058	NM_017947.4(MOCOS):c.1203del (p.Ile402fs)	Pathogenic
4704002	NM_017947.4(MOCOS):c.1886del (p.Lys629fs)	Pathogenic
4777751	NM_017947.4(MOCOS):c.1690C>T (p.Gln564Ter)	Pathogenic
1179050	NM_017947.4(MOCOS):c.2164+2T>C	Likely pathogenic
1179104	NM_017947.4(MOCOS):c.1335+1G>T	Likely pathogenic
2072695	NM_017947.4(MOCOS):c.1218+1G>C	Likely pathogenic
2081555	NM_017947.4(MOCOS):c.2164+1del	Likely pathogenic
2633841	NM_017947.4(MOCOS):c.2287G>T (p.Glu763Ter)	Likely pathogenic
2636897	NM_017947.4(MOCOS):c.493del (p.Ala164_Ile165insTer)	Likely pathogenic
2833333	NM_017947.4(MOCOS):c.1960+2_1960+3del	Likely pathogenic
2904323	NM_017947.4(MOCOS):c.232+1G>A	Likely pathogenic
3065846	NM_017947.4(MOCOS):c.2271-1G>A	Likely pathogenic
3341371	NM_017947.4(MOCOS):c.2367del (p.Glu790fs)	Likely pathogenic
3391007	NM_017947.4(MOCOS):c.1546C>T (p.Gln516Ter)	Likely pathogenic
3583241	NM_017947.4(MOCOS):c.124G>T (p.Glu42Ter)	Likely pathogenic
3583243	NM_017947.4(MOCOS):c.196G>T (p.Glu66Ter)	Likely pathogenic
3583248	NM_017947.4(MOCOS):c.281_282del (p.Val94fs)	Likely pathogenic
3583273	NM_017947.4(MOCOS):c.818del (p.Gly273fs)	Likely pathogenic
3583278	NM_017947.4(MOCOS):c.942-1G>T	Likely pathogenic
3583294	NM_017947.4(MOCOS):c.1383del (p.Thr462fs)	Likely pathogenic

SpliceAI

3053 predictions. Top by Δscore:

Variant	Effect	Δscore
18:36187679:CAG:C	donor_loss	1.0000
18:36187680:AG:A	donor_loss	1.0000
18:36187681:GGTGA:G	donor_loss	1.0000
18:36187682:G:C	donor_loss	1.0000
18:36187683:T:G	donor_loss	1.0000
18:36203104:T:TA	acceptor_gain	1.0000
18:36203108:TATA:T	acceptor_loss	1.0000
18:36203110:TAGGT:T	acceptor_loss	1.0000
18:36203111:AGGT:A	acceptor_loss	1.0000
18:36203112:G:GT	acceptor_loss	1.0000
18:36205063:AT:A	acceptor_gain	1.0000
18:36205064:T:G	acceptor_gain	1.0000
18:36254368:A:AG	acceptor_gain	1.0000
18:36257070:CCAGG:C	donor_loss	1.0000
18:36257072:AGG:A	donor_loss	1.0000
18:36257073:GGTAA:G	donor_loss	1.0000
18:36257074:GTAA:G	donor_loss	1.0000
18:36257075:T:G	donor_loss	1.0000
18:36260035:A:AG	acceptor_gain	1.0000
18:36260035:AGT:A	acceptor_gain	1.0000
18:36260036:G:GA	acceptor_gain	1.0000
18:36260036:GT:G	acceptor_gain	1.0000
18:36260036:GTG:G	acceptor_gain	1.0000
18:36260036:GTGAT:G	acceptor_gain	1.0000
18:36260173:CAGG:C	donor_loss	1.0000
18:36260174:AGGTA:A	donor_loss	1.0000
18:36260175:GGTA:G	donor_loss	1.0000
18:36260176:GT:G	donor_loss	1.0000
18:36260177:TAA:T	donor_loss	1.0000
18:36268671:G:GT	donor_gain	1.0000

AlphaMissense

5832 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:36220098:G:C	R614P	0.994
18:36200183:G:A	G267E	0.992
18:36220064:T:A	W603R	0.992
18:36220064:T:C	W603R	0.992
18:36220103:T:A	W616R	0.992
18:36220103:T:C	W616R	0.992
18:36257039:A:C	S746R	0.991
18:36257041:T:A	S746R	0.991
18:36257041:T:G	S746R	0.991
18:36200207:T:C	L275P	0.990
18:36260140:T:A	W792R	0.990
18:36260140:T:C	W792R	0.990
18:36199993:A:C	S204R	0.989
18:36199995:T:A	S204R	0.989
18:36199995:T:G	S204R	0.989
18:36213422:C:A	N425K	0.989
18:36213422:C:G	N425K	0.989
18:36200182:G:T	G267W	0.988
18:36198694:T:A	N79K	0.987
18:36198694:T:G	N79K	0.987
18:36198750:G:C	R98P	0.987
18:36199834:A:C	S151R	0.987
18:36199836:C:A	S151R	0.987
18:36199836:C:G	S151R	0.987
18:36215589:G:A	G470E	0.987
18:36215959:A:C	K593N	0.987
18:36215959:A:T	K593N	0.987
18:36215582:T:C	S468P	0.986
18:36215958:A:T	K593I	0.986
18:36205231:T:A	N391K	0.985

dbSNP variants (sampled 300 via entrez): RS1000001394 (18:36262560 G>A,T), RS1000010831 (18:36243712 C>G), RS1000029726 (18:36194502 A>G), RS1000067742 (18:36204486 A>G), RS1000075452 (18:36250079 A>G), RS1000096665 (18:36204133 G>A,T), RS1000119799 (18:36188303 T>G), RS1000160994 (18:36192856 C>T), RS1000167896 (18:36233157 C>G), RS1000234152 (18:36192496 A>C,G), RS1000261481 (18:36241136 A>G), RS1000304540 (18:36212557 A>G), RS1000305083 (18:36252551 C>G), RS1000324004 (18:36206137 C>T), RS1000360716 (18:36272636 T>C)

Disease associations

OMIM: gene MIM:613274 | disease phenotypes: MIM:603592, MIM:259900

GenCC curated gene-disease

Disease	Classification	Inheritance
xanthinuria type II	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
xanthinuria type II	Definitive	AR

Mondo (3): xanthinuria type II (MONDO:0011346), autism spectrum disorder (MONDO:0005258), primary hyperoxaluria (MONDO:0002474)

Orphanet (4): Hereditary xanthinuria (Orphanet:3467), Xanthinuria type II (Orphanet:93602), Primary hyperoxaluria (Orphanet:416), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000787	Nephrolithiasis
HP:0003326	Myalgia
HP:0003537	Hypouricemia
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0010933	Hyperxanthinemia
HP:0010934	Xanthinuria
HP:0011463	Childhood onset
HP:0011814	Increased urinary hypoxanthine level
HP:0034333	Increased circulating hypoxanthine concentration

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003262_498	Post bronchodilator FEV1	3.000000e-06
GCST003264_757	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST012299_12	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	8.000000e-06
GCST012310_1	Schizophrenia x sex interaction	1.000000e-07
GCST012311_9	Schizophrenia x sex interaction	4.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0008343	sex interaction measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006960	Hyperoxaluria, Primary	C12.050.351.968.419.313.500; C12.200.777.419.313.500; C12.950.419.313.500; C16.320.565.202.460; C18.452.648.202.460
C566358	Xanthinuria, Type II (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs594445	MOCOS		0.00	0
rs73430958	MOCOS		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	4
Valproic Acid	affects cotreatment, increases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
Tetrachlorodibenzodioxin	increases expression	3
Cyclosporine	increases expression	3
sodium arsenite	increases abundance, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
perfluoro-n-nonanoic acid	increases expression	2
entinostat	increases expression, affects cotreatment	2
Arsenic	increases abundance, increases expression	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
6-thiouric acid	decreases oxidation, decreases chemical synthesis	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
didecyldimethylammonium	increases expression	1
1-nitropyrene	increases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
6-thioxanthine	decreases chemical synthesis, decreases oxidation	1
chromium hexavalent ion	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
perfluorohexanesulfonic acid	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder