CDO1

Summary

CDO1 (cysteine dioxygenase type 1, HGNC:1795) is a protein-coding gene on chromosome 5q22.3, encoding Cysteine dioxygenase type 1 (Q16878). Catalyzes the oxidation of cysteine to cysteine sulfinic acid with addition of molecular dioxygen.

Enables cysteine dioxygenase activity; ferrous iron binding activity; and zinc ion binding activity. Predicted to be involved in L-cysteine catabolic process. Predicted to be located in cytosol.

Source: NCBI Gene 1036 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_001801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1795
Approved symbol	CDO1
Name	cysteine dioxygenase type 1
Location	5q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000129596
Ensembl biotype	protein_coding
OMIM	603943
Entrez	1036

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000250535, ENST00000502631, ENST00000504613, ENST00000504877, ENST00000896772, ENST00000896773, ENST00000896774, ENST00000896775, ENST00000896776, ENST00000896777

RefSeq mRNA: 4 — MANE Select: NM_001801 NM_001323565, NM_001323566, NM_001323567, NM_001801

CCDS: CCDS4121

Canonical transcript exons

ENST00000250535 — 5 exons

Exon	Start	End
ENSE00000972231	115816228	115816659
ENSE00001005631	115804733	115805462
ENSE00003469596	115811161	115811315
ENSE00003563075	115813181	115813258
ENSE00003683375	115806349	115806518

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 99.54.

FANTOM5 (CAGE): breadth broad, TPM avg 10.9987 / max 469.6218, expressed in 880 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63025	10.5390	877
63024	0.4137	223
203662	0.0460	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.54	gold quality
ventricular zone	UBERON:0003053	99.38	gold quality
pigmented layer of retina	UBERON:0001782	99.15	gold quality
retina	UBERON:0000966	99.12	gold quality
corpus epididymis	UBERON:0004359	98.95	gold quality
right lobe of liver	UBERON:0001114	98.88	gold quality
choroid plexus epithelium	UBERON:0003911	98.65	gold quality
synovial joint	UBERON:0002217	98.54	gold quality
liver	UBERON:0002107	98.34	gold quality
seminal vesicle	UBERON:0000998	97.82	gold quality
tibial nerve	UBERON:0001323	97.61	gold quality
ganglionic eminence	UBERON:0004023	97.35	gold quality
tendon	UBERON:0000043	96.81	gold quality
layer of synovial tissue	UBERON:0007616	96.19	gold quality
descending thoracic aorta	UBERON:0002345	95.90	gold quality
ascending aorta	UBERON:0001496	95.19	gold quality
thoracic aorta	UBERON:0001515	95.18	gold quality
adipose tissue	UBERON:0001013	94.38	gold quality
connective tissue	UBERON:0002384	94.13	gold quality
cartilage tissue	UBERON:0002418	94.12	gold quality
tendon of biceps brachii	UBERON:0008188	94.12	gold quality
placenta	UBERON:0001987	94.01	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.56	gold quality
nucleus accumbens	UBERON:0001882	93.49	gold quality
caudate nucleus	UBERON:0001873	93.48	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.91	gold quality
omental fat pad	UBERON:0010414	92.63	gold quality
peritoneum	UBERON:0002358	92.58	gold quality
pericardium	UBERON:0002407	92.54	gold quality
putamen	UBERON:0001874	92.49	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	833.54
E-HCAD-5	yes	568.06
E-MTAB-10485	yes	496.92
E-HCAD-24	yes	409.92
E-MTAB-6701	yes	133.26
E-GEOD-93593	yes	13.73
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYB

miRNA regulators (miRDB)

34 targeting CDO1, 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-548C-3P	99.99	74.01	7587
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-4540	96.90	67.46	473

Literature-anchored findings (GeneRIF, showing 37)

• CDO is capable of altering intracellular cysteine levels as well as glutathione levels. (PMID:17327371)
• Upon comparison of PBMC and skin samples of Sezary syndrome versus mycosis fungoides, CDO1 and DNM3 were found upregulated only in Sezary syndrome. (PMID:18033314)
• Cysteine dioxygenase contains a 3His ligand motif rather than 2His/1Asp. The former is essential for optimal dioxygenation activity. Mutants with a 2His/1Asp motif may give sulfoxides as byproduct due to incomplete dioxygenation. (PMID:19199799)
• DNA methylation of CDO1 predicted distant recurrence in lymph node-positive patients with estrogen receptor-positive tumors treated with adjuvant anthracycline containing therapy. (PMID:20515469)
• We confirmed that the expression of CDO1 in squamous cell carcinoma is regulated by DNA methylation of its specific promoter region. (PMID:22011669)
• CDO1 as a novel tumor suppressor gene and a potentially valuable molecular marker for human cancer (PMID:23028699)
• Our study shows the importance of CDO1 inactivation in breast cancer and its clinical potential as a biomarker and therapeutic target to overcome resistance to anthracyclines. (PMID:23630167)
• we define a three-gene panel, CDO1, HOXA9, and TAC1, which we subsequently validate in two independent cohorts of primary NSCLC samples (PMID:24486589)
• TGF-b1 suppressed Cdo1 gene transcription through the MEK/ERK pathway. (PMID:24553827)
• methylation status of serum CDO1 gene promoter may be helpful in the diagnosis of hepatocellular carcinoma (HCC) and the estimation of the HCC stages. (PMID:24646840)
• A high negative correlation between promoter DNA methylation and gene expression was observed for CDO1, ZNF331 and ZSCAN18 in gastrointestinal tumors. (PMID:24948044)
• A structural role of the Cys-Tyr cofactor coordinates the ferrous iron in the active site of CDO1. (PMID:25261132)
• Decreased expression of CDO1 is associated with esophageal squamous cell carcinoma. (PMID:25903467)
• CDO1 promoter methylation may not substitute common prognostic makers to predict ccRCC survival, but offers additional, relevant prognostic information, indicating that it might be a novel molecular marker to determine ccRCC prognosis (PMID:25904753)
• methylation of the CDO1 gene promoter could be strong prognostic indicator in primary BC without preoperative treatment. (PMID:26785325)
• CDO1 methylation could be a potent prognostic predictor in primary esophageal squamous cell carcinoma and have great potential as a prognostic factor to guide the treatment of patients who need adjuvant chemotherapy. (PMID:27629777)
• CDO1 promoter methylation is involved in gene regulation and is a potential prognostic biomarker for BCR-free survival in prostate cancer (PC) patients following radical prostatectomy. Further studies are needed to validate CDO1 methylation assays and to evaluate the clinical utility of CDO1 methylation for the management of PCa (PMID:27689475)
• High methylation of CDO1 gene is responsible of the development of the esophageal adenocarcinoma. (PMID:28184414)
• Promoter NA methylation of CDO1 was demonstrated for the first time to be a cancer-associated methylation in primary gallbladder cancer(GBC), and it has the potential to be a prognostic biomarker of GBC for high-risk patients with stage II GBC. (PMID:29161283)
• High CDO1 methylation is associated with colorectal cancer progression. (PMID:29746493)
• High expression of CDO1 gene increased chemoresistance in Colon Cancer. (PMID:30311169)
• CDO1 hypermethylation, preoperative serum CA19-9 and perineural invasion were independent prognostic factors in primary extrahepatic cholangiocarcinoma (PMID:30325974)
• The CDO1 gene shows extremely cancer-specific hypermethylation, and it can be a prognostic marker in small bowel cancer. (PMID:30677088)
• Anchorage independent growth was reduced in several gastric cancer cell lines due to forced expression of the CDO1 gene, suggesting that abnormal CDO1 gene expression may represent distant metastatic ability. (PMID:30934021)
• Data show that nitric oxide ((*)NO), an oxygen surrogate, similarly binds to uncross-linked F2-Tyr157 cysteine dioxygenase (CDO) as in wild-type CDO. (PMID:30946568)
• In the present study, we compared the 2 potential epigenetic prognostic markers of CDO1 hypermethylation and HOPX hypermethylation using the same breast cancer samples, and the final focus was given on CDO1 hypermethylation (PMID:31092420)
• CDO1 is preferentially silenced by promoter methylation in human non-small cell lung cancers (NSCLC) harboring mutations in KEAP1, the negative regulator of NRF2. CDO1 silencing promotes proliferation of NSCLC by limiting the futile metabolism of cysteine to the wasteful and toxic byproducts cysteine sulfinic acid and sulfite (SO3(2-)), and depletion of cellular NADPH. (PMID:31107239)
• Promoter DNA methylation of CDO1 is extremely specific for pancreatic ductal adenocarcinoma (PDAC) tumors and accumulates with PDAC tumor progression. It could be a definitive diagnostic marker of PDAC in pancreatic juice or endoscopic ultrasound-fine needle aspiration cytology. (PMID:31325200)
• Promoter DNA Hypermethylation of the Cysteine Dioxygenase 1 (CDO1) Gene in Intraductal Papillary Mucinous Neoplasm (IPMN). (PMID:32144623)
• Detection of Promoter DNA Methylation in Urine and Plasma Aids the Detection of Non-Small Cell Lung Cancer. (PMID:32430478)
• Prediction of Efficacy of Postoperative Chemotherapy by DNA Methylation of CDO1 in Gastric Cancer. (PMID:32777557)
• Adipose tissue cysteine dioxygenase type 1 is associated with an anti-inflammatory profile, impacting on systemic metabolic traits. (PMID:36206624)
• Targeted demethylation of the CDO1 promoter based on CRISPR system inhibits the malignant potential of breast cancer cells. (PMID:37740473)
• DNMT3L inhibits hepatocellular carcinoma progression through DNA methylation of CDO1: insights from big data to basic research. (PMID:38308276)
• TRIM47-CDO1 axis dictates hepatocellular carcinoma progression by modulating ferroptotic cell death through the ubiquitin-proteasome system. (PMID:38614226)
• LncRNA FAM83H-AS1 inhibits ferroptosis of endometrial cancer by promoting DNMT1-mediated CDO1 promoter hypermethylation. (PMID:39159808)
• [Molecular mechanism of CDO1 regulating common metabolic diseases]. (PMID:39192790)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000099389
mus_musculus	Cdo1	ENSMUSG00000033022
rattus_norvegicus	Cdo1	ENSRNOG00000000158
drosophila_melanogaster	CG5493	FBGN0034364
caenorhabditis_elegans		WBGENE00018986

Protein

Protein identifiers

Cysteine dioxygenase type 1 — Q16878 (reviewed: Q16878)

Alternative names: Cysteine dioxygenase type I

All UniProt accessions (1): Q16878

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidation of cysteine to cysteine sulfinic acid with addition of molecular dioxygen.

Subunit / interactions. Monomer.

Tissue specificity. Highly expressed in liver and placenta. Low expression in heart, brain and pancreas. Also detected in hepatoblastoma Hep-G2 cells.

Post-translational modifications. The thioether cross-link between Cys-93 and Tyr-157 plays a structural role through stabilizing the Fe(2+) ion, and prevents the production of highly damaging free hydroxyl radicals by holding the oxygen radical via hydroxyl hydrogen.

Cofactor. Binds 1 Fe(2+) cation per subunit. Zn(2+) can be used to a much lesser extent. Ni(2+) can be used to a lesser extent.

Induction. In hepatoblastoma Hep-G2 cells, down-regulated by phorbol 12-myristate 13-acetate (PMA).

Pathway. Organosulfur biosynthesis; taurine biosynthesis; hypotaurine from L-cysteine: step 1/2.

Similarity. Belongs to the cysteine dioxygenase family.

RefSeq proteins (4): NP_001310494, NP_001310495, NP_001310496, NP_001792* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010300	CDO_1	Family
IPR011051	RmlC_Cupin_sf	Homologous_superfamily
IPR014710	RmlC-like_jellyroll	Homologous_superfamily

Pfam: PF05995

Enzyme classification (BRENDA):

• EC 1.13.11.20 — cysteine dioxygenase (BRENDA: 21 organisms, 44 substrates, 96 inhibitors, 46 Km, 31 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-CYSTEINE	0.002–11.4	21
3-MERCAPTOPROPANOATE	6.7–22	9
CYSTEINE	0.45–3	4
O2	0.0471–0.0551	2
3-MERCAPTOPROPIONATE	5.7	1
BETA-MERCAPTOETHANOL	16.6	1
CYSTEAMINE	26	1
N-TERMINAL CYS OF RGS4	0.123	1
N-TERMINAL CYS OF RGS5	0.0715	1
S-CARBOXYMETHYL-L-CYSTEINE	8.21	1

Catalyzed reactions (Rhea), 1 shown:

• L-cysteine + O2 = 3-sulfino-L-alanine + H(+) (RHEA:20441)

UniProt features (33 total): strand 14, helix 5, mutagenesis site 4, binding site 3, turn 2, sequence variant 2, chain 1, sequence conflict 1, cross-link 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
6BPU	X-RAY DIFFRACTION	1.8
6CDH	X-RAY DIFFRACTION	1.82
6BPV	X-RAY DIFFRACTION	1.95
6E87	X-RAY DIFFRACTION	1.95
6BPR	X-RAY DIFFRACTION	1.96
6CDN	X-RAY DIFFRACTION	2.06
6BPS	X-RAY DIFFRACTION	2.1
6BPX	X-RAY DIFFRACTION	2.15
6N42	X-RAY DIFFRACTION	2.2
6BGM	X-RAY DIFFRACTION	2.21
6BGF	X-RAY DIFFRACTION	2.25
6N43	X-RAY DIFFRACTION	2.29
6BPT	X-RAY DIFFRACTION	2.4
6BPW	X-RAY DIFFRACTION	2.43
8VL9	X-RAY DIFFRACTION	2.5
2IC1	X-RAY DIFFRACTION	2.7
8VLB	X-RAY DIFFRACTION	2.9
9T7V	ELECTRON MICROSCOPY	2.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16878-F1	93.90	0.91

Functional residue map

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

Ligand- & substrate-binding residues (3): 86; 88; 140

Post-translational modifications (1): 93–157

Mutagenesis-validated functional residues (4):

Position	Phenotype
164	reduces enzyme activity by 20%. little effect on iron incorporation. no effect on zinc incorporation.
60	reduces enzyme activity by 70%. reduces iron and zinc incorporation by 50%.
93	reduces enzyme activity and iron incorporation by 50%. zinc incorporation increased by 20%.
157	almost total loss of enzyme activity and iron incorporation. reduces zinc incorporation by 20%.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

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

MSigDB gene sets: 178 (showing top): MODULE_93, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, CAGCTG_AP4_Q5, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_RESPONSE_TO_GLUCAGON, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS

GO Biological Process (12): sulfur amino acid biosynthetic process (GO:0000097), obsolete cysteine metabolic process (GO:0006534), inflammatory response (GO:0006954), lactation (GO:0007595), L-cysteine catabolic process (GO:0019448), response to glucagon (GO:0033762), taurine biosynthetic process (GO:0042412), response to amino acid (GO:0043200), response to ethanol (GO:0045471), response to glucocorticoid (GO:0051384), response to cAMP (GO:0051591), response to azide (GO:0097184)

GO Molecular Function (9): ferrous iron binding (GO:0008198), zinc ion binding (GO:0008270), nickel cation binding (GO:0016151), cysteine dioxygenase activity (GO:0017172), iron ion binding (GO:0005506), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen (GO:0016702), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transition metal ion binding	3
sulfur amino acid metabolic process	1
sulfur compound biosynthetic process	1
carboxylic acid biosynthetic process	1
defense response	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
sulfur amino acid catabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
response to peptide hormone	1
taurine metabolic process	1
alkanesulfonate biosynthetic process	1
response to acid chemical	1
response to alcohol	1
response to corticosteroid	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
response to nitrogen compound	1
iron ion binding	1
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	1
catalytic activity	1
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen	1
dioxygenase activity	1
cation binding	1
oxidoreductase activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CDO1	DBT	psi-mi:“MI:0914”(association)	0.530
CDO1	CYP17A1	psi-mi:“MI:0915”(physical association)	0.370
MAPK6		psi-mi:“MI:0914”(association)	0.350

BioGRID (27): LRRC58 (Affinity Capture-MS), MTMR4 (Affinity Capture-MS), DBT (Affinity Capture-MS), RERE (Affinity Capture-MS), TOPBP1 (Affinity Capture-MS), TXNRD1 (Affinity Capture-MS), CAMK1 (Affinity Capture-MS), CDO1 (Affinity Capture-MS), CDO1 (Affinity Capture-MS), CDO1 (Affinity Capture-MS), CDO1 (Affinity Capture-MS), LRRC58 (Affinity Capture-MS), TOPBP1 (Affinity Capture-MS), CAMK1 (Affinity Capture-MS), RERE (Affinity Capture-MS)

ESM2 similar proteins: A2ADY9, A5PLN9, A7MB76, D3K5L7, D3Z7P3, E2R222, O54865, O60907, O94925, P16068, P20595, P21816, P35790, P51583, P60334, P97834, Q02153, Q03555, Q13042, Q13098, Q15645, Q16878, Q32KL5, Q3SZU4, Q3TIR1, Q3UA06, Q4R8H1, Q4ZHR9, Q5F450, Q5M887, Q5RB59, Q5RBQ7, Q5RCG0, Q5XHZ9, Q5ZIN0, Q5ZML9, Q6NRT5, Q6NWZ9, Q6PFJ9, Q8BK26

Diamond homologs: D1MF76, D4AN26, P21816, P60334, Q16878, Q20893, Q3SZU4, Q5A3Z5, Q5RBQ7, Q5RLY7, Q60TI7, Q6NWZ9, Q9U8F1, O32085

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDO1	up-regulates	SHH	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1479 predictions. Top by Δscore:

Variant	Effect	Δscore
5:115808514:C:CT	acceptor_gain	1.0000
5:115808515:A:T	acceptor_gain	1.0000
5:115811313:CTG:C	acceptor_gain	1.0000
5:115813175:TTTTA:T	donor_loss	1.0000
5:115813176:TTTAC:T	donor_loss	1.0000
5:115813177:TTACC:T	donor_loss	1.0000
5:115813178:TACC:T	donor_loss	1.0000
5:115805459:TTGCC:T	acceptor_loss	0.9900
5:115805460:TGCC:T	acceptor_loss	0.9900
5:115805461:GCCT:G	acceptor_loss	0.9900
5:115805463:C:A	acceptor_loss	0.9900
5:115805463:C:CC	acceptor_gain	0.9900
5:115805464:T:G	acceptor_loss	0.9900
5:115806340:TATAC:T	donor_loss	0.9900
5:115806341:ATACT:A	donor_loss	0.9900
5:115806342:TACTC:T	donor_loss	0.9900
5:115806343:AC:A	donor_loss	0.9900
5:115806344:CTCAC:C	donor_loss	0.9900
5:115806345:TCACA:T	donor_loss	0.9900
5:115806346:C:CC	donor_loss	0.9900
5:115806347:A:AC	donor_gain	0.9900
5:115806347:A:AT	donor_loss	0.9900
5:115806348:C:CC	donor_gain	0.9900
5:115806348:CAT:C	donor_gain	0.9900
5:115806531:C:CT	acceptor_gain	0.9900
5:115806531:C:T	acceptor_gain	0.9900
5:115806532:G:T	acceptor_gain	0.9900
5:115811311:TACTG:T	acceptor_gain	0.9900
5:115811755:A:C	donor_gain	0.9900
5:115813181:C:G	donor_loss	0.9900

AlphaMissense

1344 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:115806463:G:C	S153R	0.999
5:115806463:G:T	S153R	0.999
5:115806465:T:G	S153R	0.999
5:115806500:C:G	R141P	0.999
5:115806504:G:C	H140D	0.999
5:115806421:A:C	F167L	0.998
5:115806421:A:T	F167L	0.998
5:115806423:A:G	F167L	0.998
5:115806459:G:C	H155D	0.998
5:115806490:G:C	N144K	0.998
5:115806490:G:T	N144K	0.998
5:115811285:G:C	C93W	0.998
5:115811300:A:C	H88Q	0.998
5:115811300:A:T	H88Q	0.998
5:115811308:G:C	H86D	0.998
5:115813198:C:A	W77C	0.998
5:115813198:C:G	W77C	0.998
5:115813200:A:G	W77R	0.998
5:115813200:A:T	W77R	0.998
5:115813201:A:C	C76W	0.998
5:115811286:C:T	C93Y	0.997
5:115811315:G:C	S83R	0.997
5:115811315:G:T	S83R	0.997
5:115813182:T:G	S83R	0.997
5:115813214:A:G	L72P	0.997
5:115813250:C:G	R60P	0.997
5:115816259:A:G	W47R	0.997
5:115816259:A:T	W47R	0.997
5:115806457:G:C	H155Q	0.996
5:115806457:G:T	H155Q	0.996

dbSNP variants (sampled 300 via entrez): RS1000579373 (5:115810227 T>C), RS1000727074 (5:115804259 G>A), RS1000858561 (5:115815378 G>A,C,T), RS1001042153 (5:115809133 T>C), RS1001156481 (5:115808865 G>A), RS1001281958 (5:115805341 A>G), RS1001289412 (5:115815111 C>T), RS1002074748 (5:115809779 C>A,G,T), RS1002105780 (5:115809462 A>T), RS1002804883 (5:115814724 G>A), RS1002897067 (5:115817317 C>A,T), RS1002928289 (5:115817094 T>C), RS1003078918 (5:115808643 A>G), RS1003089808 (5:115811455 A>T), RS1003110155 (5:115808418 A>T)

Disease associations

OMIM: gene MIM:603943 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002653_5	Circulating phylloquinone levels	1.000000e-07
GCST005580_266	Intraocular pressure	4.000000e-10
GCST008839_223	Height	2.000000e-12
GCST009414_25	Central corneal thickness	2.000000e-12
GCST009439_19	Age-related cognitive decline (language) (slope of z-scores)	7.000000e-06
GCST90000654_21	Central corneal thickness	1.000000e-14
GCST90011900_98	Serum alkaline phosphatase levels	4.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004618	vitamin K measurement
EFO:0004695	intraocular pressure measurement
EFO:0005213	central corneal thickness
EFO:0007710	cognitive decline measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.-.-.- Oxidoreductases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
NVS-VHL720	Binding	7.0	pKd

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
Valproic Acid	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
Dexamethasone	increases expression, affects cotreatment	2
Aflatoxin B1	affects expression, decreases expression, decreases methylation	2
dicrotophos	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
methyleugenol	decreases expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	increases methylation	1
sodium arsenite	decreases expression	1
nickel sulfate	decreases expression	1
diisodecyl phthalate	decreases expression	1
4-octylphenol	decreases expression	1
CGP 52608	affects binding, increases reaction	1
oligofectamine	increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	decreases methylation	1
Acetaminophen	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Succimer	affects cotreatment, increases expression	1
Estradiol	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tamoxifen	affects cotreatment, increases expression	1
Tunicamycin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Oxyquinoline	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice