DDAH2

Summary

DDAH2 (DDAH family member 2, ADMA-independent, HGNC:2716) is a protein-coding gene on chromosome 6p21.33, encoding Putative hydrolase DDAH2 (O95865). Putative hydrolase with unknown substrate.

This gene encodes a dimethylarginine dimethylaminohydrolase. The encoded enzyme functions in nitric oxide generation by regulating the cellular concentrations of methylarginines, which in turn inhibit nitric oxide synthase activity. The protein may be localized to the mitochondria. Alternative splicing resulting in multiple transcript variants.

Source: NCBI Gene 23564 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_001303007

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2716
Approved symbol	DDAH2
Name	DDAH family member 2, ADMA-independent
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	G6A, DDAHII
Ensembl gene	ENSG00000213722
Ensembl biotype	protein_coding
OMIM	604744
Entrez	23564

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 17 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000375787, ENST00000375789, ENST00000375792, ENST00000416410, ENST00000436437, ENST00000437288, ENST00000469963, ENST00000480913, ENST00000483792, ENST00000488119, ENST00000857390, ENST00000857391, ENST00000857392, ENST00000857393, ENST00000857394, ENST00000921342, ENST00000921343, ENST00000921344, ENST00000921345, ENST00000970327, ENST00000970328

RefSeq mRNA: 3 — MANE Select: NM_001303007 NM_001303007, NM_001303008, NM_013974

CCDS: CCDS4718

Canonical transcript exons

ENST00000375789 — 6 exons

Exon	Start	End
ENSE00001630517	31728865	31729299
ENSE00003508490	31728173	31728292
ENSE00003559933	31727543	31727692
ENSE00003587831	31728451	31728524
ENSE00003634683	31728646	31728745
ENSE00003846099	31727040	31727353

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.9157 / max 546.7403, expressed in 1801 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72805	45.2480	1786
72801	2.1773	779
72802	1.4297	728
72803	1.3580	822
72804	1.2756	643
72799	0.3301	146
72800	0.0971	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.57	gold quality
cortical plate	UBERON:0005343	98.86	gold quality
ventricular zone	UBERON:0003053	98.85	gold quality
mucosa of transverse colon	UBERON:0004991	98.48	gold quality
endocervix	UBERON:0000458	98.35	gold quality
right coronary artery	UBERON:0001625	98.11	gold quality
body of uterus	UBERON:0009853	98.08	gold quality
lower esophagus mucosa	UBERON:0035834	98.08	gold quality
ectocervix	UBERON:0012249	97.87	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.78	gold quality
left uterine tube	UBERON:0001303	97.72	gold quality
popliteal artery	UBERON:0002250	97.70	gold quality
tibial artery	UBERON:0007610	97.70	gold quality
myometrium	UBERON:0001296	97.64	gold quality
ascending aorta	UBERON:0001496	97.63	gold quality
thoracic aorta	UBERON:0001515	97.63	gold quality
adipose tissue	UBERON:0001013	97.52	gold quality
descending thoracic aorta	UBERON:0002345	97.49	gold quality
left coronary artery	UBERON:0001626	97.38	gold quality
apex of heart	UBERON:0002098	97.33	gold quality
vagina	UBERON:0000996	97.30	gold quality
uterine cervix	UBERON:0000002	97.26	gold quality
omental fat pad	UBERON:0010414	97.26	gold quality
tibial nerve	UBERON:0001323	97.23	gold quality
mucosa of stomach	UBERON:0001199	97.03	gold quality
right uterine tube	UBERON:0001302	97.03	gold quality
right lobe of thyroid gland	UBERON:0001119	96.97	gold quality
left lobe of thyroid gland	UBERON:0001120	96.90	gold quality
thoracic mammary gland	UBERON:0005200	96.81	gold quality
fallopian tube	UBERON:0003889	96.76	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	74.02
E-HCAD-5	yes	29.81
E-ANND-3	yes	16.00
E-CURD-112	yes	5.90
E-CURD-114	no	20.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARG

miRNA regulators (miRDB)

13 targeting DDAH2, 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-4482-3P	99.98	72.50	3147
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-3974	96.56	66.22	928
HSA-MIR-152-5P	96.42	66.59	960

Literature-anchored findings (GeneRIF, showing 40)

• In cultured endothelial cells, heterologously expressed human DDAH II was S-nitrosylated after cytokine induced expression of the inducible NOS isoforms. (PMID:12370443)
• DDAH2 expression in endothelial cells is altered by genetic variation in a basal promoter element (PMID:14550280)
• messenger RNA and protein were demonstrated in first trimester placental tissue, primary extravillous trophoblasts and extravillous trophoblast-derived cell lines. (PMID:16920729)
• Allelic variation for a polymorphism in the DDAH II gene may influence asymmetrical dimethyl arginine concentrations, hence the severity of organ failure in septic shock patients. (PMID:17002794)
• The purpose of this study was to investigate whether there is any association between preeclampsia and eNOS, DDAH, and VEGF gene polymorphisms.Polymorphisms in eNOS, DDAH, and VEGF gene do not seem to be risk factors for preeclampsia. (PMID:18251679)
• Lysophosphatidylcholine (LPC) impairs DDAH/ADMA/NOS/NO pathway, and DDAH2 gene transfer could improve the LPC-elicited impairments in endothelial cells. (PMID:18342305)
• results suggest that the DDAH2 common variant may play a protective role in the development of Intracerebral Hemorrhage, implicating that the DDAH2/ADMA pathway may act as a critical regulator of cerebral small-vessel disorders (PMID:19250061)
• Low expression of DDAH-2 in placenta and increased serum asymmetric dimethylarginine level might confer susceptibility to preeclampsia. (PMID:19570459)
• Single nucleotide polymorphisms in the DDAH2 gene are associated with blood pressure levels, prevalence of hypertension, and left ventricular mass and function in the general population. (PMID:19666123)
• DDAH2 mRNA expression is inversely associated with some cardiovascular risk-related features. (PMID:19822957)
• DDAH1 and DDAH2 polymorphisms are strongly and additively associated with serum ADMA concentrations in individuals with type 2 diabetes (PMID:20209122)
• a possible association between A allele / AA genotype for DDAH2 SNP1 (-1151 C/A, rs805304) and G allele / GG genotype for SNP2 (-449 C/G, rs805305) with CVD in male 35-50 year-old Egyptian patients was observed. (PMID:21677405)
• DDAH-2 could play an important role in IL-1beta-induced NO production and in osteoarthritis pathogenesis. (PMID:21898353)
• The -449G single nucleotide polymorphism within the DDAH2 gene was associated with both decreased plasma asymmetric dimethylarginine and an increased likelihood of presenting with “cold” shock in pediatric sepsis. (PMID:22428028)
• A functional polymorphism of the DDAH2 gene may confer increased risk for type 2 diabetes by affecting insulin sensitivity (PMID:22558392)
• Found that SNP rs2272592 in DDAH2 is associated with type 2 diabetes but SNP rs805304 in DDAH2 is not. DDAH2 SNP rs2272592 AG+GG genotypes are associated with genetic susceptibility to type 2 diabetes in Korean population. (PMID:22579530)
• No association was observed between the DDAH2 polymorphisms at rs805305 and rs2272592 and coronary heart disease. (PMID:22923027)
• DDAH2-1151 A/C polymorphism is associated with Chronic renal impairment in type 2 diabetes. (PMID:23129820)
• Suppression of DDAH2 expression is a culprit for homocysteine-induced impairments of DDAH/ADMA/NOS/NO pathway in endothelial cells. (PMID:23171931)
• Glucose-stimulated insulin secretion is increased in Ddah2-transgenic pancreatic islets by 33%, compared to its levels in wild-type mice. (PMID:23430976)
• There is a significant difference in distribution of DDAH2 gene polymorphism among hemodialysis patients compared to healthy individuals. (PMID:23770786)
• The rs9267551 functional variant of the DDAH2 gene is associated with chronic kidney disease with carriers of the C allele having a lower risk of renal dysfunction independently from several confounders (PMID:24125425)
• Enhancing pulmonary DDAH II activity attenuates LPS-mediated lung leak in acute lung injury. (PMID:24134589)
• Our approaches revealed signature candidates of differentially hypermethylated genes of DDAH2 and DUSP1 which can be further developed as potential biomarkers for OSCC as diagnostic, prognostic and therapeutic targets in the future. (PMID:24155659)
• -476 to -469 of the DDAH2 promoter was a NF-kB responsive element and is important for the transactivation of DDAH2. (PMID:24928011)
• Homocysteine disrupts EPCs function via inducing the hypermethylation of DDAH2 promoter, suggesting a key role of epigenetic mechanism in the progression of atherosclerosis (PMID:24934151)
• DDAH-1 is a specific molecular target for portal pressure reduction, through actions on ADMA-mediated regulation of eNOS activity. (PMID:25152204)
• increased ADMA levels in rheumatoid arthritis do not appear to relate to DDAH genetic polymorphisms (PMID:25194333)
• Our results suggest that the rs805304 C allele of the DDAH gene was associated with decreased risk of myocardial infarction and decreased risk of obesity. (PMID:25236572)
• The percentage of senescent endothelial progenitor cells increased while the expression of DDAH2 decreased concomitantly with an increase in the plasma levels of asymmetric dimethylarginine in patients with type 2 diabetes mellitus. (PMID:25701782)
• Inhibiting the expression of DDAH1, but not DDAH2, resulted in a significant increase in the sensitivity of the EVT cell line SGHPL-4 to tumour necrosis factor related apoptosis inducing ligand (TRAIL) induced apoptosis (PMID:26082478)
• expression of DDAH2 is associated with invasiveness of lung adenocarcinoma via tumor angiogenesis (PMID:26515557)
• The main finding from this study was that it demonstrated that the C-allele of rs3087894 in DDAH1 is a risk factor for hypertension in the Kazakh group but a protective factor in the Uygur group. In addition, we did not find any genotype of DDAH1 and DDAH2 associated with hypertension in the Han group. (PMID:26786611)
• Exogenous human DDAH2 gene promotes differentiation of rabbit bone marrow-derived endothelial progenitor cells into mature endothelial cells. (PMID:28150318)
• genetic variations in the DDAH2 gene may influence the ADMA concentration and erythropoietin resistance in MHD patients (PMID:28590543)
• The presence of the rs805305 SNP in the DDAH2 gene was determined using genomic DNA extraction from buffy coat and whole blood samples by LGC group (Hertfordshire, UK). (PMID:30538005)
• DDAH2 rs9267551 polymorphism is significantly associated with myocardial infarction in type 2 diabetes mellitus patients of European ancestry. (PMID:31409409)
• Polymorphism (-499C/G) in DDAH2 promoter may act as a protective factor for metabolic syndrome: A case-control study in Azar-Cohort population. (PMID:34283907)
• Assessment of DDAH1 and DDAH2 Contributions to Psychiatric Disorders via In Silico Methods. (PMID:36233204)
• Early and late-onset preeclampsia: effects of DDAH2 polymorphisms on ADMA levels and association with DDAH2 haplotypes. (PMID:38765527)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddah2	ENSDARG00000105009
mus_musculus	Ddah2	ENSMUSG00000007039
rattus_norvegicus	Ddah2	ENSRNOG00000000842
drosophila_melanogaster	CG1764	FBGN0030467
caenorhabditis_elegans		WBGENE00009549
caenorhabditis_elegans		WBGENE00020672

Paralogs (1): DDAH1 (ENSG00000153904)

Protein

Protein identifiers

Putative hydrolase DDAH2 — O95865 (reviewed: O95865)

Alternative names: DDAHII, Inactive N(G),N(G)-dimethylarginine dimethylaminohydrolase 2, Protein G6a, S-phase protein

All UniProt accessions (5): O95865, H0Y7N1, Q5SRR8, Q5SSV3, V9HW53

UniProt curated annotations — full annotation on UniProt →

Function. Putative hydrolase with unknown substrate. Does not hydrolyze N(G),N(G)-dimethyl-L-arginine (ADMA) which acts as an inhibitor of NOS. In endothelial cells, induces expression of vascular endothelial growth factor (VEGF) via phosphorylation of the transcription factor SP1 by PKA in a process that is independent of NO and NO synthase. Similarly, enhances pancreatic insulin secretion through SP1-mediated transcriptional up-regulation of secretagogin/SCGN, an insulin vesicle docking protein. Upon viral infection, relocates to mitochondria where it promotes mitochondrial fission through activation of DNM1L leading to the inhibition of innate response activation mediated by MAVS.

Subcellular location. Cytoplasm. Mitochondrion Mitochondrion.

Tissue specificity. Detected in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas, and at very low levels in brain.

Post-translational modifications. Phosphorylated by TBK1. Phosphorylation inhibits the translocation into the mitochondrion upon Sendai viral infection.

Similarity. Belongs to the DDAH family.

RefSeq proteins (3): NP_001289936, NP_001289937, NP_039268 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033199	DDAH-like	Family

Enzyme classification (BRENDA):

• EC 3.5.3.18 — dimethylargininase (BRENDA: 12 organisms, 49 substrates, 190 inhibitors, 31 Km, 21 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NG,NG-DIMETHYL-L-ARGININE	0.039–9.24	6
S-METHYL-L-THIOCITRULLINE	0.0014–0.143	6
NOMEGA,NOMEGA-DIMETHYL-L-ARGININE	0.11–13.7	4
NG-METHYL-L-ARGININE	0.044–0.67	3
NG-MONOMETHYL-L-ARGININE	0.36–1.6	3
ASYMMETRIC NOMEGA,NOMEGA-DIMETHYL-L-ARGININE	0.039	1
DIMETHYL-L-ARGININE	0.18	1
N,N-DIMETHYL-L-ARGININE	0.133	1
N5-(METHOXYCARBAMIMIDOYL)-L-ORNITHINE	0.13	1
N5-(METHYLCARBAMIMIDOYL)-L-ORNITHINE	0.106	1
N5-[2,5-DIHYDRO-1H-PYRROL-1-YL(IMINO)METHYL]-L-O	0.161	1
NG,NG-DIMETHYL-L-HOMOARGININE	33	1
NG-AMINO-L-ARGININE	1.11	1
NG-HYDROXY-L-ARGININE	2.3	1

UniProt features (12 total): mutagenesis site 9, active site 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95865-F1	93.30	0.89

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): 171 (proton donor); 276 (nucleophile)

Mutagenesis-validated functional residues (9):

Position	Phenotype
245	loss of mitochondrial translocation upon viral infection. loss of inhibition of mavs-mediated innate response activation
253	loss of mitochondrial translocation upon viral infection. loss of inhibition of mavs-mediated innate response activation
68	no effect on inhibition of mavs-mediated innate response activation.
162	no effect on inhibition of mavs-mediated innate response activation.
163	no effect on inhibition of mavs-mediated innate response activation.
183	no effect on inhibition of mavs-mediated innate response activation.
203	loss of mitochondrial translocation upon viral infection. loss of inhibition of mavs-mediated innate response activation
209	no effect on inhibition of mavs-mediated innate response activation.
211	loss of mitochondrial translocation upon viral infection. loss of inhibition of mavs-mediated innate response activation

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 152 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, FXR_IR1_Q6, AACYNNNNTTCCS_UNKNOWN, LUCAS_HNF4A_TARGETS_UP, TAL1ALPHAE47_01, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, BEIER_GLIOMA_STEM_CELL_DN, MYOD_01, GOBP_REACTIVE_NITROGEN_SPECIES_METABOLIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, P300_01, HAMAI_APOPTOSIS_VIA_TRAIL_DN, DR3_Q4

GO Biological Process (2): negative regulation of apoptotic process (GO:0043066), positive regulation of nitric oxide biosynthetic process (GO:0045429)

GO Molecular Function (3): hydrolase activity (GO:0016787), protein binding (GO:0005515), dimethylargininase activity (GO:0016403)

GO Cellular Component (3): mitochondrion (GO:0005739), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
nitric oxide biosynthetic process	1
positive regulation of biosynthetic process	1
regulation of nitric oxide biosynthetic process	1
catalytic activity	1
binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines	1
cytoplasm	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

904 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDAH2	AGXT2	Q9BYV1	787
DDAH2	NOS3	P29474	786
DDAH2	PRMT1	Q99873	759
DDAH2	PRMT2	P55345	617
DDAH2	MPIG6B	O95866	606
DDAH2	NOS1	P29475	591
DDAH2	SCGN	O76038	578
DDAH2	ARG2	P78540	569
DDAH2	PRMT3	O60678	511
DDAH2	LY6G6C	O95867	507
DDAH2	NF1	P21359	471
DDAH2	ARFGAP2	Q8N6H7	461
DDAH2	ATP12A	P54707	460
DDAH2	ATP4A	P20648	456
DDAH2	AGT	P01019	445

IntAct

71 interactions, top by confidence:

A	B	Type	Score
TRIP13	DDAH2	psi-mi:“MI:0915”(physical association)	0.760
DDAH2	TRIP13	psi-mi:“MI:0915”(physical association)	0.760
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
DDAH2	EPB41L2	psi-mi:“MI:0914”(association)	0.640
DDAH2	IGFN1	psi-mi:“MI:0915”(physical association)	0.560
DDAH2	NOXA1	psi-mi:“MI:0915”(physical association)	0.560
DDAH2	FANCL	psi-mi:“MI:0915”(physical association)	0.560
DDAH2	ACTN3	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	DDAH2	psi-mi:“MI:0915”(physical association)	0.560
SOX2	PDLIM1	psi-mi:“MI:0914”(association)	0.530
DDAH2	OGT	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
DDAH2	rep	psi-mi:“MI:0915”(physical association)	0.510
HYI	DDAH2	psi-mi:“MI:0915”(physical association)	0.500
HYI	DDAH2	psi-mi:“MI:0914”(association)	0.500
SARNP	DDAH2	psi-mi:“MI:0915”(physical association)	0.400
DAOA	DDAH2	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
DDAH2	VAC14	psi-mi:“MI:0915”(physical association)	0.370
DDAH2	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
DDAH2	ATP1B1	psi-mi:“MI:0915”(physical association)	0.370
DDAH2	CDC73	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (91): VAC14 (Two-hybrid), EPB41L2 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), EPB41L3 (Affinity Capture-MS), DDAH1 (Affinity Capture-MS), OGT (Affinity Capture-MS), HCFC1 (Affinity Capture-MS), CLNS1A (Affinity Capture-MS), DDAH2 (Two-hybrid), DDAH2 (Co-fractionation), DDAH2 (Co-fractionation), DDAH1 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), EPB41L2 (Affinity Capture-MS), CLNS1A (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PJB7, A6H603, A6QQ74, O55171, O60294, O88267, O95050, O95865, P10938, P49753, Q002B5, Q08DM2, Q1JPJ9, Q28F19, Q2KJ24, Q32KW9, Q3I5F7, Q3SX44, Q3UQ84, Q3ZBE0, Q561R2, Q568Y2, Q5RE82, Q5XIH9, Q5ZKI2, Q643R3, Q68FW7, Q6AYF9, Q6MG60, Q6NXR0, Q6PAT0, Q6Q2Z6, Q6ZPS2, Q86TX2, Q86U10, Q8IZ83, Q8K2J0, Q8N0W3, Q8N2G8, Q8N3E9

Diamond homologs: O08557, O94760, O95865, P56965, Q3SX44, Q6MG60, Q99LD8, Q9CWS0, Q9I4E3, Q9X7M4, Q9Y8N2

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
TBK1	“down-regulates activity”	DDAH2	phosphorylation
DDAH2	“up-regulates quantity”	“nitric oxide”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

840 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31727544:T:TA	donor_gain	1.0000
6:31727690:TGCC:T	acceptor_loss	1.0000
6:31727691:GCCTA:G	acceptor_loss	1.0000
6:31728180:G:GA	donor_gain	1.0000
6:31728427:C:A	donor_gain	1.0000
6:31728540:C:CT	acceptor_gain	1.0000
6:31728640:CCTCA:C	donor_loss	1.0000
6:31728641:CTCA:C	donor_loss	1.0000
6:31728642:TCA:T	donor_loss	1.0000
6:31728643:CA:C	donor_loss	1.0000
6:31728644:A:AC	donor_gain	1.0000
6:31728645:C:CC	donor_gain	1.0000
6:31728645:C:CT	donor_loss	1.0000
6:31728744:ACCT:A	acceptor_loss	1.0000
6:31728745:CCT:C	acceptor_gain	1.0000
6:31728746:C:A	acceptor_loss	1.0000
6:31728747:T:C	acceptor_gain	1.0000
6:31728747:T:TC	acceptor_gain	1.0000
6:31728752:A:AC	acceptor_gain	1.0000
6:31728752:A:C	acceptor_gain	1.0000
6:31727608:C:CT	acceptor_gain	0.9900
6:31727608:C:T	acceptor_gain	0.9900
6:31727688:ATTGC:A	acceptor_gain	0.9900
6:31727689:TTGC:T	acceptor_gain	0.9900
6:31727690:TGC:T	acceptor_gain	0.9900
6:31727691:GC:G	acceptor_gain	0.9900
6:31727692:CC:C	acceptor_gain	0.9900
6:31727693:C:CC	acceptor_gain	0.9900
6:31728167:CCT:C	donor_loss	0.9900
6:31728168:CTC:C	donor_loss	0.9900

AlphaMissense

1789 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31728282:A:T	V161D	0.999
6:31728454:G:C	F156L	0.999
6:31728454:G:T	F156L	0.999
6:31728455:A:G	F156S	0.999
6:31728456:A:G	F156L	0.999
6:31728491:G:A	T144I	0.999
6:31728657:A:T	V129D	0.999
6:31728905:G:T	A86D	0.999
6:31728456:A:T	F156I	0.998
6:31728476:G:T	A149D	0.998
6:31728479:C:T	G148E	0.998
6:31728500:G:A	S141F	0.998
6:31728512:A:G	F137S	0.998
6:31728660:T:A	D128V	0.998
6:31728926:G:T	A79D	0.998
6:31728480:C:G	G148R	0.997
6:31728480:C:T	G148R	0.997
6:31728509:A:T	V138E	0.997
6:31728515:A:G	F136S	0.997
6:31728902:A:G	L87P	0.997
6:31729121:G:T	A14D	0.997
6:31728487:A:C	N145K	0.996
6:31728487:A:T	N145K	0.996
6:31728501:A:G	S141P	0.996
6:31728506:C:T	G139D	0.996
6:31728654:A:G	L130P	0.996
6:31728661:C:A	D128Y	0.996
6:31728672:A:G	L124P	0.996
6:31728723:A:G	L107P	0.996
6:31728467:A:T	V152E	0.995

dbSNP variants (sampled 300 via entrez): RS1000238815 (6:31730980 T>C), RS1000265313 (6:31731565 G>C), RS1001367069 (6:31728385 G>A), RS1001808204 (6:31730391 T>C), RS1003032668 (6:31730243 C>G), RS1003063934 (6:31729871 G>A,T), RS1004377779 (6:31731684 A>C,G), RS1004479295 (6:31730355 A>G), RS1004762315 (6:31727969 G>A), RS1005451918 (6:31731722 A>G), RS1006155349 (6:31728842 C>A), RS1006486341 (6:31729429 G>A), RS1007622374 (6:31728117 C>G,T), RS1008510802 (6:31726646 C>T), RS1008564505 (6:31727454 G>A)

Disease associations

OMIM: gene MIM:604744 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_224	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_227	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_281	Autism spectrum disorder or schizophrenia	5.000000e-09
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_45	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST008916_111	Asthma	2.000000e-14
GCST008916_114	Asthma	1.000000e-09
GCST008916_30	Asthma	1.000000e-09
GCST008917_2	Asthma (childhood onset)	4.000000e-07
GCST008921_1	Asthma and major depressive disorder	2.000000e-16
GCST010725_43	Malaria	5.000000e-07
GCST010725_62	Malaria	3.000000e-06

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 — Dimethylarginine dimethylaminohydrolases

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression	4
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	increases expression	3
bisphenol A	affects cotreatment, decreases methylation, increases expression, affects methylation	2
entinostat	affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
tungsten carbide	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
sulforaphane	decreases expression	1
tetramethylpyrazine	decreases abundance, decreases reaction, decreases activity, decreases phosphorylation, increases reaction (+3 more)	1
cobaltous chloride	decreases expression	1
N,N-dimethylarginine	decreases expression, decreases reaction, increases abundance, increases reaction	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
lead chloride	increases expression	1
nickel sulfate	increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0WY	Ubigene KYSE-30 DDAH2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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