ADSS2

Summary

ADSS2 (adenylosuccinate synthase 2, HGNC:292) is a protein-coding gene on chromosome 1q44, encoding Adenylosuccinate synthetase isozyme 2 (P30520). Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. It is a selective cancer dependency (DepMap: 42.2% of cell lines).

This gene encodes the enzyme adenylosuccinate synthetase which catalyzes the first committed step in the conversion of inosine monophosphate to adenosine monophosphate. A pseudogene of this gene is found on chromosome 17.

Source: NCBI Gene 159 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 120 total — 42 pathogenic, 7 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 42.2% of screened cell lines
• MANE Select transcript: NM_001126

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:292
Approved symbol	ADSS2
Name	adenylosuccinate synthase 2
Location	1q44
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000035687
Ensembl biotype	protein_coding
OMIM	103060
Entrez	159

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000366535, ENST00000462358, ENST00000468215

RefSeq mRNA: 2 — MANE Select: NM_001126 NM_001126, NM_001365073

CCDS: CCDS1624

Canonical transcript exons

ENST00000366535 — 13 exons

Exon	Start	End
ENSE00000961641	244436825	244436893
ENSE00000961642	244432545	244432595
ENSE00001009299	244437666	244437768
ENSE00001441955	244451635	244451909
ENSE00001655298	244411287	244411436
ENSE00001746197	244408494	244409638
ENSE00001800158	244418760	244418914
ENSE00002038715	244424321	244424387
ENSE00003499382	244415981	244416078
ENSE00003526711	244422835	244422916
ENSE00003566308	244423953	244424060
ENSE00003682506	244417628	244417752
ENSE00003690273	244420170	244420296

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 95.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.6983 / max 1829.6016, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18389	36.1321	1823
18388	21.0051	1796
18390	2.5612	1335

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	95.91	gold quality
mononuclear cell	CL:0000842	95.72	gold quality
leukocyte	CL:0000738	95.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.19	gold quality
cortical plate	UBERON:0005343	94.64	gold quality
right testis	UBERON:0004534	94.42	gold quality
bone marrow cell	CL:0002092	94.33	gold quality
left testis	UBERON:0004533	94.31	gold quality
palpebral conjunctiva	UBERON:0001812	94.11	gold quality
adrenal tissue	UBERON:0018303	93.97	gold quality
skin of abdomen	UBERON:0001416	93.71	gold quality
bone marrow	UBERON:0002371	93.53	gold quality
calcaneal tendon	UBERON:0003701	93.41	gold quality
testis	UBERON:0000473	93.39	gold quality
rectum	UBERON:0001052	93.37	gold quality
skin of leg	UBERON:0001511	93.22	gold quality
corpus callosum	UBERON:0002336	93.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.99	gold quality
stromal cell of endometrium	CL:0002255	92.95	gold quality
pons	UBERON:0000988	92.73	gold quality
minor salivary gland	UBERON:0001830	92.53	gold quality
right lung	UBERON:0002167	92.50	gold quality
nasal cavity mucosa	UBERON:0001826	92.43	gold quality
tibia	UBERON:0000979	92.41	gold quality
zone of skin	UBERON:0000014	92.34	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.27	gold quality
bronchial epithelial cell	CL:0002328	92.25	gold quality
lower esophagus	UBERON:0013473	92.25	gold quality
esophagus	UBERON:0001043	92.18	gold quality
ganglionic eminence	UBERON:0004023	92.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	7.39
E-ANND-3	yes	6.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA, PPARG

miRNA regulators (miRDB)

119 targeting ADSS2, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-3686	99.90	70.53	2432

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 42.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Kinetic data reveal that human Ser(289) and B. subtilis Ser(262) and Ser(263) are essential for catalysis, while the ability of these Ser mutants to bind APBADP suggests that they do not contribute to substrate affinity (PMID:18469177)
• These findings suggest that the combined effects of the polymorphisms in the ADSS and ATM genes may confer susceptibility to the development of schizophrenia in a Chinese population (PMID:19115993)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	adss2	ENSDARG00000002071
mus_musculus	Adss2	ENSMUSG00000015961
rattus_norvegicus	Adss2	ENSRNOG00000004481
drosophila_melanogaster	Adss	FBGN0027493
caenorhabditis_elegans		WBGENE00016509

Paralogs (1): ADSS1 (ENSG00000185100)

Protein

Protein identifiers

Adenylosuccinate synthetase isozyme 2 — P30520 (reviewed: P30520)

Alternative names: Adenylosuccinate synthetase, acidic isozyme, Adenylosuccinate synthetase, liver isozyme, IMP–aspartate ligase 2

All UniProt accessions (2): P30520, A0A024R5Q7

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Mitochondrion.

Activity regulation. Inhibited competitively by AMP and IMP and non-competitively by fructose 1,6-bisphosphate.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Pathway. Purine metabolism; AMP biosynthesis via de novo pathway; AMP from IMP: step 1/2.

Similarity. Belongs to the adenylosuccinate synthetase family.

RefSeq proteins (2): NP_001117, NP_001352002 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001114	Adenylosuccinate_synthetase	Family
IPR018220	Adenylosuccin_syn_GTP-bd	Binding_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR027529	AdSS_2_vert	Family
IPR033128	Adenylosuccin_syn_Lys_AS	Active_site
IPR042109	Adenylosuccinate_synth_dom1	Homologous_superfamily
IPR042110	Adenylosuccinate_synth_dom2	Homologous_superfamily
IPR042111	Adenylosuccinate_synth_dom3	Homologous_superfamily

Pfam: PF00709

Catalyzed reactions (Rhea), 1 shown:

• IMP + L-aspartate + GTP = N(6)-(1,2-dicarboxyethyl)-AMP + GDP + phosphate + 2 H(+) (RHEA:15753)

UniProt features (63 total): helix 21, strand 18, binding site 16, active site 2, turn 2, chain 1, region of interest 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2V40	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30520-F1	92.90	0.85

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): 40 (proton acceptor); 68 (proton donor)

Ligand- & substrate-binding residues (16): 67; 162 (in other chain); 176; 255 (in other chain); 270 (in other chain); 330–336; 334 (in other chain); 336; 362–364; 444–447; 39–45; 40–43 (in other chain) …

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-73817	Purine ribonucleoside monophosphate biosynthesis

MSigDB gene sets: 235 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_ELECTRICAL_STIMULUS, MODULE_239, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, AAAGACA_MIR511, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (9): immune system process (GO:0002376), AMP biosynthetic process (GO:0006167), aspartate metabolic process (GO:0006531), response to purine-containing compound (GO:0014074), ‘de novo’ AMP biosynthetic process (GO:0044208), IMP metabolic process (GO:0046040), response to ammonium ion (GO:0060359), cellular response to electrical stimulus (GO:0071257), purine nucleotide biosynthetic process (GO:0006164)

GO Molecular Function (8): magnesium ion binding (GO:0000287), adenylosuccinate synthase activity (GO:0004019), GTP binding (GO:0005525), phosphate ion binding (GO:0042301), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nucleotide biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to nitrogen compound	2
cellular anatomical structure	2
cytoplasm	2
biological_process	1
purine ribonucleotide biosynthetic process	1
purine ribonucleoside monophosphate biosynthetic process	1
AMP metabolic process	1
amino acid metabolic process	1
dicarboxylic acid metabolic process	1
AMP biosynthetic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside monophosphate metabolic process	1
response to electrical stimulus	1
cellular response to abiotic stimulus	1
purine nucleotide metabolic process	1
nucleotide biosynthetic process	1
purine-containing compound biosynthetic process	1
metal ion binding	1
ligase activity, forming carbon-nitrogen bonds	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

2490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADSS2	AMPD3	Q01432	927
ADSS2	AMPD1	P23109	924
ADSS2	ASS1	P00966	923
ADSS2	AMPD2	Q01433	921
ADSS2	ADSL	P30566	856
ADSS2	IMPDH2	P12268	797
ADSS2	GMPS	P49915	770
ADSS2	PPAT	Q06203	688
ADSS2	APRT	P07741	675
ADSS2	IMPDH1	P20839	670
ADSS2	GART	P22102	666
ADSS2	ATIC	P31939	665
ADSS2	PAICS	P22234	605
ADSS2	UMPS	P11172	596
ADSS2	ITPA	Q9BY32	579

IntAct

43 interactions, top by confidence:

A	B	Type	Score
SMYD1	ADSS2	psi-mi:“MI:0914”(association)	0.780
ADSS2	SMYD1	psi-mi:“MI:0915”(physical association)	0.780
ADSS2	ADSS1	psi-mi:“MI:0915”(physical association)	0.720
NPB	CST4	psi-mi:“MI:0914”(association)	0.530
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
TANK	CNOT1	psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
NT5C3A	VWA8	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
NPB	IL16	psi-mi:“MI:0914”(association)	0.350
LGALS7		psi-mi:“MI:0914”(association)	0.350
SMYD1	CAPNS1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
RMC1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
MRPL42	UBA6	psi-mi:“MI:0914”(association)	0.350
ADSS2	SERPINB7	psi-mi:“MI:0914”(association)	0.350
ADSS1	FABP3	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
DND1	UBA6	psi-mi:“MI:0914”(association)	0.350
OAS1	UBA6	psi-mi:“MI:0914”(association)	0.350
PCDHGA9	UBA6	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
SLC22A11	CNOT1	psi-mi:“MI:0914”(association)	0.350
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (148): AASDHPPT (Co-fractionation), ADSS (Co-fractionation), ADSS (Co-fractionation), AGL (Co-fractionation), ARFIP1 (Co-fractionation), C6orf211 (Co-fractionation), GART (Co-fractionation), GNPNAT1 (Co-fractionation), HSD17B10 (Co-fractionation), IMPA2 (Co-fractionation), NME1-NME2 (Co-fractionation), NME2 (Co-fractionation), PCBD1 (Co-fractionation), PFKL (Co-fractionation), RPE (Co-fractionation)

ESM2 similar proteins: A0A2H5BHJ6, A0A2L0V130, A4Z6H1, A6R8V2, A7AU38, A7MBG0, A8Q0E3, A8QE42, A9XLG1, B0DUI8, B3M343, B3S0D3, B4JUE4, B4K8W7, B4LWK0, B4NFS5, B5DGM3, B5DGM4, B7FUM7, B8M3A8, B8MZA3, C0NL18, C0S3Z3, C1FYF6, C1GUH5, C5FC83, C5GA45, C5JKJ6, C6HBB1, C7Z193, D0NVH9, G3FFN6, P30520, P46664, P91134, Q0CM45, Q17G75, Q28GB0, Q299D3, Q2UQQ2

Diamond homologs: A0BD92, A2XD35, A3LYS9, A4RYD2, A4Z6H0, A4Z6H1, A5DIP4, A5DSZ3, A5PJR4, A6ZRM0, A7MBG0, A7TID0, A8IW34, A8NDT2, A8Q0E3, A8QE42, A8X7H5, A9SCV9, A9TIK2, A9UTP3, A9XLE1, A9XLE2, A9XLG1, B0DQB9, B0W9B4, B2VXY5, B3LP64, B3M343, B3P321, B3S0D3, B4G518, B4II68, B4JUE4, B4K8W7, B4LWK0, B4NFS5, B4PPT4, B5DGM3, B5DGM4, B5VQJ1

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ADSS2	“down-regulates quantity”	IMP	“chemical modification”
ADSS2	“down-regulates quantity”	L-aspartate(1-)	“chemical modification”
ADSS2	“up-regulates quantity”	N(6)-(1,2-dicarboxylatoethyl)-AMP(4-)	“chemical modification”
ADSS2	“up-regulates quantity”	GDP	“chemical modification”
ADSS2	up-regulates	Nucleotide_synthesis

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	42
Likely pathogenic	7
Uncertain significance	42
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
144563	GRCh38/hg38 1q43-44(chr1:243264192-244668463)x1	Pathogenic
144759	GRCh38/hg38 1q43-44(chr1:238351121-248918469)x1	Pathogenic
145361	GRCh38/hg38 1q43-44(chr1:238753749-248918467)x1	Pathogenic
147285	GRCh38/hg38 1q43-44(chr1:241625115-245453782)x3	Pathogenic
148185	GRCh38/hg38 1q43-44(chr1:240465122-248918469)x1	Pathogenic
154601	GRCh38/hg38 1q43-44(chr1:243145749-244433395)x1	Pathogenic
1703535	GRCh37/hg19 1q43-44(chr1:242816510-244797117)	Pathogenic
1807822	GRCh37/hg19 1q43-44(chr1:243258050-249224684)x3	Pathogenic
1808659	GRCh37/hg19 1q43-44(chr1:239910960-249224684)x1	Pathogenic
1808697	GRCh37/hg19 1q43-44(chr1:243085543-247137125)x3	Pathogenic
253578	GRCh37/hg19 1q43-44(chr1:242357208-246378823)x1	Pathogenic
2579272	GRCh38/hg38 1q43-44(chr1:243221458-248919110)x1	Pathogenic
2579277	GRCh38/hg38 1q43-44(chr1:242164274-245299473)x1	Pathogenic
2582785	GRCh38/hg38 1q43-44(chr1:239907336-248919110)x1	Pathogenic
2582786	GRCh38/hg38 1q43-44(chr1:242520315-246857912)x1	Pathogenic
3062700	GRCh37/hg19 1q44(chr1:244579324-246515944)x1	Pathogenic
3063488	GRCh37/hg19 1q43-44(chr1:243453390-245467768)x1	Pathogenic
3242282	GRCh37/hg19 1q43-44(chr1:243364757-245372332)x1	Pathogenic
3247849	NC_000001.10:g.(?243668551)(245027609_?)del	Pathogenic
394141	GRCh37/hg19 1q44(chr1:244385524-246707775)x1	Pathogenic
395294	GRCh37/hg19 1q43-44(chr1:242656460-249213000)x3	Pathogenic
4076009	GRCh37/hg19 1q44(chr1:244243574-245116806)x1	Pathogenic
4279184	GRCh37/hg19 1q43-44(chr1:237958865-246428627)x1	Pathogenic
442726	GRCh37/hg19 1q43-44(chr1:240620284-247690417)x1	Pathogenic
565241	GRCh37/hg19 1q43-44(chr1:241051170-249224684)x1	Pathogenic
565244	GRCh37/hg19 1q43-44(chr1:243099588-245703296)x1	Pathogenic
57260	GRCh38/hg38 1q44(chr1:243677224-244923447)x1	Pathogenic
58142	GRCh38/hg38 1q43-44(chr1:240244444-248891309)x3	Pathogenic
59654	GRCh38/hg38 1q43-44(chr1:242828731-248891309)x3	Pathogenic
60150	GRCh38/hg38 1q43-44(chr1:239629868-248924593)x1	Pathogenic

SpliceAI

2201 predictions. Top by Δscore:

Variant	Effect	Δscore
1:244417619:AATAC:A	donor_loss	1.0000
1:244417620:ATACT:A	donor_loss	1.0000
1:244417621:TAC:T	donor_loss	1.0000
1:244417622:AC:A	donor_loss	1.0000
1:244417624:TCA:T	donor_loss	1.0000
1:244417625:CACGC:C	donor_loss	1.0000
1:244417626:A:AC	donor_gain	1.0000
1:244417627:C:CA	donor_gain	1.0000
1:244417627:CG:C	donor_gain	1.0000
1:244417749:TTTC:T	acceptor_gain	1.0000
1:244417750:TTCCT:T	acceptor_loss	1.0000
1:244417753:C:CA	acceptor_loss	1.0000
1:244417753:C:CC	acceptor_gain	1.0000
1:244417754:T:A	acceptor_loss	1.0000
1:244418758:A:AC	donor_gain	1.0000
1:244418759:C:CC	donor_gain	1.0000
1:244418913:CC:C	acceptor_gain	1.0000
1:244418914:CC:C	acceptor_gain	1.0000
1:244418915:C:CC	acceptor_gain	1.0000
1:244418915:C:CG	acceptor_loss	1.0000
1:244420168:A:AC	donor_gain	1.0000
1:244420169:C:CC	donor_gain	1.0000
1:244420295:CC:C	acceptor_gain	1.0000
1:244420296:CC:C	acceptor_gain	1.0000
1:244420298:T:A	acceptor_loss	1.0000
1:244424061:C:CC	acceptor_gain	1.0000
1:244424062:T:C	acceptor_gain	1.0000
1:244424317:ATACT:A	donor_loss	1.0000
1:244424318:TA:T	donor_loss	1.0000
1:244424319:A:AC	donor_gain	1.0000

AlphaMissense

2978 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:244418883:A:C	C274W	1.000
1:244424040:C:T	G165D	1.000
1:244424041:C:G	G165R	1.000
1:244437752:C:T	G67D	1.000
1:244451699:T:A	D40V	1.000
1:244451699:T:G	D40A	1.000
1:244451700:C:G	D40H	1.000
1:244411383:A:G	W408R	0.999
1:244411383:A:T	W408R	0.999
1:244417680:A:G	W340R	0.999
1:244417680:A:T	W340R	0.999
1:244417690:T:A	R336S	0.999
1:244417690:T:G	R336S	0.999
1:244417691:C:G	R336T	0.999
1:244417712:C:T	G329D	0.999
1:244418791:C:T	G305D	0.999
1:244418792:C:G	G305R	0.999
1:244418811:T:A	K298N	0.999
1:244418811:T:G	K298N	0.999
1:244418812:T:A	K298I	0.999
1:244418813:T:C	K298E	0.999
1:244418884:C:T	C274Y	0.999
1:244418914:C:A	G264V	0.999
1:244418914:C:T	G264E	0.999
1:244420170:C:A	G264W	0.999
1:244420170:C:G	G264R	0.999
1:244420170:C:T	G264R	0.999
1:244420181:T:A	D260V	0.999
1:244420182:C:G	D260H	0.999
1:244420184:A:G	L259S	0.999

dbSNP variants (sampled 300 via entrez): RS1000098370 (1:244425072 C>T), RS1000107698 (1:244444721 T>C), RS1000193196 (1:244413343 C>T), RS1000381553 (1:244410477 T>C), RS1000396051 (1:244448520 G>A,C), RS1000429097 (1:244410873 T>C), RS1000476776 (1:244413032 G>A,C), RS1000518403 (1:244433939 G>A), RS1000579646 (1:244438128 C>T), RS1000647084 (1:244450700 T>C), RS1000678681 (1:244417811 A>G), RS1000680059 (1:244450387 G>T), RS1000693265 (1:244442116 C>T), RS1000738542 (1:244424812 T>C), RS1000967788 (1:244443788 G>A,C)

Disease associations

OMIM: gene MIM:103060 | disease phenotypes: MIM:612337, MIM:617391

GenCC curated gene-disease

Mondo (2): intellectual disability, autosomal dominant 22 (MONDO:0012869), developmental and epileptic encephalopathy, 54 (MONDO:0033363)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_882	Obesity-related traits	4.000000e-06
GCST002576_5	Epithelial ovarian cancer	4.000000e-06
GCST002593_32	Dementia and core Alzheimer’s disease neuropathologic changes	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005118	IGFBP-1 measurement
EFO:0006801	Alzheimer’s disease neuropathologic change

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567346	Chromosome 1q43-Q44 Deletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4875 (SINGLE PROTEIN)

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

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Kd	0.991	nM	CHEMBL5653589
9.00	ED50	0.991	nM	CHEMBL5653589
7.37	IC50	43	nM	CHEMBL118357
6.17	IC50	675	nM	PHOSPHOHYDANTOCIDIN
5.46	IC50	3500	nM	HADACIDIN

PubChem BioAssay actives

4 with measured affinity, of 5 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147812: Binding affinity to human ADSS incubated for 45 mins by Kinobead based pull down assay	kd	0.0010	uM
(2S)-5-[(5S,7R,8S,9R)-8,9-dihydroxy-2,4-dioxo-7-(phosphonooxymethyl)-6-oxa-1,3-diazaspiro[4.4]nonan-3-yl]-2-[formyl(hydroxy)amino]pentanoic acid	32784: Inhibitory concentration against Adenylosuccinate synthetase	ic50	0.0430	uM
[(5S,7R,8S,9R)-8,9-dihydroxy-2,4-dioxo-6-oxa-1,3-diazaspiro[4.4]nonan-7-yl]methyl dihydrogen phosphate	32784: Inhibitory concentration against Adenylosuccinate synthetase	ic50	0.6750	uM
2-[formyl(hydroxy)amino]acetic acid	32784: Inhibitory concentration against Adenylosuccinate synthetase	ic50	3.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	4
bisphenol A	decreases expression, increases expression	3
trichostatin A	affects cotreatment, decreases expression	3
Fluorouracil	decreases expression, increases expression	3
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
beta-methylcholine	affects expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants, Occupational	affects expression	1
Cadmium	increases abundance, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	affects expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650854	Binding	Binding affinity to human ADSS incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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