CDS2

Summary

CDS2 (CDP-diacylglycerol synthase 2, HGNC:1801) is a protein-coding gene on chromosome 20p12.3, encoding Phosphatidate cytidylyltransferase 2 (O95674). Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol. It is a selective cancer dependency (DepMap: 28.5% of cell lines).

Breakdown products of phosphoinositides are ubiquitous second messengers that function downstream of many G protein-coupled receptors and tyrosine kinases regulating cell growth, calcium metabolism, and protein kinase C activity. This gene encodes an enzyme which regulates the amount of phosphatidylinositol available for signaling by catalyzing the conversion of phosphatidic acid to CDP-diacylglycerol. This enzyme is an integral membrane protein localized to two subcellular domains, the matrix side of the inner mitochondrial membrane where it is thought to be involved in the synthesis of phosphatidylglycerol and cardiolipin and the cytoplasmic side of the endoplasmic reticulum where it functions in phosphatidylinositol biosynthesis. Two genes encoding this enzyme have been identified in humans, one mapping to human chromosome 4q21 and a second to 20p13.

Source: NCBI Gene 8760 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 67 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 28.5% of screened cell lines
• MANE Select transcript: NM_003818

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1801
Approved symbol	CDS2
Name	CDP-diacylglycerol synthase 2
Location	20p12.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000101290
Ensembl biotype	protein_coding
OMIM	603549
Entrez	8760

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000379070, ENST00000450570, ENST00000460006, ENST00000467923, ENST00000468817, ENST00000486875, ENST00000876935, ENST00000876936, ENST00000876937, ENST00000876938, ENST00000876939, ENST00000876940, ENST00000919092, ENST00000919093, ENST00000919094, ENST00000955323

RefSeq mRNA: 1 — MANE Select: NM_003818 NM_003818

CCDS: CCDS13088

Canonical transcript exons

ENST00000460006 — 13 exons

Exon	Start	End
ENSE00001866448	5190102	5197887
ENSE00001958684	5127008	5127149
ENSE00003459465	5182387	5182445
ENSE00003495158	5185758	5185826
ENSE00003507406	5186687	5186839
ENSE00003530520	5176648	5176745
ENSE00003547173	5189067	5189186
ENSE00003564836	5175183	5175279
ENSE00003623626	5178817	5178956
ENSE00003642382	5183061	5183143
ENSE00003668700	5189735	5189838
ENSE00003685381	5184858	5184945
ENSE00003694575	5173523	5173659

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.1554 / max 206.5848, expressed in 1822 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183330	22.4369	1818
183329	11.1334	1782
183326	1.4409	403
183328	0.7344	383
183327	0.7217	295
183325	0.3883	174
183331	0.2998	151

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	98.46	gold quality
middle temporal gyrus	UBERON:0002771	98.30	gold quality
substantia nigra pars compacta	UBERON:0001965	97.66	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.96	gold quality
postcentral gyrus	UBERON:0002581	96.65	gold quality
dorsal root ganglion	UBERON:0000044	96.61	gold quality
entorhinal cortex	UBERON:0002728	96.60	gold quality
superior vestibular nucleus	UBERON:0007227	96.58	gold quality
lateral globus pallidus	UBERON:0002476	96.57	gold quality
parietal lobe	UBERON:0001872	96.38	gold quality
ventral tegmental area	UBERON:0002691	95.92	gold quality
superior frontal gyrus	UBERON:0002661	95.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.85	gold quality
trigeminal ganglion	UBERON:0001675	95.43	gold quality
pons	UBERON:0000988	95.23	gold quality
globus pallidus	UBERON:0001875	94.91	gold quality
medial globus pallidus	UBERON:0002477	94.83	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.25	gold quality
subthalamic nucleus	UBERON:0001906	94.02	gold quality
inferior vagus X ganglion	UBERON:0005363	93.77	gold quality
islet of Langerhans	UBERON:0000006	93.29	gold quality
occipital lobe	UBERON:0002021	92.93	gold quality
medulla oblongata	UBERON:0001896	92.80	gold quality
primary visual cortex	UBERON:0002436	92.67	gold quality
endothelial cell	CL:0000115	92.37	gold quality
adult organism	UBERON:0007023	92.26	gold quality
saphenous vein	UBERON:0007318	92.26	gold quality
vena cava	UBERON:0004087	91.98	gold quality
midbrain	UBERON:0001891	91.92	gold quality
left ventricle myocardium	UBERON:0006566	91.65	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	2107.06
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

207 targeting CDS2, 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-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-570-3P	99.96	72.41	4910

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 28.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• distinct properties of the two isoforms of CDP-diacylglycerol synthase (PMID:25375833)
• CDS1 and CDS2 are important novel regulators of lipid storage. (PMID:26946540)
• CDP-DAG synthase 1 and 2 regulate lipid droplet growth through distinct mechanisms (PMID:31548309)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cds2	ENSDARG00000035577
mus_musculus	Cds2	ENSMUSG00000058793
rattus_norvegicus	Cds2	ENSRNOG00000021265
drosophila_melanogaster	Cds	FBGN0010350
caenorhabditis_elegans		WBGENE00016384

Paralogs (1): CDS1 (ENSG00000163624)

Protein

Protein identifiers

Phosphatidate cytidylyltransferase 2 — O95674 (reviewed: O95674)

Alternative names: CDP-DAG synthase 2, CDP-DG synthase 2, CDP-diacylglycerol synthase 2, CDP-diglyceride pyrophosphorylase 2, CDP-diglyceride synthase 2, CTP:phosphatidate cytidylyltransferase 2

All UniProt accessions (1): O95674

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol. Exhibits specificity for the nature of the acyl chains at the sn-1 and sn-2 positions in the substrate, PA and the preferred acyl chain composition is 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid. Plays an important role in regulating the growth and maturation of lipid droplets which are storage organelles at the center of lipid and energy homeostasis.

Subunit / interactions. Homodimer.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed. Expressed in heart, brain and retina, and to a lesser extent in placenta, lung, liver, skeletal muscle, kidney and pancreas.

Activity regulation. Inhibited by its anionic phospholipid end products, with phosphatidylinositol-(4,5)- bisphosphate (PIP2) showing the strongest inhibition. Inhibition is also acyl chain specific, with 1-stearoyl-2-arachidonoyl-snphosphatidylinositol showing the strongest inhibition.

Pathway. Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP-diacylglycerol from sn-glycerol 3-phosphate: step 3/3.

Similarity. Belongs to the CDS family.

Isoforms (2)

UniProt ID	Names	Canonical?
O95674-1	1	yes
O95674-2	2

RefSeq proteins (1): NP_003809* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000374	PC_trans	Family
IPR016720	PC_Trfase_euk	Family

Pfam: PF01148

Enzyme classification (BRENDA):

• EC 2.7.7.41 — phosphatidate cytidylyltransferase (BRENDA: 29 organisms, 110 substrates, 66 inhibitors, 36 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CTP	0.076–1	9
PHOSPHATIDIC ACID	0.08–0.3	7
PHOSPHATIDATE	0.067–2.5	6
DCTP	0.26–0.9	4
1,2-DIOLEOYL-SN-GLYCEROL 3-PHOSPHATE	0.114	1
1-PALMITOYL-2-[12-[(7-NITRO-2-1,3-BENZOXADIAZOL-	0.067	1
1-STEAROYL-2-ARACHIDONOYL-SN-GLYCERO-3-PHOSPHATE	0.102	1
1-STEAROYL-2-ARACHIDONOYL-SN-PHOSPHATIDIC ACID	—	0
1-STEAROYL-2-LINOLEOYL-SN-PHOSPHATIDIC ACID	—	0

Catalyzed reactions (Rhea), 9 shown:

• a 1,2-diacyl-sn-glycero-3-phosphate + CTP + H(+) = a CDP-1,2-diacyl-sn-glycerol + diphosphate (RHEA:16229)
• 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-cytidine-5’-diphosphate + diphosphate (RHEA:45648)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-cytidine-5’-diphosphate + diphosphate (RHEA:45652)
• 1,2-di-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate + CTP + H(+) = 1,2-di-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-cytidine-5’-diphosphate + diphosphate (RHEA:45656)
• 1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-cytidine-5’-diphosphate + diphosphate (RHEA:45660)
• 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-cytidine-5’-diphosphate + diphosphate (RHEA:45664)
• 1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-cytidine-5’-diphosphate + diphosphate (RHEA:45668)
• 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-cytidine-5’-diphosphate + diphosphate (RHEA:45672)
• 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-cytidine-5’-diphosphate + diphosphate (RHEA:45676)

UniProt features (18 total): transmembrane region 6, modified residue 6, splice variant 3, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95674-F1	81.70	0.45

Functional residue map

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

Post-translational modifications (6): 31, 33, 35, 37, 51, 21

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1483148	Synthesis of PG
R-HSA-1430728	Metabolism
R-HSA-1483206	Glycerophospholipid biosynthesis
R-HSA-1483257	Phospholipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 201 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_6HR_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_ORGANELLE_ASSEMBLY, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS

GO Biological Process (5): phosphatidylglycerol biosynthetic process (GO:0006655), CDP-diacylglycerol biosynthetic process (GO:0016024), lipid droplet formation (GO:0140042), lipid metabolic process (GO:0006629), phospholipid biosynthetic process (GO:0008654)

GO Molecular Function (5): phosphatidate cytidylyltransferase activity (GO:0004605), protein binding (GO:0005515), transferase activity (GO:0016740), transferase activity, transferring phosphorus-containing groups (GO:0016772), nucleotidyltransferase activity (GO:0016779)

GO Cellular Component (4): mitochondrial inner membrane (GO:0005743), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycerophospholipid biosynthetic process	2
phosphatidylglycerol metabolic process	1
CDP-diacylglycerol metabolic process	1
lipid storage	1
lipid droplet organization	1
membraneless organelle assembly	1
primary metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
cytidylyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
transferase activity, transferring phosphorus-containing groups	1
organelle inner membrane	1
mitochondrial membrane	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDS2	TAMM41	Q96BW9	983
CDS2	CDIPT	O14735	665
CDS2	PGS1	Q32NB8	642
CDS2	CRLS1	Q9UJA2	531
CDS2	SELENOI	Q9C0D9	511
CDS2	TMEM269	A0A1B0GVZ9	507
CDS2	PLPP2	O43688	492
CDS2	PCYT1B	Q9Y5K3	489
CDS2	PCYT1A	P49585	469
CDS2	PISD	Q9UG56	465
CDS2	MBOAT2	Q6ZWT7	450
CDS2	CEPT1	Q9Y6K0	437
CDS2	GK2	Q14410	430
CDS2	TAFAZZIN	Q16635	427
CDS2	PLPP3	O14495	423

IntAct

203 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CDS1	CDS2	psi-mi:“MI:0914”(association)	0.670
CDS1	CDS2	psi-mi:“MI:0915”(physical association)	0.670
CDS2	FGFR3	psi-mi:“MI:0915”(physical association)	0.660
CDS2	TMX2	psi-mi:“MI:0915”(physical association)	0.560
CDS2	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
CDS2	MTIF3	psi-mi:“MI:0915”(physical association)	0.560
CDS2	JSRP1	psi-mi:“MI:0915”(physical association)	0.560
CDS2	MR1	psi-mi:“MI:0915”(physical association)	0.560
CDS2	TSPAN12	psi-mi:“MI:0915”(physical association)	0.560
CDS2	MYG1	psi-mi:“MI:0915”(physical association)	0.560
CDS2	GPX8	psi-mi:“MI:0915”(physical association)	0.560
CDS2	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
CDS2	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
CDS2	RNF122	psi-mi:“MI:0915”(physical association)	0.560
CDS2	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
CDS2	GPR152	psi-mi:“MI:0915”(physical association)	0.560
CDS2	HIBADH	psi-mi:“MI:0915”(physical association)	0.560
CDS2	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
CDS2	IL10RA	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (135): CDS2 (Proximity Label-MS), CDS2 (Two-hybrid), CDS2 (Two-hybrid), CDS2 (Affinity Capture-MS), CDS2 (Proximity Label-MS), CDS2 (Affinity Capture-MS), CDS2 (Affinity Capture-MS), TSPAN12 (Two-hybrid), HIBADH (Two-hybrid), IL10RA (Two-hybrid), TIMMDC1 (Two-hybrid), MTIF3 (Two-hybrid), FAM209A (Two-hybrid), ERGIC3 (Two-hybrid), RNF122 (Two-hybrid)

ESM2 similar proteins: A0JNC1, A2VE61, A7XZ53, B1H3H9, D3ZEH5, F4HXY7, O35052, O95674, P48651, P98191, Q00576, Q01685, Q0JR55, Q0VCK9, Q28CY9, Q28H54, Q2KHY9, Q5EA65, Q5N8Q3, Q5R7B1, Q5U239, Q5ZKD1, Q5ZKJ0, Q5ZM65, Q6AXM5, Q6DD44, Q6DED0, Q6I628, Q7ZYQ3, Q803C9, Q8BGS7, Q8BXA5, Q8CIF6, Q8NBJ9, Q91XU8, Q91ZQ0, Q92903, Q96KA5, Q99KU0, Q99L43

Diamond homologs: A0JNC1, O04928, O04940, O35052, O49639, O67292, O95674, P0ABG1, P0ABG2, P0ABG3, P38221, P53439, P56079, P75160, P98191, Q1PE48, Q49433, Q55D90, Q68WV5, Q91XU8, Q92903, Q95ZE3, Q99L43, Q9P381, Q9X1B7, P73548, Q94A03, P76091, Q1RII7, Q92I31, Q9ZDA8, Q4ULR7, O25004, O31752, P0C102, P44937, P63759, P9WPF6, P9WPF7, Q2YRP9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDS2	up-regulates	CDP-diacylglycerol(2-)	“chemical modification”
CDS2	“down-regulates quantity”	“phosphatidic acid”	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metal ion SLC transporters	5	40.1×	4e-05
R-HSA-425366	5	12.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2126 predictions. Top by Δscore:

Variant	Effect	Δscore
20:5175168:T:TA	acceptor_gain	1.0000
20:5175175:T:TA	acceptor_gain	1.0000
20:5175179:CTA:C	acceptor_loss	1.0000
20:5175180:TAG:T	acceptor_loss	1.0000
20:5175181:A:AG	acceptor_gain	1.0000
20:5175181:AGAT:A	acceptor_gain	1.0000
20:5175182:G:GA	acceptor_gain	1.0000
20:5175182:GATG:G	acceptor_gain	1.0000
20:5175275:TAATC:T	donor_gain	1.0000
20:5175276:AATC:A	donor_gain	1.0000
20:5175277:ATC:A	donor_gain	1.0000
20:5175278:TC:T	donor_gain	1.0000
20:5175280:G:GG	donor_gain	1.0000
20:5176742:GCTG:G	donor_gain	1.0000
20:5178915:G:GG	donor_gain	1.0000
20:5182452:G:GT	donor_gain	1.0000
20:5182453:A:T	donor_gain	1.0000
20:5183059:A:AG	acceptor_gain	1.0000
20:5183059:AGTTT:A	acceptor_gain	1.0000
20:5183060:G:GG	acceptor_gain	1.0000
20:5183060:GTT:G	acceptor_gain	1.0000
20:5183060:GTTT:G	acceptor_gain	1.0000
20:5183060:GTTTG:G	acceptor_gain	1.0000
20:5184852:TTCTA:T	acceptor_loss	1.0000
20:5184853:TCTAG:T	acceptor_loss	1.0000
20:5184854:CTAGG:C	acceptor_loss	1.0000
20:5184855:TAGGT:T	acceptor_loss	1.0000
20:5184856:A:AG	acceptor_gain	1.0000
20:5184857:G:GG	acceptor_gain	1.0000
20:5184857:G:GT	acceptor_loss	1.0000

AlphaMissense

2949 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:5178956:G:A	G177R	1.000
20:5178956:G:C	G177R	1.000
20:5182387:G:A	G177E	1.000
20:5182398:T:C	F181L	1.000
20:5182400:T:A	F181L	1.000
20:5182400:T:G	F181L	1.000
20:5182411:T:C	L185P	1.000
20:5182437:T:C	F194L	1.000
20:5182439:C:A	F194L	1.000
20:5182439:C:G	F194L	1.000
20:5183065:G:A	G198D	1.000
20:5183067:T:A	W199R	1.000
20:5183067:T:C	W199R	1.000
20:5184891:T:A	N235K	1.000
20:5184891:T:G	N235K	1.000
20:5184892:G:C	D236H	1.000
20:5184892:G:T	D236Y	1.000
20:5184893:A:C	D236A	1.000
20:5184893:A:G	D236G	1.000
20:5184893:A:T	D236V	1.000
20:5184894:C:A	D236E	1.000
20:5184894:C:G	D236E	1.000
20:5184914:G:A	G243D	1.000
20:5184926:G:A	G247D	1.000
20:5184938:T:A	L251H	1.000
20:5184938:T:C	L251P	1.000
20:5185772:G:C	K258N	1.000
20:5185772:G:T	K258N	1.000
20:5185782:G:C	G262R	1.000
20:5185783:G:A	G262D	1.000

dbSNP variants (sampled 300 via entrez): RS1000006799 (20:5126851 C>G), RS1000030624 (20:5140082 G>A), RS1000125279 (20:5132926 A>C,G), RS1000129024 (20:5191968 G>A), RS1000175222 (20:5182605 T>C), RS1000185396 (20:5176818 G>A), RS1000244732 (20:5171550 G>A), RS1000253058 (20:5137406 G>A), RS1000282329 (20:5166397 G>GT), RS1000332175 (20:5194277 G>A), RS1000384724 (20:5194001 G>A), RS1000426008 (20:5143107 G>A), RS1000434266 (20:5160524 A>G), RS1000453559 (20:5183072 C>A,T), RS1000464762 (20:5127071 A>G)

Disease associations

OMIM: gene MIM:603549 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066264 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.36	Kd	4334	nM	CHEMBL3752910
5.36	ED50	4334	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148056: Binding affinity to human CDS2 incubated for 45 mins by Kinobead based pull down assay	kd	4.3341	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
bisphenol A	increases expression, affects cotreatment	2
Aflatoxin B1	decreases methylation, increases methylation	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
sodium arsenite	decreases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
K 7174	increases expression	1
abrine	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Acrolein	increases abundance, affects cotreatment, increases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Tetrachlorodibenzodioxin	increases expression	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651098	Binding	Binding affinity to human CDS2 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.