CDR2

Summary

CDR2 (cerebellar degeneration related protein 2, HGNC:1799) is a protein-coding gene on chromosome 16p12.2, encoding Cerebellar degeneration-related protein 2 (Q01850).

Predicted to be located in cytoplasm.

Source: NCBI Gene 1039 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 159 total — 23 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_001802

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1799
Approved symbol	CDR2
Name	cerebellar degeneration related protein 2
Location	16p12.2
Locus type	gene with protein product
Status	Approved
Aliases	CDR62, Yo
Ensembl gene	ENSG00000140743
Ensembl biotype	protein_coding
OMIM	117340
Entrez	1039

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000268383, ENST00000561630, ENST00000563573, ENST00000564542, ENST00000567010, ENST00000567406, ENST00000569045, ENST00000961655

RefSeq mRNA: 1 — MANE Select: NM_001802 NM_001802

CCDS: CCDS32404

Canonical transcript exons

ENST00000268383 — 5 exons

Exon	Start	End
ENSE00001302197	22345936	22347823
ENSE00001310999	22374231	22374619
ENSE00003529119	22349701	22349849
ENSE00003570788	22364902	22365014
ENSE00003680803	22349279	22349443

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.0423 / max 156.2980, expressed in 1774 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156755	15.9181	1773
156754	0.1242	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.93	gold quality
pigmented layer of retina	UBERON:0001782	97.56	gold quality
retina	UBERON:0000966	97.53	gold quality
oocyte	CL:0000023	97.01	gold quality
jejunal mucosa	UBERON:0000399	95.45	gold quality
choroid plexus epithelium	UBERON:0003911	95.11	gold quality
calcaneal tendon	UBERON:0003701	94.86	gold quality
sperm	CL:0000019	94.51	gold quality
cartilage tissue	UBERON:0002418	93.43	gold quality
male germ cell	CL:0000015	92.90	gold quality
left lobe of thyroid gland	UBERON:0001120	92.73	gold quality
thyroid gland	UBERON:0002046	92.62	gold quality
right lobe of thyroid gland	UBERON:0001119	92.48	gold quality
mucosa of stomach	UBERON:0001199	92.18	gold quality
adult organism	UBERON:0007023	92.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.93	gold quality
left testis	UBERON:0004533	91.60	gold quality
cauda epididymis	UBERON:0004360	91.53	gold quality
renal glomerulus	UBERON:0000074	91.46	gold quality
metanephric glomerulus	UBERON:0004736	91.40	gold quality
islet of Langerhans	UBERON:0000006	91.36	gold quality
right testis	UBERON:0004534	91.13	gold quality
urinary bladder	UBERON:0001255	90.96	gold quality
popliteal artery	UBERON:0002250	90.83	gold quality
tibial artery	UBERON:0007610	90.83	gold quality
testis	UBERON:0000473	90.59	gold quality
aorta	UBERON:0000947	90.57	gold quality
duodenum	UBERON:0002114	90.53	gold quality
ascending aorta	UBERON:0001496	90.48	gold quality
nephron tubule	UBERON:0001231	90.44	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.50

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
AURKA	Activation
CENPE	Activation
NUF2	Activation
TTK	Activation

Upstream regulators (CollecTRI, top): MYRF

miRNA regulators (miRDB)

66 targeting CDR2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-223-3P	99.99	70.14	1140
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-3692-3P	99.98	70.27	2139
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4804-3P	99.65	67.78	866

Literature-anchored findings (GeneRIF, showing 15)

• Identifies c-Myc interaction with cdr2 by co-IP and co-localization in cytoplasm of cerebellar Purkinje neurons. Sera from 6/6 patients with cdr2 autoantibodies and paraneoplastic cerebellar degeneration block this interaction. (PMID:10465786)
• In patients with paraneoplastic cerebellar degeneration and anti-Yo antibodies, IFN-gamma-secreting cell responses towards Cdr2 isoforms are not detected, suggesting a limited role for cytotoxic T lymphocyte-mediated tumor immunity in this patient group. (PMID:15081253)
• Mycoplasma fermentans, in infecting human B cells, generates a Mycoplasma component that interacts with CD21, which is involved in B cell proliferation. (PMID:16054780)
• Cdr2 protein strongly accumulates in papillary renal cell carcinoma, attenuates the HIF response to tumor hypoxia and may become of diagnostic importance as novel renal tumor marker. (PMID:19581925)
• The association between Yo and CCDC104 antibodies in paraneoplastic neurological syndromes may indicate functional similarities. (PMID:19680650)
• The results suggest that Yo antibodies are not only related to the expression of CDR2 alone, but also to immune dysregulation. (PMID:21080165)
• This study shows a very high frequency of HER2 overexpression in breast cancers in patients with anti-Yo-associated paraneoplastic cerebellar degeneration. (PMID:22351748)
• Onconeuronal antigen Cdr2 correlates with HIF prolyl-4-hydroxylase PHD1 and worse prognosis in renal cell carcinoma. (PMID:23531419)
• the role of cdr2 in experimental models of Parkinson’s disease, is reported. (PMID:27253404)
• Both cerebellar degeneration related protein 2 (CDR2) and cerebellar degeneration-related antigen CDR2L (CDR2L) are more widely expressed than previously thought, both in normal and cancerous tissues. (PMID:28710511)
• Paraneoplastic cerebellar degenerations with anti-Yo antibodies (Yo-PCD) tumors differed from the 116 control tumors by more abundant T and B cells infiltration occasionally organized in tertiary lymphoid structures harboring CDR2L protein deposits. 65% of Yo-PCD tumors cohort presented at least one somatic mutation in CDR2 and CDR2L with a predominance of missense mutations. (PMID:29299667)
• Our data pinpointed the enrichment of acquired immune response, particularly high density of CD8+ lymphocytes, and high-level expression of CDR-related antigens in anti-Yo paraneoplastic cerebellar degeneration ovarian tumours. (PMID:29899393)
• MicroRNA 452 regulates ASB8, NOL8, and CDR2 expression in colorectal cancer cells. (PMID:33398662)
• A cerebellar degeneration-related protein 2-like cell-based assay for anti-Yo detection in patients with paraneoplastic cerebellar degeneration. (PMID:36912432)
• Identifies cdr2-specific T cells in patients with paraneoplastic cerebellar degeneration; cells are evident by standard CTL, and by cross-presentation of apoptotic cdr2-expressing cells. (PMID:9809559)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdr2a	ENSDARG00000035952
danio_rerio	cdr2b	ENSDARG00000037359
mus_musculus	Cdr2	ENSMUSG00000030878
rattus_norvegicus	Cdr2	ENSRNOG00000017260
drosophila_melanogaster	Cen	FBGN0032876

Paralogs (1): CDR2L (ENSG00000109089)

Protein

Protein identifiers

Cerebellar degeneration-related protein 2 — Q01850 (reviewed: Q01850)

Alternative names: Major Yo paraneoplastic antigen, Paraneoplastic cerebellar degeneration-associated antigen

All UniProt accessions (6): Q01850, H3BN65, H3BQS4, H3BTR1, H3BU23, H3BUE0

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the CDR2 family.

RefSeq proteins (1): NP_001793* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026079	CDR2	Family

UniProt features (8 total): coiled-coil region 3, sequence conflict 2, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01850-F1	74.84	0.48

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 (1): 311

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 231 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_TOLERANCE_INDUCTION, BROWNE_HCMV_INFECTION_8HR_UP, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GENTILE_RESPONSE_CLUSTER_D3, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, WANG_LMO4_TARGETS_DN, FISCHER_G2_M_CELL_CYCLE, GENTILE_UV_HIGH_DOSE_DN, GOBP_ALPHA_BETA_T_CELL_ACTIVATION

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	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
CDR2	BRSK1	Q8TDC3	778
CDR2	ITIH4	Q14624	771
CDR2	MYC	P01106	748
CDR2	WEE1	P30291	718
CDR2	IGHV4-38-2	P0DP08	715
CDR2	DUSP5	Q16690	665
CDR2	CD1D	P15813	651
CDR2	CD19	P15391	613
CDR2	DUSP1	P28562	610
CDR2	SUCO	Q9UBS9	610
CDR2	IGLL5	B9A064	594
CDR2	CD4	P01730	577
CDR2	TRDV1	A0A1B0GX56	571
CDR2	BRSK2	Q8IWQ3	571
CDR2	EXOC1	Q9NV70	554

IntAct

371 interactions, top by confidence:

A	B	Type	Score
C4orf46	CDR2	psi-mi:“MI:0915”(physical association)	0.870
CDR2	TCHP	psi-mi:“MI:0915”(physical association)	0.790
TCHP	CDR2	psi-mi:“MI:0915”(physical association)	0.790
COX5B	CDR2	psi-mi:“MI:0915”(physical association)	0.780
CDR2	TXLNA	psi-mi:“MI:0915”(physical association)	0.780
CHIC2	CDR2	psi-mi:“MI:0915”(physical association)	0.780
CDR2	COX5B	psi-mi:“MI:0915”(physical association)	0.780
CDR2	CHIC2	psi-mi:“MI:0915”(physical association)	0.780
CDR2	KTN1	psi-mi:“MI:0914”(association)	0.730
PSMD7	PSMD11	psi-mi:“MI:0914”(association)	0.730
CDR2	TRIM23	psi-mi:“MI:0915”(physical association)	0.720
PKN1	CDR2	psi-mi:“MI:0915”(physical association)	0.720
FAM161A	CDR2	psi-mi:“MI:0915”(physical association)	0.720
C1orf216	CDR2	psi-mi:“MI:0915”(physical association)	0.720
CCHCR1	CDR2	psi-mi:“MI:0915”(physical association)	0.720
SMARCE1	CDR2	psi-mi:“MI:0915”(physical association)	0.720
CDR2	LENG1	psi-mi:“MI:0915”(physical association)	0.720
SCNM1	CDR2	psi-mi:“MI:0915”(physical association)	0.720
ENKD1	CDR2	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (200): CDR2 (Biochemical Activity), CDR2 (Two-hybrid), COX5B (Two-hybrid), KIFC3 (Two-hybrid), PKN1 (Two-hybrid), SMARCE1 (Two-hybrid), TTR (Two-hybrid), EIF4E2 (Two-hybrid), HDAC4 (Two-hybrid), TMCC2 (Two-hybrid), MRPL28 (Two-hybrid), CHIC2 (Two-hybrid), RSPH14 (Two-hybrid), AMOTL2 (Two-hybrid), CCHCR1 (Two-hybrid)

ESM2 similar proteins: A0PJP4, A0PJT0, A2VDP1, A4IFK7, D3ZUQ0, E9PSL7, O14578, O75665, P0C219, P49025, P97817, Q01850, Q0IHE5, Q14BN4, Q17QG3, Q28623, Q3LGD4, Q3SYW5, Q3URD3, Q3V079, Q4R3X1, Q4R7Y8, Q58A65, Q5DTM8, Q5EBL4, Q5R5R4, Q5VTR2, Q5ZJA3, Q5ZLS3, Q62172, Q62796, Q68CZ1, Q6AYA0, Q6DFC2, Q6DH86, Q6NRH3, Q6ZUS6, Q7Z3E2, Q86VS8, Q8BR07

Diamond homologs: A2A6T1, P97817, Q01850, Q5ZJA3, Q6NZT2, Q86X02

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CDR2	“up-regulates activity”	MYC	binding
CDR2	“up-regulates quantity by expression”	CENPE	“transcriptional regulation”
CDR2	“up-regulates quantity by expression”	TTK	“transcriptional regulation”
CDR2	“up-regulates quantity by expression”	NUF2	“transcriptional regulation”
CDR2	“up-regulates quantity by expression”	AURKA	“transcriptional regulation”
APC-c	“down-regulates quantity by destabilization”	CDR2	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	8
Uncertain significance	107
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1330168	GRCh37/hg19 16p12.2(chr16:21964695-22376385)x1	Pathogenic
1330186	GRCh37/hg19 16p12.2(chr16:21781158-22825913)x1	Pathogenic
1330200	GRCh37/hg19 16p12.2(chr16:21869250-22524572)x1	Pathogenic
1330202	GRCh37/hg19 16p12.2(chr16:21747532-22824584)x1	Pathogenic
1341992	GRCh37/hg19 16p12.2(chr16:21837492-22407931)x1	Pathogenic
1684662	NC_000016.10:g.21936825_22429665del	Pathogenic
1703589	GRCh37/hg19 16p12.2(chr16:21801889-22431357)	Pathogenic
1703608	GRCh37/hg19 16p12.2(chr16:21817921-22710614)	Pathogenic
1808703	GRCh37/hg19 16p12.2(chr16:21761405-22710614)x1	Pathogenic
1808745	GRCh37/hg19 16p12.2(chr16:21931248-22431357)x1	Pathogenic
221993	GRCh37/hg19 16p12.2(chr16:21771016-22409463)x1	Pathogenic
3063414	GRCh37/hg19 16p12.2(chr16:21946522-22710614)x1	Pathogenic
3063437	GRCh37/hg19 16p12.2(chr16:21801889-22431357)x1	Pathogenic
3242336	GRCh37/hg19 16p12.2(chr16:21805656-22441329)x1	Pathogenic
393797	GRCh37/hg19 16p12.2(chr16:21986752-22407872)x1	Pathogenic
564299	GRCh37/hg19 16p12.2(chr16:21801889-22431357)x1	Pathogenic
564303	GRCh37/hg19 16p12.2(chr16:21841455-22710614)x1	Pathogenic
564304	GRCh37/hg19 16p12.2(chr16:21931247-22710614)x1	Pathogenic
625599	GRCh37/hg19 16p12.2(chr16:21976691-22386881)	Pathogenic
625686	GRCh37/hg19 16p12.2(chr16:21964083-22386845)	Pathogenic
815810	GRCh37/hg19 16p12.2(chr16:21576802-22431357)x1	Pathogenic
988930	GRCh37/hg19 16p12.2(chr16:21946438-22441358)x1	Pathogenic
997048	GRCh37/hg19 16p12.2(chr16:21951379-22407931)	Pathogenic
1879352	GRCh37/hg19 16p12.2(chr16:21780595-22385630)x1	Likely pathogenic
3024602	GRCh37/hg19 16p12.2(chr16:21964745-22456395)x1	Likely pathogenic
4755355	GRCh38/hg38 16p12.2(chr16:21828019-22541459)x1	Likely pathogenic
4820250	GRCh37/hg19 16p12.2(chr16:21801488-22710614)x1	Likely pathogenic
545194	NC_000016.10:g.(?21928119)(22428075_?)del	Likely pathogenic
625577	GRCh37/hg19 16p12.2(chr16:21943463-22702769)	Likely pathogenic
625677	GRCh37/hg19 16p12.2(chr16:21973828-22361172)	Likely pathogenic

SpliceAI

589 predictions. Top by Δscore:

Variant	Effect	Δscore
16:22347819:AGTGT:A	acceptor_gain	1.0000
16:22347820:GTGT:G	acceptor_gain	1.0000
16:22347821:TGT:T	acceptor_gain	1.0000
16:22347822:GT:G	acceptor_gain	1.0000
16:22347822:GTC:G	acceptor_loss	1.0000
16:22347823:TC:T	acceptor_loss	1.0000
16:22347824:C:CC	acceptor_gain	1.0000
16:22347824:CTAG:C	acceptor_loss	1.0000
16:22349277:A:AC	donor_gain	1.0000
16:22349278:C:CC	donor_gain	1.0000
16:22349278:CTGG:C	donor_gain	1.0000
16:22349696:TTTA:T	donor_loss	1.0000
16:22349697:TTA:T	donor_loss	1.0000
16:22349698:TACC:T	donor_loss	1.0000
16:22349700:C:CA	donor_loss	1.0000
16:22349846:GATA:G	acceptor_gain	1.0000
16:22349847:ATA:A	acceptor_gain	1.0000
16:22349848:TA:T	acceptor_gain	1.0000
16:22349850:C:CC	acceptor_gain	1.0000
16:22364897:ATTAC:A	donor_loss	1.0000
16:22364898:TTAC:T	donor_loss	1.0000
16:22364899:TACCT:T	donor_loss	1.0000
16:22364901:C:CG	donor_loss	1.0000
16:22364905:AATTT:A	donor_gain	1.0000
16:22365015:C:CC	acceptor_gain	1.0000
16:22374226:CTCAC:C	donor_loss	1.0000
16:22374227:TCACC:T	donor_loss	1.0000
16:22374228:CACCT:C	donor_loss	1.0000
16:22374229:ACCT:A	donor_loss	1.0000
16:22374230:CCTTG:C	donor_gain	1.0000

AlphaMissense

2986 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:22349441:A:G	L115P	0.997
16:22349420:A:G	L122P	0.996
16:22349761:A:G	L94P	0.996
16:22349771:C:G	A91P	0.996
16:22349845:A:G	L66P	0.996
16:22349399:A:G	L129P	0.995
16:22349821:C:G	R74P	0.995
16:22364972:C:G	R41P	0.995
16:22347052:A:C	F426L	0.993
16:22347052:A:T	F426L	0.993
16:22347054:A:G	F426L	0.993
16:22347263:A:G	L356P	0.993
16:22364981:A:G	L38S	0.993
16:22364991:C:G	G35R	0.993
16:22364991:C:T	G35R	0.993
16:22365000:C:G	A32P	0.993
16:22365002:G:T	A31D	0.993
16:22365011:A:G	L28P	0.992
16:22347040:A:C	F430L	0.991
16:22347040:A:T	F430L	0.991
16:22347042:A:G	F430L	0.991
16:22364991:C:A	G35W	0.991
16:22364993:A:G	L34P	0.991
16:22349740:A:G	L101P	0.990
16:22349824:A:G	L73P	0.990
16:22364978:A:G	L39P	0.990
16:22365005:A:G	L30P	0.990
16:22349782:A:G	L87S	0.989
16:22349801:C:G	A81P	0.989
16:22364960:A:G	L45S	0.989

dbSNP variants (sampled 300 via entrez): RS1000024422 (16:22371646 A>G), RS1000084435 (16:22374421 C>A,G,T), RS1000161068 (16:22354360 G>T), RS1000289175 (16:22374586 C>A,G), RS1000297932 (16:22354685 C>T), RS1000328774 (16:22368652 T>A), RS1000344359 (16:22361146 T>G), RS1000428055 (16:22361669 TA>T), RS1000691816 (16:22373880 A>G), RS1000716787 (16:22355309 G>A,T), RS1000806140 (16:22347914 T>C,G), RS1000841220 (16:22361540 G>T), RS1000891370 (16:22373494 T>A,C), RS1000900920 (16:22366721 G>A), RS1000948106 (16:22361947 G>C)

Disease associations

OMIM: gene MIM:117340 | disease phenotypes: MIM:136570, MIM:611913, MIM:181500

GenCC curated gene-disease

Mondo (3): chromosome 16p12.1 deletion syndrome, 520kb (MONDO:0007631), proximal 16p11.2 microdeletion syndrome (MONDO:0012756), schizophrenia (MONDO:0005090)

Orphanet (2): Proximal 16p11.2 microdeletion syndrome (Orphanet:261197), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012490_285	Femur bone mineral density x serum urate levels interaction	4.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C579850	16p11.2 Deletion Syndrome (supp.)
C565001	Fragile Site 16p12 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066280 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.96	Kd	109.2	nM	CHEMBL5653589
6.52	ED50	303	nM	CHEMBL5653589
5.03	Kd	9436	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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	2148055: Binding affinity to human CDR2 incubated for 45 mins by Kinobead based pull down assay	kd	0.1092	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148055: Binding affinity to human CDR2 incubated for 45 mins by Kinobead based pull down assay	kd	9.4363	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, affects expression, decreases expression	3
Valproic Acid	affects cotreatment, increases expression	3
Cyclosporine	increases expression	3
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
sodium arsenate	increases abundance, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
pentabromodiphenyl ether	increases expression	1
corosolic acid	decreases expression	1
K 7174	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Dexamethasone	decreases expression, affects cotreatment	1
Estradiol	increases expression	1
Hydralazine	increases expression, affects cotreatment	1
Indomethacin	affects cotreatment, decreases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Dihydrotestosterone	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Dronabinol	decreases expression	1
Thiram	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
CHEMBL5651097	Binding	Binding affinity to human CDR2 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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1AD	Ubigene OVCAR-3 CDR2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety