CHN2

Summary

CHN2 (chimerin 2, HGNC:1944) is a protein-coding gene on chromosome 7p14.3, encoding Beta-chimaerin (P52757). GTPase-activating protein for p21-rac.

This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that contains a phorbol-ester/diacylglycerol (DAG)-type zinc finger, a Rho-GAP domain, and an SH2 domain. The encoded protein translocates from the cytosol to the Golgi apparatus membrane upon binding by diacylglycerol (DAG). Activity of this protein is important in cell proliferation and migration, and expression changes in this gene have been detected in cancers. A mutation in this gene has also been associated with schizophrenia in men. Alternative transcript splicing and the use of alternative promoters results in multiple transcript variants.

Source: NCBI Gene 1124 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 82 total
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_004067

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1944
Approved symbol	CHN2
Name	chimerin 2
Location	7p14.3
Locus type	gene with protein product
Status	Approved
Aliases	ARHGAP3, RhoGAP3
Ensembl gene	ENSG00000106069
Ensembl biotype	protein_coding
OMIM	602857
Entrez	1124

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 19 protein_coding, 11 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000222792, ENST00000409041, ENST00000409350, ENST00000409922, ENST00000409964, ENST00000410098, ENST00000412536, ENST00000412711, ENST00000421775, ENST00000424025, ENST00000433720, ENST00000439384, ENST00000439711, ENST00000446446, ENST00000461824, ENST00000467441, ENST00000470261, ENST00000474070, ENST00000478128, ENST00000482820, ENST00000483081, ENST00000491856, ENST00000493906, ENST00000706158, ENST00000706159, ENST00000706160, ENST00000706161, ENST00000706162, ENST00000706163, ENST00000706164, ENST00000886103, ENST00000886104, ENST00000886105, ENST00000886106, ENST00000886107, ENST00000943494

RefSeq mRNA: 14 — MANE Select: NM_004067 NM_001039936, NM_001293070, NM_001293071, NM_001293072, NM_001293073, NM_001293075, NM_001293076, NM_001293077, NM_001293078, NM_001293079, NM_001293080, NM_001293081, NM_001398427, NM_004067

CCDS: CCDS47566, CCDS5420, CCDS78217, CCDS78218, CCDS78219, CCDS78220, CCDS94072, CCDS94073

Canonical transcript exons

ENST00000222792 — 13 exons

Exon	Start	End
ENSE00001643225	29400543	29400828
ENSE00001657073	29507228	29507365
ENSE00003497781	29499867	29500040
ENSE00003504153	29504744	29504821
ENSE00003583210	29495952	29496036
ENSE00003994937	29509301	29509406
ENSE00003994940	29194775	29194990
ENSE00003994941	29480279	29480356
ENSE00003994950	29512564	29514328
ENSE00003997498	29393679	29393710
ENSE00003997499	29367932	29367987
ENSE00003997500	29398373	29398486
ENSE00003997502	29354625	29354663

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 98.14.

FANTOM5 (CAGE): breadth broad, TPM avg 13.7559 / max 1023.9353, expressed in 898 samples.

FANTOM5 promoters (29 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77886	5.9651	650
77868	1.2792	535
77902	1.0306	79
77884	0.8322	252
77907	0.8159	140
77880	0.7671	188
77906	0.7667	112
77869	0.4370	214
77867	0.2243	122
77905	0.2159	78

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellum	UBERON:0002037	98.14	gold quality
cerebellar cortex	UBERON:0002129	98.13	gold quality
cerebellar hemisphere	UBERON:0002245	98.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.26	gold quality
corpus callosum	UBERON:0002336	96.67	gold quality
duodenum	UBERON:0002114	96.64	gold quality
monocyte	CL:0000576	93.69	gold quality
leukocyte	CL:0000738	92.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.85	gold quality
cortical plate	UBERON:0005343	91.71	gold quality
primary visual cortex	UBERON:0002436	91.25	gold quality
superior frontal gyrus	UBERON:0002661	90.36	gold quality
body of pancreas	UBERON:0001150	90.19	gold quality
adrenal tissue	UBERON:0018303	90.13	gold quality
prefrontal cortex	UBERON:0000451	89.64	gold quality
liver	UBERON:0002107	89.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.18	gold quality
Ammon’s horn	UBERON:0001954	88.65	gold quality
substantia nigra	UBERON:0002038	88.13	gold quality
right lobe of liver	UBERON:0001114	87.89	gold quality
small intestine	UBERON:0002108	87.63	gold quality
nucleus accumbens	UBERON:0001882	87.51	gold quality
frontal cortex	UBERON:0001870	87.35	gold quality
frontal lobe	UBERON:0016525	87.35	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.95	gold quality
brain	UBERON:0000955	86.92	gold quality
cerebral cortex	UBERON:0000956	86.90	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.67	gold quality
temporal lobe	UBERON:0001871	85.92	gold quality
amygdala	UBERON:0001876	85.90	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-81608	yes	73.70
E-MTAB-7316	yes	48.51
E-GEOD-137537	yes	21.94
E-MTAB-5061	yes	16.33
E-HCAD-35	yes	12.23
E-ANND-3	yes	11.10
E-ENAD-27	no	3.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting CHN2, 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-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-450A-1-3P	100.00	69.33	1837
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777

Literature-anchored findings (GeneRIF, showing 20)

• beta 2 chimerin has a role in rac-GAP-dependent inhibition of breast cancer cell proliferation (PMID:15863513)
• Data demonstrate that beta2-chimaerin provides a novel, diacylglycerol-dependent mechanism for Rac regulation in T cells and suggest a functional role for this protein in Rac-mediated cytoskeletal remodeling. (PMID:16352660)
• Beta2-chimaerin regulates the proliferation and migration of vascular smooth muscle cells downstream of growth factor signaling pathway implicating human atherogenesis. (PMID:16525710)
• results suggest Tyr-21 phosphorylation of beta2-chimaerin as a novel, Src-family kinase-dependent mechanism that negatively regulates beta2-chimaerin Rac-GAP activity (PMID:17560670)
• the interaction of diacylglycerol kinase gamma with the Src homology 2 and C1 domains of beta2-chimaerin is induced synergistically by Phorbol ester and hydrogen peroxide (PMID:17803461)
• Identify chimaerins as candidates for the downmodulation of Rac1 in T-lymphocytes and, in addition, uncover a novel regulatory mechanism that mediates their activation in T-cells. (PMID:18249095)
• Tyr-153 is the Lck-dependent phosphorylation residue and its phosphorylation negatively regulates membrane stabilization of beta2-chimaerin, decreasing its GAP activity to Rac (PMID:19201754)
• results suggest that beta2-chimaerin is activated by EphA receptors and mediates the EphA receptor-dependent regulation of cell migration (PMID:19306875)
• Likely digenic cause of insulin resistance and growth deficiency resulting from the combined heterozygous disruption of INSR and CHN2, implicating CHN2 for the first time as a key element of proximal insulin signaling in vivo. (PMID:19720790)
• the Rac-GAP beta2-chimaerin is negatively regulated by protein kinase Cdelta-mediated phosphorylation (PMID:20335173)
• genetic association studies in a Chinese population with type 2 diabetes: An SNP in CHN2 (rs39059) is associated with diabetic retinopathy in a Chinese population of type 2 diabetic patients. (PMID:21911749)
• A significant association of the novel rs186911567 polymorphism was found for the CHN2 gene with smoking. (PMID:23941981)
• genetic association studies in a population in Taiwan: Data suggest that an SNP in CHN2 (rs1002630) is associated with non-proliferative diabetic retinopathy in patients with diabetes type 2 in the Han Chinese population studied. (PMID:24854763)
• CHN2, ABCB1 and PPP1R9A expression on chromosome 7 is implicated in the pathogenesis of hepatosplenic T-cell lymphoma distinguishing it from other malignancies. (PMID:25057852)
• CHN2 is consistently hypermethylated and downregulated in small bowel adenocarcinoma with diagnostic potential (PMID:26315110)
• our data redefine the role of beta2-chimaerin as tumor suppressor and provide the first in vivo evidence of a dual function in breast cancer, suppressing tumor initiation but favoring tumor progression. (PMID:27058424)
• this study shows that serum chemerin is an independent risk factor of prognosis of non-small cell lung cancer patients (PMID:28160556)
• The findings indicate that differential methylation at CpG sites upstream of the CHN2 and JAK2 TSS regions are possible peripheral predictors of antidepressant treatment response. (PMID:31594917)
• Chemerin regulates formation and function of brown adipose tissue: Ablation results in increased insulin resistance with high fat challenge and aging. (PMID:34089273)
• Prenatal phthalate exposure and cord blood DNA methylation. (PMID:37120575)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	chn2	ENSDARG00000011845
mus_musculus	Chn2	ENSMUSG00000004633
rattus_norvegicus	Chn2	ENSRNOG00000009411
drosophila_melanogaster	RhoGAP5A	FBGN0029778
caenorhabditis_elegans		WBGENE00015267

Paralogs (4): SYDE2 (ENSG00000097096), SYDE1 (ENSG00000105137), CHN1 (ENSG00000128656), ARHGAP35 (ENSG00000160007)

Protein

Protein identifiers

Beta-chimaerin — P52757 (reviewed: P52757)

Alternative names: Beta-chimerin, Rho GTPase-activating protein 3

All UniProt accessions (15): P52757, A0A2X0TVW3, A0A994J535, A0A994J5D1, A0A994J5D6, A0A994J5R0, A0A994J7L4, A0A994J7Z1, A0A994J7Z5, B3VCF4, B3VCF5, B3VCF6, B7Z1V0, H7C0V3, H7C138

UniProt curated annotations — full annotation on UniProt →

Function. GTPase-activating protein for p21-rac. Insufficient expression of beta-2 chimaerin is expected to lead to higher Rac activity and could therefore play a role in the progression from low-grade to high-grade tumors.

Subcellular location. Membrane.

Tissue specificity. Highest levels in the brain and pancreas. Also expressed in the heart, placenta, and weakly in the kidney and liver. Expression is much reduced in the malignant gliomas, compared to normal brain or low-grade astrocytomas.

Activity regulation. In the inactive state, the N terminus protrudes into the active site of the Rho-GAP domain, sterically blocking Rac binding. Phospholipid binding to the Phorbol-ester/DAG-type zinc-finger/C1 domain triggers the cooperative dissociation of these interactions, allowing the N-terminus to move out of the active site and thereby activating the enzyme.

Isoforms (9)

UniProt ID	Names	Canonical?
P52757-1	Beta-2	yes
P52757-2	Beta-1
P52757-3	3
P52757-4	4, B1-CHNdel ex7p
P52757-5	5, B1-CHNdel ex9
P52757-6	6, B1-CHNdel ex7p,11
P52757-7	7
P52757-8	8
P52757-9	Beta-3

RefSeq proteins (14): NP_001035025, NP_001279999, NP_001280000, NP_001280001, NP_001280002, NP_001280004, NP_001280005, NP_001280006, NP_001280007, NP_001280008, NP_001280009, NP_001280010, NP_001385356, NP_004058* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR000980	SH2	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR017356	CHN1/CHN2	Family
IPR020454	DAG/PE-bd	Domain
IPR035840	Chimaerin_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR037860	RhoGAP_chimaerin	Domain
IPR046349	C1-like_sf	Homologous_superfamily
IPR051854	Rho-type_GAP	Family

Pfam: PF00017, PF00130, PF00620

UniProt features (56 total): helix 18, strand 11, turn 9, splice variant 8, domain 2, sequence variant 2, chain 1, sequence conflict 1, zinc finger region 1, region of interest 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1XA6	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52757-F1	85.06	0.68

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 (1): 313 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9013149	RAC1 GTPase cycle

MSigDB gene sets: 260 (showing top): BENPORATH_ES_WITH_H3K27ME3, JAEGER_METASTASIS_DN, GOBP_VESICLE_ORGANIZATION, ATACCTC_MIR202, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, ATGCAGT_MIR217, AP2_Q3, GOBP_MALE_GAMETE_GENERATION, LHX3_01, FOXD3_01, MODULE_66, WEI_MYCN_TARGETS_WITH_E_BOX, TCF4_Q5, GOBP_SECRETORY_GRANULE_ORGANIZATION

GO Biological Process (4): acrosome assembly (GO:0001675), signal transduction (GO:0007165), regulation of small GTPase mediated signal transduction (GO:0051056), positive regulation of GTPase activity (GO:0043547)

GO Molecular Function (4): GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): cytosol (GO:0005829), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	2
cellular anatomical structure	2
developmental process involved in reproduction	1
spermatid development	1
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
cytoplasm	1
cell junction	1

Protein interactions and networks

STRING

982 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHN2	CPVL	Q9H3G5	651
CHN2	DGKG	P49619	650
CHN2	AKT1	P31749	628
CHN2	CTSB	P07858	624
CHN2	FRMD3	A2A2Y4	621
CHN2	EPHA4	P54764	565
CHN2	TMED10	P49755	536
CHN2	CTSC	P53634	531
CHN2	RASA1	P20936	518
CHN2	KLC1	Q07866	479
CHN2	CTSL	P07711	477
CHN2	SEMA3F	Q13275	476
CHN2	CALM1	P02593	443
CHN2	CNDP2	Q96KP4	440
CHN2	TMTC4	Q5T4D3	431

IntAct

34 interactions, top by confidence:

A	B	Type	Score
CHN2	RAC1	psi-mi:“MI:0915”(physical association)	0.590
RAC1	CHN2	psi-mi:“MI:2364”(proximity)	0.590
RAC1	CHN2	psi-mi:“MI:0403”(colocalization)	0.590
CHN2	ANKK1	psi-mi:“MI:0915”(physical association)	0.560
NCK2	CHN2	psi-mi:“MI:0915”(physical association)	0.560
NCK1	CHN2	psi-mi:“MI:0915”(physical association)	0.560
CHN2	SENP8	psi-mi:“MI:0915”(physical association)	0.560
CHN2	SHF	psi-mi:“MI:0915”(physical association)	0.560
CHN2	ERBB3	psi-mi:“MI:0407”(direct interaction)	0.440
CHN1	CHN2	psi-mi:“MI:0915”(physical association)	0.400
PTGDS	CHN2	psi-mi:“MI:0915”(physical association)	0.400
CHN2	RANBP3	psi-mi:“MI:0915”(physical association)	0.370
TP53RK	CHN2	psi-mi:“MI:0915”(physical association)	0.370
CHN2	SMARCD1	psi-mi:“MI:0915”(physical association)	0.370
RB1	CHN2	psi-mi:“MI:0915”(physical association)	0.370
ALS2	CHN2	psi-mi:“MI:0914”(association)	0.350
ANKK1	CHN2	psi-mi:“MI:0915”(physical association)	0.000
NCK2	CHN2	psi-mi:“MI:0915”(physical association)	0.000
CHN2	NCK1	psi-mi:“MI:0915”(physical association)	0.000
CHN2	NCK2	psi-mi:“MI:0915”(physical association)	0.000
CHN2	SHF	psi-mi:“MI:0915”(physical association)	0.000
CHN2	SENP8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): RANBP3 (Two-hybrid), RB1 (Two-hybrid), SMARCD1 (Two-hybrid), TP53RK (Two-hybrid), CHN2 (Reconstituted Complex), CHN2 (Affinity Capture-MS), CHN2 (Affinity Capture-MS), CHN2 (Two-hybrid), BAG6 (Two-hybrid), SHF (Two-hybrid), NCK1 (Two-hybrid), SENP8 (Two-hybrid), ANKK1 (Two-hybrid), CHN2 (FRET), CHN2 (Affinity Capture-MS)

ESM2 similar proteins: A0A7U2QYM2, A0FKG7, A1Z6E0, A2X0Q3, A8QGZ7, A8XT88, B0X9V1, B3MDR0, B3NRP1, B4F739, B4GBN7, B4HQ29, B4J6Q0, B4KNC5, B4LMQ3, B4MR59, B4P4K8, B4QE02, D4ABP9, P0C2W1, P0CH38, P15882, P18163, P29074, P37287, P52757, Q16XV7, Q18223, Q1JPS1, Q27601, Q290L5, Q2RAX3, Q3SX24, Q6NZ03, Q6YXZ7, Q7QGL9, Q7ZXY1, Q8K3B1, Q91V57, Q9JID6

Diamond homologs: A0A0G2JTR4, A1A4S6, A2AB59, A2RUV4, A4IF90, A4II46, A6QNS3, A6X8Z5, A7KAX9, A7YY57, A8WRJ2, D3ZFJ3, E7EZG2, E7F3F0, F1LXF1, O14559, O94466, P11274, P15882, P30337, P34288, P38339, P46941, P52757, P55194, P81128, P97393, Q03070, Q08DP6, Q10164, Q12979, Q13017, Q15311, Q17QN0, Q20498, Q2M1Z3, Q3TBD2, Q3UIA2, Q52LW3, Q53QZ3

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
FYN	down-regulates	CHN2	phosphorylation
SRC	down-regulates	CHN2	phosphorylation
PRKCD	down-regulates	CHN2	phosphorylation
CHN2	“down-regulates activity”	RAC1	“gtpase-activating protein”
LCK	“down-regulates activity”	CHN2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	8
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

4221 predictions. Top by Δscore:

Variant	Effect	Δscore
7:29194988:CCGG:C	donor_loss	1.0000
7:29194989:CGG:C	donor_loss	1.0000
7:29194990:GGTG:G	donor_loss	1.0000
7:29194992:T:A	donor_loss	1.0000
7:29393711:G:GG	donor_gain	1.0000
7:29398371:A:AG	acceptor_gain	1.0000
7:29398372:G:GG	acceptor_gain	1.0000
7:29398483:TCAGG:T	donor_loss	1.0000
7:29398487:G:GG	donor_gain	1.0000
7:29398487:GTGA:G	donor_loss	1.0000
7:29398488:T:A	donor_loss	1.0000
7:29480964:GGGT:G	donor_gain	1.0000
7:29504739:A:AG	acceptor_gain	1.0000
7:29504739:AACAG:A	acceptor_gain	1.0000
7:29504741:CAGG:C	acceptor_loss	1.0000
7:29504742:A:AC	acceptor_loss	1.0000
7:29504742:A:AG	acceptor_gain	1.0000
7:29504742:AG:A	acceptor_gain	1.0000
7:29504743:G:GA	acceptor_gain	1.0000
7:29504743:GG:G	acceptor_gain	1.0000
7:29504743:GGA:G	acceptor_gain	1.0000
7:29504743:GGATT:G	acceptor_gain	1.0000
7:29504818:AGAGG:A	donor_loss	1.0000
7:29504819:GAG:G	donor_gain	1.0000
7:29504822:G:GA	donor_loss	1.0000
7:29504822:G:GG	donor_gain	1.0000
7:29504823:T:A	donor_loss	1.0000
7:29507362:GCAA:G	donor_gain	1.0000
7:29507363:CAA:C	donor_gain	1.0000
7:29507363:CAAG:C	donor_loss	1.0000

AlphaMissense

3089 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:29354651:T:A	W26R	1.000
7:29354651:T:C	W26R	1.000
7:29398477:T:C	L94P	1.000
7:29400610:T:C	F120L	1.000
7:29400612:T:A	F120L	1.000
7:29400612:T:G	F120L	1.000
7:29400629:T:C	L126P	1.000
7:29480345:C:G	H215D	1.000
7:29480352:T:C	F217S	1.000
7:29495961:T:C	F222L	1.000
7:29495962:T:C	F222S	1.000
7:29495963:C:A	F222L	1.000
7:29495963:C:G	F222L	1.000
7:29495978:G:C	W227C	1.000
7:29495978:G:T	W227C	1.000
7:29495979:T:A	C228S	1.000
7:29495979:T:C	C228R	1.000
7:29495980:G:A	C228Y	1.000
7:29495980:G:C	C228S	1.000
7:29495980:G:T	C228F	1.000
7:29495981:T:G	C228W	1.000
7:29495988:T:A	C231S	1.000
7:29495988:T:C	C231R	1.000
7:29495989:G:A	C231Y	1.000
7:29495989:G:C	C231S	1.000
7:29495989:G:T	C231F	1.000
7:29495990:T:G	C231W	1.000
7:29495997:T:C	F234L	1.000
7:29495998:T:C	F234S	1.000
7:29495999:C:A	F234L	1.000

dbSNP variants (sampled 300 via entrez): RS1000015142 (7:29175232 T>C), RS1000019046 (7:29304346 A>T), RS1000023597 (7:29337804 C>A,T), RS1000054070 (7:29353077 GC>G), RS1000057646 (7:29358640 A>G), RS1000063035 (7:29258631 T>C), RS1000063784 (7:29199392 T>G), RS1000065102 (7:29482650 C>G), RS1000068472 (7:29190550 A>C), RS1000076070 (7:29460842 A>G), RS1000092046 (7:29304223 A>C,G), RS1000094977 (7:29225111 G>A), RS1000102254 (7:29280601 C>A), RS1000102871 (7:29453500 A>G), RS1000106641 (7:29321453 G>A)

Disease associations

OMIM: gene MIM:602857 | disease phenotypes: MIM:181500, MIM:618184

GenCC curated gene-disease

Mondo (3): schizophrenia (MONDO:0005090), primary ovarian failure (MONDO:0005387), neuropathy, congenital hypomyelinating, 2 (MONDO:0020765)

Orphanet (2): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001762_157	Obesity-related traits	6.000000e-06
GCST001762_704	Obesity-related traits	3.000000e-06
GCST002211_1	Psychosis (atypical)	2.000000e-07
GCST003772_11	Loneliness (linear analysis)	7.000000e-06
GCST004136_12	Methadone dose in opioid dependence	9.000000e-06
GCST004727_2	Facial emotion recognition	3.000000e-06
GCST004728_1	Facial emotion recognition (angry faces)	4.000000e-06
GCST004730_3	Facial emotion recognition (sad faces)	4.000000e-06
GCST004862_121	Itch intensity from mosquito bite adjusted by bite size	5.000000e-06
GCST005331_5	CSF tryptophan concentration in tuberculous meningitis	3.000000e-06
GCST006218_95	Erosive tooth wear (severe vs non-severe)	9.000000e-06
GCST006226_20	Erosive tooth wear (severe vs none or mild)	5.000000e-06
GCST008161_124	Waist circumference adjusted for body mass index	8.000000e-06
GCST009532_5	Circulating leptin levels in high cardiovascular risk	2.000000e-07
GCST010244_187	Triglyceride levels	3.000000e-08
GCST010818_7	Gut microbiota alpha diversity (PD_whole_tree index)	3.000000e-06

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight
EFO:0005106	body composition measurement
EFO:0007865	loneliness measurement
EFO:0007907	methadone dose measurement
EFO:0008329	facial emotion recognition measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0008534	tryptophan measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0005000	leptin measurement
EFO:0004530	triglyceride measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4504 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.82	Ki	1500	nM	CHEMBL275750

PubChem BioAssay actives

1 with measured affinity, of 1 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
[2-[(2R,4R)-4-[(1R,3S,4S,5S)-3-(benzylamino)-4-hydroxy-5-methylcyclohexyl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]-2-oxoethyl] pentanoate	41905: Binding affinity towards beta chimerin	ki	1.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	6
Valproic Acid	affects cotreatment, increases expression	5
Aflatoxin B1	affects expression, decreases expression, decreases methylation	4
trichostatin A	affects cotreatment, increases expression	3
Acetaminophen	decreases expression, increases expression	2
Estradiol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
GSK-J4	increases expression	1
fluorene-9-bisphenol	increases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects methylation, affects cotreatment	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	affects methylation	1
dibenzo(a,l)pyrene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Sunitinib	decreases expression	1
Fulvestrant	affects methylation, increases methylation, affects cotreatment	1
Vorinostat	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
CHEMBL653433	Binding	Binding affinity towards beta chimerin	Molecular models of N-benzyladriamycin-14-valerate (AD 198) in complex with the phorbol ester-binding C1b domain of protein kinase C-delta. — J Med Chem

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