STARD13

Summary

STARD13 (StAR related lipid transfer domain containing 13, HGNC:19164) is a protein-coding gene on chromosome 13q13.1, encoding StAR-related lipid transfer protein 13 (Q9Y3M8). GTPase-activating protein for RhoA, and perhaps for Cdc42.

This gene encodes a protein which contains an N-terminal sterile alpha motif (SAM) for protein-protein interactions, followed by an ATP/GTP-binding motif, a GTPase-activating protein (GAP) domain, and a C-terminal STAR-related lipid transfer (START) domain. It may be involved in regulation of cytoskeletal reorganization, cell proliferation, and cell motility, and acts as a tumor suppressor in hepatoma cells. The gene is located in a region of chromosome 13 that is associated with loss of heterozygosity in hepatocellular carcinomas. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 90627 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 181 total
• MANE Select transcript: NM_178006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19164
Approved symbol	STARD13
Name	StAR related lipid transfer domain containing 13
Location	13q13.1
Locus type	gene with protein product
Status	Approved
Aliases	GT650, DLC2, ARHGAP37
Ensembl gene	ENSG00000133121
Ensembl biotype	protein_coding
OMIM	609866
Entrez	90627

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000255486, ENST00000336934, ENST00000344312, ENST00000399365, ENST00000439831, ENST00000487412, ENST00000491333, ENST00000498019, ENST00000567873, ENST00000925947

RefSeq mRNA: 5 — MANE Select: NM_178006 NM_001243476, NM_001411014, NM_052851, NM_178006, NM_178007

CCDS: CCDS91800, CCDS9348, CCDS9349, CCDS9350

Canonical transcript exons

ENST00000336934 — 14 exons

Exon	Start	End
ENSE00000907341	33106758	33106934
ENSE00000907343	33109873	33110090
ENSE00000907345	33110686	33110907
ENSE00000907347	33111778	33111892
ENSE00000907348	33112721	33112931
ENSE00000907350	33118065	33118263
ENSE00000907352	33126081	33126240
ENSE00000907353	33127373	33127546
ENSE00000907354	33128929	33130289
ENSE00003370084	33103137	33105710
ENSE00003528361	33285470	33285755
ENSE00003565495	33167551	33167622
ENSE00003576913	33142310	33142373
ENSE00003615488	33165337	33165418

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 96.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.2667 / max 326.7407, expressed in 1562 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136731	10.2003	1388
136733	1.9616	840
136736	1.5312	459
136726	1.2863	246
136727	0.3652	145
136723	0.3463	117
136732	0.2040	81
136725	0.0904	36
136729	0.0746	36
136728	0.0556	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.75	gold quality
tibial nerve	UBERON:0001323	93.99	gold quality
adrenal tissue	UBERON:0018303	93.80	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.95	gold quality
colonic epithelium	UBERON:0000397	90.34	gold quality
dorsal root ganglion	UBERON:0000044	90.06	gold quality
trigeminal ganglion	UBERON:0001675	88.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.63	gold quality
lower esophagus	UBERON:0013473	88.58	gold quality
right lung	UBERON:0002167	88.10	gold quality
thyroid gland	UBERON:0002046	87.80	gold quality
left lobe of thyroid gland	UBERON:0001120	87.65	gold quality
right lobe of thyroid gland	UBERON:0001119	87.59	gold quality
calcaneal tendon	UBERON:0003701	87.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.23	gold quality
stromal cell of endometrium	CL:0002255	87.01	gold quality
sigmoid colon	UBERON:0001159	86.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.73	gold quality
tendon	UBERON:0000043	86.30	gold quality
myometrium	UBERON:0001296	86.30	gold quality
tibia	UBERON:0000979	86.23	gold quality
popliteal artery	UBERON:0002250	86.23	gold quality
tibial artery	UBERON:0007610	86.21	gold quality
decidua	UBERON:0002450	86.15	gold quality
left coronary artery	UBERON:0001626	85.75	gold quality
body of uterus	UBERON:0009853	85.70	gold quality
endocervix	UBERON:0000458	85.64	gold quality
aorta	UBERON:0000947	85.52	gold quality
medial globus pallidus	UBERON:0002477	85.42	gold quality
coronary artery	UBERON:0001621	85.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	32.92
E-ANND-3	yes	12.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MITF

miRNA regulators (miRDB)

35 targeting STARD13, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-4669	97.94	62.71	224
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-5694	97.06	67.70	682

Literature-anchored findings (GeneRIF, showing 24)

• has GAP activity specific for RhoA and Cdc42; inhibits the Rho mediated assembly of actin stress fibers in cultured cells and is underexpressed in hepatocellular carcinoma tissues (PMID:12531887)
• underexpression is associated with poor prognosis in patients with hepatocellular carcinoma (PMID:18651974)
• DLC2 inhibits the activity of Raf-1-ERK1/2-p70S6K via its RhoGAP function, resulting in the suppression of cell growth. (PMID:20629949)
• Authors detected an increase in p-ERK in StarD13 knockdown cells, uncovering a potential link between Rho GTPases and ERK activation. (PMID:22614672)
• role of miR-125b in pro-metastasis by targeting STARD13 (PMID:22693547)
• RhoGAP protein Stard13 is an essential regulator of pancreas tissue architecture in the mammalian embryo; Stard13 acts by regulating Rho signalling spatially and temporally during pancreas development. (PMID:23175628)
• In the present review, we discuss the family of RhoGTPases, their regulation and their RhoGAPs, focusing mainly on STARD13. [review] (PMID:23316797)
• The present study further describes the role of StarD13 as a tumor suppressor as well as a Rho GAP. (PMID:24253896)
• Importance of the regulation of RhoA activity in focal adhesions of astrocytoma cells and StarD13 is a GAP playing a major role in this process. (PMID:24333506)
• Study describes STARD13 as a tumor suppressor playing a positive role in cancer motility. (PMID:24627003)
• Dimerization of DLC2 was required for its interaction with GKAP, which, in turn, potentiated GKAP self-association. (PMID:24938595)
• meta-analysis of two Caucasian cohorts did not show an association between five aneurysm associated loci and sporadic brain Arteriovenous malformations. (PMID:25053769)
• The tumor suppressor DLC2 and Kif1B are central components of a signaling network that guides spindle positioning, cell-cell adhesion and mitotic fidelity. (PMID:25518808)
• Low STARD13 expression is associated with metastasis of breast cancer. (PMID:26985770)
• miR-125b functions as an oncogene in gastric cancer and represents a new potential therapeutic target for gastric cancer. (PMID:27220320)
• Study elucidated StarD13 messenger RNA as a Competitive endogenous messenger RNA (ceRNA) in regulating migration and invasion of breast cancer cells. MicroRNA-125b was identified to induce metastasis of MCF-7 cells and bind with both StarD13 3’UTR and TP53INP1 3’UTR. Therefore, a ceRNA interaction between StarD13 and TP53INP1 mediated by competitively binding to miR-125b was indicated. (PMID:29146309)
• activation of STARD13-correlated ceRNA network was negatively correlated with YAP/TAZ activity in breast cancer. (PMID:29848346)
• DLC2 is abundantly expressed in hepatocellular carcinoma, in which the DLC2 gene is diploid. (PMID:30827083)
• Differential regulation of rho GTPases during lung adenocarcinoma migration and invasion reveals a novel role of the tumor suppressor StarD13 in invadopodia regulation. (PMID:32900380)
• Identifying Cancer-Relevant Mutations in the DLC START Domain Using Evolutionary and Structure-Function Analyses. (PMID:33142932)
• StarD13 differentially regulates migration and invasion in prostate cancer cells. (PMID:33420961)
• LINC01089 suppresses lung adenocarcinoma cell proliferation and migration via miR-301b-3p/STARD13 axis. (PMID:34281560)
• StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42. (PMID:34958986)
• MicroRNA-9-5p Facilitates Lung Adenocarcinoma Cell Malignant Progression via Targeting STARD13. (PMID:35119587)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stard13a	ENSDARG00000079542
danio_rerio	stard13b	ENSDARG00000098954
mus_musculus	Stard13	ENSMUSG00000016128
rattus_norvegicus	Stard13	ENSRNOG00000001090
caenorhabditis_elegans		WBGENE00001559

Paralogs (2): STARD8 (ENSG00000130052), DLC1 (ENSG00000164741)

Protein

Protein identifiers

StAR-related lipid transfer protein 13 — Q9Y3M8 (reviewed: Q9Y3M8)

Alternative names: 46H23.2, Deleted in liver cancer 2 protein, Rho GTPase-activating protein, START domain-containing protein 13

All UniProt accessions (4): B2R789, Q9Y3M8, H3BRG5, H3BUW7

UniProt curated annotations — full annotation on UniProt →

Function. GTPase-activating protein for RhoA, and perhaps for Cdc42. May be involved in regulation of cytoskeletal reorganization, cell proliferation and cell motility. Acts a tumor suppressor in hepatocellular carcinoma cells.

Subunit / interactions. Homodimer. Interacts with TAX1BP1.

Subcellular location. Cytoplasm. Membrane. Mitochondrion membrane. Lipid droplet.

Tissue specificity. Ubiquitously expressed. Underexpressed in hepatocellular carcinoma cells and some breast cancer cell lines.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9Y3M8-1	1, DLC2alpha	yes
Q9Y3M8-2	2, DLC2beta
Q9Y3M8-3	3, DLC2gamma
Q9Y3M8-4	4
Q9Y3M8-5	5

RefSeq proteins (5): NP_001230405, NP_001397943, NP_443083, NP_821074, NP_821075 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR001660	SAM	Domain
IPR002913	START_lipid-bd_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR023393	START-like_dom_sf	Homologous_superfamily

Pfam: PF00620, PF01852, PF07647

UniProt features (54 total): strand 13, helix 10, splice variant 5, compositionally biased region 4, sequence variant 4, domain 3, mutagenesis site 3, sequence conflict 3, region of interest 3, modified residue 2, turn 2, chain 1, site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2PSO	X-RAY DIFFRACTION	2.8
2H80	SOLUTION NMR
2JW2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3M8-F1	66.01	0.38

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

Post-translational modifications (2): 1, 411

Mutagenesis-validated functional residues (3):

Position	Phenotype
699	loss of rhogap activity.
736	loss of rhogap activity.
740	loss of rhogap activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 288 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_NEGATIVE_REGULATION_OF_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, ATACCTC_MIR202, AREB6_03, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, TATTATA_MIR374, AP4_Q6, TAL1ALPHAE47_01, GGGTGGRR_PAX4_03, CHANDRAN_METASTASIS_DN, CAGCTG_AP4_Q5, chr13q13

GO Biological Process (9): signal transduction (GO:0007165), actin cytoskeleton organization (GO:0030036), regulation of Rho protein signal transduction (GO:0035023), endothelial cell migration (GO:0043542), regulation of small GTPase mediated signal transduction (GO:0051056), negative regulation of cell migration involved in sprouting angiogenesis (GO:0090051), endothelial tube lumen extension (GO:0097498), negative regulation of sprouting angiogenesis (GO:1903671), negative regulation of cell migration (GO:0030336)

GO Molecular Function (3): GTPase activator activity (GO:0005096), lipid binding (GO:0008289), protein binding (GO:0005515)

GO Cellular Component (6): lipid droplet (GO:0005811), cytosol (GO:0005829), mitochondrial membrane (GO:0031966), cytoplasm (GO:0005737), mitochondrion (GO:0005739), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	4
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell migration	2
binding	2
cytoplasm	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytoskeleton organization	1
actin filament-based process	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
cell migration involved in sprouting angiogenesis	1
negative regulation of blood vessel endothelial cell migration	1
regulation of cell migration involved in sprouting angiogenesis	1
endothelial tube morphogenesis	1
sprouting angiogenesis	1
negative regulation of angiogenesis	1
regulation of sprouting angiogenesis	1
regulation of cell migration	1
negative regulation of cell motility	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
intracellular membraneless organelle	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1252 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STARD13	RHOA	P06749	882
STARD13	RSPH3	Q86UC2	784
STARD13	KIF23	Q02241	777
STARD13	CNNM2	Q9H8M5	765
STARD13	CDC42	P21181	719
STARD13	RASA1	P20936	657
STARD13	TNS2	Q63HR2	581
STARD13	LIMK1	P53667	560
STARD13	ARHGEF1	Q92888	540
STARD13	RDX	P35241	540
STARD13	MSN	P26038	537
STARD13	STARD5	P59094	521
STARD13	ROCK1	Q13464	516
STARD13	PUM2	Q8TB72	512
STARD13	RBBP8	Q99708	510

IntAct

56 interactions, top by confidence:

A	B	Type	Score
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
STARD13	TAX1BP1	psi-mi:“MI:0915”(physical association)	0.510
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
STARD13	MRPS9	psi-mi:“MI:0915”(physical association)	0.400
STARD13	TUBA4A	psi-mi:“MI:0915”(physical association)	0.400
STARD13	SERPINB4	psi-mi:“MI:0915”(physical association)	0.400
STARD13	PCNA	psi-mi:“MI:0915”(physical association)	0.370
TUBA1B	STARD13	psi-mi:“MI:0915”(physical association)	0.370
HMGCR	STARD13	psi-mi:“MI:0915”(physical association)	0.370
EPB41L1	STARD13	psi-mi:“MI:0915”(physical association)	0.370
STARD13	ITPR1	psi-mi:“MI:0915”(physical association)	0.370
HSP90AB1	STARD13	psi-mi:“MI:0915”(physical association)	0.370
ADGRB2	STARD13	psi-mi:“MI:0915”(physical association)	0.370
STARD13	KIF1B	psi-mi:“MI:0915”(physical association)	0.370
STARD13	SMAD1	psi-mi:“MI:0915”(physical association)	0.370
E6	TRAFD1	psi-mi:“MI:0914”(association)	0.350
C6orf141	ITPRID2	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FAM170A	MCM3AP	psi-mi:“MI:0914”(association)	0.350
HHIPL1	CYTH3	psi-mi:“MI:0914”(association)	0.350
PIM1	IDH3B	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
PPP2R2C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PTX3	OFD1	psi-mi:“MI:0914”(association)	0.350
WRAP73	GOLIM4	psi-mi:“MI:0914”(association)	0.350

BioGRID (53): TAX1BP1 (Affinity Capture-Western), S100A7 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), STARD13 (Affinity Capture-MS), KIF13B (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), STARD13 (Affinity Capture-MS), GIGYF1 (Affinity Capture-MS), CGN (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), STARD13 (Affinity Capture-MS), STARD13 (Affinity Capture-MS), STARD13 (Affinity Capture-MS), STARD13 (Affinity Capture-MS), STARD13 (Affinity Capture-MS)

ESM2 similar proteins: A0JM95, A1A4S6, A2A2Y4, A4II46, A4IJ06, A6NI28, B2RQE8, B5DFQ4, F1LVW7, O60879, O60890, O70566, O95267, P0C7A6, P0CAX5, Q02384, Q07889, Q07890, Q08DP6, Q0P4Q4, Q28EC1, Q4V7P7, Q566W7, Q5R6F6, Q5R803, Q5U4T3, Q62245, Q69ZK0, Q6DBW1, Q6DHR3, Q6NTL4, Q6PCS4, Q6Y5D8, Q6ZM89, Q7YQL5, Q7YQL6, Q8AVG0, Q8BHD4, Q8IV61, Q8N9B8

Diamond homologs: A1A4S6, A6NI28, A6X8Z5, A7E300, B2RQE8, B5DFQ4, B9VTT2, D3ZFJ3, D3ZZN9, E9Q6X9, F1LQX4, O43182, O60890, P0CAX5, P15882, P30337, P55194, P81128, P83509, P98171, Q07960, Q08DP6, Q13459, Q14CB8, Q17QN0, Q17R89, Q2M1Z3, Q3KRB8, Q54FF4, Q54PG5, Q54TH9, Q54VW7, Q553X3, Q559A0, Q5FWK3, Q5SSM3, Q5TG30, Q5U4T3, Q62172, Q63358

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STARD13	“down-regulates activity”	RHOA	“gtpase-activating protein”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 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
RHO GTPase Effectors	9	13.6×	7e-06
Signaling by Rho GTPases	11	8.4×	9e-06
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	11	8.2×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	144
Likely benign	13
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

2912 predictions. Top by Δscore:

Variant	Effect	Δscore
13:33106751:CACTT:C	donor_loss	1.0000
13:33106752:ACTTA:A	donor_loss	1.0000
13:33106753:CTTAC:C	donor_loss	1.0000
13:33106754:TTA:T	donor_loss	1.0000
13:33106755:TACTT:T	donor_loss	1.0000
13:33106756:A:AC	donor_gain	1.0000
13:33106756:A:C	donor_loss	1.0000
13:33106757:C:CT	donor_gain	1.0000
13:33106757:CT:C	donor_gain	1.0000
13:33106757:CTT:C	donor_gain	1.0000
13:33106757:CTTCA:C	donor_gain	1.0000
13:33106932:GTCCT:G	acceptor_loss	1.0000
13:33106934:CCTG:C	acceptor_loss	1.0000
13:33106935:C:CC	acceptor_gain	1.0000
13:33106935:C:CG	acceptor_loss	1.0000
13:33106936:T:A	acceptor_loss	1.0000
13:33109925:A:AC	donor_gain	1.0000
13:33109926:C:CC	donor_gain	1.0000
13:33110088:CACCT:C	acceptor_gain	1.0000
13:33110090:CC:C	acceptor_loss	1.0000
13:33110090:CCT:C	acceptor_gain	1.0000
13:33110680:GATTA:G	donor_loss	1.0000
13:33110681:ATTAC:A	donor_loss	1.0000
13:33110682:TTAC:T	donor_loss	1.0000
13:33110683:TA:T	donor_loss	1.0000
13:33110685:C:T	donor_loss	1.0000
13:33111773:CTCA:C	donor_loss	1.0000
13:33111774:TCAC:T	donor_loss	1.0000
13:33111775:CAC:C	donor_loss	1.0000
13:33111888:TGACT:T	acceptor_gain	1.0000

AlphaMissense

7370 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:33109991:A:G	W977R	0.999
13:33109991:A:T	W977R	0.999
13:33112772:A:G	L814P	0.999
13:33118127:C:G	R740P	0.999
13:33118138:T:A	K736N	0.999
13:33118138:T:G	K736N	0.999
13:33118139:T:A	K736I	0.999
13:33118140:T:C	K736E	0.999
13:33118149:C:G	D733H	0.999
13:33118214:C:G	R711P	0.999
13:33118241:C:T	G702E	0.999
13:33118251:G:T	R699S	0.999
13:33118253:A:G	F698S	0.999
13:33130220:A:G	W153R	0.999
13:33130220:A:T	W153R	0.999
13:33130245:C:A	W144C	0.999
13:33130245:C:G	W144C	0.999
13:33130247:A:G	W144R	0.999
13:33130247:A:T	W144R	0.999
13:33142359:A:G	L113S	0.999
13:33110023:A:T	V966D	0.998
13:33111815:A:G	L857P	0.998
13:33112774:A:C	C813W	0.998
13:33112776:A:G	C813R	0.998
13:33112799:A:G	M805T	0.998
13:33118148:T:A	D733V	0.998
13:33118148:T:C	D733G	0.998
13:33118148:T:G	D733A	0.998
13:33118151:G:T	A732E	0.998
13:33118152:C:G	A732P	0.998

dbSNP variants (sampled 300 via entrez): RS1000002973 (13:33528868 A>G), RS1000009352 (13:33626344 A>G), RS1000019025 (13:33323596 G>A,C), RS1000023608 (13:33358209 C>A,T), RS1000040681 (13:33488386 C>A,G), RS1000040942 (13:33236185 C>T), RS1000043415 (13:33386633 A>C,G), RS1000047152 (13:33618795 G>C), RS1000058534 (13:33659609 C>A), RS1000064004 (13:33345044 T>C), RS1000065589 (13:33166536 T>C), RS1000073276 (13:33307596 G>A), RS1000073962 (13:33408315 C>T), RS1000075464 (13:33645042 G>A), RS1000079579 (13:33534994 T>C)

Disease associations

OMIM: gene MIM:609866 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	No Known Disease Relationship	Unknown

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000646_6	Intracranial aneurysm	3.000000e-09
GCST001945_2	Body mass index in asthmatics	3.000000e-06
GCST002360_7	Plasma amyloid beta peptide concentrations (ABx-40)	7.000000e-06
GCST006479_67	Diverticular disease	7.000000e-07
GCST007856_78	Colorectal cancer or advanced adenoma	3.000000e-07
GCST010083_296	Hemoglobin levels	6.000000e-11
GCST011105_4	Metamizole-induced agranulocytosis or neutropenia	1.000000e-06
GCST90002383_21	Hematocrit	1.000000e-12
GCST90002384_324	Hemoglobin	1.000000e-13
GCST90002400_741	Plateletcrit	5.000000e-11
GCST90002402_210	Platelet count	3.000000e-09
GCST90002403_469	Red blood cell count	3.000000e-10
GCST90026416_18	Mild age-related type 2 diabetes	8.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005659	plasma beta-amyloid 1-40 measurement
EFO:0009959	diverticular disease
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	4
Cadmium Chloride	decreases expression, increases abundance, increases expression	4
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
bisphenol A	decreases expression, affects cotreatment, affects methylation	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
potassium chromate(VI)	decreases expression, affects cotreatment	2
Leflunomide	increases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects methylation, decreases methylation, increases expression	2
Asbestos, Crocidolite	affects methylation, increases expression	2
FR900359	increases phosphorylation	1
titanium dioxide	increases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1

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