LHX6

Summary

LHX6 (LIM homeobox 6, HGNC:21735) is a protein-coding gene on chromosome 9q33.2, encoding LIM/homeobox protein Lhx6 (Q9UPM6). Probable transcription factor required for the expression of a subset of genes involved in interneurons migration and development.

This gene encodes a member of a large protein family that contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein has tandem LIM domains as well as a DNA-binding homeodomain. The protein functions as a transcription factor involved in embryogenesis and head development and is highly expressed in neural crest derived mesenchyme cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 26468 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_014368

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21735
Approved symbol	LHX6
Name	LIM homeobox 6
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	LHX6.1, hLHX6
Ensembl gene	ENSG00000106852
Ensembl biotype	protein_coding
OMIM	608215
Entrez	26468

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000340587, ENST00000373754, ENST00000373755, ENST00000394319, ENST00000464484, ENST00000482062, ENST00000541397, ENST00000558672, ENST00000559529, ENST00000559895, ENST00000560152, ENST00000560485

RefSeq mRNA: 6 — MANE Select: NM_014368 NM_001242333, NM_001242334, NM_001242335, NM_001348190, NM_014368, NM_199160

CCDS: CCDS56583, CCDS56584, CCDS59144, CCDS6837, CCDS6838, CCDS87683

Canonical transcript exons

ENST00000394319 — 10 exons

Exon	Start	End
ENSE00000725160	122226848	122227030
ENSE00002543537	122202582	122204780
ENSE00002553637	122228657	122228957
ENSE00003573679	122226376	122226497
ENSE00003596301	122217068	122217288
ENSE00003688327	122227409	122227480
ENSE00003696949	122214283	122214383
ENSE00003698290	122213606	122213780
ENSE00003698959	122209614	122209717
ENSE00003701003	122213974	122214069

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 85.17.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9082 / max 93.1041, expressed in 607 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102387	0.7924	245
102384	0.6858	258
102383	0.5108	233
102382	0.4780	163
102381	0.3051	139
102386	0.0628	13
102385	0.0508	29
102380	0.0224	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.17	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.88	gold quality
cortical plate	UBERON:0005343	82.84	gold quality
prefrontal cortex	UBERON:0000451	82.77	gold quality
anterior cingulate cortex	UBERON:0009835	82.55	gold quality
cingulate cortex	UBERON:0003027	82.48	gold quality
endothelial cell	CL:0000115	81.86	silver quality
orbitofrontal cortex	UBERON:0004167	80.80	gold quality
Brodmann (1909) area 46	UBERON:0006483	80.61	gold quality
neocortex	UBERON:0001950	80.27	gold quality
ganglionic eminence	UBERON:0004023	80.22	gold quality
visceral pleura	UBERON:0002401	80.07	gold quality
frontal cortex	UBERON:0001870	79.98	gold quality
pleura	UBERON:0000977	79.72	gold quality
parietal pleura	UBERON:0002400	79.52	gold quality
omental fat pad	UBERON:0010414	79.02	gold quality
peritoneum	UBERON:0002358	78.95	gold quality
caudate nucleus	UBERON:0001873	78.84	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.61	gold quality
adipose tissue	UBERON:0001013	78.40	gold quality
adipose tissue of abdominal region	UBERON:0007808	78.38	gold quality
cerebral cortex	UBERON:0000956	78.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.16	gold quality
superior frontal gyrus	UBERON:0002661	78.12	gold quality
right frontal lobe	UBERON:0002810	77.92	gold quality
apex of heart	UBERON:0002098	77.53	gold quality
connective tissue	UBERON:0002384	77.39	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.15	gold quality
telencephalon	UBERON:0001893	77.01	gold quality
postcentral gyrus	UBERON:0002581	76.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	14.11
E-ANND-3	yes	11.48

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
LHX6
PITX2

JASPAR motifs

Motif	Name	Family
MA0658.1	LHX6	HD-LIM
MA0658.2	LHX6	HD-LIM

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): LHX6, LHX8, NKX2-1, PITX2

miRNA regulators (miRDB)

199 targeting LHX6, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777

Literature-anchored findings (GeneRIF, showing 18)

• differentially methylated hypermethylation of LHX6 is a good cancer marker in HNSCC as well as in other kinds of neoplasias and confirm the importance of searching for markers of epigenetic dysregulation in cancer (PMID:16732332)
• Hypermethylation of LHX6 is associated with cervical cancer. (PMID:20428825)
• hLHX6.1 could be a new tumor suppressor gene in the cervix. (PMID:21240459)
• found positive association of LHX6 with Tourette syndrome in some European populations, not others. LHX6 demonstrates a high degree of population differentiation and is correlated with the North to South axis of European genetic variation. (PMID:22435649)
• LHX6 is a transcriptional repressor that interacts with pituitary homeobox 2 (PITX2) to regulate odontogenesis (PMID:23229549)
• LHX6 is a putative tumour suppressor gene with epigenetic silencing in lung cancer. (PMID:24157876)
• LHX6 inhibits breast cancer cell proliferation and invasion via repression of the Wnt/beta-catenin signaling pathway. (PMID:26129710)
• that down-regulation of miR-214 may reverse acquired resistance to erlotinib in NSCLC through mediating its direct target gene LHX6 expression. (PMID:28396596)
• The orthotopic implantation model showed that miR-1290 overexpression promoted tumor growth while LHX6 overexpression inhibited it. MiR-1290 could promote glioma cell propagation and metastasis by inhibiting LHX6. (PMID:29226322)
• The downregulation of LHX6 expression might be important in promoting cancer progression. [review] (PMID:29533904)
• expression of the single transcription factor LHX6 under GABAergic interneurons differentiation condition is sufficient to robustly induce human parvalbumin and somatostatin subtypes. (PMID:30251953)
• LHX6 gene expression is regulated by DNA methylation and can inhibit the proliferation, invasion and migration through Wnt/beta-catenin and P53 signaling pathways during the Microcystin-LR-induced hepatocarcinogenesis. (PMID:31151060)
• LHX6 is essential for the migration of human pluripotent stem cell-derived GABAergic interneurons. (PMID:31907793)
• Methylation-mediated silencing of the LIM homeobox 6 (LHX6) gene promotes cell proliferation in human pancreatic cancer. (PMID:32248980)
• Tumor suppressor LHX6 upregulation contributes to the inhibitory effect of miR-346 knockdown on colorectal cancer cell growth. (PMID:34773443)
• The exon 12-containing LHX6 isoforms promote cervical cancer cell proliferation by regulating the MAPK signaling pathway. (PMID:35384355)
• LHX6 promoter hypermethylation in oncological pediatric patients conceived by IVF. (PMID:36154949)
• Lhx6 deficiency causes human embryonic palatal mesenchymal cell mitophagy dysfunction in cleft palate. (PMID:39438838)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lhx6a	ENSDARG00000006896
danio_rerio	lhx6b	ENSDARG00000052165
mus_musculus	Lhx6	ENSMUSG00000026890
rattus_norvegicus	Lhx6	ENSRNOG00000005996

Paralogs (20): FHL1 (ENSG00000022267), LMO3 (ENSG00000048540), LHX5 (ENSG00000089116), ZFHX4 (ENSG00000091656), LHX2 (ENSG00000106689), LHX3 (ENSG00000107187), LHX4 (ENSG00000121454), LMO2 (ENSG00000135363), ZFHX2 (ENSG00000136367), LMX1B (ENSG00000136944), ZFHX3 (ENSG00000140836), LMO4 (ENSG00000143013), LHX9 (ENSG00000143355), CRIP3 (ENSG00000146215), LHX8 (ENSG00000162624), LMX1A (ENSG00000162761), LMO1 (ENSG00000166407), CRIP2 (ENSG00000182809), CRIP1 (ENSG00000213145), LHX1 (ENSG00000273706)

Protein

Protein identifiers

LIM/homeobox protein Lhx6 — Q9UPM6 (reviewed: Q9UPM6)

Alternative names: LIM/homeobox protein Lhx6.1

All UniProt accessions (4): Q9UPM6, H0YKH7, H0YMH3, H0YMY8

UniProt curated annotations — full annotation on UniProt →

Function. Probable transcription factor required for the expression of a subset of genes involved in interneurons migration and development. Functions in the specification of cortical interneuron subtypes and in the migration of GABAergic interneuron precursors from the subpallium to the cerebral cortex.

Subunit / interactions. Interacts with LDB1 (via the LIM zinc-binding domains).

Subcellular location. Nucleus.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9UPM6-1	1, Lhx6.1a	yes
Q9UPM6-2	2, Lhx6.1b
Q9UPM6-3	3
Q9UPM6-4	4
Q9UPM6-5	5
Q9UPM6-6	6

RefSeq proteins (6): NP_001229262, NP_001229263, NP_001229264, NP_001335119, NP_055183, NP_954629 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR001781	Znf_LIM	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR050453	LIM_Homeobox_TF	Family

Pfam: PF00046, PF00412

UniProt features (16 total): splice variant 4, region of interest 4, domain 2, sequence conflict 2, compositionally biased region 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPM6-F1	68.43	0.41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 274 (showing top): GOBP_FOREBRAIN_NEURON_DEVELOPMENT, YAATNRNNNYNATT_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEUROGENESIS, AP2_Q3, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_GABAERGIC_NEURON_DIFFERENTIATION, GOBP_FOREBRAIN_GENERATION_OF_NEURONS, NKX61_01, GOBP_FOREBRAIN_CELL_MIGRATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, IRF7_01, CEBP_Q2, GOBP_CEREBRAL_CORTEX_NEURON_DIFFERENTIATION

GO Biological Process (10): regulation of transcription by RNA polymerase II (GO:0006357), cerebral cortex radially oriented cell migration (GO:0021799), cerebral cortex tangential migration (GO:0021800), cerebral cortex GABAergic interneuron migration (GO:0021853), forebrain neuron development (GO:0021884), neuron differentiation (GO:0030182), cell maturation (GO:0048469), regulation of DNA-templated transcription (GO:0006355), nervous system development (GO:0007399), cell differentiation (GO:0030154)

GO Molecular Function (8): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
cerebral cortex cell migration	2
cellular developmental process	2
transcription cis-regulatory region binding	2
transcription by RNA polymerase II	1
interneuron migration from the subpallium to the cortex	1
cerebral cortex GABAergic interneuron development	1
interneuron migration	1
forebrain neuron differentiation	1
central nervous system neuron development	1
cell differentiation	1
generation of neurons	1
cell development	1
anatomical structure maturation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
system development	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transcription regulator activity	1
cation binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1502 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LHX6	PDE1C	Q14123	890
LHX6	RAB2A	P08886	825
LHX6	SST	P01166	815
LHX6	LDB1	Q86U70	805
LHX6	NKX2-1	P43699	800
LHX6	DLX2	Q07687	774
LHX6	CALB2	P22676	746
LHX6	PVALB	P20472	744
LHX6	DLX1	P56177	730
LHX6	MSX1	P28360	724
LHX6	PDE1A	P54750	722
LHX6	TBR1	Q16650	718
LHX6	FOXG1	P55315	716
LHX6	NPY	P01303	708
LHX6	DLX5	P56178	685

IntAct

85 interactions, top by confidence:

A	B	Type	Score
LDB1	LHX6	psi-mi:“MI:0915”(physical association)	0.760
LHX6	LDB1	psi-mi:“MI:0915”(physical association)	0.760
FIGLA	LHX6	psi-mi:“MI:0915”(physical association)	0.560
LDB1	LHX6	psi-mi:“MI:0915”(physical association)	0.560
KLF3	LHX6	psi-mi:“MI:0915”(physical association)	0.560
ZNF76	LHX6	psi-mi:“MI:0915”(physical association)	0.560
FAM90A1	LHX6	psi-mi:“MI:0915”(physical association)	0.560
NRF1	LHX6	psi-mi:“MI:0915”(physical association)	0.560
CPNE1	LHX6	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	LHX6	psi-mi:“MI:0915”(physical association)	0.560
ROR2	LHX6	psi-mi:“MI:0915”(physical association)	0.560
LHX6	A2M	psi-mi:“MI:0915”(physical association)	0.560
LHX6		psi-mi:“MI:0915”(physical association)	0.560
GRN	LHX6	psi-mi:“MI:0915”(physical association)	0.560
LHX6	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
LHX6	PHYH	psi-mi:“MI:0915”(physical association)	0.560
LHX6	PMP22	psi-mi:“MI:0915”(physical association)	0.560
LHX6	WFS1	psi-mi:“MI:0915”(physical association)	0.560
LHX6	RNF11	psi-mi:“MI:0915”(physical association)	0.560
SNCA	LHX6	psi-mi:“MI:0915”(physical association)	0.560
HTT	LHX6	psi-mi:“MI:0915”(physical association)	0.560
ATXN3	LHX6	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	LHX6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (100): LHX6 (Two-hybrid), LDB1 (Affinity Capture-MS), ATG2B (Affinity Capture-MS), SSBP4 (Affinity Capture-MS), SSBP3 (Affinity Capture-MS), SSBP2 (Affinity Capture-MS), ZNF507 (Affinity Capture-MS), ARID3B (Affinity Capture-MS), EHMT2 (Affinity Capture-MS), NUDT22 (Affinity Capture-MS), GTF2H2 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), TLK2 (Affinity Capture-MS), CARD8 (Affinity Capture-MS), WDR45 (Affinity Capture-MS)

ESM2 similar proteins: A4FV57, M0R7T9, O09112, O35652, O43189, O75398, O77562, O88450, O88942, P21580, Q0IHH1, Q0VE29, Q15139, Q3V038, Q4R8W3, Q5RA30, Q5T6S3, Q5XI70, Q5XIS9, Q60769, Q62101, Q68FF6, Q68G74, Q6A039, Q6GR30, Q6P5H6, Q6ZN18, Q7SXV2, Q8BUL6, Q8BZ03, Q8IRC7, Q8K214, Q8K4G5, Q8NHH1, Q8TBP0, Q96GD3, Q96K76, Q99767, Q99NA9, Q9BYE7

Diamond homologs: A0JNI8, A2I8Z7, A2PZF9, G5EC36, G5EE86, O14639, O35652, O60663, O88609, O94929, O97581, P20154, P25791, P25800, P25801, P29673, P29674, P34764, P34765, P36198, P36200, P37137, P48742, P50211, P50212, P50458, P50480, P50481, P52889, P53405, P53406, P53407, P53408, P53409, P53410, P53411, P53412, P53413, P53667, P53668

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1796 predictions. Top by Δscore:

Variant	Effect	Δscore
9:122213604:A:AC	donor_gain	1.0000
9:122213605:C:CC	donor_gain	1.0000
9:122213605:CT:C	donor_gain	1.0000
9:122213605:CTCT:C	donor_gain	1.0000
9:122213985:T:A	donor_gain	1.0000
9:122214070:CTGCG:C	acceptor_loss	1.0000
9:122217062:GGGTA:G	donor_loss	1.0000
9:122217063:GGTAC:G	donor_loss	1.0000
9:122217064:GTACC:G	donor_loss	1.0000
9:122217065:TAC:T	donor_loss	1.0000
9:122217067:CCGTT:C	donor_gain	1.0000
9:122217298:G:T	acceptor_gain	1.0000
9:122226370:GCCTA:G	donor_loss	1.0000
9:122226371:CCTAC:C	donor_loss	1.0000
9:122226372:CTAC:C	donor_loss	1.0000
9:122226373:TAC:T	donor_loss	1.0000
9:122226374:ACCTG:A	donor_loss	1.0000
9:122226375:C:CT	donor_loss	1.0000
9:122226494:TGAC:T	acceptor_gain	1.0000
9:122226498:C:CA	acceptor_loss	1.0000
9:122226498:C:CC	acceptor_gain	1.0000
9:122226499:T:A	acceptor_loss	1.0000
9:122226835:ACC:A	donor_gain	1.0000
9:122226836:CCC:C	donor_gain	1.0000
9:122226843:CTCA:C	donor_loss	1.0000
9:122228651:GCTCA:G	donor_loss	1.0000
9:122228652:CTCA:C	donor_loss	1.0000
9:122228653:TCA:T	donor_loss	1.0000
9:122228654:CA:C	donor_loss	1.0000
9:122213601:CTT:C	donor_loss	0.9900

AlphaMissense

2559 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:122213747:T:C	K276E	1.000
9:122213748:T:A	K275N	1.000
9:122213748:T:G	K275N	1.000
9:122213749:T:A	K275I	1.000
9:122213750:T:C	K275E	1.000
9:122213756:G:A	R273C	1.000
9:122213756:G:T	R273S	1.000
9:122213758:G:A	A272V	1.000
9:122213758:G:T	A272E	1.000
9:122213761:C:T	R271Q	1.000
9:122213762:G:A	R271W	1.000
9:122213762:G:C	R271G	1.000
9:122213766:G:C	N269K	1.000
9:122213766:G:T	N269K	1.000
9:122213767:T:A	N269I	1.000
9:122213767:T:C	N269S	1.000
9:122213767:T:G	N269T	1.000
9:122213768:T:A	N269Y	1.000
9:122213768:T:C	N269D	1.000
9:122213768:T:G	N269H	1.000
9:122213769:T:A	Q268H	1.000
9:122213769:T:G	Q268H	1.000
9:122213771:G:T	Q268K	1.000
9:122213772:A:C	F267L	1.000
9:122213772:A:T	F267L	1.000
9:122213773:A:C	F267C	1.000
9:122213773:A:G	F267S	1.000
9:122213774:A:C	F267V	1.000
9:122213774:A:G	F267L	1.000
9:122213774:A:T	F267I	1.000

dbSNP variants (sampled 300 via entrez): RS1000037055 (9:122203968 A>T), RS1000068487 (9:122219726 G>A), RS1000084821 (9:122203984 A>G), RS1000110021 (9:122210075 C>T), RS1000114675 (9:122216960 C>G,T), RS1000422202 (9:122221888 C>T), RS1000452972 (9:122230040 C>T), RS1000516422 (9:122207008 C>T), RS1000598234 (9:122214999 G>A), RS1000612488 (9:122214171 G>A,T), RS1000667744 (9:122221137 G>A), RS1000891316 (9:122225524 G>A), RS1000910037 (9:122226214 T>A), RS1000955739 (9:122225929 C>G,T), RS1001241118 (9:122204124 C>T)

Disease associations

OMIM: gene MIM:608215 | 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

3 associations (top):

Study	Trait	p-value
GCST010725_17	Malaria	5.000000e-06
GCST010725_29	Malaria	1.000000e-06
GCST010725_96	Malaria	9.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Aldehydes	increases expression	1
Atrazine	increases expression	1
Camptothecin	increases expression	1
Cisplatin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Methapyrilene	increases methylation	1
Niclosamide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A3W2	SEES3-1V human LHX6, clone1	Embryonic stem cell	Male
CVCL_A3W3	SEES3-1V human LHX6, clone2	Embryonic stem cell	Male
CVCL_A3W4	SEES3-1V human LHX6, clone3	Embryonic stem cell	Male

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