EMX2

Summary

EMX2 (empty spiracles homeobox 2, HGNC:3341) is a protein-coding gene on chromosome 10q26.11, encoding Homeobox protein EMX2 (Q04743). Transcription factor, which in cooperation with EMX1, acts to generate the boundary between the roof and archipallium in the developing brain.

This gene encodes a homeobox-containing transcription factor that is the homolog to the ’empty spiracles’ gene in Drosophila. Research on this gene in humans has focused on its expression in three tissues: dorsal telencephalon, olfactory neuroepithelium, and urogenetial system. It is expressed in the dorsal telencephalon during development in a low rostral-lateral to high caudal-medial gradient and is proposed to pattern the neocortex into defined functional areas. It is also expressed in embryonic and adult olfactory neuroepithelia where it complexes with eukaryotic translation initiation factor 4E (eIF4E) and possibly regulates mRNA transport or translation. In the developing urogenital system, it is expressed in epithelial tissues and is negatively regulated by HOXA10. Alternative splicing results in multiple transcript variants encoding distinct proteins.

Source: NCBI Gene 2018 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizencephaly (Moderate, GenCC)
• GWAS associations: 22
• Clinical variants (ClinVar): 56 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 3
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_004098

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3341
Approved symbol	EMX2
Name	empty spiracles homeobox 2
Location	10q26.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170370
Ensembl biotype	protein_coding
OMIM	600035
Entrez	2018

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000442245, ENST00000546446, ENST00000553456, ENST00000616794

RefSeq mRNA: 2 — MANE Select: NM_004098 NM_001165924, NM_004098

CCDS: CCDS53583, CCDS7601

Canonical transcript exons

ENST00000553456 — 3 exons

Exon	Start	End
ENSE00001449036	117542746	117543673
ENSE00003614049	117545632	117545816
ENSE00003721617	117548065	117549546

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 98.64.

FANTOM5 (CAGE): breadth broad, TPM avg 10.9701 / max 574.1446, expressed in 582 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107274	3.9350	371
107281	1.3573	432
107279	1.2262	335
107275	1.0723	216
107278	0.8087	284
107273	0.6764	181
107272	0.6251	157
107276	0.4455	156
107271	0.4255	131
107283	0.2078	101

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	98.64	gold quality
caput epididymis	UBERON:0004358	98.28	gold quality
cauda epididymis	UBERON:0004360	97.51	gold quality
seminal vesicle	UBERON:0000998	97.35	gold quality
body of uterus	UBERON:0009853	96.61	gold quality
ventricular zone	UBERON:0003053	96.28	gold quality
ganglionic eminence	UBERON:0004023	96.21	gold quality
endocervix	UBERON:0000458	95.53	gold quality
nephron tubule	UBERON:0001231	94.49	gold quality
myometrium	UBERON:0001296	94.48	gold quality
right uterine tube	UBERON:0001302	93.57	gold quality
endometrium	UBERON:0001295	93.28	gold quality
germinal epithelium of ovary	UBERON:0001304	92.95	gold quality
metanephros cortex	UBERON:0010533	92.73	gold quality
adult mammalian kidney	UBERON:0000082	92.47	gold quality
uterus	UBERON:0000995	92.44	gold quality
left uterine tube	UBERON:0001303	92.35	gold quality
renal medulla	UBERON:0000362	91.74	gold quality
kidney epithelium	UBERON:0004819	91.60	gold quality
kidney	UBERON:0002113	91.01	gold quality
saphenous vein	UBERON:0007318	88.46	gold quality
renal glomerulus	UBERON:0000074	88.32	gold quality
metanephric glomerulus	UBERON:0004736	87.82	gold quality
adult organism	UBERON:0007023	87.69	gold quality
caudate nucleus	UBERON:0001873	87.41	gold quality
metanephros	UBERON:0000081	87.36	gold quality
amygdala	UBERON:0001876	87.36	gold quality
sperm	CL:0000019	87.05	gold quality
decidua	UBERON:0002450	86.99	gold quality
stromal cell of endometrium	CL:0002255	86.38	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	43.37
E-HCAD-10	yes	33.80
E-ANND-3	yes	27.41
E-HCAD-5	yes	21.05

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
EGFR	Repression
EMX2
FBN1
FGF8
PCNA	Repression
RASSF1
SOX2	Unknown
SP8
WNT1
WNT2

JASPAR motifs

Motif	Name	Family
MA0886.1	EMX2	NK
MA0886.2	EMX2	NK

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): BARX1, CTNNB1, EMX2, HAND2, HOXA10, HOXD13, PAX6, PBX2

miRNA regulators (miRDB)

110 targeting EMX2, 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-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 27)

• EMX2 gene has been reported in schezencephaly (cleft brain) including epilepsy in some patients. (PMID:12185771)
• In these studies we identify and characterize the regulation of EMX2 by HOXA10. (PMID:12482956)
• Endometrial EMX2 expression is aberrant in women with endometriosis and is mediated by altered HOXA10 expression. (PMID:15126568)
• EMX2 levels in cortical progenitors of EMX2 transgenic mice disproportionately specify sizes and positions of primary cortical areas. (PMID:15294144)
• It is unlikely that the EMX2 or PTEN gene variants investigated contribute to risk for initiation and/or development of endometriosis. (PMID:17563403)
• provide results of EMX2 sequencing in 39 new schizencephaly patients, detecting no pathogenic mutations (PMID:18409201)
• These data support recent reports that EMX2 but not PAX6 is more directly involved in arealization, highlighting that analysis of human development allows better spatio-temporal resolution than studies in rodents. (PMID:18973570)
• promoter. Restoration of EMX2 expression in lung cancer cells lacking endogenous EMX2 expression suppressed cell proliferation and invasive phenotypes (PMID:20697358)
• Data show that human teneurin-1 is directly regulated by EMX2 at a conserved promoter region upstream of the transcription start site, and identify and characterize the EMX2 dependent promoter element of human teneurin-1. (PMID:21651764)
• Downregulation of EMX2 is associated with clinical outcomes in lung adenocarcinoma. (PMID:21726823)
• Study analyzed mutations of EMX2 gene in 45 prostate carcinomas, 51 non-small cell lung cancers, 43 gastric carcinomas, 44 colorectal carcinomas, and 43 breast carcinomas by polymerase chain reaction and single-strand conformation polymorphism assay. (PMID:21917011)
• EMX2 expression led to inhibition of cell proliferation and Wnt signaling pathway both in vitro and in a gastric cancer xenograft model in vivo. (PMID:23029345)
• downregulation of empty spiracles homeobox 2 (EMX2) was associated with tumor progression and may be a critical factor in the carcinogenesis and progression of endometrial cancer (PMID:23370654)
• Deletions of EMX2 have been associated with a wide range of DSD. (PMID:24975717)
• EMX2 expression is downregulated in advanced cases of malignant pleural mesothelioma and may serve as an important prognostic and predictive molecular biomarker of progression-free survival. (PMID:25023662)
• Although it is uncommon (0.19%), EMX2 is the first gene identified that if perturbed may cause isolated incomplete mullerian fusion. (PMID:25577462)
• EMX2 expression was down-regulated in lung SCC tissue compared to matched adjacent normal tissue. EMX2 expression was associated with improved overall survival. Knockdown promoted chemo-resistance and cell migration. (PMID:26132438)
• Emx2 is a novel promising tool for therapy of glioblastoma and prevention of its recurrences. (PMID:27191499)
• EMX2 inhibits proliferation and tumorigenesis through inactivation of the Wnt/beta-catenin pathway in CRC cells. (PMID:27712600)
• EMX2 is frequently down-regulated in human colorectal cancer, and down-regulation of EMX2 is a prognostic marker for disease-free and overall survival. (PMID:28830374)
• Low EMX2 expression is associated with multiple myeloma. (PMID:30450775)
• In the three variants of papillary thyroid cancer (PTC), EMX2 was significantly downregulated in classical PTC, while EMX2OS was significantly downregulated in follicular and classical PTC, compared with adjacent normal tissues. Kaplan-Meier survival curves showed that EMX2 and EMX2OS expression was not related to relapse-free survival in follicular PTC. (PMID:30576338)
• Results identify the EMX2 mRNA as a major miss-spliced down stream target of SNRPE with heterozygous missense mutation causing microcephaly. (PMID:31671093)
• Regulation of sarcomagenesis by the empty spiracles homeobox genes EMX1 and EMX2. (PMID:34016958)
• Empty spiracles homeobox genes EMX1 and EMX2 regulate WNT pathway activation in sarcomagenesis. (PMID:34364391)
• Spatial control of astrogenesis progression by cortical arealization genes. (PMID:35818636)
• EMX2 inhibits clear cell renal cell carcinoma progress via modulating Akt/FOXO3a pathway. (PMID:38362840)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	emx2	ENSDARG00000039701
mus_musculus	Emx2	ENSMUSG00000043969
rattus_norvegicus	Emx2	ENSRNOG00000009482

Paralogs (3): VAX2 (ENSG00000116035), EMX1 (ENSG00000135638), VAX1 (ENSG00000148704)

Protein

Protein identifiers

Homeobox protein EMX2 — Q04743 (reviewed: Q04743)

Alternative names: Empty spiracles homolog 2, Empty spiracles-like protein 2

All UniProt accessions (2): Q04743, A0A087WWJ6

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor, which in cooperation with EMX1, acts to generate the boundary between the roof and archipallium in the developing brain. May function in combination with OTX1/2 to specify cell fates in the developing central nervous system. In the inner ear, it controls the distribution of GPR156 at hair cell boundaries, and regulates the organization of stereociliary bundles in opposite orientations across the line of polarity reversal (LPR).

Subunit / interactions. Interacts with translation initiation factor EIF4E.

Subcellular location. Nucleus. Cell projection. Axon.

Tissue specificity. Cerebral cortex.

Disease relevance. Schizencephaly (SCHZC) [MIM:269160] Extremely rare human congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. These clefts are lined with gray matter and most commonly involve the parasylvian regions. Large portions of the cerebral hemispheres may be absent and replaced by cerebro-spinal fluid. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the EMX homeobox family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q04743-1	1	yes
Q04743-2	2

RefSeq proteins (2): NP_001159396, NP_004089* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000047	HTH_motif	Conserved_site
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR050877	EMX-VAX-Noto_Homeobox_TFs	Family

Pfam: PF00046

UniProt features (6 total): chain 1, DNA-binding region 1, region of interest 1, compositionally biased region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04743-F1	67.26	0.22

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9830364	Formation of the nephric duct

MSigDB gene sets: 228 (showing top): RNGTGGGC_UNKNOWN, GOBP_DENTATE_GYRUS_DEVELOPMENT, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_URETER_DEVELOPMENT, TGCACTT_MIR519C_MIR519B_MIR519A, SP3_Q3, MAZ_Q6, GOBP_NEUROGENESIS, AP2_Q3, AAAYRNCTG_UNKNOWN, GOBP_CELL_PROLIFERATION_IN_FOREBRAIN, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_FOREBRAIN_REGIONALIZATION, GOBP_FOREBRAIN_CELL_MIGRATION, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION

GO Biological Process (17): neuron migration (GO:0001764), regulation of transcription by RNA polymerase II (GO:0006357), central nervous system development (GO:0007417), brain development (GO:0007420), response to xenobiotic stimulus (GO:0009410), anterior/posterior pattern specification (GO:0009952), dentate gyrus development (GO:0021542), cerebral cortex regionalization (GO:0021796), cell proliferation in forebrain (GO:0021846), forebrain cell migration (GO:0021885), neuron differentiation (GO:0030182), ureter morphogenesis (GO:0072197), stereocilium bundle organization (GO:0160194), regulation of DNA-templated transcription (GO:0006355), regulation of gene expression (GO:0010468), cerebral cortex development (GO:0021987), forebrain development (GO:0030900)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), axon (GO:0030424), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
cell migration	2
generation of neurons	2
regionalization	2
forebrain development	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
nervous system development	1
system development	1
central nervous system development	1
animal organ development	1
head development	1
response to chemical	1
hippocampus development	1
telencephalon regionalization	1
cerebral cortex development	1
neural precursor cell proliferation	1
cell differentiation	1
animal organ morphogenesis	1
tube morphogenesis	1
ureter development	1
cellular component organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
pallium development	1
brain development	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1

Protein interactions and networks

STRING

1468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EMX2	PAX2	Q02962	788
EMX2	SP8	Q8IXZ3	731
EMX2	FOXG1	P55315	717
EMX2	NEUROG2	Q9H2A3	703
EMX2	FGF8	P55075	692
EMX2	SHH	Q15465	647
EMX2	GFRA1	P56159	632
EMX2	TBR1	Q16650	630
EMX2	EIF4E	P06730	630
EMX2	HOXA11	P31270	628
EMX2	NR2F1	P10589	626
EMX2	LHX1	P48742	622
EMX2	PBX1	P40424	621
EMX2	SOX2	P48431	605
EMX2	OTX2	P32243	599

IntAct

13 interactions, top by confidence:

A	B	Type	Score
EMX2	EIF4E	psi-mi:“MI:0915”(physical association)	0.590
EIF4E	EMX2	psi-mi:“MI:0915”(physical association)	0.590
EMX2	OTUD6A	psi-mi:“MI:0915”(physical association)	0.560
EMX2	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
EMX2	MEIS1	psi-mi:“MI:0915”(physical association)	0.370
EMX2	TLE2	psi-mi:“MI:0915”(physical association)	0.370
EMX2	LRP4	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
OTUD6A	EMX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): OTUD6A (Two-hybrid), EMX2 (Proximity Label-MS), EMX2 (Proximity Label-MS), EMX2 (Proximity Label-MS), EMX2 (Proximity Label-MS), HIST2H2BF (Proximity Label-MS), JPH2 (Proximity Label-MS), EMX2 (Affinity Capture-RNA), C9orf142 (Affinity Capture-MS), SSRP1 (Affinity Capture-MS), HMCES (Affinity Capture-MS), SUPT16H (Affinity Capture-MS), LRP2 (Affinity Capture-MS), PNKP (Affinity Capture-MS), LIG3 (Affinity Capture-MS)

ESM2 similar proteins: D2KQB0, O08656, O13023, O60479, O88181, O93353, P09022, P23682, P23759, P43120, P46692, P47239, P49639, P50575, P53770, P53771, P54655, P56177, P56178, P70062, P70063, P70064, P70396, Q01702, Q03014, Q04743, Q04744, Q05640, Q28DP6, Q2TAQ8, Q3V5Z9, Q4V5A3, Q64205, Q6F2E3, Q6GL68, Q800Q5, Q8AWG6, Q8VIB5, Q90229, Q90270

Diamond homologs: A2RU54, A5YC49, A6NHT5, A6NJ46, A8XJD0, D2KQB0, O08686, O13023, O35762, O43711, O43763, O55144, O57601, O70218, O88181, O93366, O93367, O93590, P15858, P15860, P19601, P20009, P20269, P22544, P22807, P22809, P31314, P40764, P42580, P42581, P43120, P43345, P43687, P50574, P50576, P53772, P53775, P56177, P56407, P63156

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HOXA10	“up-regulates quantity by expression”	EMX2	“transcriptional regulation”
PBX2	“up-regulates quantity by expression”	EMX2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	31
Likely benign	12
Benign	2

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
9519	NM_004098.4(EMX2):c.575_576insA (p.Ser192fs)	Pathogenic
9520	NM_004098.4(EMX2):c.407-1G>A	Pathogenic
9521	NM_004098.4(EMX2):c.407-4G>T	Pathogenic
9522	NM_004098.4(EMX2):c.407G>T (p.Gly136Val)	Pathogenic
3896705	NM_004098.4(EMX2):c.595A>C (p.Lys199Gln)	Likely pathogenic

SpliceAI

584 predictions. Top by Δscore:

Variant	Effect	Δscore
10:117545777:G:GT	donor_gain	1.0000
10:117544206:G:GG	donor_gain	0.9900
10:117545812:CTCAG:C	donor_loss	0.9900
10:117545813:TCAG:T	donor_loss	0.9900
10:117545814:CAG:C	donor_loss	0.9900
10:117545815:AG:A	donor_loss	0.9900
10:117545816:GGTG:G	donor_loss	0.9900
10:117545817:G:T	donor_loss	0.9900
10:117545818:T:A	donor_loss	0.9900
10:117548057:A:AG	acceptor_gain	0.9900
10:117548058:C:G	acceptor_gain	0.9900
10:117548060:CGCA:C	acceptor_loss	0.9900
10:117548061:GCA:G	acceptor_loss	0.9900
10:117548062:CA:C	acceptor_loss	0.9900
10:117548063:A:AC	acceptor_loss	0.9900
10:117548063:A:AG	acceptor_gain	0.9900
10:117548064:G:GG	acceptor_gain	0.9900
10:117548064:G:GT	acceptor_loss	0.9900
10:117548064:GGT:G	acceptor_gain	0.9900
10:117548064:GGTA:G	acceptor_gain	0.9900
10:117548064:GGTAA:G	acceptor_gain	0.9900
10:117545626:CCGCA:C	acceptor_loss	0.9800
10:117545627:CGCA:C	acceptor_loss	0.9800
10:117545628:GCA:G	acceptor_loss	0.9800
10:117545629:CA:C	acceptor_loss	0.9800
10:117545630:A:AG	acceptor_gain	0.9800
10:117545630:A:C	acceptor_loss	0.9800
10:117545630:AG:A	acceptor_gain	0.9800
10:117545631:G:GG	acceptor_gain	0.9800
10:117545631:GG:G	acceptor_gain	0.9800

AlphaMissense

1637 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:117543295:T:C	F10L	1.000
10:117543296:T:C	F10S	1.000
10:117543297:C:A	F10L	1.000
10:117543297:C:G	F10L	1.000
10:117543302:T:A	I12N	1.000
10:117543311:T:C	L15P	1.000
10:117545682:A:G	K153E	1.000
10:117545688:A:G	K155E	1.000
10:117545689:A:T	K155M	1.000
10:117545690:G:C	K155N	1.000
10:117545690:G:T	K155N	1.000
10:117545691:C:T	R156W	1.000
10:117545697:C:G	R158G	1.000
10:117545698:G:A	R158Q	1.000
10:117545698:G:T	R158L	1.000
10:117545700:A:T	T159S	1.000
10:117545701:C:A	T159N	1.000
10:117545701:C:G	T159S	1.000
10:117545701:C:T	T159I	1.000
10:117545704:C:A	A160D	1.000
10:117545706:T:A	F161I	1.000
10:117545706:T:C	F161L	1.000
10:117545706:T:G	F161V	1.000
10:117545707:T:C	F161S	1.000
10:117545707:T:G	F161C	1.000
10:117545708:C:A	F161L	1.000
10:117545708:C:G	F161L	1.000
10:117545709:T:C	S162P	1.000
10:117545710:C:T	S162F	1.000
10:117545720:G:C	Q165H	1.000

dbSNP variants (sampled 300 via entrez): RS1000103340 (10:117547007 TG>T,TGG), RS1000183187 (10:117541880 C>G,T), RS1000214367 (10:117541643 A>G), RS1000245583 (10:117542845 G>T), RS1000433461 (10:117547212 C>G), RS1000548677 (10:117542543 G>A), RS1000643189 (10:117542604 C>G), RS1001031216 (10:117548752 C>G,T), RS1001150618 (10:117547537 G>A), RS1001369525 (10:117547810 G>A), RS1001660299 (10:117542274 G>C), RS1001757521 (10:117542143 G>A), RS1002152601 (10:117542453 G>A,T), RS1002394195 (10:117543726 T>C,G), RS1002654672 (10:117545427 C>G,T)

Disease associations

OMIM: gene MIM:600035 | disease phenotypes: MIM:269160

GenCC curated gene-disease

Disease	Classification	Inheritance
schizencephaly	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
schizencephaly	Limited	AD

Mondo (2): schizencephaly (MONDO:0010011), congenital hypogonadotropic hypogonadism (MONDO:0015770)

Orphanet (2): Schizencephaly (Orphanet:799), Congenital hypogonadotropic hypogonadism (Orphanet:174590)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0001274	Agenesis of corpus callosum
HP:0002120	Cerebral cortical atrophy
HP:0010636	Schizencephaly

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST001559_2	Early cardiac repolarization	6.000000e-06
GCST001621_22	Airflow obstruction	1.000000e-07
GCST001762_329	Obesity-related traits	5.000000e-06
GCST001918_2	Pulmonary function in asthmatics	6.000000e-07
GCST002112_11	Celiac disease	7.000000e-07
GCST002251_6	Homeostasis model assessment of beta-cell function (dietary factor interaction)	3.000000e-08
GCST003992_35	Photic sneeze reflex	1.000000e-28
GCST004369_3	Ovarian disease with few adhesions	4.000000e-07
GCST005232_37	Neuroticism	2.000000e-10
GCST005897_39	Low tan response	7.000000e-24
GCST005983_36	Serum uric acid levels	2.000000e-09
GCST006092_1	Double-edged eyelids	8.000000e-15
GCST006092_2	Double-edged eyelids	2.000000e-07
GCST006295_7	Response to quetiapine in schizophrenia	3.000000e-06
GCST007451_4	Skin, hair and eye pigmentation (multivariate analysis)	2.000000e-08
GCST007452_2	Skin pigmentation	2.000000e-10
GCST007576_223	Chronotype	5.000000e-08
GCST007725_5	Serum uric acid levels	3.000000e-11
GCST008971_26	Urate levels	7.000000e-06
GCST008972_51	Urate levels	2.000000e-08
GCST008972_72	Urate levels	2.000000e-12
GCST010678_6	Liver fibrosis (total hepatic collagen content)	8.000000e-06

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004885	early cardiac repolarization measurement
EFO:0003892	pulmonary function measurement
EFO:0004469	HOMA-B
EFO:0008111	diet measurement
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0007660	neuroticism measurement
EFO:0004279	suntan
EFO:0004761	uric acid measurement
EFO:0009764	eye colour measurement
EFO:0008328	chronotype measurement
EFO:0004531	urate measurement
EFO:0010576	liver fibrosis measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065707	Schizencephaly	C10.500.507.500.750; C16.131.666.507.500.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, increases expression, affects cotreatment	8
methylmercuric chloride	decreases expression, increases expression	3
trichostatin A	affects cotreatment, decreases expression	3
bisphenol A	decreases methylation, affects cotreatment, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	2
Resveratrol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
ascorbate-2-phosphate	affects binding, affects cotreatment, decreases expression	1
sodium arsenite	decreases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
15-acetyldeoxynivalenol	increases expression	1
azoxystrobin	decreases expression	1
entinostat	decreases expression	1
Chir 99021	affects cotreatment, increases expression, affects binding, decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
MRK 003	increases expression	1
XAV939	affects binding, affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
MT19c compound	decreases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, increases expression	1
Amphotericin B	decreases expression	1
Arbutin	decreases expression	1
Ascorbic Acid	affects binding, affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases response to substance	1
Copper	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1J2	SEES3-1V human EMX2, clone1	Embryonic stem cell	Male
CVCL_A1J3	SEES3-1V human EMX2, clone2	Embryonic stem cell	Male
CVCL_A1J4	SEES3-1V human EMX2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01914172	Not specified	COMPLETED	Health Needs of Patients With Kallmann Syndrome