EMX2

empty spiracles homeobox 2, the group of NKL subclass homeoboxes and pseudogenes

Basic information

Region (hg38): 10:117542445-117549546

Links

ENSG00000170370 ∙ NCBI:2018 ∙ OMIM:600035 ∙ HGNC:3341 ∙ Uniprot:Q04743 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizencephaly (Limited), mode of inheritance: AD
• schizencephaly (Moderate), mode of inheritance: AD
• schizencephaly (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schizencephaly	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	8528262; 9359037; 17506092; 18409201

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EMX2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EMX2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	5	1	8
missense			12	2		14
nonsense						0
start loss						0
frameshift						0
inframe indel			1	2		3
splice donor/acceptor (+/-2bp)						0
splice region			1	2		3
non coding						0
Total	0	0	15	9	1

Variants in EMX2

This is a list of pathogenic ClinVar variants found in the EMX2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-117543280-G-C		Inborn genetic diseases	Uncertain significance (Jul 06, 2024)
10-117543281-C-G		Inborn genetic diseases	Uncertain significance (Jul 20, 2021)
10-117543309-G-A		EMX2-related disorder	Likely benign (Oct 19, 2022)
10-117543348-C-G			Uncertain significance (Jan 16, 2017)
10-117543368-C-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
10-117543372-A-T		not specified	Benign/Likely benign (Dec 31, 2019)
10-117543379-T-C		Schizencephaly	Uncertain significance (Dec 11, 2021)
10-117543388-T-G		Inborn genetic diseases	Likely benign (Oct 12, 2021)
10-117543424-T-A		Inborn genetic diseases	Uncertain significance (Jun 25, 2024)
10-117543426-GGCC-G			Likely benign (Sep 01, 2022)
10-117543426-GGCCGCC-G		not specified • EMX2-related disorder	Benign/Likely benign (Jul 13, 2017)
10-117543426-G-GGCC		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 31, 2022)
10-117543426-G-GGCCGCC		Schizencephaly	Uncertain significance (Mar 24, 2020)
10-117543478-T-G		Inborn genetic diseases	Uncertain significance (Jul 31, 2024)
10-117543498-C-G		Schizencephaly	Uncertain significance (Aug 27, 2021)
10-117543505-A-G		Inborn genetic diseases	Uncertain significance (May 01, 2023)
10-117543519-A-C			Likely benign (Feb 01, 2024)
10-117543527-C-T		Schizencephaly	Uncertain significance (Mar 02, 2021)
10-117543575-A-T		Inborn genetic diseases	Uncertain significance (Sep 10, 2024)
10-117543578-C-T		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
10-117543615-G-T			Uncertain significance (May 23, 2017)
10-117543627-C-T			Likely benign (Apr 10, 2018)
10-117545628-G-T		Schizencephaly	Pathogenic (Jan 01, 1996)
10-117545631-G-A		Schizencephaly	Pathogenic (Jan 01, 1996)
10-117545632-G-A		Inborn genetic diseases	Uncertain significance (Nov 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EMX2	protein_coding	protein_coding	ENST00000553456	3	7102

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.951	0.0492	113689	0	1	113690	0.00000440

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	94	148	0.637	0.00000676	1608
Missense in Polyphen		18	41.449	0.43427		486
Synonymous	0.503	63	68.3	0.923	0.00000342	523
Loss of Function	2.85	0	9.47	0.00	4.33e-7	96

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000214	0.0000101
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor, which in cooperation with EMX2, acts to generate the boundary between the roof and archipallium in the developing brain. May function in combinations with OTX1/2 to specify cell fates in the developing central nervous system.

Recessive Scores

• pRec: 0.315

Intolerance Scores

• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.938
• hipred: Y
• hipred_score: 0.837
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.772

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Emx2
• Phenotype: renal/urinary system phenotype; skeleton phenotype; vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; cellular phenotype; craniofacial phenotype; taste/olfaction phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: emx2
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: orientation

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;anterior/posterior pattern specification;dentate gyrus development;cerebral cortex regionalization;cell proliferation in forebrain;forebrain cell migration;neuron differentiation;response to drug;renal system development
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;protein binding;sequence-specific DNA binding