EN2

engrailed homeobox 2, the group of NKL subclass homeoboxes and pseudogenes

Basic information

Region (hg38): 7:155458129-155464831

Links

ENSG00000164778 ∙ NCBI:2020 ∙ OMIM:131310 ∙ HGNC:3343 ∙ Uniprot:P19622 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Disputed Evidence), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EN2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EN2 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				1	4	5
missense			36			36
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	36	1	4

Variants in EN2

This is a list of pathogenic ClinVar variants found in the EN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-155458393-C-A		not specified	Uncertain significance (Jan 03, 2022)
7-155458432-C-T		not specified	Uncertain significance (Sep 04, 2024)
7-155458456-G-C		not specified	Uncertain significance (Oct 25, 2023)
7-155458466-G-A		not specified	Uncertain significance (Apr 15, 2024)
7-155458496-C-G		not specified	Uncertain significance (Jul 19, 2023)
7-155458504-G-C		not specified	Uncertain significance (Apr 15, 2024)
7-155458510-C-T		not specified	Uncertain significance (Nov 27, 2023)
7-155458531-G-T		not specified	Uncertain significance (Oct 11, 2024)
7-155458549-G-A		not specified	Uncertain significance (Oct 12, 2022)
7-155458580-A-G		not specified	Uncertain significance (Feb 02, 2022)
7-155458608-C-G			Benign (Jul 10, 2018)
7-155458646-C-G		not specified	Uncertain significance (Feb 05, 2024)
7-155458658-G-A		not specified	Uncertain significance (Oct 20, 2021)
7-155458682-G-A		not specified	Uncertain significance (Nov 08, 2024)
7-155458700-G-C		not specified	Uncertain significance (Jan 18, 2022)
7-155458703-C-T		not specified	Uncertain significance (May 15, 2024)
7-155458707-G-C		not specified	Uncertain significance (Dec 04, 2024)
7-155458717-G-A		not specified	Uncertain significance (Aug 23, 2021)
7-155458744-G-C		not specified	Uncertain significance (Feb 06, 2024)
7-155458754-C-T		not specified	Uncertain significance (May 14, 2024)
7-155458765-C-G		not specified	Uncertain significance (Oct 10, 2023)
7-155458774-C-A		not specified	Uncertain significance (Jun 17, 2024)
7-155458796-G-A		not specified	Uncertain significance (Oct 12, 2022)
7-155458802-C-T		not specified	Uncertain significance (Jul 20, 2022)
7-155458817-G-T		not specified	Uncertain significance (Aug 13, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EN2	protein_coding	protein_coding	ENST00000297375	2	6703

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.634	0.359	121986	0	1	121987	0.00000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.08	88	122	0.724	0.00000590	2054
Missense in Polyphen		31	48.778	0.63554		669
Synonymous	-0.232	58	55.8	1.04	0.00000269	698
Loss of Function	2.20	1	7.48	0.134	3.65e-7	107

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)	0.00000902	0.00000902
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Note=Genetic variations in EN2 may be associated with susceptibility to autism.
• Pathway: Dopaminergic Neurogenesis (Consensus)

Recessive Scores

• pRec: 0.415

Haploinsufficiency Scores

• pHI: 0.195
• hipred: Y
• hipred_score: 0.670
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.885

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: En2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; embryo 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); digestive/alimentary phenotype; 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)

Zebrafish Information Network

• Gene name: en2a
• Affected structure: optic tectum
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: multicellular organism development;midbrain development;hindbrain development;negative regulation of neuron apoptotic process;positive regulation of transcription by RNA polymerase II;neuron development;embryonic brain development
• Cellular component: fibrillar center;nucleus;nucleolus;membrane
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;sequence-specific DNA binding