EN1

engrailed homeobox 1, the group of NKL subclass homeoboxes and pseudogenes

Basic information

Region (hg38): 2:118842171-118847648

Links

ENSG00000163064 ∙ NCBI:2019 ∙ OMIM:131290 ∙ HGNC:3342 ∙ Uniprot:Q05925 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ENDOVE syndrome, limb-only type (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
ENDOVE syndrome, limb-brain type	AR	Renal	Among other findings, an individual has been described with bilateral hydronephrosis and recurrent urinary tract infections, and awareness may allow eaerly diagnosis, preventative measures, and management of infections	Musculoskeletal; Neurologic; Renal	33568816
The conditions are due to deletions and genomic rearrangements of a domain upstream of EN1

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EN1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EN1 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				3		3
missense			27	2		29
nonsense						0
start loss						0
frameshift						0
inframe indel				2		2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	27	7	0

Variants in EN1

This is a list of pathogenic ClinVar variants found in the EN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-118842949-C-T		not specified	Uncertain significance (Apr 25, 2022)
2-118843000-T-A		not specified	Uncertain significance (Dec 04, 2024)
2-118843024-T-C		not specified	Uncertain significance (Dec 06, 2023)
2-118843078-T-C		not specified	Uncertain significance (Dec 07, 2024)
2-118843113-G-C		not specified	Uncertain significance (Nov 09, 2024)
2-118843167-C-T		not specified	Uncertain significance (May 23, 2023)
2-118843203-C-T		not specified	Uncertain significance (Sep 01, 2021)
2-118843217-C-G		not specified	Uncertain significance (Jun 10, 2024)
2-118846420-T-C		not specified	Uncertain significance (Nov 07, 2022)
2-118846432-C-T		not specified	Uncertain significance (Jun 30, 2024)
2-118846467-C-A		not specified	Uncertain significance (Mar 04, 2024)
2-118846489-C-A		not specified	Uncertain significance (Jun 21, 2021)
2-118846503-T-G		not specified	Uncertain significance (Nov 23, 2024)
2-118846507-A-T		not specified	Uncertain significance (Nov 17, 2022)
2-118846520-TGCGGCCGCCGCCGCCGCCGCCACTGCCGCC-T			Likely benign (Jan 01, 2024)
2-118846529-CGCCGCCGCCGCCACTGCCGCCGCG-C		EN1-related disorder	Likely benign (Jan 10, 2022)
2-118846565-C-G			Likely benign (Oct 01, 2024)
2-118846569-G-A		not specified	Uncertain significance (Jan 16, 2024)
2-118846593-G-A		not specified	Uncertain significance (Dec 06, 2024)
2-118846599-G-A		not specified	Uncertain significance (Dec 11, 2023)
2-118846603-C-G		not specified	Uncertain significance (Jul 11, 2023)
2-118846655-G-A			Likely benign (Jun 01, 2022)
2-118846656-C-T		not specified	Uncertain significance (Feb 26, 2024)
2-118846683-C-G		not specified	Uncertain significance (Nov 08, 2021)
2-118846696-G-T		not specified	Uncertain significance (May 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EN1	protein_coding	protein_coding	ENST00000295206	2	5508

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.931	0.0683	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	137	178	0.768	0.00000805	2446
Missense in Polyphen		15	45.707	0.32817		501
Synonymous	-1.69	101	81.6	1.24	0.00000391	855
Loss of Function	2.71	0	8.54	0.00	3.67e-7	112

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

dbNSFP

Source: dbNSFP

• Pathway: Dopaminergic Neurogenesis;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways (Consensus)

Recessive Scores

• pRec: 0.265

Haploinsufficiency Scores

• pHI: 0.608
• hipred: Y
• hipred_score: 0.559
• ghis: 0.447

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.887

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: En1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system 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); normal phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation 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); limbs/digits/tail phenotype; immune system phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;skeletal system development;adult locomotory behavior;anatomical structure morphogenesis;dorsal/ventral pattern formation;proximal/distal pattern formation;cerebellum development;midbrain development;midbrain-hindbrain boundary development;embryonic forelimb morphogenesis;social behavior;multicellular organism growth;drinking behavior;pigmentation;negative regulation of neuron apoptotic process;positive regulation of transcription by RNA polymerase II;neuron development;motor learning;dopaminergic neuron differentiation;embryonic brain development
• Cellular component: nucleus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific