EN1

protein-coding

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

Gene summary

Homeobox-containing genes are thought to have a role in controlling development. In Drosophila, the 'engrailed' (en) gene plays an important role during development in segmentation, where it is required for the formation of posterior compartments. Different mutations in the mouse homologs, En1 and En2, produced different developmental defects that frequently are lethal. The human engrailed homologs 1 and 2 encode homeodomain-containing proteins and have been implicated in the control of pattern formation during development of the central nervous system. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001426.4

Inheritance

ClinVar variants

P:1U:68B:9

Top phenotype

ENDOVE syndrome, limb-brain type

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr2:118,842,171-118,847,648

External References & Databases

Ensembl (ENSG00000163064)

Transcript & Mutation Effects

hg38 • Region Span ~5.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

EN1-related dorsoventral syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:1040032

Submitter: PanelApp Australia

ENDOVE syndrome, limb-only typeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030978

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

ENDOVE syndrome, limb-brain typeAR

Manifestation: Musculoskeletal; Neurologic; Renal

Intervention: Renal

Rationale: 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

Comments: The conditions are due to deletions and genomic rearrangements of a domain upstream of EN1

Refs: 33568816

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EN1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 74

not providedTotal: 6

EN1-related disorderTotal: 2

EN1 syndromeTotal: 1

ENDOVE syndrome, limb-brain typeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001426.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar		5
missense			68 clinvar	4 clinvar		72
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	1	0	68	9	0	78

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001426.4	RefSeq	NP_001417.3	2	MANE Select
ENST00000295206.7	Ensembl	ENSP00000295206.5	2	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Dopaminergic Neurogenesis
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways

Biological Process

negative regulation of transcription by RNA polymerase II
skeletal system development
adult locomotory behavior
anatomical structure morphogenesis
dorsal/ventral pattern formation

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295206
Coding exons: 2
Length: 5508
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	137	178	0.768	0.00000805	2446
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.265

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.887

Gene Damage Prediction

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