EN1

Chr 2AR

engrailed homeobox 1

Also known as: ENDOVESLB

NCBI Gene: 2019ENSG00000163064UniProt: Q05925

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]

Primary Disease Associations & Inheritance

?ENDOVE syndrome, limb-brain typeMIM #619218
AR
1
Active trials
22
Pathogenic / LP
103
ClinVar variants
27
Pubs (1 yr)
1.1
Missense Z
0.35
LOEUF
Clinical Summary— EN1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 71 VUS of 103 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — EN1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.35LOEUF
pLI 0.931
Z-score 2.71
OE 0.00 (0.00–0.35)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.10Z-score
OE missense 0.77 (0.67–0.89)
137 obs / 178.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.35)
0≤0.351.4
Missense OE0.77 (0.67–0.89)
0≤0.61.4
Synonymous OE1.24
0≤1.21.6
LoF obs/exp: 0 / 8.5Missense obs/exp: 137 / 178.3Syn Z: -1.69
LOF
DN
0.2897th %ile
GOF
0.2995th %ile
LOF
0.89top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.35

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

103 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS71
Likely Benign10
20
Pathogenic
2
Likely Pathogenic
71
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
19
0
20
Likely Pathogenic
0
0
2
0
2
VUS
0
68
3
0
71
Likely Benign
0
4
2
4
10
Benign
0
0
0
0
0
Total172264103

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

EN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Synergistic Interactions between Nitrogen Fixation and Phosphorus Uptake in Legumes: Insights from the Root Nodule Bacterium En1.
Xu Y et al.·J Agric Food Chem
2025
NSGO-FANDANGO/ENGOT-EN1: A randomized phase II study of first-line combination chemotherapy with nintedanib/placebo in advanced/recurrent endometrial cancer.
Lindemann K et al.·Gynecol Oncol
2025
Transcriptome analysis reveals the potential role of neural factor EN1 for long-terms survival in estrogen receptor-independent breast cancer.
Ren H et al.·Mol Ther Oncol
2025Open Access
Heterozygous loss of Engrailed-1 and α-synucleinopathy (En1/SYN): A dual-hit preclinical mouse model of Parkinson's disease, analyzed with artificial intelligence.
Stetzik L et al.·Neurobiol Dis
2024Open AccessFunctional
[En1 promotes cell proliferation and migration via Hedgehog signaling pathway in esophageal squamous cell carcinoma].
Zhao N et al.·Zhonghua Zhong Liu Za Zhi
2024
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients