EN1

Summary

EN1 (engrailed homeobox 1, HGNC:3342) is a protein-coding gene on chromosome 2q14.2, encoding Homeobox protein engrailed-1 (Q05925). Required for proper formation of the apical ectodermal ridge and correct dorsal-ventral patterning in the limb.

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.

Source: NCBI Gene 2019 — RefSeq curated summary.

At a glance

• Gene–disease (curated): EN1-related dorsoventral syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 34
• Clinical variants (ClinVar): 80 total — 1 pathogenic
• Phenotypes (HPO): 22
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_001426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3342
Approved symbol	EN1
Name	engrailed homeobox 1
Location	2q14.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163064
Ensembl biotype	protein_coding
OMIM	131290
Entrez	2019

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000295206, ENST00000546667

RefSeq mRNA: 1 — MANE Select: NM_001426 NM_001426

CCDS: CCDS2123

Canonical transcript exons

ENST00000295206 — 2 exons

Exon	Start	End
ENSE00001071267	118846306	118847648
ENSE00001071269	118842171	118843254

Expression profiles

Bgee: expression breadth broad, 85 present calls, max score 83.41.

FANTOM5 (CAGE): breadth broad, TPM avg 5.2615 / max 607.9204, expressed in 541 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30389	3.4520	330
30386	0.5930	333
30391	0.3265	146
30390	0.2980	114
30387	0.2436	142
30392	0.2218	77
30388	0.1266	47

Top tissues by expression

246 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
substantia nigra pars reticulata	UBERON:0001966	83.41	gold quality
skin of leg	UBERON:0001511	79.69	gold quality
gastrocnemius	UBERON:0001388	79.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.62	gold quality
muscle of leg	UBERON:0001383	78.39	gold quality
substantia nigra pars compacta	UBERON:0001965	78.39	gold quality
zone of skin	UBERON:0000014	77.86	gold quality
muscle organ	UBERON:0001630	76.77	gold quality
skin of abdomen	UBERON:0001416	76.20	gold quality
skin of hip	UBERON:0001554	76.19	gold quality
upper leg skin	UBERON:0004262	75.92	gold quality
upper arm skin	UBERON:0004263	75.40	silver quality
biceps brachii	UBERON:0001507	74.90	silver quality
triceps brachii	UBERON:0001509	73.22	gold quality
quadriceps femoris	UBERON:0001377	72.20	silver quality
substantia nigra	UBERON:0002038	71.86	gold quality
vastus lateralis	UBERON:0001379	71.48	silver quality
skeletal muscle tissue	UBERON:0001134	71.28	gold quality
diaphragm	UBERON:0001103	71.24	gold quality
gluteal muscle	UBERON:0002000	71.18	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.90	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	70.35	gold quality
subcutaneous adipose tissue	UBERON:0002190	69.68	gold quality
midbrain	UBERON:0001891	69.24	gold quality
muscle tissue	UBERON:0002385	67.17	gold quality
deltoid	UBERON:0001476	64.55	silver quality
adipose tissue	UBERON:0001013	62.97	gold quality
connective tissue	UBERON:0002384	61.93	gold quality
lymph node	UBERON:0000029	60.17	gold quality
tibialis anterior	UBERON:0001385	59.99	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.01

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets.

Target	Regulation
CCK
CTNNB1	Repression
DST	Unknown
FGF8	Unknown
GLI3
SLC18A2
TTN	Unknown
TUBB3
UTRN	Repression
WNT1
WNT7A	Repression

JASPAR motifs

Motif	Name	Family
MA0027.2	EN1	NK
MA0027.3	EN1	NK

JASPAR matrix evidence (PMIDs): PMID:8096059

Upstream regulators (CollecTRI, top): BPTF, DEAF1, EBF1, FOXA1, FOXA2, SMARCA1, WNT1

miRNA regulators (miRDB)

64 targeting EN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-944	99.82	70.85	3042

Literature-anchored findings (GeneRIF, showing 27)

• En-1 exerts its repressive effect by a mechanism negatively controlling the level of beta-catenin. (PMID:16571670)
• When beta-catenin is activated in transgenic En1 expressing cells, it induces Dermo1 expression in all cells of the En1 domain and disrupts muscle gene expression. (PMID:16730693)
• Genetic variation in human engrailed 1 may influence antipsychotic response in schizophrenia. (PMID:18698228)
• Single nucleotide polymorphisms genotyped in the EN1 gene were associated with schizophrenia symptoms (PMID:18698228)
• The result of this study found a strong association between the EN1 rs1438852 polymorphism and Parkinson’s disease. (PMID:19345444)
• Epigenetic suppression along 2q14.2 is common to most colorectal cancers and the presence of a methylated EN1 CpG island in stool DNA might be used as biomarker of neoplastic disease. (PMID:19384295)
• EN1 might be a negative regulatory factor for UTROPHIN. (PMID:21482524)
• Homeobox protein engrailed-1 protein regulates transcription of the utrophin gene. (PMID:21672318)
• EN1 is a biologic predictor of poor prognosis in patients with salivary adenoid cystic carcinoma. (PMID:21800291)
• EN1 is an activator of intrinsic inflammatory pathways associated with prosurvival in basal-like breast cancer. (PMID:24141779)
• The current review describes the role of two such factors, Nurr1 and engrailed, in differentiation, maturation, and in normal physiological functions including acquisition of neurotransmitter identity. (PMID:24685177)
• low-frequency non-coding variant near a novel locus, EN1, with an effect on bone mineral density–which was also associated with a decreased risk of fracture (PMID:26367794)
• FGFR Inhibitor Ameliorates Hypophosphatemia and Impaired Engrailed-1/Wnt Signaling in FGF2 High Molecular Weight Isoform (PMID:26762209)
• our finding suggested that the EN1 rs4144782 might contribute to the susceptibility of knee OA. (PMID:28430581)
• Study found that EN1 was significantly overexpressed in triple-negative breast cancer (TNBC). In breast cancer cell lines EN1 was more highly expressed in TNBC than in other breast cancer subtypes. EN1 expressions analysis in TNBC tissue samples revealed that EN1 protein expression was positively associated with reduced overall survival rate in patients with quintuple-negative, but not those with basal-like breast cancer. (PMID:29333926)
• Engrailed homeobox 1 was expressed specifically in normal eccrine glands and was expressed in most of the tumour cells of sweat gland neoplasms with eccrine gland differentiation. (PMID:29436004)
• EN1 transcription factor regulates neurogenesis-related genes and is associated with brain metastasis in triple-negative breast cancer. (PMID:31239270)
• Engrailed Homeobox 1 and Cytokeratin 19 Are Independent Diagnostic Markers of Eccrine Porocarcinoma and Distinguish It From Squamous Cell Carcinoma. (PMID:32556098)
• Homeobox transcription factor engrailed homeobox 1 is a possible diagnostic marker for adenoid cystic carcinoma and polymorphous adenocarcinoma. (PMID:33333616)
• Repeated mutation of a developmental enhancer contributed to human thermoregulatory evolution. (PMID:33850016)
• Engrailed 1 coordinates cytoskeletal reorganization to induce myofibroblast differentiation. (PMID:34259830)
• Converting fibroblastic fates leads to wound healing without scar. (PMID:34471094)
• EN1 Regulates Cell Growth and Proliferation in Human Glioma Cells via Hedgehog Signaling. (PMID:35163043)
• Engrailed-1 Promotes Pancreatic Cancer Metastasis. (PMID:38110836)
• The osteoporosis susceptibility SNP rs188303909 at 2q14.2 regulates EN1 expression by modulating DNA methylation and E2F6 binding. (PMID:38153509)
• TGFbeta-induced EN1 promotes tumor budding of adenoid cystic carcinoma in patient-derived organoid model. (PMID:38282121)
• [En1 promotes cell proliferation and migration via Hedgehog signaling pathway in esophageal squamous cell carcinoma]. (PMID:38418183)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	en1a	ENSDARG00000014321
danio_rerio	en1b	ENSDARG00000098730
mus_musculus	En1	ENSMUSG00000058665
rattus_norvegicus	En1	ENSRNOG00000056580
drosophila_melanogaster	en	FBGN0000577
drosophila_melanogaster	inv	FBGN0001269
caenorhabditis_elegans		WBGENE00000439

Paralogs (3): EN2 (ENSG00000164778), CPHXL (ENSG00000283755), CPHXL2 (ENSG00000284484)

Protein

Protein identifiers

Homeobox protein engrailed-1 — Q05925 (reviewed: Q05925)

All UniProt accessions (1): Q05925

UniProt curated annotations — full annotation on UniProt →

Function. Required for proper formation of the apical ectodermal ridge and correct dorsal-ventral patterning in the limb.

Subcellular location. Nucleus.

Disease relevance. ENDOVE syndrome, limb-only type (ENDOVESL) [MIM:619217] An autosomal recessive disorder characterized by severe shortening and deformation of the legs and feet, 3/4 syndactyly of the hands, and toenails partially displaced to plantar surface. Radiographs show normal femora but severely shortened tibiae, triangular fibulae and malformed or absent bones in the feet. In addition, genitourinary anomalies have been observed. The gene represented in this entry is involved in disease pathogenesis. Homozygous structural variants on chromosome 2 located 300 kb upstream of EN1 result in altered EN1 expression with pathological consequences. ENDOVE syndrome, limb-brain type (ENDOVESLB) [MIM:619218] An autosomal recessive disorder characterized by marked mesomelic shortening of the lower limbs, severe hypoplasia of the tibia and fibula, absent talus, and rudimentary and short foot bones. Hands show short and malformed fingers with a missing digit, and nails are absent on some fingers. Affected individuals manifest neurologic symptoms including seizures and generalized hypotonia. Brain imaging reveals absence of the cerebellum and hypoplasia of the brain stem. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the engrailed homeobox family.

RefSeq proteins (1): NP_001417* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000747	HD_engrailed	Domain
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR019549	Homeobox-engrailed_C-terminal	Domain
IPR019737	Homeobox-engrailed_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR050720	Engrailed_Homeobox_TFs	Family

Pfam: PF00046, PF10525

UniProt features (12 total): compositionally biased region 5, region of interest 4, chain 1, DNA-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05925-F1	58.76	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 288 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, GOBP_METENCEPHALON_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_COCAINE, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, NKX25_02

GO Biological Process (30): negative regulation of transcription by RNA polymerase II (GO:0000122), skeletal system development (GO:0001501), regulation of transcription by RNA polymerase II (GO:0006357), adult locomotory behavior (GO:0008344), anatomical structure morphogenesis (GO:0009653), dorsal/ventral pattern formation (GO:0009953), proximal/distal pattern formation (GO:0009954), cerebellum development (GO:0021549), central nervous system neuron differentiation (GO:0021953), neuron differentiation (GO:0030182), midbrain development (GO:0030901), midbrain-hindbrain boundary development (GO:0030917), embryonic forelimb morphogenesis (GO:0035115), social behavior (GO:0035176), multicellular organism growth (GO:0035264), response to cocaine (GO:0042220), drinking behavior (GO:0042756), pigmentation (GO:0043473), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of transcription by RNA polymerase II (GO:0045944), neuron development (GO:0048666), motor learning (GO:0061743), dopaminergic neuron differentiation (GO:0071542), embryonic brain development (GO:1990403), regulation of DNA-templated transcription (GO:0006355), multicellular organism development (GO:0007275), regulation of gene expression (GO:0010468), embryonic limb morphogenesis (GO:0030326), hindbrain development (GO:0030902), limb development (GO:0060173)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regionalization	2
brain development	2
negative regulation of DNA-templated transcription	1
system development	1
regulation of DNA-templated transcription	1
locomotory behavior	1
adult behavior	1
developmental process	1
metencephalon development	1
central nervous system development	1
neuron differentiation	1
cell differentiation	1
generation of neurons	1
rostrocaudal neural tube patterning	1
embryonic limb morphogenesis	1
forelimb morphogenesis	1
behavior	1
biological process involved in intraspecies interaction between organisms	1
multicellular organismal process	1
developmental growth	1
response to alkaloid	1
response to oxygen-containing compound	1
feeding behavior	1
biological_process	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1

Protein interactions and networks

STRING

1150 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EN1	PAX2	Q02962	833
EN1	WNT1	P04628	765
EN1	FGF8	P55075	764
EN1	FOXA2	Q9Y261	742
EN1	NR4A2	P43354	697
EN1	LBH	Q53QV2	668
EN1	SHH	Q15465	639
EN1	KCNJ6	P48051	593
EN1	ZNF224	P17033	584
EN1	CORIN	Q9Y5Q5	583
EN1	PAX6	P26367	582
EN1	TH	P07101	564
EN1	SLC18A2	Q05940	559
EN1	FOXG1	P55315	551
EN1	RTTN	Q86VV8	548

IntAct

7 interactions, top by confidence:

A	B	Type	Score
NFIA	EN1	psi-mi:“MI:0915”(physical association)	0.470
NFIB	EN1	psi-mi:“MI:0915”(physical association)	0.470
EN1	NFIB	psi-mi:“MI:2364”(proximity)	0.470
NFIC	EN1	psi-mi:“MI:0915”(physical association)	0.400
EN1	RPA1	psi-mi:“MI:0914”(association)	0.350
EN1	MEIS1	psi-mi:“MI:0914”(association)	0.350

BioGRID (119): EN1 (Reconstituted Complex), GINS3 (Affinity Capture-MS), AHCYL2 (Affinity Capture-MS), SIRT1 (Affinity Capture-MS), ANKHD1-EIF4EBP3 (Affinity Capture-MS), AHCYL1 (Affinity Capture-MS), DROSHA (Affinity Capture-MS), SSU72 (Affinity Capture-MS), NAP1L3 (Affinity Capture-MS), PBX2 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), PBK (Affinity Capture-MS), TLE1 (Affinity Capture-MS), TRIM37 (Affinity Capture-MS)

ESM2 similar proteins: A1YER7, A1YF08, A1YFD8, A1YFY3, A1YG85, A2D4P8, A2D5I1, A2T6X6, A2T756, A2T7H5, A6NCS4, A6NJT0, O08934, O14813, O42230, O43763, O70218, O93367, P06798, P09016, P10284, P10628, P13378, P17277, P17483, P18111, P23683, P23813, P31277, P31310, P35452, P47902, P49640, P50223, P52945, P52946, P52947, P70118, P82976, P97830

Diamond homologs: A9ZPC9, F1R2J1, O02491, O42370, O43365, O60479, O93353, O93528, P02831, P02836, P05527, P09015, P09065, P09066, P09075, P09076, P09089, P09090, P09145, P09532, P10105, P14150, P15858, P17487, P19622, P20009, P20269, P23397, P27609, P27610, P31316, P31533, P31534, P31535, P31536, P31537, P31538, P34326, P34684, P42580

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
HNuRF	“up-regulates quantity by expression”	EN1
DEAF1	“up-regulates quantity by expression”	EN1	“transcriptional regulation”
EN1	“down-regulates quantity by repression”	FGF8	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

80 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	69
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
989394	NM_001426.4(EN1):c.317dup (p.Ile107fs)	Pathogenic

SpliceAI

379 predictions. Top by Δscore:

Variant	Effect	Δscore
2:118843250:CGGAC:C	acceptor_gain	0.9900
2:118843252:GAC:G	acceptor_gain	0.9900
2:118843253:AC:A	acceptor_gain	0.9900
2:118843254:CC:C	acceptor_gain	0.9900
2:118843255:C:CC	acceptor_gain	0.9900
2:118843255:CTGC:C	acceptor_loss	0.9900
2:118843251:GGAC:G	acceptor_gain	0.9800
2:118843262:G:T	acceptor_gain	0.9800
2:118843265:G:T	acceptor_gain	0.9800
2:118843261:C:CT	acceptor_gain	0.9700
2:118843264:C:CT	acceptor_gain	0.9700
2:118845765:T:A	donor_gain	0.9700
2:118846087:T:TA	donor_gain	0.9700
2:118843253:ACCTG:A	acceptor_gain	0.9600
2:118843254:CCT:C	acceptor_gain	0.9600
2:118846300:ACTC:A	donor_loss	0.9600
2:118846301:CTC:C	donor_loss	0.9600
2:118846302:TCACC:T	donor_loss	0.9600
2:118846303:CACCG:C	donor_loss	0.9600
2:118846304:ACCG:A	donor_loss	0.9600
2:118846305:C:CT	donor_loss	0.9600
2:118843252:GACCT:G	acceptor_gain	0.9500
2:118843255:CTGCA:C	acceptor_gain	0.9500
2:118843259:A:T	acceptor_gain	0.9500
2:118844092:T:TA	donor_gain	0.9500
2:118844099:T:A	donor_gain	0.9500
2:118845777:T:TA	donor_gain	0.9500
2:118846297:GGTAC:G	donor_loss	0.9500
2:118846298:GTAC:G	donor_loss	0.9500
2:118846299:TAC:T	donor_loss	0.9500

AlphaMissense

2512 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:118842977:G:C	H380Q	1.000
2:118842977:G:T	H380Q	1.000
2:118842978:T:C	H380R	1.000
2:118842979:G:C	H380D	1.000
2:118842980:G:C	N379K	1.000
2:118842980:G:T	N379K	1.000
2:118842984:T:C	Y378C	1.000
2:118842985:A:C	Y378D	1.000
2:118842985:A:G	Y378H	1.000
2:118842987:A:G	L377P	1.000
2:118842987:A:T	L377Q	1.000
2:118842990:C:A	G376V	1.000
2:118842990:C:T	G376E	1.000
2:118842991:C:G	G376R	1.000
2:118842991:C:T	G376R	1.000
2:118842993:T:G	Q375P	1.000
2:118842997:C:G	A374P	1.000
2:118842998:C:A	M373I	1.000
2:118842998:C:G	M373I	1.000
2:118842998:C:T	M373I	1.000
2:118842999:A:G	M373T	1.000
2:118843002:A:C	L372R	1.000
2:118843002:A:G	L372P	1.000
2:118843002:A:T	L372H	1.000
2:118843003:G:A	L372F	1.000
2:118843008:A:G	L370P	1.000
2:118843014:A:G	L368P	1.000
2:118843014:A:T	L368Q	1.000
2:118843036:C:G	A361P	1.000
2:118843037:T:A	K360N	1.000

dbSNP variants (sampled 300 via entrez): RS1000120526 (2:118843466 G>A), RS1000996333 (2:118849589 C>T), RS1001293117 (2:118842766 A>C,G), RS1001346452 (2:118842442 G>A,C), RS1001366688 (2:118846947 A>C,G,T), RS1001566400 (2:118849180 G>T), RS1002273321 (2:118846880 C>G), RS1002854807 (2:118843719 C>T), RS1003013260 (2:118849359 A>G), RS1003044310 (2:118849040 A>G), RS1003240042 (2:118842091 G>T), RS1003350206 (2:118847908 G>A,C), RS1003511973 (2:118847920 A>T), RS1003966138 (2:118847483 CA>C,CAA), RS1003975007 (2:118847590 A>G)

Disease associations

OMIM: gene MIM:131290 | disease phenotypes: MIM:619218

GenCC curated gene-disease

Disease	Classification	Inheritance
EN1-related dorsoventral syndrome	Strong	Autosomal recessive
ENDOVE syndrome, limb-only type	Limited	Unknown

Mondo (3): ENDOVE syndrome, limb-brain type (MONDO:0030979), ENDOVE syndrome, limb-only type (MONDO:0030978), EN1-related dorsoventral syndrome (MONDO:1040032)

Orphanet (0):

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000011	Neurogenic bladder
HP:0000126	Hydronephrosis
HP:0000252	Microcephaly
HP:0000750	Delayed speech and language development
HP:0001252	Hypotonia
HP:0001290	Generalized hypotonia
HP:0001382	Joint hypermobility
HP:0001508	Failure to thrive
HP:0001537	Umbilical hernia
HP:0001770	Toe syndactyly
HP:0002365	Hypoplasia of the brainstem
HP:0002754	Osteomyelitis
HP:0003577	Congenital onset
HP:0009460	Aplasia of the 3rd finger
HP:0011167	Focal tonic seizure
HP:0012642	Cerebellar agenesis
HP:0030884	Gastrojejunal tube feeding in infancy
HP:0031260	Triangular tibia
HP:0032988	Persistent head lag
HP:0033977	Talar aplasia

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST000269_9	Multiple sclerosis	7.000000e-06
GCST003388_5	Bone mineral density (spine)	1.000000e-12
GCST003389_2	Bone mineral density (hip)	8.000000e-13
GCST003389_4	Bone mineral density (hip)	3.000000e-10
GCST003996_19	Monobrow	8.000000e-10
GCST004250_27	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	2.000000e-07
GCST004350_16	Bone ultrasound measurement (velocity of sound)	2.000000e-07
GCST004744_75	Lung adenocarcinoma	7.000000e-07
GCST004863_58	Mosquito bite size	2.000000e-07
GCST005544_2	Femoral neck bone mineral density	7.000000e-15
GCST005544_3	Femoral neck bone mineral density	2.000000e-06
GCST005545_1	Lumbar spine bone mineral density	1.000000e-09
GCST005545_2	Lumbar spine bone mineral density	2.000000e-14
GCST005545_4	Lumbar spine bone mineral density	2.000000e-09
GCST005795_15	Femoral neck bone mineral density	3.000000e-09
GCST006288_234	Heel bone mineral density	2.000000e-44
GCST006288_235	Heel bone mineral density	2.000000e-09
GCST006288_236	Heel bone mineral density	3.000000e-27
GCST006288_270	Heel bone mineral density	2.000000e-41
GCST006288_271	Heel bone mineral density	2.000000e-09
GCST006288_272	Heel bone mineral density	2.000000e-20
GCST006288_496	Heel bone mineral density	2.000000e-17
GCST006288_497	Heel bone mineral density	7.000000e-08
GCST006288_498	Heel bone mineral density	3.000000e-46
GCST006288_578	Heel bone mineral density	6.000000e-88
GCST006483_12	Lung function (FVC)	4.000000e-08
GCST006979_29	Heel bone mineral density	5.000000e-141
GCST006979_30	Heel bone mineral density	9.000000e-11
GCST006979_31	Heel bone mineral density	4.000000e-52
GCST006979_32	Heel bone mineral density	4.000000e-41

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0007701	spine bone mineral density
EFO:0007702	hip bone mineral density
EFO:0007906	synophrys measurement
EFO:0007965	response to combination chemotherapy
EFO:0004514	bone quantitative ultrasound measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0007785	femoral neck bone mineral density
EFO:0009270	heel bone mineral density
EFO:0004312	vital capacity
EFO:0003924	hair color
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Acetaminophen	decreases expression	2
Dexamethasone	increases expression, affects cotreatment	2
bisphenol F	increases expression, affects cotreatment	1
arsenite	increases methylation	1
bisphenol S	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Decitabine	increases expression	1
Fulvestrant	decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Ascorbic Acid	decreases expression, decreases reaction, increases methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression, decreases reaction, increases methylation, affects methylation	1
Copper	affects binding, decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Malathion	decreases expression	1
Mercury	increases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Vitamin B 6	decreases expression, decreases reaction	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1J5	SEES3-1V human EN1, clone1	Embryonic stem cell	Male
CVCL_A1J6	SEES3-1V human EN1, clone2	Embryonic stem cell	Male
CVCL_A1J7	SEES3-1V human EN1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.