EFNA4 ephrin A4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: EFNA4provided by HGNC
Official Full Name: ephrin A4provided by HGNC
Primary source: HGNC:HGNC:3224
See related: Ensembl:ENSG00000243364 MIM:601380; AllianceGenome:HGNC:3224
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EFL4; EPLG4; LERK4; LERK-4
Summary: This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. This gene encodes an EFNA class ephrin that has been implicated in proliferation and metastasis of several types of cancers. [provided by RefSeq, May 2022]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is locus in the vicinity of disease-associated variant(s).
Expression: Ubiquitous expression in skin (RPKM 7.7), colon (RPKM 6.4) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q21.3

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (155063740..155069553)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (154203127..154208932)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (155036216..155042029)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Interference of EFNA4 suppresses cell proliferation, invasion and angiogenesis in hepatocellular carcinoma by downregulating PYGO2.
Title: Interference of EFNA4 suppresses cell proliferation, invasion and angiogenesis in hepatocellular carcinoma by downregulating PYGO2.
Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells.
Title: Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells.
Study present for the first time in vitro and in vivo evidence suggesting that the major role of two ephrin A4 isoforms in chronic lymphocytic leukemia could be related with a non-previously described mechanism of survival linked to extravasation strongly dependent on integrin signaling.
Title: EphrinA4 plays a critical role in α4 and αL mediated survival of human CLL cells during extravasation.
The present study provides evidence that microglia upregulates endothelial ephrin-A3 and ephrin-A4 to facilitate in vitro angiogenesis of brain endothelial cells, which is mediated by microglia-released TNF-alpha.
Title: Ephrin-A3 and ephrin-A4 contribute to microglia-induced angiogenesis in brain endothelial cells.
The interaction between ephrin-As, Eph receptors and integrin alpha3 is plausibly important for the crosstalk between Eph and integrin signalling pathways at the membrane protrusions and in the migration of brain cancer cells.
Title: Ephrin-As, Eph receptors and integrin α3 interact and colocalise at membrane protrusions of U251MG glioblastoma cells.
Observational study of gene-disease association. (HuGE Navigator)
Title: Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis.
The cytoplasmic pattern of ephrin A4 could identify a subgroup of primary osteosarcoma patients with a high liability for progression, poor prognosis, and inferior response to chemotherapy.
Title: Ephrin A4 expression in osteosarcoma, impact on prognosis, and patient outcome.
EFNA4-EphA2 interactions are involved in Chronic lymphocytic leukemia cell trafficking between blood and the tissues
Title: An impaired transendothelial migration potential of chronic lymphocytic leukemia (CLL) cells can be linked to ephrin-A4 expression.
CLL B-cells showed a more heterogeneous Eph/EFN profile, specially EFNA4, EphB6 and EphA10. EphB6 and EFNA4 were further related with the clinical course of CLL.
Title: Expression profile of Eph receptors and ephrin ligands in healthy human B lymphocytes and chronic lymphocytic leukemia B-cells.
This provides genetic evidence that Twist1, Msx2 and Efna4 function together in boundary formation and the pathogenesis of coronal synostosis.
Title: Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-154992 (e-PCR)
- UniSTS:182045

RH66543 (e-PCR)
- UniSTS:69666

NoName (e-PCR)
- UniSTS:490060

EFNA4_1473 (e-PCR)
- UniSTS:462172

MARC_26096-26097:1032793492:3 (e-PCR)
- UniSTS:268937

Readthrough ADAM15-EFNA4

Readthrough gene: ADAM15-EFNA4, Included gene: ADAM15

Readthrough EFNA4-EFNA3

Readthrough gene: EFNA4-EFNA3, Included gene: EFNA3

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ephrin receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables ephrin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane-ephrin receptor activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in ephrin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in extracellular region	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed
located_in side of membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: ephrin-A4

Names: eph-related receptor tyrosine kinase ligand 4; ligand of eph-related kinase 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029561.1 RefSeqGene

Range

5004..10817

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001406810.1 → NP_001393739.1 ephrin-A4 isoform d

Status: REVIEWED

Source sequence(s)

AL691442
NM_005227.3 → NP_005218.1 ephrin-A4 isoform a precursor

See identical proteins and their annotated locations for NP_005218.1

Status: REVIEWED

Description

Transcript Variant: This variant (1), also known as ephrin-A4 (m), is the longest transcript and it encodes isoform a. Isoform a is a membrane-bound protein.

Source sequence(s)

AI459151, BE780161, BQ940212, CD671399

Consensus CDS

CCDS1089.1

UniProtKB/Swiss-Prot

C9JHJ8, G3XAK2, O95457, P52798, Q5SR71, Q6FI57

Related

ENSP00000357394.3, ENST00000368409.8

Conserved Domains (1) summary

cd10425
Location:27 → 152

Ephrin-A_Ectodomain; Ectodomain of Ephrin A
NM_182689.2 → NP_872631.1 ephrin-A4 isoform b precursor

See identical proteins and their annotated locations for NP_872631.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, compared to variant 1, that results in a downstream translation termination. It encodes isoform b which has a little longer and distinct C-terminus compared to isoform a.

Source sequence(s)

AI459151, BE780161, BM740848, BQ940212

Consensus CDS

CCDS44237.1

UniProtKB/Swiss-Prot

P52798

Related

ENSP00000414378.2, ENST00000427683.2

Conserved Domains (1) summary

cd10425
Location:27 → 152

Ephrin-A_Ectodomain; Ectodomain of Ephrin A
NM_182690.3 → NP_872632.2 ephrin-A4 isoform c precursor

See identical proteins and their annotated locations for NP_872632.2

Status: REVIEWED

Description

Transcript Variant: This variant (3), also known as ephrin-A4 (s), uses an alternate splice site in the 3' coding region, compared to variant 1, that results in a downstream translation termination. It encodes isoform c which has a distinct and slightly shorter C-terminus compared to isoform a. Isoform c lacks a characteristic transmembrane domain and the GPI-signal sequence contained in isoform a. Isoform c is a secreted molecule.

Source sequence(s)

AJ006353, AL691442, BM740848

Consensus CDS

CCDS41407.1

UniProtKB/Swiss-Prot

P52798

Related

ENSP00000352789.4, ENST00000359751.8

Conserved Domains (1) summary

cd10425
Location:27 → 152

Ephrin-A_Ectodomain; Ectodomain of Ephrin A