EFNA5

Summary

EFNA5 (ephrin A5, HGNC:3225) is a protein-coding gene on chromosome 5q21.3, encoding Ephrin-A5 (P52803). Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development.

Ephrin-A5, a member of the ephrin gene family, prevents axon bundling in cocultures of cortical neurons with astrocytes, a model of late stage nervous system development and differentiation. The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, particularly in the nervous system. EPH receptors typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin ligands and receptors have been named by the Eph Nomenclature Committee (1997). 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. The Eph family of receptors are similarly divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands.

Source: NCBI Gene 1946 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_001962

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3225
Approved symbol	EFNA5
Name	ephrin A5
Location	5q21.3
Locus type	gene with protein product
Status	Approved
Aliases	AF1, LERK7
Ensembl gene	ENSG00000184349
Ensembl biotype	protein_coding
OMIM	601535
Entrez	1946

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000333274, ENST00000504941, ENST00000505499, ENST00000509503, ENST00000510359

RefSeq mRNA: 2 — MANE Select: NM_001962 NM_001410773, NM_001962

CCDS: CCDS4097, CCDS93759

Canonical transcript exons

ENST00000333274 — 5 exons

Exon	Start	End
ENSE00001300960	107670489	107670937
ENSE00003483798	107387706	107387771
ENSE00003504222	107427217	107427509
ENSE00003548905	107387235	107387315
ENSE00003845172	107376894	107381376

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.8129 / max 301.4259, expressed in 1232 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62809	2.5193	815
62838	1.0223	662
62832	1.0095	515
62831	0.3637	171
62833	0.2925	132
62830	0.1878	63
62837	0.1287	43
62835	0.1243	52
62836	0.0991	47
62834	0.0658	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hair follicle	UBERON:0002073	97.18	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.00	gold quality
cervix squamous epithelium	UBERON:0006922	91.80	silver quality
middle temporal gyrus	UBERON:0002771	91.09	gold quality
primary visual cortex	UBERON:0002436	89.94	gold quality
germinal epithelium of ovary	UBERON:0001304	89.46	gold quality
synovial joint	UBERON:0002217	89.27	gold quality
parietal pleura	UBERON:0002400	89.12	gold quality
esophagus squamous epithelium	UBERON:0006920	88.75	gold quality
nipple	UBERON:0002030	88.66	gold quality
endothelial cell	CL:0000115	88.44	gold quality
pancreatic ductal cell	CL:0002079	88.38	silver quality
cortical plate	UBERON:0005343	88.36	gold quality
squamous epithelium	UBERON:0006914	87.73	gold quality
occipital lobe	UBERON:0002021	87.71	gold quality
endometrium epithelium	UBERON:0004811	86.87	gold quality
secondary oocyte	CL:0000655	85.94	gold quality
gingival epithelium	UBERON:0001949	85.80	gold quality
pleura	UBERON:0000977	85.79	gold quality
layer of synovial tissue	UBERON:0007616	85.75	gold quality
cerebellar vermis	UBERON:0004720	85.65	gold quality
lower esophagus mucosa	UBERON:0035834	84.57	gold quality
superior frontal gyrus	UBERON:0002661	84.45	gold quality
epithelium of esophagus	UBERON:0001976	84.43	gold quality
seminal vesicle	UBERON:0000998	84.37	gold quality
parietal lobe	UBERON:0001872	84.26	gold quality
skin of abdomen	UBERON:0001416	83.87	gold quality
postcentral gyrus	UBERON:0002581	83.67	gold quality
renal medulla	UBERON:0000362	83.48	gold quality
oocyte	CL:0000023	83.32	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	1972.79
E-GEOD-180759	yes	1632.22
E-MTAB-10485	yes	290.89
E-HCAD-25	yes	84.72
E-HCAD-35	yes	66.05
E-CURD-119	yes	49.15
E-ANND-3	yes	11.39
E-GEOD-83139	yes	9.75
E-CURD-46	yes	9.65
E-MTAB-5061	yes	6.05
E-MTAB-6108	no	293.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, E2F6, FOXD1, MSX2

miRNA regulators (miRDB)

315 targeting EFNA5, 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-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642

Literature-anchored findings (GeneRIF, showing 18)

• analysis of molecular surfaces in ephrin-A5 essential for a functional interaction with EphA3 (PMID:15901737)
• ephrin-A5-induced cell-morphologic changes of EphA3-positive LK63 pre-B acute lymphoblastic leukemia cells (PMID:18385452)
• These observations indicate that only a subset of signal transduction pathways is required for ephrin-A5-induced growth cone collapse. (PMID:18563700)
• ephrinA5 acted as a tumor suppressor in glioma, and its negative regulation of EGFR contributed to the suppressive effects. (PMID:19270726)
• EFNA5 down-regulation is a consistent finding in chondrosarcomas (PMID:19695673)
• This study presented that EFNA5 showed strong associations with alcohol withdrawal symptoms. (PMID:22072270)
• Data suggest that ephrinA5 mRNA/protein levels are reduced in colon adenocarcinoma compared to normal colon tissue; staging/grading indicates that ephrinA5 inhibits colon adenocarcinoma progression via c-Cbl-mediated EGFR ubiquitination/degradation. (PMID:22074469)
• EphrinA5, especially ephrinA5S, acts as a tumor suppressor in hepatocarcinogenesis. (PMID:22860012)
• Transgenic ephrin-A5 plays a critical role in postnatal lens fiber organization to maintain lens transparency: cells in the ephrin-A5-deficient lens are severely disorganized (PMID:23401654)
• Data indicate that ephrin-A5 binding directly facilitates the formation of Eph/ephrin clusters by inducing conformational changes in the ligand-binding domain (LBD) of EphA4. (PMID:23959867)
• The genetic variations c.668C>T (rs201008479), c.102C>T (rs199980747) and c.-27C>G (rs200187971) may present an additional genetic risk factor for age-related cataract in the Chinese population. (PMID:25300504)
• MiR-96 and miR-182 are upregulated in hepatocellular carcinoma and negatively associated with ephrin A5 expression. (PMID:25663355)
• the structure of the ligand-binding domain of the EphA3 receptor in complex with its preferred ligand, ephrin-A5, is reported. (PMID:25993310)
• These results indicate a novel mechanism of ephrin-Eph signaling independent of direct cell contact and proteolytic cleavage and suggest the participation of EphB2(+) extracellular vesicles in neural development and synapse physiology. (PMID:27354374)
• EFNA5, BAHD1 and PPP2R5E were particularly good candidates for novel disease loci (PMID:30352868)
• Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma. (PMID:31988455)
• PIWIL1 interacting RNA piR-017061 inhibits pancreatic cancer growth via regulating EFNA5. (PMID:33389678)
• Aggressive and recurrent ovarian cancers upregulate ephrinA5, a non-canonical effector of EphA2 signaling duality. (PMID:33893375)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	efna5a	ENSDARG00000089790
danio_rerio	efna5b	ENSDARG00000098625
mus_musculus	Efna5	ENSMUSG00000048915
rattus_norvegicus	Efna5	ENSRNOG00000034177
drosophila_melanogaster	Ephrin	FBGN0040324
caenorhabditis_elegans		WBGENE00001163
caenorhabditis_elegans		WBGENE00001164
caenorhabditis_elegans		WBGENE00001165
caenorhabditis_elegans		WBGENE00006869

Paralogs (7): EFNB1 (ENSG00000090776), EFNA2 (ENSG00000099617), EFNB3 (ENSG00000108947), EFNB2 (ENSG00000125266), EFNA3 (ENSG00000143590), EFNA1 (ENSG00000169242), EFNA4 (ENSG00000243364)

Protein

Protein identifiers

Ephrin-A5 — P52803 (reviewed: P52803)

Alternative names: AL-1, EPH-related receptor tyrosine kinase ligand 7

All UniProt accessions (2): D6RDV5, P52803

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate receptor. This signaling event requires the activity of the Fyn tyrosine kinase. Activates the EPHA3 receptor to regulate cell-cell adhesion and cytoskeletal organization. With the receptor EPHA2 may regulate lens fiber cells shape and interactions and be important for lens transparency maintenance. May function actively to stimulate axon fasciculation. The interaction of EFNA5 with EPHA5 also mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion. Cognate/functional ligand for EPHA7, their interaction regulates brain development modulating cell-cell adhesion and repulsion.

Subunit / interactions. Binds to EPHB2. Interacts with EPHA8; activates EPHA8. Binds to the receptor tyrosine kinases EPHA2, EPHA3 and EPHB1. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function.

Subcellular location. Cell membrane. Membrane. Caveola.

Similarity. Belongs to the ephrin family.

RefSeq proteins (2): NP_001397702, NP_001953* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001799	Ephrin_RBD	Domain
IPR008972	Cupredoxin	Homologous_superfamily
IPR019765	Ephrin_CS	Conserved_site
IPR031328	Ephrin	Family
IPR034252	Ephrin-A_Ecto	Domain

Pfam: PF00812

UniProt features (26 total): strand 10, helix 4, disulfide bond 2, signal peptide 1, chain 1, sequence variant 1, turn 1, propeptide 1, domain 1, region of interest 1, compositionally biased region 1, lipid moiety-binding region 1, glycosylation site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4L0P	X-RAY DIFFRACTION	2.26
4M4R	X-RAY DIFFRACTION	3.13
3MX0	X-RAY DIFFRACTION	3.51
4BK5	X-RAY DIFFRACTION	4
2X11	X-RAY DIFFRACTION	4.83
4BKA	X-RAY DIFFRACTION	5.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52803-F1	79.44	0.51

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 203

Disulfide bonds (2): 62–102, 90–151

Glycosylation sites (1): 37

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-3928663	EPHA-mediated growth cone collapse
R-HSA-3928665	EPH-ephrin mediated repulsion of cells

MSigDB gene sets: 439 (showing top): RNGTGGGC_UNKNOWN, E2F_Q4, GOBP_LENS_FIBER_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_COLLATERAL_SPROUTING, GOBP_NEURON_RECOGNITION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, PAX4_01, E2F4DP1_01, GOBP_SYNAPSE_ASSEMBLY, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_RETINAL_GANGLION_CELL_AXON_GUIDANCE

GO Biological Process (22): nervous system development (GO:0007399), axon guidance (GO:0007411), regulation of cell-cell adhesion (GO:0022407), regulation of cell morphogenesis (GO:0022604), retinal ganglion cell axon guidance (GO:0031290), regulation of actin cytoskeleton organization (GO:0032956), regulation of GTPase activity (GO:0043087), ephrin receptor signaling pathway (GO:0048013), collateral sprouting (GO:0048668), positive regulation of collateral sprouting (GO:0048672), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), regulation of focal adhesion assembly (GO:0051893), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of synapse assembly (GO:0051965), regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061178), regulation of microtubule cytoskeleton organization (GO:0070507), cellular response to follicle-stimulating hormone stimulus (GO:0071372), synaptic membrane adhesion (GO:0099560), negative regulation of substrate adhesion-dependent cell spreading (GO:1900025), cellular response to forskolin (GO:1904322), cell differentiation (GO:0030154), negative chemotaxis (GO:0050919)

GO Molecular Function (8): neurotrophin TRKA receptor binding (GO:0005168), neurotrophin TRKB receptor binding (GO:0005169), neurotrophin TRKC receptor binding (GO:0005170), transmembrane receptor protein tyrosine kinase activator activity (GO:0030297), chemorepellent activity (GO:0045499), ephrin receptor binding (GO:0046875), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (9): basement membrane (GO:0005604), plasma membrane (GO:0005886), caveola (GO:0005901), adherens junction (GO:0005912), external side of plasma membrane (GO:0009897), GABA-ergic synapse (GO:0098982), membrane (GO:0016020), cell periphery (GO:0071944), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
EPH-Ephrin signaling	2
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neurotrophin TRK receptor binding	3
cellular anatomical structure	3
axonogenesis	2
cell-cell adhesion	2
regulation of cytoskeleton organization	2
signaling receptor activator activity	2
signaling receptor binding	2
membrane	2
system development	1
neuron projection guidance	1
regulation of cell adhesion	1
cell morphogenesis	1
regulation of anatomical structure morphogenesis	1
axon guidance	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
GTPase activity	1
regulation of hydrolase activity	1
cell surface receptor protein tyrosine kinase signaling pathway	1
developmental cell growth	1
developmental growth involved in morphogenesis	1
positive regulation of cell growth	1
positive regulation of developmental growth	1
collateral sprouting	1
regulation of collateral sprouting	1
positive regulation of axonogenesis	1
positive regulation of protein phosphorylation	1
peptidyl-tyrosine phosphorylation	1
regulation of peptidyl-tyrosine phosphorylation	1
regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of cell-substrate junction assembly	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
insulin secretion involved in cellular response to glucose stimulus	1

Protein interactions and networks

STRING

1814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EFNA5	EPHA4	P54764	998
EFNA5	EPHA2	P29317	997
EFNA5	EPHA3	P29320	997
EFNA5	EPHB2	P29323	996
EFNA5	EPHA5	P54756	996
EFNA5	EPHA1	P21709	995
EFNA5	EPHA7	Q15375	995
EFNA5	RPTOR	Q8N122	975
EFNA5	EPHA8	P29322	938
EFNA5	NTRK2	Q16620	928
EFNA5	EPHA10	Q5JZY3	920
EFNA5	RRAGD	Q9NQL2	843
EFNA5	EPHB6	O15197	813
EFNA5	EPHB4	P54760	773
EFNA5	SLC38A9	Q8NBW4	770

IntAct

127 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
EPHA2	EFNA5	psi-mi:“MI:0407”(direct interaction)	0.810
EPHA2	EFNA5	psi-mi:“MI:0915”(physical association)	0.810
EPHA4	EFNA5	psi-mi:“MI:0407”(direct interaction)	0.790
EFNA5	EPHA4	psi-mi:“MI:0407”(direct interaction)	0.790
EFNA5	RHCG	psi-mi:“MI:0915”(physical association)	0.670
EPHA8	EFNA5	psi-mi:“MI:0914”(association)	0.610
EPHA7	EFNA5	psi-mi:“MI:0407”(direct interaction)	0.590
EFNA5	KASH5	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	YIPF6	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
	EFNA5	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	MS4A3	psi-mi:“MI:0915”(physical association)	0.560
CYB561	EFNA5	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	EFNA5	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	AQP6	psi-mi:“MI:0915”(physical association)	0.560
HIBADH	EFNA5	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	SLC10A2	psi-mi:“MI:0915”(physical association)	0.560
AQP2	EFNA5	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	GPR161	psi-mi:“MI:0915”(physical association)	0.560
CD53	EFNA5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (90): EFNA5 (Affinity Capture-MS), EFNA5 (Affinity Capture-MS), EFNA5 (Affinity Capture-MS), EFNA5 (Affinity Capture-MS), EFNA5 (Affinity Capture-MS), EFNA5 (Affinity Capture-RNA), EFNA5 (Affinity Capture-MS), EFNA5 (Two-hybrid), EFNA5 (Two-hybrid), EFNA5 (Two-hybrid), EFNA5 (Two-hybrid), EFNA5 (Two-hybrid), EFNA5 (Two-hybrid), EFNA5 (Two-hybrid), EFNA5 (Two-hybrid)

ESM2 similar proteins: B3NBB6, B4HVU2, B4PD96, B4QMF4, B6ZK76, B6ZK77, C5IAW9, F1QWZ4, G5EDE5, O08543, O08545, O14788, O35235, O35312, O35622, O97827, P06213, P10731, P15127, P15208, P19021, P52794, P52797, P52802, P52803, P52804, P54631, P59823, P59824, P60029, P79727, P79728, P85857, P97605, Q26261, Q6DE92, Q6UX71, Q7YQL9, Q80TS3, Q8IUK5

Diamond homologs: O08542, O08543, O08545, O35393, O43921, O73612, O73874, P20827, P52793, P52794, P52795, P52796, P52797, P52798, P52799, P52800, P52801, P52802, P52803, P52804, P79727, P79728, P97553, P97605, P98172, Q06AS9, Q15768, Q3ZC64, O13097, O44516

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
EFNA5	up-regulates	EPHA2	binding
EFNA5	up-regulates	EPHA3	binding
EFNA5	up-regulates	EPHA4	binding
EFNA5	up-regulates	EPHA5	binding
EFNA5	up-regulates	EPHA8	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
EPHA-mediated growth cone collapse	6	50.8×	3e-07
EPH-ephrin mediated repulsion of cells	6	29.3×	4e-06
EPH-Ephrin signaling	6	22.1×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	7	42.2×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3456 predictions. Top by Δscore:

Variant	Effect	Δscore
5:107387704:A:AC	donor_gain	1.0000
5:107387705:C:CC	donor_gain	1.0000
5:107387784:C:CT	acceptor_gain	1.0000
5:107390262:T:A	donor_gain	1.0000
5:107427215:A:AC	donor_gain	1.0000
5:107427216:C:CC	donor_gain	1.0000
5:107427509:TC:T	acceptor_loss	1.0000
5:107427510:C:CA	acceptor_loss	1.0000
5:107427510:C:CC	acceptor_gain	1.0000
5:107427513:T:TC	acceptor_gain	1.0000
5:107442774:G:C	donor_gain	1.0000
5:107516657:A:AC	donor_gain	1.0000
5:107516658:A:C	donor_gain	1.0000
5:107614170:T:TA	donor_gain	1.0000
5:107661464:T:TA	donor_gain	1.0000
5:107670484:CTTA:C	donor_loss	1.0000
5:107670485:TTA:T	donor_loss	1.0000
5:107670486:TA:T	donor_loss	1.0000
5:107670488:C:CG	donor_loss	1.0000
5:107381170:C:A	donor_gain	0.9900
5:107387312:CTAT:C	acceptor_gain	0.9900
5:107387782:C:CT	acceptor_gain	0.9900
5:107387785:A:T	acceptor_gain	0.9900
5:107387795:C:CT	acceptor_gain	0.9900
5:107387796:A:T	acceptor_gain	0.9900
5:107427216:CAG:C	donor_gain	0.9900
5:107427343:TGA:T	donor_gain	0.9900
5:107427506:GAATC:G	acceptor_gain	0.9900
5:107427507:AAT:A	acceptor_gain	0.9900
5:107427507:AATCT:A	acceptor_gain	0.9900

AlphaMissense

1516 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:107387723:A:T	V156D	1.000
5:107387729:A:G	L154P	1.000
5:107387729:A:T	L154H	1.000
5:107427228:T:C	Y136C	1.000
5:107427229:A:G	Y136H	1.000
5:107427245:G:C	F130L	1.000
5:107427245:G:T	F130L	1.000
5:107427246:A:C	F130C	1.000
5:107427246:A:G	F130S	1.000
5:107427247:A:C	F130V	1.000
5:107427247:A:G	F130L	1.000
5:107427247:A:T	F130I	1.000
5:107427248:T:A	E129D	1.000
5:107427248:T:G	E129D	1.000
5:107427250:C:T	E129K	1.000
5:107427251:A:C	F128L	1.000
5:107427251:A:T	F128L	1.000
5:107427252:A:C	F128C	1.000
5:107427252:A:G	F128S	1.000
5:107427253:A:G	F128L	1.000
5:107427255:C:A	G127V	1.000
5:107427255:C:T	G127E	1.000
5:107427256:C:G	G127R	1.000
5:107427256:C:T	G127R	1.000
5:107427258:A:G	L126P	1.000
5:107427261:G:A	S125F	1.000
5:107427261:G:C	S125C	1.000
5:107427263:A:C	F124L	1.000
5:107427263:A:T	F124L	1.000
5:107427264:A:C	F124C	1.000

dbSNP variants (sampled 300 via entrez): RS1000008660 (5:107538433 A>G), RS1000019048 (5:107596049 A>C,G), RS1000055955 (5:107655734 T>C), RS1000082383 (5:107549562 C>T), RS1000084573 (5:107418546 T>C), RS1000119154 (5:107509148 A>C,G), RS1000136355 (5:107549284 C>A), RS1000139918 (5:107429550 A>G), RS1000142671 (5:107447566 A>G,T), RS1000156479 (5:107589380 G>C), RS1000165521 (5:107649699 A>G), RS1000172903 (5:107532911 A>G), RS1000184262 (5:107405875 A>G), RS1000200256 (5:107422489 A>G), RS1000209268 (5:107555030 A>G)

Disease associations

OMIM: gene MIM:601535 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000461_2	Hippocampal atrophy	2.000000e-07
GCST001868_12	Alzheimer’s disease biomarkers	6.000000e-07
GCST005951_149	Body mass index	1.000000e-08
GCST006046_1	Number of children ever born	1.000000e-08
GCST006061_32	Atrial fibrillation	3.000000e-06
GCST006110_31	Nose morphology	5.000000e-08
GCST006625_3	Neonatal cytokine/chemokine levels (maternal genetic effect)	1.000000e-09
GCST006913_2	Sedentary behaviour duration	3.000000e-09
GCST007327_165	Smoking status (ever vs never smokers)	1.000000e-10
GCST007576_194	Chronotype	5.000000e-09
GCST007576_419	Chronotype	1.000000e-08
GCST008179_21	Moderate-to-late spontaneous preterm birth	4.000000e-06
GCST008295_11	Number of decayed, missing and filled tooth surfaces or use of dentures	4.000000e-08
GCST008306_38	Dentures	3.000000e-08
GCST008399_15	Cocaine dependence	2.000000e-06
GCST008595_163	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	1.000000e-09
GCST008810_67	Smoking initiation (ever regular vs never regular)	2.000000e-09
GCST009190_8	Medial orbital frontal cortex volume	4.000000e-06
GCST009384_2	Longitudinal cocaine use	3.000000e-07
GCST009384_8	Longitudinal cocaine use	5.000000e-06
GCST009391_264	Metabolite levels	9.000000e-06
GCST009516_4	Non-del(5q) myelodysplastic syndromes	4.000000e-06
GCST009524_93	Household income (MTAG)	2.000000e-08
GCST010988_336	Adult body size	2.000000e-08
GCST011494_21	Daytime nap	2.000000e-09
GCST011494_22	Daytime nap	7.000000e-09
GCST90000047_105	Age at first sexual intercourse	4.000000e-10
GCST90011898_127	Alanine aminotransferase levels	6.000000e-11
GCST90013407_51	Liver enzyme levels (gamma-glutamyl transferase)	7.000000e-61
GCST90013663_75	Alanine aminotransferase levels	5.000000e-13

EFO canonical traits (22, from GWAS)

EFO ID	Trait name
EFO:0005039	hippocampal atrophy
EFO:0005194	amyloid-beta measurement
EFO:0004340	body mass index
EFO:0009102	number of children ever born measurement
EFO:0004747	protein measurement
EFO:0005939	parental genotype effect measurement
EFO:0008173	interleukin 16 measurement
EFO:0008002	physical activity measurement
EFO:0004318	smoking behavior
EFO:0008328	chronotype measurement
EFO:0006917	spontaneous preterm birth
EFO:0010078	dentures
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0005670	smoking initiation
EFO:0010553	cocaine use measurement
EFO:0010426	triacylglycerol 54:8 measurement
EFO:0009695	household income
EFO:0007828	daytime rest measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	4
Valproic Acid	affects cotreatment, decreases expression	4
methylmercuric chloride	decreases expression, increases expression	2
bisphenol A	increases expression, affects methylation	2
entinostat	decreases expression, affects cotreatment	2
bisphenol S	decreases methylation, increases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Estradiol	decreases expression, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, affects expression	2
aristolochic acid I	decreases expression	1
arsenite	decreases reaction, increases expression, decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
mirdametinib	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
(+)-JQ1 compound	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	decreases reaction, increases expression, decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression, decreases expression, decreases reaction	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0CD	Ubigene HeLa EFNA5 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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