EIF5AL1

Summary

EIF5AL1 (eukaryotic translation initiation factor 5A like 1, HGNC:17419) is a protein-coding gene on chromosome 10q22.3, encoding Eukaryotic translation initiation factor 5A-1-like (Q6IS14). Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts. It is a selective cancer dependency (DepMap: 20.9% of cell lines).

Predicted to enable translation elongation factor activity. Predicted to be involved in translational elongation. Predicted to be located in endoplasmic reticulum membrane and nucleus.

Source: NCBI Gene 143244 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 32 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 20.9% of screened cell lines
• MANE Select transcript: NM_001099692

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17419
Approved symbol	EIF5AL1
Name	eukaryotic translation initiation factor 5A like 1
Location	10q22.3
Locus type	gene with protein product
Status	Approved
Aliases	bA342M3.3
Ensembl gene	ENSG00000253626
Ensembl biotype	protein_coding
Entrez	143244

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000520547

RefSeq mRNA: 1 — MANE Select: NM_001099692 NM_001099692

CCDS: CCDS53546

Canonical transcript exons

ENST00000520547 — 1 exons

Exon	Start	End
ENSE00002138115	79512533	79516440

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 77.51.

FANTOM5 (CAGE): breadth broad, TPM avg 0.3894 / max 6.7852, expressed in 198 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105801	0.3894	198

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trachea	UBERON:0003126	77.51	gold quality
dorsal plus ventral thalamus	UBERON:0001897	76.86	gold quality
dorsal root ganglion	UBERON:0000044	76.37	gold quality
endometrium epithelium	UBERON:0004811	73.99	gold quality
testis	UBERON:0000473	73.73	gold quality
left testis	UBERON:0004533	73.47	gold quality
right testis	UBERON:0004534	73.35	gold quality
thymus	UBERON:0002370	72.92	silver quality
frontal pole	UBERON:0002795	72.53	gold quality
paraflocculus	UBERON:0005351	72.30	gold quality
middle frontal gyrus	UBERON:0002702	71.98	gold quality
metanephric glomerulus	UBERON:0004736	66.31	gold quality
layer of synovial tissue	UBERON:0007616	65.79	gold quality
mucosa of transverse colon	UBERON:0004991	63.95	gold quality
stromal cell of endometrium	CL:0002255	63.91	gold quality
vastus lateralis	UBERON:0001379	60.50	gold quality
quadriceps femoris	UBERON:0001377	60.28	gold quality
bone marrow cell	CL:0002092	60.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	58.83	gold quality
cortical plate	UBERON:0005343	58.53	silver quality
epithelium of bronchus	UBERON:0002031	58.19	gold quality
lower esophagus mucosa	UBERON:0035834	57.79	gold quality
liver	UBERON:0002107	57.61	gold quality
cerebellar vermis	UBERON:0004720	57.59	gold quality
gastrocnemius	UBERON:0001388	57.21	gold quality
muscle of leg	UBERON:0001383	57.13	gold quality
right lobe of liver	UBERON:0001114	56.27	gold quality
bone marrow	UBERON:0002371	56.25	gold quality
skeletal muscle tissue	UBERON:0001134	55.88	gold quality
colonic epithelium	UBERON:0000397	55.45	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	210.84
E-ANND-3	yes	14.85
E-GEOD-76312	no	83.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

94 targeting EIF5AL1, 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-432-3P	100.00	67.86	705
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3692-3P	99.98	70.27	2139
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-3148	99.97	75.06	6478
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-33A-3P	99.70	70.27	3362

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• EIF5AL1 expression is associated with colorectal cancer metastasis. (PMID:30132996)
• Comparison of Human Eukaryotic Translation Initiation Factors 5A1 and 5AL1: Identification of Amino Acid Residues Important for EIF5A1 Lysine 50 Hypusination and Its Protein Stability. (PMID:37047039)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Eif5a	ENSMUSG00000078812
rattus_norvegicus	Eif5a	ENSRNOG00000016478
drosophila_melanogaster	eEF5	FBGN0285952
caenorhabditis_elegans		WBGENE00002064
caenorhabditis_elegans		WBGENE00002065

Paralogs (2): EIF5A (ENSG00000132507), EIF5A2 (ENSG00000163577)

Protein

Protein identifiers

Eukaryotic translation initiation factor 5A-1-like — Q6IS14 (reviewed: Q6IS14)

Alternative names: Eukaryotic initiation factor 5A isoform 1-like

All UniProt accessions (1): Q6IS14

UniProt curated annotations — full annotation on UniProt →

Function. Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts. Binds between the exit (E) and peptidyl (P) site of the ribosome and promotes rescue of stalled ribosome: specifically required for efficient translation of polyproline-containing peptides as well as other motifs that stall the ribosome. Acts as a ribosome quality control (RQC) cofactor by joining the RQC complex to facilitate peptidyl transfer during CAT tailing step. Also involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity.

Subcellular location. Cytoplasm. Nucleus. Endoplasmic reticulum membrane.

Post-translational modifications. Lys-50 undergoes hypusination, a unique post-translational modification that consists in the addition of a butylamino group from spermidine to lysine side chain, leading to the formation of the unusual amino acid hypusine. eIF-5As are the only known proteins to undergo this modification, which is essential for their function.

Similarity. Belongs to the eIF-5A family.

RefSeq proteins (1): NP_001093162* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001884	IF5A-like	Family
IPR008991	Translation_prot_SH3-like_sf	Homologous_superfamily
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR014722	Rib_uL2_dom2	Homologous_superfamily
IPR019769	Trans_elong_IF5A_hypusine_site	PTM
IPR020189	IF5A_C	Domain
IPR048670	IF5A-like_N	Domain

Pfam: PF01287, PF21485

UniProt features (2 total): chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IS14-F1	88.92	0.78

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): 50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): GOBP_REGULATION_OF_TRANSLATIONAL_ELONGATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_TRANSLATIONAL_TERMINATION, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_TRANSLATIONAL_ELONGATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_POSITIVE_REGULATION_OF_TRANSLATION, GOBP_REGULATION_OF_TRANSLATION, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOBP_POSITIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_TRANSLATION_ELONGATION_FACTOR_ACTIVITY, GOMF_RIBONUCLEOPROTEIN_COMPLEX_BINDING

GO Biological Process (4): translational elongation (GO:0006414), positive regulation of translational elongation (GO:0045901), positive regulation of translational termination (GO:0045905), translation (GO:0006412)

GO Molecular Function (3): RNA binding (GO:0003723), translation elongation factor activity (GO:0003746), ribosome binding (GO:0043022)

GO Cellular Component (5): nucleus (GO:0005634), endoplasmic reticulum membrane (GO:0005789), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational elongation	3
macromolecule biosynthetic process	2
positive regulation of translation	2
translational termination	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
translation	1
regulation of translational elongation	1
regulation of translational termination	1
positive regulation of protein-containing complex disassembly	1
peptidyltransferase activity	1
translational initiation	1
protein metabolic process	1
protein biosynthetic process	1
nucleic acid binding	1
translation factor activity	1
ribonucleoprotein complex binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

2609 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF5AL1	DHPS	P49366	837
EIF5AL1	DOHH	Q9BU89	833
EIF5AL1	XPO4	Q9C0E2	685
EIF5AL1	EEF2	P13639	666
EIF5AL1	EEF1G	P26641	560
EIF5AL1	EIF1AY	O14602	525
EIF5AL1	OLA1	Q9NTK5	506
EIF5AL1	PEAK1	Q9H792	477
EIF5AL1	EIF1AX	P47813	474
EIF5AL1	EIF6	P56537	453
EIF5AL1	EIF5	P55010	447
EIF5AL1	ODC1	P11926	434
EIF5AL1	EIF3B	P55884	434
EIF5AL1	EIF4A1	P04765	433
EIF5AL1	EEF1A1	P04719	419

IntAct

9 interactions, top by confidence:

A	B	Type	Score
SH3GL3	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
GAB2	HSPD1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
sifA	AP3D1	psi-mi:“MI:0914”(association)	0.350
NS	MYO1C	psi-mi:“MI:0914”(association)	0.350
DYRK2	POLRMT	psi-mi:“MI:2364”(proximity)	0.270
DYRK2	HNRNPCL2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (37): EIF5AL1 (Co-fractionation), EIF5AL1 (Co-fractionation), EIF5AL1 (Co-fractionation), EIF5AL1 (Co-fractionation), TAGLN2 (Co-fractionation), EIF5AL1 (Proximity Label-MS), EIF5AL1 (Affinity Capture-MS), EIF5AL1 (Affinity Capture-MS), EIF5AL1 (Affinity Capture-MS), EIF5AL1 (Affinity Capture-MS), EIF5AL1 (Affinity Capture-MS), EIF5AL1 (Affinity Capture-MS), EIF5AL1 (Affinity Capture-MS), EIF5AL1 (Affinity Capture-MS), EIF5AL1 (Affinity Capture-MS)

ESM2 similar proteins: A4GVE9, E9AXF0, O94083, O97472, P10160, P13651, P19211, P23301, P24922, P26564, P34563, P38672, P56289, P56333, P56335, P56336, P56337, P62924, P62925, P63241, P63242, P69039, P69040, P80639, Q07460, Q09121, Q20728, Q20751, Q387H6, Q3T1J1, Q5R898, Q6EWQ7, Q6IS14, Q6NX89, Q7SA95, Q7ZXG3, Q8BGY2, Q93VP3, Q945F4, Q9AXJ4

Diamond homologs: A0B9S8, A1RS27, A1RX88, A2BNB6, A3CU49, A3DNK3, A3MTA0, A4FXY5, A4GVE9, A4WLN5, A4YHK9, A5ULK4, A6UNS4, A6UVH4, A6VFP3, A7I807, A8ABK3, A8MD73, A9AAZ2, B0R6B4, B1L7A5, B1Y9U5, B6YTM4, B8D4W8, B8GEC0, B9LP76, C3MPN5, C3MYM9, C3N5B1, C3NDW5, C3NHT8, C4KGX7, C5A5M5, C6A117, E9AXF0, O26955, O29612, O50089, P10160, P19211

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	30
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
832057	NC_000010.10:g.(?80961390)(81319734_?)del	Pathogenic

SpliceAI

165 predictions. Top by Δscore:

Variant	Effect	Δscore
10:79513079:G:GT	donor_gain	0.9700
10:79513129:G:GA	donor_gain	0.9500
10:79513128:T:TA	donor_gain	0.9300
10:79513024:GAA:G	donor_gain	0.8800
10:79513024:G:GT	donor_gain	0.8400
10:79512935:GA:G	donor_gain	0.8000
10:79512968:G:T	donor_gain	0.7900
10:79513027:G:GG	donor_gain	0.7300
10:79513061:C:CG	donor_gain	0.7300
10:79512907:G:GT	donor_gain	0.7200
10:79513013:GAGAT:G	donor_gain	0.7200
10:79513026:A:AG	donor_gain	0.7200
10:79513130:GCA:G	donor_gain	0.7200
10:79512973:ACCAG:A	donor_gain	0.6900
10:79512968:G:GT	donor_gain	0.6800
10:79512908:A:T	donor_gain	0.6700
10:79513107:C:T	donor_gain	0.6600
10:79513138:GGC:G	donor_gain	0.6600
10:79512796:C:T	donor_gain	0.6500
10:79512731:A:T	donor_gain	0.5500
10:79512847:G:T	donor_gain	0.5300
10:79512944:C:G	donor_gain	0.5200
10:79513082:G:GT	donor_gain	0.5200
10:79512726:G:GG	donor_gain	0.5100
10:79512730:G:GT	donor_gain	0.4900
10:79512817:C:A	donor_gain	0.4800
10:79513031:G:GT	donor_gain	0.4800
10:79513083:C:T	donor_gain	0.4700
10:79512887:G:GT	donor_gain	0.4600
10:79512725:C:G	donor_gain	0.4500

AlphaMissense

1015 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:79512814:G:C	K55N	0.974
10:79512814:G:T	K55N	0.974
10:79512799:G:C	K50N	0.972
10:79512799:G:T	K50N	0.972
10:79512839:T:C	F64L	0.967
10:79512841:T:A	F64L	0.967
10:79512841:T:G	F64L	0.967
10:79512737:T:C	F30L	0.964
10:79512739:T:A	F30L	0.964
10:79512739:T:G	F30L	0.964
10:79512891:T:A	V81D	0.964
10:79512766:G:C	K39N	0.960
10:79512766:G:T	K39N	0.960
10:79512804:G:A	G52D	0.957
10:79512802:C:A	H51Q	0.956
10:79512802:C:G	H51Q	0.956
10:79512715:C:G	C22W	0.953
10:79512894:C:A	P82H	0.952
10:79512701:T:C	F18L	0.946
10:79512703:C:A	F18L	0.946
10:79512703:C:G	F18L	0.946
10:79512828:G:A	G60D	0.945
10:79512723:T:C	L25S	0.944
10:79512827:G:C	G60R	0.942
10:79512741:T:A	V31E	0.941
10:79512795:G:A	G49D	0.941
10:79512797:A:G	K50E	0.941
10:79512750:A:T	K34I	0.937
10:79512763:T:G	C38W	0.934
10:79512907:G:C	R86S	0.933

dbSNP variants (sampled 300 via entrez): RS1000541403 (10:79514913 T>A), RS1000618802 (10:79513382 A>G), RS1001141439 (10:79516267 C>A), RS1001489190 (10:79516548 C>T), RS1001752271 (10:79513307 C>A), RS1003428165 (10:79511736 G>A,T), RS1003997826 (10:79512138 C>T), RS1004990041 (10:79513738 A>G), RS1005830289 (10:79510862 G>A), RS1007283375 (10:79516120 T>C), RS1007335658 (10:79515914 A>G), RS1008944925 (10:79514832 C>G,T), RS1008997512 (10:79514626 T>A,G), RS1009566236 (10:79514866 T>C), RS1011353590 (10:79513575 G>A,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
lead acetate	decreases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Diethylstilbestrol	increases expression	1
Doxorubicin	decreases expression	1
Oxygen	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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