EIF5A

Summary

EIF5A (eukaryotic translation initiation factor 5A, HGNC:3300) is a protein-coding gene on chromosome 17p13.1, encoding Eukaryotic translation initiation factor 5A-1 (P63241). Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts. It is a common-essential gene (DepMap: required in 92.4% of cancer cell lines).

Enables U6 snRNA binding activity. Involved in several processes, including cellular response to virus; positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator; and tumor necrosis factor-mediated signaling pathway. Located in annulate lamellae; cytoplasm; and nucleus. Part of nuclear pore. Biomarker of colorectal cancer.

Source: NCBI Gene 1984 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Faundes-Banka syndrome (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 53 total — 5 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 42
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 92.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_001970

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3300
Approved symbol	EIF5A
Name	eukaryotic translation initiation factor 5A
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	EIF5A1, EIF-5A, MGC99547, MGC104255
Ensembl gene	ENSG00000132507
Ensembl biotype	protein_coding
OMIM	600187
Entrez	1984

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 49 protein_coding, 2 retained_intron

ENST00000336452, ENST00000336458, ENST00000355068, ENST00000416016, ENST00000419711, ENST00000571955, ENST00000572815, ENST00000573542, ENST00000573714, ENST00000575001, ENST00000576930, ENST00000894295, ENST00000894296, ENST00000894297, ENST00000894298, ENST00000894299, ENST00000894300, ENST00000894301, ENST00000894302, ENST00000894303, ENST00000894304, ENST00000894305, ENST00000894306, ENST00000894307, ENST00000894308, ENST00000894309, ENST00000894310, ENST00000939950, ENST00000939951, ENST00000939952, ENST00000939953, ENST00000939954, ENST00000939955, ENST00000939956, ENST00000939957, ENST00000939958, ENST00000939959, ENST00000939960, ENST00000939961, ENST00000939962, ENST00000939963, ENST00000939964, ENST00000939965, ENST00000939966, ENST00000939967, ENST00000943430, ENST00000943431, ENST00000943432, ENST00000943433, ENST00000943434, ENST00000943435

RefSeq mRNA: 6 — MANE Select: NM_001970 NM_001143760, NM_001143761, NM_001143762, NM_001370420, NM_001370421, NM_001970

CCDS: CCDS11099, CCDS45601

Canonical transcript exons

ENST00000336458 — 6 exons

Exon	Start	End
ENSE00001274883	7307628	7307752
ENSE00001615830	7311578	7311651
ENSE00001755330	7311350	7311481
ENSE00001791569	7311018	7311122
ENSE00003547593	7309615	7309800
ENSE00003748086	7311822	7312463

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 555.1925 / max 4469.7713, expressed in 1828 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159136	434.5155	1828
159135	56.2070	1819
159139	36.9996	1814
159134	15.1459	1747
159133	4.6507	1354
159131	2.5160	1179
159132	1.9816	1037
159140	1.5614	746
159138	0.9564	630
159137	0.6582	331

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.44	gold quality
esophagus mucosa	UBERON:0002469	99.42	gold quality
skin of abdomen	UBERON:0001416	99.36	gold quality
zone of skin	UBERON:0000014	99.35	gold quality
skin of leg	UBERON:0001511	99.35	gold quality
stromal cell of endometrium	CL:0002255	99.26	gold quality
mucosa of transverse colon	UBERON:0004991	99.24	gold quality
right testis	UBERON:0004534	99.23	gold quality
vermiform appendix	UBERON:0001154	99.21	gold quality
left testis	UBERON:0004533	99.21	gold quality
esophagus	UBERON:0001043	99.19	gold quality
gastrocnemius	UBERON:0001388	99.19	gold quality
islet of Langerhans	UBERON:0000006	99.17	gold quality
right adrenal gland	UBERON:0001233	99.16	gold quality
left adrenal gland	UBERON:0001234	99.15	gold quality
left adrenal gland cortex	UBERON:0035825	99.15	gold quality
placenta	UBERON:0001987	99.13	gold quality
body of pancreas	UBERON:0001150	99.09	gold quality
pancreas	UBERON:0001264	99.09	gold quality
lymph node	UBERON:0000029	99.08	gold quality
vagina	UBERON:0000996	99.07	gold quality
transverse colon	UBERON:0001157	99.06	gold quality
left uterine tube	UBERON:0001303	99.06	gold quality
right adrenal gland cortex	UBERON:0035827	99.06	gold quality
rectum	UBERON:0001052	99.05	gold quality
body of stomach	UBERON:0001161	99.03	gold quality
adrenal gland	UBERON:0002369	99.03	gold quality
upper lobe of left lung	UBERON:0008952	99.02	gold quality
omental fat pad	UBERON:0010414	99.01	gold quality
smooth muscle tissue	UBERON:0001135	98.99	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	22.96
E-MTAB-9388	yes	11.32
E-MTAB-10596	no	1143.09
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TP53	Activation

Upstream regulators (CollecTRI, top): NFKB, ZNF331

miRNA regulators (miRDB)

58 targeting EIF5A, 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-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-302C-5P	99.97	72.56	3642
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-6825-5P	99.96	69.81	3431
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-491-5P	99.13	65.98	1468

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 92.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Eukaryotic initiation factor 5A (eIF5A) (eIF-4D, eIF-5A) stimulates ribosomal peptidyltransferase activity, transport of HIV-1-mRNAs and binds exportins 1 and 4. Contains hypusine at lys 50. Human EIF5A1 and EIF5A2 encode two isoforms: eIF5AI and eIF5AII. (PMID:11161802)
• Heat stress-induced loss of eukaryotic initiation factor 5A (eIF-5A) in a human pancreatic cancer cell line (PMID:11870779)
• Subcellular distribution of eIF-5A by indirect immunofluorescent staining and by direct visualization of green fluorescent protein tagged eIF-5A (GFP-eIF5A) (PMID:12210765)
• Patients having a higher eIF-5A protein expression showed a relatively poorer survival suggesting the use of eIF-5A as prognostic marker in lung adenocarcinoma. (PMID:12687616)
• EIF-5A expression inhibition by antisense oligodeoxynucleotides significantly enhanced the stimulating effect of GM-CSF on cell growth. Therefore, the eIF-5A accumulation played important roles in the apoptosis induced by UP inhibitors. (PMID:12894223)
• eIF5A may be a regulator of p53, and syntenin might regulate p53 by balancing the regulation of eIF5A signaling to p53 for apoptosis (PMID:15371445)
• These findings suggest that the failure to detect eIF5A-2 protein even in eIF5A-2 mRNA positive cells is, at least in part, due to inefficient translation. (PMID:16519677)
• Recombinant human eIF-5A was crystallized by the hanging-drop vapor diffusion method (PMID:16522190)
• molecular model for the human eIF5A protein based on the crystal structure of the eIF5A from Leishmania brasiliensis (PMID:16842744)
• data suggest that eIF5A mediates important cellular processes like cell viability and senescence through its effects on the stability of certain mRNAs (PMID:16987817)
• analysis of differences in global protein expression in BCR-ABL-positive K562 cells treated with or without imatinib revealed down-regulation of eIF5A; hypusination inhibitors exerted an antiproliferative effect (PMID:17008552)
• These findings collectively indicate that unhypusinated eIF5A may have pro-apoptotic functions and that eIF5A is rapidly translocated to the nucleus following the induction of apoptotic cell death (PMID:17187778)
• analysis of the deoxyhypusine hydroxylase-eukaryotic translation initiation factor (eIF5A) interaction (PMID:17213197)
• Mutational analyses of human eIF5A-1–identification of amino acid residues critical for eIF5A activity and hypusine modification (PMID:18067580)
• Results suggest that the stability of eIF5A may have an important role in determining the fate of the particular cell type after severe heat stress. (PMID:19160416)
• These findings provide strong evidence that the hypusine modification of eIF5A dictates its localization in the cytoplasmic compartment where it is required for protein synthesis. (PMID:19379712)
• These data support the importance of eIF5A and hypusine formation in HIV-1 gene expression. (PMID:19825182)
• High eIF5A expression is associated with hepatocellular carcinoma. (PMID:19998337)
• These observations collectively indicate that unhypusinated eIF5A1 plays a central role in the regulation of apoptosis. (PMID:20232312)
• findings suggested that overexpression of eIF5A-2 correlates with local invasion of NSCLC, and might serve as an adverse prognostic marker of survival for stage I NSCLC patients (PMID:20830705)
• loss of eIF5A activity by this SSAT1-mediated acetylation confirms the strict structural requirement for the hypusine side chain and suggests a possible regulation of eIF5A by hypusine acetylation/deacetylation (PMID:20942800)
• EGF-induced upregulation of eIF5A stimulates corneal epithelial cell proliferation in vitro (PMID:21224998)
• HIV-1 Rev cofactors Sam68, eIF5A, hRIP, and DDX3 also function in the translation of HIV-1 RNA. (PMID:21360055)
• hybrid exercise increases expression of eukaryotic translation initiation factor 5A (EIFSA), peroxisomal biogenesis factor 6 (PEX6) and histone cluster 1 H4 (HIST1H4), compared with electrical stimulation alone (PMID:21778671)
• identified PCAF as the major cellular acetyltransferase of eIF5A, and HDAC6 and SIRT2 as its major deacetylases. Inhibition of the deacetylases or impaired hypusination increased acetylation of eIF5A, leading to nuclear accumulation. (PMID:22771473)
• a novel role for miR-331-3p and miR-642-5p in the control of prostate cancer cell growth via the regulation of DOHH expression and eIF5A activity. (PMID:22908221)
• eIF-5A as well as the hypusine-forming enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) are highly overexpressed in glioblastoma patient sample (PMID:22927971)
• acetylation regulates the subcellular localization of eIF5A2 (PMID:23132580)
• Overexpression of EIF5A is associated with early-onset colorectal cancer. (PMID:23322277)
• Altered expression of Hsc70 and eIF5A-1 may cause defects in nucleocytoplasmic transport and play a role in esophageal carcinogenesis. (PMID:23539416)
• The expression of eIF5A-2 was up-regulated following EMT phenotype changes in A549 cells, which correlated with enhanced tumor invasion and metastatic capabilities. (PMID:23733422)
• Data indicate that the signal of EIF5A2, MYCN, and MCL1 genes is decreased in hydroxyurea (HU) and gemcitabine (GEM) treated UACC-1598 ovarian cancer cell line. (PMID:23991020)
• mature eIF5A controls a translational network of cancer-driving genes, termed the eIF5A regulon, at the levels of mRNA abundance and translation (PMID:24220243)
• The findings that eIF5A and EF-P are important for specific cellular processes and play a role in the relief of ribosome stalling caused by specific amino acid sequences (PMID:24402910)
• Data suggest a regulatory mechanism for the pro-apoptotic protein eukaryotic translation initiation factor 5A1 (eIF5A1) in which its level is possibly modulated by NF-kappaB in lung cells. (PMID:24491565)
• Mature eIF5A (hypusinated form) is not involved in the autophagic pathway. (PMID:25218134)
• eIF5A proteins utilize PEAK1 as a downstream effector to drive pancreatic ductal adenocarcinoma (PDAC) pathogenesis. (PMID:25261239)
• eIF5A has been shown to regulate a number of gene products specifically, termed the eIF5A regulon, and its role in translating proline-rich sequences has recently been identified. (PMID:25979826)
• eIF5A-2 protein was highly expressed in gastric cancer tissues (PMID:26282002)
• Upregulation of translation initiation factor 5a observed in thalassemia is a novel finding and plays a protective role toward cell survival under oxidative stress. (PMID:26403856)

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): EIF5A2 (ENSG00000163577), EIF5AL1 (ENSG00000253626)

Protein

Protein identifiers

Eukaryotic translation initiation factor 5A-1 — P63241 (reviewed: P63241)

Alternative names: Eukaryotic initiation factor 5A isoform 1, Rev-binding factor, eIF-4D

All UniProt accessions (3): P63241, I3L397, I3L504

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. With syntenin SDCBP, functions as a regulator of p53/TP53 and p53/TP53-dependent apoptosis. Also regulates TNF-mediated apoptosis. Mediates effects of polyamines on neuronal process extension and survival. Is required for autophagy by assisting the ribosome in translating the ATG3 protein at a specific amino acid sequence, the ‘ASP-ASP-Gly’ motif, leading to the increase of the efficiency of ATG3 translation and facilitation of LC3B lipidation and autophagosome formation. (Microbial infection) Cellular cofactor of human T-cell leukemia virus type I (HTLV-1) Rex protein and of human immunodeficiency virus type 1 (HIV-1) Rev protein, essential for mRNA export of retroviral transcripts.

Subunit / interactions. Binds to 80S ribosomes. Actively translating ribosomes show mutually exclusive binding of eIF5a (EIF5A or EIF5A2) and EEF2/eEF2. Interacts with DAPL1; interaction takes place at the polypeptide exit tunnel of hibernating ribosomes and prevents translation. Interacts with DHPS. Interacts with SDCBP. Interacts with DOHH. (Microbial infection) Interacts with HIV-1 protein Rev.

Subcellular location. Cytoplasm. Nucleus. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in umbilical vein endothelial cells and several cancer cell lines (at protein level).

Post-translational modifications. Acetylated by PCAF/KAT2B, regulating its subcellular localization. Deacetylated by SIRT2. 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.

Disease relevance. Faundes-Banka syndrome (FABAS) [MIM:619376] An autosomal dominant disorder characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphic features. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the eIF-5A family.

Isoforms (2)

UniProt ID	Names	Canonical?
P63241-1	1, B, C, D	yes
P63241-2	2, A

RefSeq proteins (6): NP_001137232, NP_001137233, NP_001137234, NP_001357349, NP_001357350, NP_001961* (*=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 (39 total): strand 10, mutagenesis site 8, sequence variant 6, sequence conflict 4, modified residue 4, helix 2, initiator methionine 1, chain 1, region of interest 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3CPF	X-RAY DIFFRACTION	2.5
8A0E	ELECTRON MICROSCOPY	2.8
5DLQ	X-RAY DIFFRACTION	3.2
8Y0W	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63241-F1	89.07	0.81

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 (4): 2, 47, 50, 121

Mutagenesis-validated functional residues (8):

Position	Phenotype
47	abolishes acetylation.
47	causes total inactivation of eif5a in supporting yeast growth.
49	causes total inactivation of eif5a in supporting yeast growth.
50	decreases significantly the acetylation at position k-47 and causes total inactivation of eif5a in supporting yeast grow
50	causes total inactivation of eif5a in supporting yeast growth.
52	causes total inactivation of eif5a in supporting yeast growth.
55	causes total inactivation of eif5a in supporting yeast growth.
81	leads to temperature sensitivity when expressed in yeast cells.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-204626	Hypusine synthesis from eIF5A-lysine

MSigDB gene sets: 385 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GGGACCA_MIR133A_MIR133B, CREL_01, ELVIDGE_HYPOXIA_DN, E2F_Q4_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_CELLULAR_RESPONSE_TO_VIRUS, PAX4_01, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPONSE_TO_PEPTIDE, DARWICHE_SKIN_TUMOR_PROMOTER_DN, GOBP_REGULATION_OF_TRANSLATIONAL_ELONGATION, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_DN

GO Biological Process (9): translational elongation (GO:0006414), tumor necrosis factor-mediated signaling pathway (GO:0033209), positive regulation of translational elongation (GO:0045901), positive regulation of translational termination (GO:0045905), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to virus (GO:0098586), positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator (GO:1902255), translation (GO:0006412), positive regulation of apoptotic process (GO:0043065)

GO Molecular Function (5): RNA binding (GO:0003723), translation elongation factor activity (GO:0003746), U6 snRNA binding (GO:0017070), ribosome binding (GO:0043022), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), annulate lamellae (GO:0005642), nuclear pore (GO:0005643), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), synapse (GO:0045202), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational elongation	3
cellular anatomical structure	3
macromolecule biosynthetic process	2
positive regulation of translation	2
translational termination	2
intracellular membrane-bounded organelle	2
nuclear outer membrane-endoplasmic reticulum membrane network	2
cytoplasm	2
translation	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
regulation of translational elongation	1
regulation of translational termination	1
positive regulation of protein-containing complex disassembly	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
response to virus	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
positive regulation of signal transduction by p53 class mediator	1
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1
positive regulation of intrinsic apoptotic signaling pathway	1
peptidyltransferase activity	1
translational initiation	1
protein metabolic process	1
protein biosynthetic process	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
nucleic acid binding	1
translation factor activity	1
snRNA binding	1
ribonucleoprotein complex binding	1
binding	1
membrane	1
nuclear envelope	1
nuclear protein-containing complex	1
intracellular anatomical structure	1
organelle membrane	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

140 interactions, top by confidence:

A	B	Type	Score
EIF5A2	DHPS	psi-mi:“MI:0914”(association)	0.830
DHPS	EIF5A	psi-mi:“MI:0915”(physical association)	0.720
EIF5A	DHPS	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PTPN3	MCC	psi-mi:“MI:0914”(association)	0.660
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
EIF5A	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
EIF5A	CRX	psi-mi:“MI:0915”(physical association)	0.560
EIF5A	REL	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	EIF5A	psi-mi:“MI:0915”(physical association)	0.560
CRX	EIF5A	psi-mi:“MI:0915”(physical association)	0.560
REL	EIF5A	psi-mi:“MI:0915”(physical association)	0.560
EIF5A	PICK1	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	EIF5A	psi-mi:“MI:0915”(physical association)	0.560
LBX1	EIF5A	psi-mi:“MI:0915”(physical association)	0.560
GSC2	EIF5A	psi-mi:“MI:0915”(physical association)	0.560
MEI4	EIF5A	psi-mi:“MI:0915”(physical association)	0.560
DOHH	IDE	psi-mi:“MI:0914”(association)	0.530
E6	CASK	psi-mi:“MI:0914”(association)	0.520
DOHH	EIF5A	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (326): EIF5A (Affinity Capture-MS), EIF5A (Two-hybrid), EIF5A (Two-hybrid), MEOX2 (Two-hybrid), REL (Two-hybrid), EIF5A (Affinity Capture-MS), EIF5A (Reconstituted Complex), EIF5A (Affinity Capture-MS), EIF5A (Proximity Label-MS), EIF5A (Affinity Capture-MS), EIF5A (Affinity Capture-MS), EIF5A (Affinity Capture-MS), EIF5A (Affinity Capture-MS), EIF5A (Affinity Capture-MS), EIF5A (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, O94083, P10160

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
DHPS	“up-regulates activity”	EIF5A	“post translational modification”
EIF5A	“up-regulates quantity by expression”	TP53	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 155 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
Negative regulation of MAPK pathway	5	12.9×	7e-03
PTEN Regulation	5	11.1×	8e-03
ESR-mediated signaling	7	8.7×	4e-03
Transcriptional regulation by RUNX1	6	8.5×	8e-03
Cellular Senescence	6	8.0×	9e-03
Signaling by Nuclear Receptors	7	6.9×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	8
Uncertain significance	21
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1164078	NM_001970.5(EIF5A):c.143C>A (p.Thr48Asn)	Pathogenic
1164079	NM_001970.5(EIF5A):c.325C>G (p.Arg109Gly)	Pathogenic
1164081	NM_001970.5(EIF5A):c.324dup (p.Arg109fs)	Pathogenic
3369240	NM_001970.5(EIF5A):c.316G>A (p.Gly106Arg)	Pathogenic
4247995	NM_001970.5(EIF5A):c.136dup (p.Ser46fs)	Pathogenic
1064810	NM_001970.5(EIF5A):c.77G>C (p.Arg26Pro)	Likely pathogenic
1327680	NM_001970.5(EIF5A):c.343C>T (p.Pro115Ser)	Likely pathogenic
1695672	NM_001970.5(EIF5A):c.124G>A (p.Glu42Lys)	Likely pathogenic
2413190	NM_001970.5(EIF5A):c.191_192del (p.Phe64fs)	Likely pathogenic
2580665	NM_001970.5(EIF5A):c.270+1G>A	Likely pathogenic
3088079	NM_001970.5(EIF5A):c.165+1G>A	Likely pathogenic
3234785	NM_001970.5(EIF5A):c.344_345del (p.Pro115fs)	Likely pathogenic
3257725	NM_001970.5(EIF5A):c.415_416delinsAT (p.Ser139Ile)	Likely pathogenic

SpliceAI

1073 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7309606:T:TA	acceptor_gain	1.0000
17:7309607:G:A	acceptor_gain	1.0000
17:7309610:TCTA:T	acceptor_loss	1.0000
17:7309611:CTA:C	acceptor_loss	1.0000
17:7309613:A:AG	acceptor_gain	1.0000
17:7309613:AG:A	acceptor_loss	1.0000
17:7309613:AGTT:A	acceptor_gain	1.0000
17:7309613:AGTTG:A	acceptor_gain	1.0000
17:7309614:G:GG	acceptor_gain	1.0000
17:7309614:GTT:G	acceptor_gain	1.0000
17:7309614:GTTG:G	acceptor_gain	1.0000
17:7309614:GTTGG:G	acceptor_gain	1.0000
17:7309798:AAGGT:A	donor_loss	1.0000
17:7309799:AGGTT:A	donor_loss	1.0000
17:7309800:GGT:G	donor_loss	1.0000
17:7309801:G:GA	donor_loss	1.0000
17:7311122:GGTA:G	donor_loss	1.0000
17:7311123:G:GG	donor_gain	1.0000
17:7311124:T:G	donor_loss	1.0000
17:7311345:CCCA:C	acceptor_loss	1.0000
17:7311348:A:AC	acceptor_loss	1.0000
17:7311348:A:AG	acceptor_gain	1.0000
17:7311348:AGCT:A	acceptor_gain	1.0000
17:7311349:G:GA	acceptor_gain	1.0000
17:7311349:GC:G	acceptor_gain	1.0000
17:7311349:GCT:G	acceptor_gain	1.0000
17:7311349:GCTG:G	acceptor_gain	1.0000
17:7311349:GCTGA:G	acceptor_gain	1.0000
17:7311454:G:GT	donor_gain	1.0000
17:7311454:GAA:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000026684 (17:7305466 A>T), RS1000549212 (17:7310867 G>GT), RS1000569480 (17:7309248 T>A), RS1001212533 (17:7306648 C>A,G,T), RS1001218157 (17:7311819 T>A,C,G), RS1001533081 (17:7309936 C>T), RS1001585865 (17:7311991 T>A), RS1002367398 (17:7306906 C>A,T), RS1002958354 (17:7309192 C>A,G), RS1003031549 (17:7308959 G>A), RS1003296960 (17:7308242 G>C), RS1003961560 (17:7310438 T>C), RS1004038415 (17:7310264 C>G,T), RS1004277630 (17:7305352 G>C), RS1004848368 (17:7311302 G>A,C)

Disease associations

OMIM: gene MIM:600187 | disease phenotypes: MIM:619376

GenCC curated gene-disease

Disease	Classification	Inheritance
Faundes-Banka syndrome	Strong	Autosomal dominant

Mondo (2): neurodevelopmental disorder (MONDO:0700092), Faundes-Banka syndrome (MONDO:0859163)

Orphanet (0):

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000175	Cleft palate
HP:0000219	Thin upper lip vermilion
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000378	Cupped ear
HP:0000405	Conductive hearing impairment
HP:0000414	Bulbous nose
HP:0000430	Underdeveloped nasal alae
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000637	Long palpebral fissure
HP:0000729	Autistic behavior
HP:0000823	Delayed puberty
HP:0001252	Hypotonia
HP:0001319	Neonatal hypotonia
HP:0001357	Plagiocephaly
HP:0001382	Joint hypermobility
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001763	Pes planus
HP:0001791	Fetal ascites
HP:0001800	Hypoplastic toenails
HP:0002007	Frontal bossing
HP:0002015	Dysphagia
HP:0002020	Gastroesophageal reflux
HP:0002209	Sparse scalp hair

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009030_23	Venous thromboembolism	1.000000e-07
GCST90013406_251	Liver enzyme levels (alkaline phosphatase)	1.000000e-32

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105862 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects binding, increases reaction, decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	3
Estradiol	affects cotreatment, increases expression, affects reaction, decreases expression	3
bisphenol A	affects expression, decreases expression, affects reaction	2
arsenite	affects binding, increases reaction, affects response to substance	2
Resveratrol	decreases acetylation, increases expression	2
Cocaine	decreases expression, increases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, affects localization	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
TAK-243	increases sumoylation	1
beauvericin	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sulforaphane	affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
epigallocatechin gallate	increases expression	1
microcystin RR	increases expression	1
CD 437	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4034223	Binding	Inhibition of eIF5A-1 (unknown origin) at 1 uM	Structure, synthesis and biological properties of the pentacyclic guanidinium alkaloids. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice