EIF1AX

Summary

EIF1AX (eukaryotic translation initiation factor 1A X-linked, HGNC:3250) is a protein-coding gene on chromosome Xp22.12, encoding Eukaryotic translation initiation factor 1A, X-chromosomal (P47813). Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5’-untranslated region, and locates the initiation codon. It is a common-essential gene (DepMap: required in 90.6% of cancer cell lines).

This gene encodes an essential eukaryotic translation initiation factor. The protein is required for the binding of the 43S complex (a 40S subunit, eIF2/GTP/Met-tRNAi and eIF3) to the 5’ end of capped RNA.

Source: NCBI Gene 1964 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 60 total — 2 likely-pathogenic
• Cancer driver (intOGen): activating (oncogene-like) across 6 cancer types
• Cancer dependency (DepMap): dependent in 90.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_001412

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3250
Approved symbol	EIF1AX
Name	eukaryotic translation initiation factor 1A X-linked
Location	Xp22.12
Locus type	gene with protein product
Status	Approved
Aliases	eIF-1A, eIF-4C
Ensembl gene	ENSG00000173674
Ensembl biotype	protein_coding
OMIM	300186
Entrez	1964

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000379593, ENST00000379607, ENST00000877865, ENST00000877866, ENST00000914219, ENST00000914220

RefSeq mRNA: 1 — MANE Select: NM_001412 NM_001412

CCDS: CCDS14196

Canonical transcript exons

ENST00000379607 — 7 exons

Exon	Start	End
ENSE00001199818	20130516	20130607
ENSE00001326974	20124525	20128311
ENSE00001481854	20141625	20141838
ENSE00001689602	20138539	20138622
ENSE00001733715	20132182	20132263
ENSE00001742922	20135738	20135841
ENSE00001801842	20133957	20134007

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.1524 / max 576.1547, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198673	42.1524	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.64	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.00	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.96	gold quality
biceps brachii	UBERON:0001507	96.75	gold quality
pons	UBERON:0000988	96.53	gold quality
ganglionic eminence	UBERON:0004023	96.36	gold quality
cortical plate	UBERON:0005343	96.20	gold quality
pericardium	UBERON:0002407	96.11	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.00	gold quality
postcentral gyrus	UBERON:0002581	95.79	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.74	gold quality
cerebellar vermis	UBERON:0004720	95.45	gold quality
islet of Langerhans	UBERON:0000006	95.41	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.29	gold quality
stromal cell of endometrium	CL:0002255	95.28	gold quality
superior frontal gyrus	UBERON:0002661	95.28	gold quality
subthalamic nucleus	UBERON:0001906	95.27	gold quality
parietal lobe	UBERON:0001872	95.26	gold quality
ventricular zone	UBERON:0003053	95.26	gold quality
calcaneal tendon	UBERON:0003701	95.20	gold quality
gastrocnemius	UBERON:0001388	95.04	gold quality
muscle of leg	UBERON:0001383	94.95	gold quality
lateral globus pallidus	UBERON:0002476	94.95	gold quality
left ovary	UBERON:0002119	94.93	gold quality
superior vestibular nucleus	UBERON:0007227	94.90	gold quality
parotid gland	UBERON:0001831	94.86	gold quality
muscle organ	UBERON:0001630	94.80	gold quality
deltoid	UBERON:0001476	94.69	gold quality
middle temporal gyrus	UBERON:0002771	94.69	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	59.95
E-HCAD-5	yes	17.70
E-CURD-135	no	905.87
E-MTAB-8271	no	6.82
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

187 targeting EIF1AX, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1468-3P	99.96	72.74	3797
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

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 90.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 35)

• Remarkable conservation of translation initiation factors: IF1/eIF1A and IF2/eIF5B are universally distributed phylogenetic markers. (PMID:11699879)
• Exp5 exports eEF1A via tRNA from nuclei and synergizes with other transport pathways to confine translation to the cytoplasm. (PMID:12426392)
• determination of binding site on eukaryotic initiation factor 5B (PMID:12569173)
• The efficiency of the EF-1alpha promoter was higher than that of the cytomegalovirus promoter in all embryonic stem cells trnasfected. (PMID:17784828)
• eIF3j/HCR1 closely cooperates with the eIF3b/PRT1 RNA recognition motif and eIF1A on the ribosome to ensure proper formation of the scanning-arrested conformation required for stringent AUG recognition (PMID:20060839)
• Coordinated movements of eukaryotic translation initiation factors eIF1, eIF1A, and eIF5 trigger phosphate release from eIF2 in response to start codon recognition by the ribosomal preinitiation complex (PMID:23293029)
• the newly identified driver mutations in EIF1AX and SF3B1, specifically found in uveal melanomas with disomy 3, confirm and extend the established classification model of uveal melanoma. (PMID:23793026)
• Then, activated p38 further enhanced the docking of activating transcription factor 4 (ATF4) onto the CHOP (CCAAT/enhancer-binding protein homologous protein) promoter via eIF2alpha to enhance apoptosis (PMID:24874742)
• The effect of an EIF1AX mutation is estimated to be a decreased odds of metastasis in uveal melanoma. (PMID:24970262)
• The finding of this study suggested that an SF3B1 or EIF1AX mutation is present in a substantial subset of primary LMNs underscores that these tumors genetically resemble uveal melanoma and are different from cutaneous melanoma at the genetic level. (PMID:26769193)
• We report here the occurrence of EIF1AX mutations not only in thyroid cancer, but also in benign thyroid nodules, and demonstrate that phenotypically these mutations are associated with the encapsulated follicular variant of papillary thyroid carcinoma and benign follicular-pattern nodules. (PMID:26911375)
• Patients with uveal melanoma can be classified into 3 groups, of which EIF1AX-mutated tumors and tumors without BAP1, SF3B1, or EIF1AX mutations are associated with prolonged survival and low metastatic risk, SF3B1-mutated tumors are associated with late metastasis (PMID:26923342)
• EIF1AX alterations occurred infrequently in low-grade gliomas (1.4%), uterus endometrial carcinoma (1.25%), thyroid carcinoma (1%), and lung adenocarcinoma (0.4%). (PMID:27089234)
• BAP1, SF3B1, and EIF1AX mutations occur during uveal melanoma tumor progression in an almost mutually exclusive manner and are associated with different levels of metastatic risk. (PMID:27123562)
• results indicate that the interactions between eIF1A and eIF5B are being continuously rearranged during translation initiation; presentation of a model how the dynamic eIF1A/eIF5B interaction network can promote remodeling of the translation initiation complexes, and the roles in the process played by intrinsically disordered protein segments (PMID:27325746)
• In this report we show that patients with uveal melanoma harbor mutation-specific chromosomal patterns in the tumor. These chromosomal patterns are characterized by different types of chromosomal anomalies, thus illustrating that distinct biological mechanisms underlie uveal melanoma pathogenesis. (PMID:27916271)
• Short 5’UTR mRNAs are enriched with TISU (translation initiator of short 5’UTR), a 12-nucleotide element directing efficient scanning-independent translation. This study demonstrate that TISU is particularly dependent on eukaryotic initiation factor 1A (eIF1A) which interacts with both RPS3 and RPS10e. (PMID:28584194)
• Coexpression of mutant NRAS and EIF1AX proteins promoted proliferation and clonogenic survival in LGSC cells, providing the first example of co-occurring, growth-promoting mutational events in ovarian cancer. (PMID:28646021)
• we find iris melanomas to be related genetically to choroidal and ciliary body melanomas, frequently harboring GNAQ, GNA11, and EIF1AX mutations. (PMID:28700778)
• Mutation in EIF1AX gene is associated with Uveal Melanoma. (PMID:28810145)
• Study identified a new RNA-induced silencing complex component, eIF1A, which directly interacts with the MID-domain of Ago2 and functions in DICER-independent miRNA biogenesis and miRNA-mediated RNA interference. (PMID:29236257)
• Its mutation is found in patients with meningeal melanocytic tumor. (PMID:29476293)
• EIF1AX p.Ala113_splice mutation is associated with thyroid cancer tumourigenesis and progression. (PMID:29968046)
• Regarding time to clinically detected metastases, the first 2 peaks appear to be associated with BAP1-mutated tumors and the late peak to SF3B1-mutated tumors. None of the tumors with only an EIF1AX mutation metastasized. (PMID:30073324)
• We found only one of the 301 tumors (0.3%) harboring A113_splice site mutation at the intron 5/exon 6 splice site of EIF1AX gene (PMID:30269267)
• Results identified a mutation in EIF1AX in non-aggressive primary orbital melanoma (POM) tumors suggesting a role in determining the clinical course of POM. (PMID:30558566)
• Five clusters with distinct copy number variations patterns and concomitant mutations in BAP1, SF3B1, or EIF1AX were identified. Incorporating clinico-histopathological, cluster and mutation data in the analysis results in good performance for uveal melanoma-related disease free survival prediction. (PMID:31425584)
• Mutations of GNAQ, GNA11, SF3B1, EIF1AX, PLCB4 and CYSLTR in Uveal Melanoma in Chinese Patients. (PMID:31614358)
• Transcriptional repression of p21 by EIF1AX promotes the proliferation of breast cancer cells. (PMID:32926483)
• Characterization and Clinical Significance of EIF1AX Mutations and Co-Mutations in Cytologically Indeterminate Thyroid Nodules: A 5-Year Retrospective Analysis. (PMID:34075760)
• Long noncoding RNA EIF1AX-AS1 promotes endometrial cancer cell apoptosis by affecting EIF1AX mRNA stabilization. (PMID:35080085)
• Clinicopathological features and outcomes of thyroid nodules with EIF1AX mutations. (PMID:35609001)
• eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining. (PMID:35732735)
• EIF1AX mutation in thyroid tumors: a retrospective analysis of cytology, histopathology and co-mutation profiles. (PMID:36371345)
• XPO1-Mediated EIF1AX Cytoplasmic Relocation Promotes Tumor Migration and Invasion in Endometrial Carcinoma. (PMID:36589683)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif1axa	ENSDARG00000029003
danio_rerio	eif1axb	ENSDARG00000057912
mus_musculus	Eif1ax	ENSMUSG00000067194
rattus_norvegicus	Eif1ax	ENSRNOG00000005736
drosophila_melanogaster	eIF1A	FBGN0026250
caenorhabditis_elegans		WBGENE00019162

Paralogs (1): EIF1AY (ENSG00000198692)

Protein

Protein identifiers

Eukaryotic translation initiation factor 1A, X-chromosomal — P47813 (reviewed: P47813)

Alternative names: Eukaryotic translation initiation factor 4C

All UniProt accessions (2): P47813, X6RAC9

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5’-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1.

Subunit / interactions. Component of the 43S pre-initiation complex (43S PIC), which is composed of the 40S ribosomal subunit, EIF1, eIF1A (EIF1AX), eIF3 complex, EIF5 and eIF2-GTP-initiator tRNA complex (eIF2 ternary complex). Interacts with EIF5; this interaction contributes to the maintenance of EIF1 within the open 43S PIC. Interacts through its C-terminal domain (CTD) with the CTD of EIF5B; from the location of the start codon by the 43S complex until the formation of the 80S complex. (Microbial infection) Interacts with human respiratory syncytial virus (HRSV) nucleoprotein; this interaction recruits EIF1AX to the viral replication complex to facilitate viral genomic RNA synthesis and virus production.

Subcellular location. Cytoplasm.

Similarity. Belongs to the eIF-1A family.

RefSeq proteins (1): NP_001403* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001253	TIF_eIF-1A	Family
IPR006196	RNA-binding_domain_S1_IF1	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR018104	TIF_eIF-1A_CS	Conserved_site

Pfam: PF01176

UniProt features (21 total): strand 10, compositionally biased region 3, helix 2, turn 2, region of interest 2, chain 1, domain 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
8PPL	ELECTRON MICROSCOPY	2.65
6ZP4	ELECTRON MICROSCOPY	2.9
8PJ5	ELECTRON MICROSCOPY	2.9
8PJ6	ELECTRON MICROSCOPY	2.9
9H74	ELECTRON MICROSCOPY	2.9
6YBW	ELECTRON MICROSCOPY	3.1
8SUP	ELECTRON MICROSCOPY	3.1
7TQL	ELECTRON MICROSCOPY	3.2
8PJ4	ELECTRON MICROSCOPY	3.2
9KN5	ELECTRON MICROSCOPY	3.2
9KN6	ELECTRON MICROSCOPY	3.3
8PJ1	ELECTRON MICROSCOPY	3.4
8PJ2	ELECTRON MICROSCOPY	3.4
7A09	ELECTRON MICROSCOPY	3.5
7SYS	ELECTRON MICROSCOPY	3.5
8OZ0	ELECTRON MICROSCOPY	3.5
3ZJY	X-RAY DIFFRACTION	3.6
7SYR	ELECTRON MICROSCOPY	3.6
6ZMW	ELECTRON MICROSCOPY	3.7
7QP7	ELECTRON MICROSCOPY	3.7
7SYW	ELECTRON MICROSCOPY	3.7
7SYX	ELECTRON MICROSCOPY	3.7
8PJ3	ELECTRON MICROSCOPY	3.7
7SYQ	ELECTRON MICROSCOPY	3.8
7SYV	ELECTRON MICROSCOPY	3.9
7QP6	ELECTRON MICROSCOPY	4.7
4KZY	X-RAY DIFFRACTION	7.01
4KZZ	X-RAY DIFFRACTION	7.03
1D7Q	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P47813-F1	78.15	0.45

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-72649	Translation initiation complex formation
R-HSA-72689	Formation of a pool of free 40S subunits
R-HSA-72695	Formation of the ternary complex, and subsequently, the 43S complex
R-HSA-72702	Ribosomal scanning and start codon recognition
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit

MSigDB gene sets: 245 (showing top): MORF_DNMT1, GOBP_RIBOSOME_BIOGENESIS, MORF_SMC1L1, GU_PDEF_TARGETS_DN, E2F4DP1_01, PAL_PRMT5_TARGETS_UP, MORF_UBE2I, MORF_HDAC1, MORF_UBE2N, GOBP_TRANSLATIONAL_INITIATION, GOBP_RIBOSOME_ASSEMBLY, MORF_HDAC2, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, GGGTGGRR_PAX4_03, GOLDRATH_ANTIGEN_RESPONSE

GO Biological Process (3): translational initiation (GO:0006413), ribosome assembly (GO:0042255), translation (GO:0006412)

GO Molecular Function (5): tRNA binding (GO:0000049), RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), translation factor activity, RNA binding (GO:0008135), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), eukaryotic 43S preinitiation complex (GO:0016282), eukaryotic 48S preinitiation complex (GO:0033290), multi-eIF complex (GO:0043614), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Eukaryotic Translation Initiation	1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	2
translational initiation	2
RNA binding	2
translation factor activity	2
cellular anatomical structure	2
cytoplasm	2
cytosolic small ribosomal subunit	2
cytosolic translation preinitiation complex	2
formation of translation initiation ternary complex	1
metabolic process	1
ribosome biogenesis	1
membraneless organelle assembly	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
nucleic acid binding	1
binding	1
intracellular anatomical structure	1
ribonucleoprotein complex	1
cell junction	1

Protein interactions and networks

STRING

3168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF1AX	EIF1	P41567	898
EIF1AX	EIF4A2	Q14240	862
EIF1AX	EIF4A1	P04765	842
EIF1AX	DHX29	Q7Z478	839
EIF1AX	GNA11	P29992	777
EIF1AX	GNAQ	P50148	717
EIF1AX	EIF4B	P23588	714
EIF1AX	SF3B1	O75533	673
EIF1AX	PLCB4	Q15147	671
EIF1AX	CYSLTR2	Q9NS75	668
EIF1AX	EIF4G1	Q04637	640
EIF1AX	BAP1	Q92560	623
EIF1AX	BRAF	P15056	616
EIF1AX	PIK3CA	P42336	615
EIF1AX	NRAS	P01111	614

IntAct

83 interactions, top by confidence:

A	B	Type	Score
RAMAC	RNMT	psi-mi:“MI:0914”(association)	0.810
IPO13	EIF1AX	psi-mi:“MI:0915”(physical association)	0.750
EIF1AX	IPO13	psi-mi:“MI:0915”(physical association)	0.750
IPO13	EIF1AX	psi-mi:“MI:0407”(direct interaction)	0.750
GATAD2A	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
CRHBP	CCNB2	psi-mi:“MI:0914”(association)	0.640
RFPL3	EIF1AX	psi-mi:“MI:0915”(physical association)	0.560
NCR3LG1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
EIF1AY	EIF1AX	psi-mi:“MI:0914”(association)	0.530
EIF3A	EIF1AX	psi-mi:“MI:0407”(direct interaction)	0.520
EIF1AX	EIF3A	psi-mi:“MI:0914”(association)	0.520
EIF3C	EIF1AX	psi-mi:“MI:0407”(direct interaction)	0.520
EIF1AX	EIF5	psi-mi:“MI:0915”(physical association)	0.510
EIF5	EIF1AX	psi-mi:“MI:0915”(physical association)	0.510
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
EIF1AX	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
EIF1AX		psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350

BioGRID (156): EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), EIF1AX (Affinity Capture-MS)

ESM2 similar proteins: A0A324, A1XQR9, A4FUI2, A5JSS2, A6MZM2, G1SHQ2, O09167, O14602, O35900, O60739, P20280, P25800, P41567, P46778, P47813, P48024, P49666, P51971, P61220, P62303, P62304, P62305, P62308, P62309, Q09028, Q0D5W6, Q0P5B3, Q2KIA3, Q3B8H4, Q3ZBL0, Q4R4X9, Q503U0, Q5E938, Q5RA42, Q5RBW7, Q5RFF4, Q60872, Q60972, Q6GVM3, Q6QN05

Diamond homologs: A2STQ8, A4FYM5, A4YEH8, A6UUK8, A6VJQ7, A9A6C2, B0R7D8, B8D5N1, C3MK60, C3MU29, C3N0P1, C3N8M9, C3NMA0, C4KK84, O14602, O27085, O29481, O59280, P38912, P47813, P47814, P47815, P55877, P56331, P57676, Q03590, Q12YN5, Q18EX1, Q18JF4, Q2NEP1, Q3IT14, Q469I9, Q469J2, Q4JA54, Q54YJ6, Q57887, Q5JH78, Q5RA42, Q5UZM2, Q60872

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EIF1AX	“up-regulates activity”	Ternary_GTP_eIF2_tRNA_complex	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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
Ribosomal scanning and start codon recognition	7	22.6×	1e-05
Formation of the ternary complex, and subsequently, the 43S complex	6	21.9×	5e-05
Translation initiation complex formation	6	19.4×	8e-05
GTP hydrolysis and joining of the 60S ribosomal subunit	8	13.6×	3e-05
Formation of a pool of free 40S subunits	7	13.3×	9e-05
L13a-mediated translational silencing of Ceruloplasmin expression	7	12.0×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	5	71.1×	5e-06
translational initiation	5	22.7×	5e-04
obsolete positive regulation of NF-kappaB transcription factor activity	6	15.6×	5e-04
T cell receptor signaling pathway	6	11.5×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 6 cancer types — LUNG, PRAD, SKCM, UCEC, UM, WDTC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	4
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4279440	GRCh37/hg19 Xp22.12(chrX:20016146-20891895)x2	Likely pathogenic
800345	NM_001412.4(EIF1AX):c.295G>A (p.Glu99Lys)	Likely pathogenic

SpliceAI

919 predictions. Top by Δscore:

Variant	Effect	Δscore
X:20130512:TTA:T	donor_loss	1.0000
X:20130513:TA:T	donor_loss	1.0000
X:20130514:A:AC	donor_gain	1.0000
X:20130514:ACG:A	donor_loss	1.0000
X:20130514:ACGT:A	donor_gain	1.0000
X:20130515:C:CA	donor_gain	1.0000
X:20130515:CG:C	donor_gain	1.0000
X:20130515:CGT:C	donor_gain	1.0000
X:20130515:CGTC:C	donor_gain	1.0000
X:20130515:CGTCA:C	donor_gain	1.0000
X:20130603:TTTAG:T	acceptor_gain	1.0000
X:20130604:TTAG:T	acceptor_gain	1.0000
X:20130604:TTAGC:T	acceptor_loss	1.0000
X:20130605:TAG:T	acceptor_gain	1.0000
X:20130606:AG:A	acceptor_gain	1.0000
X:20130607:GCTAA:G	acceptor_loss	1.0000
X:20130608:C:CC	acceptor_gain	1.0000
X:20130608:CT:C	acceptor_loss	1.0000
X:20130615:C:CT	acceptor_gain	1.0000
X:20130618:A:T	acceptor_gain	1.0000
X:20132169:A:C	donor_gain	1.0000
X:20132176:CATTA:C	donor_loss	1.0000
X:20132179:TA:T	donor_loss	1.0000
X:20132180:ACCA:A	donor_loss	1.0000
X:20132181:CCATG:C	donor_gain	1.0000
X:20133952:TTTAC:T	donor_loss	1.0000
X:20133954:TACCT:T	donor_loss	1.0000
X:20133955:ACCTG:A	donor_loss	1.0000
X:20133956:CCTGG:C	donor_loss	1.0000
X:20135736:ACCT:A	donor_loss	1.0000

AlphaMissense

968 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:20132211:A:G	L103P	1.000
X:20132211:A:T	L103Q	1.000
X:20132220:G:T	A100D	1.000
X:20132221:C:G	A100P	1.000
X:20132247:A:T	V91E	1.000
X:20134000:A:T	I71K	1.000
X:20134002:C:A	W70C	1.000
X:20134002:C:G	W70C	1.000
X:20134004:A:G	W70R	1.000
X:20134004:A:T	W70R	1.000
X:20135754:C:A	G63V	1.000
X:20135754:C:T	G63E	1.000
X:20135755:C:G	G63R	1.000
X:20135755:C:T	G63R	1.000
X:20135760:A:C	I61S	1.000
X:20135760:A:T	I61N	1.000
X:20135765:A:C	C59W	1.000
X:20135766:C:T	C59Y	1.000
X:20135767:A:G	C59R	1.000
X:20135789:A:C	C51W	1.000
X:20135791:A:G	C51R	1.000
X:20135802:A:G	L47P	1.000
X:20135805:C:G	R46P	1.000
X:20135808:C:T	G45E	1.000
X:20135814:C:A	G43V	1.000
X:20135814:C:T	G43E	1.000
X:20135815:C:G	G43R	1.000
X:20135815:C:T	G43R	1.000
X:20135835:G:T	A36D	1.000
X:20135836:C:G	A36P	1.000

dbSNP variants (sampled 300 via entrez): RS1000232341 (X:20124737 G>A,C), RS1000572844 (X:20128881 A>C), RS1000724353 (X:20131227 G>T), RS1000941361 (X:20139331 A>C), RS1001156720 (X:20131489 G>A), RS1001881940 (X:20134516 T>G), RS1001897576 (X:20130682 T>A), RS1002162141 (X:20138866 T>A), RS1002328387 (X:20131164 T>C), RS1002417691 (X:20134776 T>C), RS1002556619 (X:20124220 C>T), RS1002711981 (X:20134769 T>C,G), RS1002822812 (X:20139666 T>C), RS1002826718 (X:20135120 T>G), RS1002852292 (X:20140404 A>C)

Disease associations

OMIM: gene MIM:300186 | disease phenotypes: MIM:254500

GenCC curated gene-disease

Mondo (1): plasma cell myeloma (MONDO:0009693)

Orphanet (2): Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	3
cobaltous chloride	decreases expression	2
Cisplatin	affects reaction, decreases expression	2
Valproic Acid	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
decabromobiphenyl ether	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
nickel chloride	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	affects expression	1
S-1,2-dichlorovinyl-N-acetylcysteine	affects expression	1
K 7174	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_8607	92-1 [Human uveal melanoma]	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	PHASE4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	PHASE4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	PHASE4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	PHASE4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	PHASE4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	PHASE4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	PHASE4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	PHASE4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	PHASE4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	PHASE4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	PHASE4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	PHASE4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	PHASE4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	PHASE4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	PHASE4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	PHASE4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	PHASE4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	PHASE4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	PHASE4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	PHASE4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	PHASE4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	PHASE4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	PHASE4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	PHASE4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	PHASE4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	PHASE4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	PHASE4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05855122	PHASE4	UNKNOWN	Safety and ASCT-related Symptom Burden Optimization of Tocilizumab in ASCT Following HD Melphalan Conditioning for Multiple Myeloma Patients
NCT05944783	PHASE4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg
NCT06057402	PHASE4	RECRUITING	Elranatamab Post Trial Access Study for Participants With Multiple Myeloma (MM)
NCT06251076	PHASE4	RECRUITING	Plan Development for Giving Teclistamab in the Outpatient Setting