EIF4EBP2

Summary

EIF4EBP2 (eukaryotic translation initiation factor 4E binding protein 2, HGNC:3289) is a protein-coding gene on chromosome 10q22.1, encoding Eukaryotic translation initiation factor 4E-binding protein 2 (Q13542). Repressor of translation initiation involved in synaptic plasticity, learning and memory formation.

This gene encodes a member of the eukaryotic translation initiation factor 4E binding protein family. The gene products of this family bind eIF4E and inhibit translation initiation. However, insulin and other growth factors can release this inhibition via a phosphorylation-dependent disruption of their binding to eIF4E. Regulation of protein production through these gene products have been implicated in cell proliferation, cell differentiation and viral infection.

Source: NCBI Gene 1979 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 27 total — 1 pathogenic
• MANE Select transcript: NM_004096

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3289
Approved symbol	EIF4EBP2
Name	eukaryotic translation initiation factor 4E binding protein 2
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000148730
Ensembl biotype	protein_coding
OMIM	602224
Entrez	1979

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000373218, ENST00000892260

RefSeq mRNA: 1 — MANE Select: NM_004096 NM_004096

CCDS: CCDS7303

Canonical transcript exons

ENST00000373218 — 3 exons

Exon	Start	End
ENSE00001027213	70419914	70420099
ENSE00001459802	70421716	70428618
ENSE00001459803	70404145	70404546

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 97.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 163.7683 / max 10070.2463, expressed in 1829 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105378	151.3388	1827
105379	6.3497	1725
105383	2.7659	1187
105384	2.0770	890
105382	0.7258	422
105386	0.3314	130
105385	0.1796	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.12	gold quality
esophagus squamous epithelium	UBERON:0006920	96.53	gold quality
epithelium of esophagus	UBERON:0001976	96.27	gold quality
medial globus pallidus	UBERON:0002477	95.83	gold quality
parotid gland	UBERON:0001831	95.56	gold quality
colonic epithelium	UBERON:0000397	95.53	gold quality
amniotic fluid	UBERON:0000173	95.42	gold quality
jejunal mucosa	UBERON:0000399	95.41	gold quality
ganglionic eminence	UBERON:0004023	95.40	gold quality
squamous epithelium	UBERON:0006914	95.08	gold quality
palpebral conjunctiva	UBERON:0001812	95.04	gold quality
ileal mucosa	UBERON:0000331	94.97	gold quality
globus pallidus	UBERON:0001875	94.97	gold quality
cortical plate	UBERON:0005343	94.88	gold quality
adrenal tissue	UBERON:0018303	94.67	gold quality
tendon of biceps brachii	UBERON:0008188	94.66	gold quality
pigmented layer of retina	UBERON:0001782	94.49	gold quality
endometrium epithelium	UBERON:0004811	94.49	gold quality
adipose tissue	UBERON:0001013	94.33	gold quality
monocyte	CL:0000576	94.29	gold quality
connective tissue	UBERON:0002384	94.23	gold quality
leukocyte	CL:0000738	94.21	gold quality
mononuclear cell	CL:0000842	94.19	gold quality
parietal pleura	UBERON:0002400	94.15	gold quality
embryo	UBERON:0000922	94.08	gold quality
duodenum	UBERON:0002114	94.05	gold quality
thoracic mammary gland	UBERON:0005200	94.03	gold quality
mammary gland	UBERON:0001911	94.00	gold quality
upper arm skin	UBERON:0004263	93.90	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.89	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-70580	no	344.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

243 targeting EIF4EBP2, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192

Literature-anchored findings (GeneRIF, showing 16)

• 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin. (PMID:11847216)
• PHAS-II, but not PHAS-III, contributes to the control of protein synthesis by insulin (PMID:14507920)
• The C-terminal His74-Glu89 region of 4EBP2 acts as an auxiliary function for the major binding of Y(X)4L -binding motif (Tyr54-Leu60) to eIF4E. (PMID:18789325)
• 4E-BPs regulate the stress granule localization of eIF4E (PMID:19244480)
• isoaspartate formation repair modulates the interaction of deamidated 4E-BP2 with mTORC1 in brain (PMID:20424163)
• Data show that the eIF4E binding preference for 4E-BP2 over 4E-BP1 is based on stacking of Arg63 side chain on Trp73 indole ring of eIF4E and construction of hydrophobic space around the Trp73 indole ring by the Leu59-Leu60 sequence of 4E-BP2. (PMID:21661078)
• mTORC1 controls mitochondrial activity and biogenesis by selectively promoting translation of nucleus-encoded mitochondria-related mRNAs via inhibition of the eukaryotic translation initiation factor 4E (eIF4E)-binding proteins (4E-BPs). (PMID:24206664)
• results highlight stabilization of a phosphorylation-induced fold as the essential mechanism for phospho-regulation of the 4E-BP:eIF4E interaction and exemplify a new mode of biological regulation mediated by intrinsically disordered proteins (PMID:25533957)
• Results suggest that IGF2BP3 promotes eIF4E-mediated translational activation through the reduction of EIF4E-BP2 via mRNA degradation, leading to enhanced cell proliferation. (PMID:26522719)
• molecular dynamics simulations to investigate both the folded and unfolded states of 4E-BP2 under different phosphorylation states of T37 and T46 (PMID:28068774)
• Study demonstrated key roles for 4E-BP1 and 4E-BP2 during tumor development and during tumor hypoxia. These factors maintain an ability to slow tumor progression in prostate cancer in the face of constitutive mTOR activation arising from loss of PTEN, and are also important in promoting survival of hypoxic cells once cancer has developed (PMID:29453322)
• This study combines molecular dynamics simulations and discrete path sampling to construct energy landscapes for a doubly phosphorylated 4E-BP218-62. These results explain some interesting experimental observations, including the low stability of doubly phosphorylated 4E-BP2 and its moderate binding to eIF4E and the inability of phosphorylated Y54A/L59A to fold. (PMID:31774674)
• 4EBP2-regulated protein translation has a critical role in high-fat diet-induced insulin resistance in hepatocytes. (PMID:37797700)
• The human eIF4E:4E-BP2 complex structure for studying hyperphosphorylation. (PMID:38511550)
• mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism. (PMID:38744825)
• Genetic evidence supporting potential causal roles of EIF4 family in breast cancer: a two-sample randomized Mendelian study. (PMID:39215053)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif4ebp2	ENSDARG00000031819
danio_rerio	gra	ENSDARG00000078754
mus_musculus	Eif4ebp2	ENSMUSG00000020091
rattus_norvegicus	Eif4ebp2	ENSRNOG00000070935
drosophila_melanogaster	Thor	FBGN0261560

Paralogs (2): EIF4EBP1 (ENSG00000187840), EIF4EBP3 (ENSG00000243056)

Protein

Protein identifiers

Eukaryotic translation initiation factor 4E-binding protein 2 — Q13542 (reviewed: Q13542)

All UniProt accessions (1): Q13542

UniProt curated annotations — full annotation on UniProt →

Function. Repressor of translation initiation involved in synaptic plasticity, learning and memory formation. Regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form of EIF4EBP2 competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. EIF4EBP2 is enriched in brain and acts as a regulator of synapse activity and neuronal stem cell renewal via its ability to repress translation initiation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.

Subunit / interactions. Hypophosphorylated EIF4EBP2 interacts with EIF4E; phosphorylation of EIF4EBP2 by mTORC1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. Interacts with RPTOR; promoting phosphorylation by mTORC1. Interacts with PCMT1; required to prevent isoaspartate accumulation and convert isoaspartate to Asp.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Phosphorylation at Thr-37, Thr-46, Ser-65, Thr-70 and Ser-83 is mediated by MTOR and corresponds to the hyperphosphorylated form: it abolishes binding to EIF4E by inducing folding of intrinsically disordered regions. First phosphorylated at Thr-37 and Thr-46 by MTOR, inducing folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000. Phosphorylated in response to insulin, EGF and PDGF. Deamidated at Asn-99 and Asn-102 to aspartate (Asp) in brain. Deamidation promotes interaction with RPTOR, subsequent phosphorylation by mTORC1 and increased translation, leading to impair kinetics of excitatory synaptic transmission. Deamidation takes place during postnatal development, when the PI3K-Akt-mTOR signaling is reduced, suggesting it acts as a compensatory mechanism to promote translation despite attenuated PI3K-Akt-mTOR signaling in neuron development. Deamidation converts Asn residues into a mixture of Asp and isoaspartate; interactions with PCMT1 is required to prevent isoaspartate accumulation and convert isoaspartate to Asp.

Domain organisation. The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex. Intrinsically disordered protein that undergoes folding upon phosphorylation. Hypophosphorylated form interacts strongly with EIF4E using (1) the YXXXXLPhi motif, that undergoes a disorder-to-helix transition upon binding and (2) the secondary EIF4E binding sites (residues 78-82). Phosphorylation at Thr-37 and Thr-46 induces folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000.

Similarity. Belongs to the eIF4E-binding protein family.

RefSeq proteins (1): NP_004087* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008606	EIF4EBP	Family

Pfam: PF05456

UniProt features (23 total): modified residue 7, mutagenesis site 6, short sequence motif 3, region of interest 2, strand 2, chain 1, turn 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3AM7	X-RAY DIFFRACTION	2.2
2MX4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13542-F1	75.93	0.44

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 (7): 83, 99, 102, 37, 46, 65, 70

Mutagenesis-validated functional residues (6):

Position	Phenotype
37	acidic residues do not mimic phosphorylation state. does not induce folding of the intrinsically disordered protein; whe
39	abolishes folding of the intrinsically disordered protein without affecting greatly affinity for eif4e even when the pro
46	acidic residues do not mimic phosphorylation state. does not induce folding of the intrinsically disordered protein; whe
48	abolishes folding of the intrinsically disordered protein without affecting greatly affinity for eif4e even when the pro
54–60	impaired binding to eif4e.
78–82	impaired binding to eif4e.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 251 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_MEMORY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_COGNITION, GOBP_BEHAVIOR, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_HDAC1, GOBP_TRANSLATIONAL_INITIATION, MORF_HDAC2, FOXO1_01, MODULE_149, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION

GO Biological Process (10): translation (GO:0006412), memory (GO:0007613), insulin receptor signaling pathway (GO:0008286), TOR signaling (GO:0031929), social behavior (GO:0035176), negative regulation of translational initiation (GO:0045947), regulation of synaptic plasticity (GO:0048167), modulation of chemical synaptic transmission (GO:0050804), regulation of translation (GO:0006417), negative regulation of translation (GO:0017148)

GO Molecular Function (3): eukaryotic initiation factor 4E binding (GO:0008190), translation repressor activity (GO:0030371), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), neuronal ribonucleoprotein granule (GO:0071598), postsynapse (GO:0098794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational initiation	2
negative regulation of translation	2
translation	2
cellular anatomical structure	2
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
learning or memory	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
intracellular signal transduction	1
behavior	1
biological process involved in intraspecies interaction between organisms	1
regulation of translational initiation	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
translation initiation factor binding	1
translation regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasmic ribonucleoprotein granule	1
neuron projection cytoplasm	1
synapse	1

Protein interactions and networks

STRING

460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF4EBP2	EIF4E	P06730	998
EIF4EBP2	RPS6KB1	P23443	780
EIF4EBP2	EIF4G1	Q04637	661
EIF4EBP2	SGPL1	O95470	647
EIF4EBP2	EIF4B	P23588	644
EIF4EBP2	RPTOR	Q8N122	635
EIF4EBP2	EIF4G3	O43432	590
EIF4EBP2	MLST8	Q9BVC4	587
EIF4EBP2	MKNK1	Q9BUB5	576
EIF4EBP2	RICTOR	Q6R327	573
EIF4EBP2	IRF7	Q92985	570
EIF4EBP2	RPS6KB2	Q9UBS0	569
EIF4EBP2	H7C0V5	H7C0V5	568
EIF4EBP2	EEF2	P13639	559
EIF4EBP2	RHEB	Q15382	546

IntAct

30 interactions, top by confidence:

A	B	Type	Score
EIF4EBP2	EIF4E	psi-mi:“MI:0915”(physical association)	0.960
EIF4E	EIF4EBP2	psi-mi:“MI:0915”(physical association)	0.960
EIF4EBP2	EIF4E	psi-mi:“MI:0407”(direct interaction)	0.960
EIF4E	EIF4EBP2	psi-mi:“MI:0407”(direct interaction)	0.960
EIF4E	EIF4G3	psi-mi:“MI:0914”(association)	0.810
EIF4E2	GIGYF1	psi-mi:“MI:0914”(association)	0.730
EIF4E	RNMT	psi-mi:“MI:0407”(direct interaction)	0.630
RDH12	NME2P1	psi-mi:“MI:0914”(association)	0.530
EIF4EBP2	Eif4e2	psi-mi:“MI:0407”(direct interaction)	0.440
EIF4E	EIF4EBP2	psi-mi:“MI:0915”(physical association)	0.370
EIF4E2	TARSL2	psi-mi:“MI:0914”(association)	0.350
NFYA	NME2P1	psi-mi:“MI:0914”(association)	0.350
EIF4E	EIF3F	psi-mi:“MI:0914”(association)	0.350
EIF4E	EIF4E1B	psi-mi:“MI:0914”(association)	0.350
EIF4E2	TARS3	psi-mi:“MI:0914”(association)	0.350
EIF4E	POTEF	psi-mi:“MI:0914”(association)	0.350
EIF4E	EIF4EBP2	psi-mi:“MI:0915”(physical association)	0.000
EIF4EBP2	glmU	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (52): EIF4EBP2 (Two-hybrid), EIF4EBP2 (Affinity Capture-MS), EIF4EBP2 (Affinity Capture-Western), EIF4EBP2 (Affinity Capture-Western), EIF4E (Co-fractionation), EIF4EBP2 (Co-fractionation), EIF4EBP2 (Co-fractionation), EIF4EBP2 (Co-fractionation), TBCA (Co-fractionation), EIF4EBP2 (Affinity Capture-MS), EIF4EBP2 (Affinity Capture-MS), EIF4EBP2 (Affinity Capture-MS), EIF4EBP2 (Affinity Capture-MS), LSM3 (Two-hybrid), FHL3 (Two-hybrid)

ESM2 similar proteins: A1A5R9, A2RSX4, A5WUY6, A6QQ60, A8MTA8, A8MYP8, B1AR13, H3BNL1, O94888, P21580, P54277, Q08BC4, Q13542, Q14161, Q14CM0, Q2TBS4, Q3KQ80, Q3UGM2, Q4KLY8, Q4R8V9, Q4R8W3, Q5BK20, Q5M8M2, Q5RDJ2, Q5RDU9, Q5REY7, Q5TH74, Q5ZLS2, Q60769, Q658L1, Q6IE70, Q6KAU4, Q6P5G6, Q6PGH2, Q6ZWH5, Q8BGF7, Q8BQB6, Q8C8J0, Q8IWR0, Q8K2D3

Diamond homologs: O60516, P70445, Q0P5A7, Q13541, Q13542, Q54DU8, Q60876, Q62622, Q80VV3, Q98TT6, Q9XZ56

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MTOR	down-regulates	EIF4EBP2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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.

GO biological processes:

GO term	Partners	Fold	FDR
translational initiation	5	163.0×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1460012	NC_000010.10:g.(?72183370)(72201347_?)del	Pathogenic

SpliceAI

468 predictions. Top by Δscore:

Variant	Effect	Δscore
10:70404544:G:GT	donor_gain	1.0000
10:70419909:TCCA:T	acceptor_loss	1.0000
10:70419910:CCA:C	acceptor_loss	1.0000
10:70419911:CA:C	acceptor_loss	1.0000
10:70419913:GGA:G	acceptor_gain	1.0000
10:70420046:TAG:T	donor_gain	1.0000
10:70420047:AGA:A	donor_gain	1.0000
10:70420095:AGTTG:A	donor_loss	1.0000
10:70420096:GTTG:G	donor_gain	1.0000
10:70420097:TTGG:T	donor_loss	1.0000
10:70420100:G:GG	donor_gain	1.0000
10:70420100:GTA:G	donor_loss	1.0000
10:70420101:T:A	donor_loss	1.0000
10:70421904:G:T	donor_gain	1.0000
10:70404542:GGGAG:G	donor_gain	0.9900
10:70404543:GGAG:G	donor_gain	0.9900
10:70404543:GGAGG:G	donor_gain	0.9900
10:70404544:G:T	donor_gain	0.9900
10:70404544:GAGGT:G	donor_loss	0.9900
10:70404545:AGG:A	donor_loss	0.9900
10:70404546:GGTGA:G	donor_loss	0.9900
10:70404547:G:T	donor_loss	0.9900
10:70404548:T:G	donor_loss	0.9900
10:70404805:GCT:G	donor_gain	0.9900
10:70419900:A:G	acceptor_gain	0.9900
10:70419912:A:AG	acceptor_gain	0.9900
10:70419912:AG:A	acceptor_gain	0.9900
10:70419913:G:GA	acceptor_gain	0.9900
10:70419913:GG:G	acceptor_gain	0.9900
10:70419913:GGAA:G	acceptor_gain	0.9900

AlphaMissense

789 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:70404519:G:A	G40R	1.000
10:70404519:G:C	G40R	1.000
10:70404519:G:T	G40W	1.000
10:70404520:G:A	G40E	1.000
10:70404520:G:T	G40V	1.000
10:70404528:T:C	F43L	1.000
10:70404529:T:C	F43S	1.000
10:70404530:C:A	F43L	1.000
10:70404530:C:G	F43L	1.000
10:70404544:G:A	G48E	1.000
10:70404544:G:T	G48V	1.000
10:70404546:G:A	G49R	1.000
10:70404546:G:C	G49R	1.000
10:70419914:G:A	G49E	1.000
10:70419914:G:T	G49V	1.000
10:70419917:C:T	T50I	1.000
10:70419923:T:A	I52N	1.000
10:70419923:T:C	I52T	1.000
10:70419923:T:G	I52S	1.000
10:70419926:T:A	I53N	1.000
10:70419928:T:C	Y54H	1.000
10:70419928:T:G	Y54D	1.000
10:70419935:G:C	R56T	1.000
10:70419935:G:T	R56I	1.000
10:70419936:A:C	R56S	1.000
10:70419936:A:T	R56S	1.000
10:70419940:T:C	F58L	1.000
10:70419942:T:A	F58L	1.000
10:70419942:T:G	F58L	1.000
10:70419944:T:A	L59Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000089512 (10:70409420 T>C), RS1000121871 (10:70421409 T>C), RS1000229945 (10:70412135 A>G), RS1000257142 (10:70405614 C>T), RS1000353731 (10:70405788 A>G), RS1000619212 (10:70418567 A>G), RS1000872607 (10:70408926 A>G), RS1000924956 (10:70408657 C>T), RS1000994433 (10:70414704 C>T), RS1001178859 (10:70421322 T>C), RS1001281610 (10:70415621 A>G,T), RS1001364140 (10:70420704 T>G), RS1001400197 (10:70420454 G>A,C), RS1001418443 (10:70416004 C>T), RS1001478862 (10:70427530 T>C)

Disease associations

OMIM: gene MIM:602224 | disease phenotypes: MIM:603553, MIM:270100

GenCC curated gene-disease

Mondo (2): familial hemophagocytic lymphohistiocytosis 2 (MONDO:0011337), heterotaxy, visceral, 5, autosomal (MONDO:0700112)

Orphanet (2): Visceral heterotaxy (Orphanet:450), Familial hemophagocytic lymphohistiocytosis (Orphanet:540)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537250	Hemophagocytic lymphohistiocytosis, familial, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
4-oxoretinoic acid	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Pioglitazone	increases expression	1
Sunitinib	decreases expression	1
Alitretinoin	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Calcitriol	decreases expression	1
Catechin	decreases expression, affects cotreatment	1
Coumestrol	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylstilbestrol	increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SL80	HAP1 EIF4EBP2 (-) 1	Cancer cell line	Male
CVCL_SL81	HAP1 EIF4EBP2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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