EIF4H

Summary

EIF4H (eukaryotic translation initiation factor 4H, HGNC:12741) is a protein-coding gene on chromosome 7q11.23, encoding Eukaryotic translation initiation factor 4H (Q15056). Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. It is a selective cancer dependency (DepMap: 13.0% of cell lines).

This gene encodes one of the translation initiation factors, which functions to stimulate the initiation of protein synthesis at the level of mRNA utilization. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternative splicing of this gene generates 2 transcript variants.

Source: NCBI Gene 7458 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 18 total
• Phenotypes (HPO): 186
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 13.0% of screened cell lines
• MANE Select transcript: NM_022170

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12741
Approved symbol	EIF4H
Name	eukaryotic translation initiation factor 4H
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	WSCR1, KIAA0038
Ensembl gene	ENSG00000106682
Ensembl biotype	protein_coding
OMIM	603431
Entrez	7458

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000265753, ENST00000353999, ENST00000479338, ENST00000489484, ENST00000495187, ENST00000677570, ENST00000677681, ENST00000677998, ENST00000678341, ENST00000678438, ENST00000678815, ENST00000679161, ENST00000679266, ENST00000679287

RefSeq mRNA: 2 — MANE Select: NM_022170 NM_022170, NM_031992

CCDS: CCDS5564, CCDS5565

Canonical transcript exons

ENST00000265753 — 7 exons

Exon	Start	End
ENSE00000693358	74194741	74194878
ENSE00001879754	74195169	74197096
ENSE00001946404	74174356	74174442
ENSE00003491152	74190247	74190306
ENSE00003548576	74187611	74187798
ENSE00003615791	74189822	74189918
ENSE00003675831	74189673	74189737

Expression profiles

Bgee: expression breadth ubiquitous, 306 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 106.9357 / max 1037.6486, expressed in 1826 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79075	103.3867	1826
79074	2.1837	1337
204481	0.8937	634
204479	0.3444	109
79077	0.0738	3
204480	0.0535	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.06	gold quality
skin of leg	UBERON:0001511	98.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.95	gold quality
body of pancreas	UBERON:0001150	98.92	gold quality
esophagus squamous epithelium	UBERON:0006920	98.91	gold quality
gastrocnemius	UBERON:0001388	98.87	gold quality
lower esophagus	UBERON:0013473	98.87	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.87	gold quality
mucosa of stomach	UBERON:0001199	98.86	gold quality
esophagus	UBERON:0001043	98.84	gold quality
esophagus mucosa	UBERON:0002469	98.84	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.84	gold quality
prefrontal cortex	UBERON:0000451	98.82	gold quality
skin of abdomen	UBERON:0001416	98.82	gold quality
cerebellar hemisphere	UBERON:0002245	98.81	gold quality
body of stomach	UBERON:0001161	98.80	gold quality
muscle of leg	UBERON:0001383	98.80	gold quality
epithelium of nasopharynx	UBERON:0001951	98.80	gold quality
cerebellar cortex	UBERON:0002129	98.80	gold quality
spinal cord	UBERON:0002240	98.80	gold quality
right frontal lobe	UBERON:0002810	98.80	gold quality
nasopharynx	UBERON:0001728	98.78	gold quality
lower esophagus mucosa	UBERON:0035834	98.78	gold quality
calcaneal tendon	UBERON:0003701	98.76	gold quality
body of uterus	UBERON:0009853	98.76	gold quality
zone of skin	UBERON:0000014	98.75	gold quality
left uterine tube	UBERON:0001303	98.75	gold quality
ventricular zone	UBERON:0003053	98.74	gold quality
ectocervix	UBERON:0012249	98.74	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-93593	no	7.50
E-MTAB-5061	no	3.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, NFKB, RELA

miRNA regulators (miRDB)

105 targeting EIF4H, 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-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6888-3P	99.97	65.95	1170
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-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• data indicate that eIF4B and 4H stimulate the nuclease activity of herpes simplex virus vhs, and they provide evidence that additional mammalian factors are required for targeting to the encephalomyocarditis virus IRES (PMID:15078951)
• eIF4H binding is required for herpes simplex virus virion host shutoff-induced degradation of many mRNAs, perhaps by targeting Vhs to mRNAs and to preferred sites within mRNAs. (PMID:18448541)
• The interaction of eIF4AI with two accessory factors, eIF4B and eIF4H, was studied. (PMID:18719248)
• Study reports the topology of the eIF4A/4G/4H helicase complex, which is built from multiple experimentally observed domain-domain contacts. (PMID:19203580)
• Data show that reduced levels of eIF4B, eIF4H, or polyA-binding protein, also trigger SG formation. (PMID:19369421)
• results suggest that eIF4H isoform 1 plays an important role in carcinogenesis through the activation of oncogenic signaling and could be a promising molecular target for cancer therapy (PMID:20473909)
• Studies indicate that eIF4A (DDX2), together with its accessory proteins eIF4B and eIF4H, is thought to act as a helicase that unwinds secondary structures in the mRNA 5’ UTR. (PMID:21427765)
• Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-kappaB. (PMID:23776612)
• Results demonstrate that eukaryotic translation initiation factor 4H (eIF4H) plays a crucial role in translational control. (PMID:26498689)
• The results from these procedures revealed eIF4H to be one of the targets of miR-519d. Downregulated eIF4H was analogous to the overexpressed miR-519d obtained from miR-519d agomir and si-eIF4H transfection. In summary, it can be concluded that miR-519d targets eIF4H in lung adenocarcinoma to inhibit cell proliferation and invasion (PMID:28351305)
• eIF4B and eIF4H mediate GR production from expanded G4C2 in a Drosophila model for C9orf72-associated amyotrophic lateral sclerosis. (PMID:31023341)
• RNA binding motif protein 10 suppresses lung cancer progression by controlling alternative splicing of eukaryotic translation initiation factor 4H. (PMID:33130397)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif4h	ENSDARG00000042252
mus_musculus	Eif4h	ENSMUSG00000040731
rattus_norvegicus	Eif4h	ENSRNOG00000001454
drosophila_melanogaster	eIF4H2	FBGN0039797
drosophila_melanogaster	eIF4H1	FBGN0262734
caenorhabditis_elegans		WBGENE00019157

Paralogs (1): EIF4B (ENSG00000063046)

Protein

Protein identifiers

Eukaryotic translation initiation factor 4H — Q15056 (reviewed: Q15056)

Alternative names: Williams-Beuren syndrome chromosomal region 1 protein

All UniProt accessions (6): Q15056, A0A7I2V385, A0A7I2V3D5, A0A7I2V3E4, A0A7I2V4E4, A0A7I2V4V9

UniProt curated annotations — full annotation on UniProt →

Function. Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA.

Subunit / interactions. (Microbial infection) Interacts with HHV-1 Vhs.

Subcellular location. Cytoplasm. Perinuclear region.

Tissue specificity. The short isoform is the predominant isoform and is expressed alone in liver and skeletal muscle. Both isoforms are expressed in fibroblast, spleen, testis and bone marrow. Levels are high in lung and pancreas and low in heart, frontal cortex and kidney.

Disease relevance. EIF4H is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of EIF4H may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15056-1	Long	yes
Q15056-2	Short

RefSeq proteins (2): NP_071496, NP_114381 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034229	eIF4H_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (24 total): modified residue 12, compositionally biased region 5, region of interest 3, initiator methionine 1, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15056-F1	61.11	0.01

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 (12): 2, 13, 14, 19, 21, 22, 24, 32, 136, 166, 175, 230

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-72649	Translation initiation complex formation
R-HSA-72662	Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
R-HSA-72702	Ribosomal scanning and start codon recognition
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit

MSigDB gene sets: 630 (showing top): MORF_SMC1L1, MORF_UBE2I, GOBP_GROWTH, MORF_HDAC1, MORF_UBE2N, MORF_RAD21, HSIAO_HOUSEKEEPING_GENES, GOBP_TRANSLATIONAL_INITIATION, MORF_HDAC2, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, MODULE_149, MORF_PSMC2, TTGGGAG_MIR150, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION

GO Biological Process (6): formation of translation preinitiation complex (GO:0001731), regulation of translational initiation (GO:0006446), developmental growth (GO:0048589), eukaryotic translation initiation factor 4F complex assembly (GO:0097010), translation (GO:0006412), translational initiation (GO:0006413)

GO Molecular Function (9): RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), translation factor activity, RNA binding (GO:0008135), RNA strand annealing activity (GO:0033592), RNA strand-exchange activity (GO:0034057), ribosomal small subunit binding (GO:0043024), cadherin binding (GO:0045296), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): cytosol (GO:0005829), membrane (GO:0016020), eukaryotic translation initiation factor 4F complex (GO:0016281), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cap-dependent Translation Initiation	3
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
cellular anatomical structure	4
translational initiation	3
cytoplasm	3
translation	2
translation factor activity	2
single-stranded RNA binding	2
binding	2
cytoplasmic translational initiation	1
protein-RNA complex assembly	1
regulation of translation	1
developmental process	1
growth	1
protein-containing complex assembly	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
formation of translation initiation ternary complex	1
metabolic process	1
nucleic acid binding	1
RNA binding	1
catalytic activity, acting on RNA	1
annealing activity	1
double-stranded RNA binding	1
ribosome binding	1
cell adhesion molecule binding	1
RNA cap binding complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF4H	EIF4A1	P04765	991
EIF4H	EIF4A2	Q14240	986
EIF4H	EIF4G1	Q04637	969
EIF4H	EIF4E	P06730	926
EIF4H	EIF4B	P23588	915
EIF4H	CLIP2	Q9UDT6	815
EIF4H	LIMK1	P53667	792
EIF4H	TBL2	Q9Y4P3	783
EIF4H	BAZ1B	Q9UIG0	736
EIF4H	EIF5B	O60841	729
EIF4H	EIF5	P55010	714
EIF4H	GTF2IRD1	Q9UHL9	706
EIF4H	BCL7B	Q9BQE9	704
EIF4H	EIF6	P56537	697
EIF4H	NSUN5	Q96P11	675

IntAct

91 interactions, top by confidence:

A	B	Type	Score
EIF4H	C11orf68	psi-mi:“MI:0915”(physical association)	0.740
C11orf68	EIF4H	psi-mi:“MI:0915”(physical association)	0.740
rep	GTF2F2	psi-mi:“MI:0914”(association)	0.730
PKMYT1	CCNB2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
EIF4H	LNX1	psi-mi:“MI:0915”(physical association)	0.670
LNX1	EIF4H	psi-mi:“MI:0915”(physical association)	0.670
EIF4H	EIF4A1	psi-mi:“MI:0407”(direct interaction)	0.540
EIF4H	EIF4A1	psi-mi:“MI:0915”(physical association)	0.540
PCNA	EIF4H	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Csde1	TXNDC9	psi-mi:“MI:0914”(association)	0.350
LIN54	HDAC3	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
RIN3		psi-mi:“MI:0914”(association)	0.350
DISC1	AGRN	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
MAP2K2	IPO5	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (163): C11orf68 (Two-hybrid), LNX1 (Two-hybrid), EIF4H (Affinity Capture-RNA), EIF4H (Affinity Capture-MS), C11orf68 (Two-hybrid), EIF4H (Affinity Capture-RNA), EIF4H (Co-fractionation), EIF4H (Co-fractionation), EIF4H (Co-fractionation), EIF4H (Co-fractionation), EIF4H (Co-fractionation), EIF4H (Co-fractionation), EIF4H (Co-fractionation), EIF4H (Co-fractionation), EIF4H (Co-fractionation)

ESM2 similar proteins: A0A0D1DZT6, A6R3L3, A7VJC2, B7FAL5, D0VWM8, O19049, O88569, P0CO44, P0CO45, P17130, P21522, P22626, P25555, P38922, P51990, P61978, P61979, P61980, P78814, P92964, P98179, Q01560, Q09911, Q13151, Q14498, Q15056, Q1JPH6, Q28521, Q2HJ60, Q2QKB3, Q32P51, Q3T0D0, Q4R4M6, Q4WXV6, Q5R5H8, Q5RBR8, Q5RBU8, Q5RC80, Q5XI72, Q7KMJ6

Diamond homologs: J9VI89, O14369, P23588, P27476, P41891, Q03250, Q05966, Q15056, Q1JPH6, Q5RBR8, Q5XI72, Q6Z1C0, Q8BGD9, Q9WUK2, A0A2R8Y4L2, A4FV72, A5A6H4, A7VJC2, G5EFS2, O13741, O13759, O13845, O22173, O43347, O88569, P04256, P09651, P09867, P17130, P19682, P19683, P19684, P22626, P28644, P32831, P33240, P39697, P42696, P49312, P49313

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EIF4H	“up-regulates activity”	EIF4A1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 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
Dengue Virus Genome Translation and Replication	5	26.0×	7e-04
Infectious disease	11	4.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1011 predictions. Top by Δscore:

Variant	Effect	Δscore
7:74174439:GAGG:G	donor_gain	1.0000
7:74174440:AGGGT:A	donor_loss	1.0000
7:74174441:GG:G	donor_gain	1.0000
7:74174441:GGGT:G	donor_loss	1.0000
7:74174442:GG:G	donor_gain	1.0000
7:74174442:GGTGA:G	donor_loss	1.0000
7:74174443:G:GA	donor_loss	1.0000
7:74174444:T:G	donor_loss	1.0000
7:74187795:AAAGG:A	donor_loss	1.0000
7:74187797:AGGT:A	donor_loss	1.0000
7:74187798:GGTG:G	donor_loss	1.0000
7:74187799:G:C	donor_loss	1.0000
7:74187800:T:A	donor_loss	1.0000
7:74189669:CCAGG:C	acceptor_loss	1.0000
7:74189670:CAGGA:C	acceptor_loss	1.0000
7:74189671:A:AG	acceptor_gain	1.0000
7:74189671:AG:A	acceptor_gain	1.0000
7:74189672:G:GG	acceptor_gain	1.0000
7:74189672:GG:G	acceptor_gain	1.0000
7:74189672:GGA:G	acceptor_gain	1.0000
7:74189733:GTGCA:G	donor_gain	1.0000
7:74189734:TGCA:T	donor_gain	1.0000
7:74189735:GCA:G	donor_gain	1.0000
7:74189735:GCAG:G	donor_gain	1.0000
7:74189735:GCAGT:G	donor_loss	1.0000
7:74189736:CAGT:C	donor_loss	1.0000
7:74189737:AG:A	donor_loss	1.0000
7:74189738:GT:G	donor_loss	1.0000
7:74189738:GTAA:G	donor_gain	1.0000
7:74189739:TAAG:T	donor_loss	1.0000

AlphaMissense

1625 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:74187681:G:C	A44P	1.000
7:74187682:C:A	A44E	1.000
7:74187684:T:A	Y45N	1.000
7:74187684:T:G	Y45D	1.000
7:74187688:T:A	V46E	1.000
7:74187690:G:A	G47R	1.000
7:74187690:G:C	G47R	1.000
7:74187691:G:A	G47E	1.000
7:74187691:G:T	G47V	1.000
7:74187697:T:A	L49Q	1.000
7:74187697:T:C	L49P	1.000
7:74187697:T:G	L49R	1.000
7:74187712:T:A	V54D	1.000
7:74187716:G:C	Q55H	1.000
7:74187716:G:T	Q55H	1.000
7:74187724:T:A	I58K	1.000
7:74187724:T:G	I58R	1.000
7:74187733:T:A	I61N	1.000
7:74187736:T:C	F62S	1.000
7:74187762:C:G	R71G	1.000
7:74187763:G:C	R71P	1.000
7:74187766:T:A	L72Q	1.000
7:74187766:T:C	L72P	1.000
7:74187769:T:A	V73D	1.000
7:74187772:G:T	R74I	1.000
7:74187773:A:C	R74S	1.000
7:74187773:A:T	R74S	1.000
7:74187792:T:C	F81L	1.000
7:74187794:T:A	F81L	1.000
7:74187794:T:G	F81L	1.000

dbSNP variants (sampled 300 via entrez): RS1000329975 (7:74174741 G>C), RS1000615236 (7:74175858 G>A,T), RS1000680264 (7:74174618 G>A), RS1000813234 (7:74180643 A>G,T), RS1000867435 (7:74180315 G>A,T), RS1000964402 (7:74175472 A>G), RS1001026259 (7:74192167 G>A), RS1001028714 (7:74185961 C>T), RS1001071513 (7:74176120 T>G), RS1001078867 (7:74192022 A>G), RS1001378110 (7:74186195 T>C), RS1001530495 (7:74182886 C>A), RS1001750621 (7:74194543 G>A,T), RS1001866127 (7:74181649 G>T), RS1001976016 (7:74187526 C>A,T)

Disease associations

OMIM: gene MIM:603431 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

186 total (30 of 186 shown, HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000025	Functional abnormality of male internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000075	Renal duplication
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000093	Proteinuria
HP:0000121	Nephrocalcinosis
HP:0000125	Pelvic kidney
HP:0000147	Polycystic ovaries
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293274 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

173 measured of 217 human assays (223 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
MLS001008494	IC50	1030 nM
MLS001212885	IC50	1080 nM
cid_6603239	IC50	1300 nM
(8S)-7-(4-chlorobenzoyl)-3-(3-methacrylamidophenyl)-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	IC50	1540 nM
2-{(E)-2-[3-Methoxy-4-(o-tolylcarbamoyl-methoxy)-phenyl]-vinyl}-1-methyl-pyridinium	IC50	1560 nM
3-[6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-5-phenyl-pentanoic acid	IC50	1610 nM
MLS000117135	EC50	2020 nM
MLS000037873	IC50	2020 nM
1-(1-cyclohex-3-enylmethoxy)-3-(3-ethyl-2-methyl-1-benzimidazol-1-iumyl)-2-propanol;iodide	IC50	2120 nM
N-(3,4-dimethylphenyl)-2-[[5-[3-(4-methoxyphenyl)propyl]-1,3,4-oxadiazol-2-yl]sulfanyl]ethanamide	IC50	2180 nM
(5Z)-3-(3-chlorophenyl)-5-(4-hydroxy-3-methoxy-5-nitro-benzylidene)thiazolidine-2,4-quinone	IC50	2210 nM
[(1R,5S)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl] (2R)-3-oxidanyl-2-phenyl-propanoate;iodide	IC50	2230 nM
SMR000564432	IC50	2240 nM
N-(3-methoxyphenyl)-1-methylpyridin-1-ium-3-carboxamide;iodide	IC50	2330 nM
MLS001030075	IC50	2360 nM
cid_16240614	IC50	2480 nM
(4-hydroxy-4,4-diphenylbut-2-ynyl)-dimethyl-propan-2-ylazanium;bromide	IC50	2550 nM
N-[3-[4-methyl-5-(2-morpholin-4-yl-2-oxidanylidene-ethyl)sulfanyl-1,2,4-triazol-3-yl]phenyl]benzamide	IC50	2620 nM
SMR000425384	IC50	2620 nM
cid_24746774	IC50	2710 nM
cid_9593400	IC50	2740 nM
4-propyl-1,2,3,5,6,7-hexahydrodicyclopenta[1,2-c:1’,2’-g]pyridin-8-imine;hydroiodide	IC50	2760 nM
MLS000766745	IC50	2790 nM
SMR000555824	IC50	2790 nM
SMR000427247	IC50	2800 nM
(6E)-6-[(4-methoxyphenyl)methylidene]-1-methyl-piperazine-2,5-dione	IC50	2810 nM
(6E)-6-[(1-pyridin-1-iumylamino)methylidene]-1-cyclohexa-2,4-dienone;iodide	IC50	2880 nM
[2-(furan-2-ylmethylamino)-2-oxoethyl] 2-(4-bromo-2-methylphenyl)sulfanylacetate	IC50	2940 nM
2-[4-(2-naphthalenylsulfonyl)-1-piperazinyl]-N-propan-2-ylpropanamide	IC50	3380 nM
(4S,5R,6R)-1-ethyl-2-(2-methoxyethylamino)-6-methyl-4-(2-phenylethyl)-5,6-dihydro-4H-pyrimidine-5-carboxylic acid methyl ester	IC50	3390 nM
2-chloranyl-N-ethyl-5-(4-ethylpiperazin-1-yl)sulfonyl-N-[2-[(4-methoxyphenyl)amino]-2-oxidanylidene-ethyl]benzamide	IC50	3400 nM
SMR000672087	IC50	3510 nM
MLS000829960	IC50	3560 nM
N-[1-[4-ethyl-5-[2-oxidanylidene-2-[(phenylmethyl)amino]ethyl]sulfanyl-1,2,4-triazol-3-yl]-2-oxidanyl-ethyl]benzamide	IC50	3670 nM
SMR000672072	IC50	3860 nM
MLS000560945	IC50	4150 nM
cid_5989040	IC50	4300 nM
MLS001217275	IC50	4370 nM
cid_1051609	IC50	4440 nM
[2-({3-[(2,4-dichlorobenzyl)oxy]-4-methoxybenzylidene}hydrazono)-4-oxo-1,3-thiazolidin-5-yl]acetic acid	IC50	4480 nM
SMR000465526	IC50	4700 nM
9-chloro-2-keto-8,8-dimethyl-pyrano[2,3-f]chromene-10-carbaldehyde oxime	IC50	4970 nM
(4E)-2,3-dihydroxy-4-[[(2-methylimino-4-thiophen-2-yl-1,3-thiazol-3-yl)amino]methylidene]cyclohexa-2,5-dien-1-one	EC50	5050 nM
(4-methoxy-1,3-benzothiazol-2-yl)-[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]amine	IC50	5160 nM
[2-(2-methoxy-4-nitroanilino)-2-oxoethyl] 3-oxo-4H-1,4-benzothiazine-6-carboxylate	IC50	5180 nM
MLS-0267981.0001	IC50	5320 nM
MLS000877007	IC50	5430 nM
SMR000515267	IC50	5460 nM
methyl (4S)-1-ethyl-6-methyl-4-phenyl-2-(prop-2-enylamino)-4H-pyrimidine-5-carboxylate	IC50	5620 nM
SMR000608344	IC50	5630 nM

ChEMBL bioactivities

29 potent at pChembl≥5 of 119 total, top 29 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.16	IC50	700	nM	CHEMBL1542453
5.94	IC50	1140	nM	CHEMBL1497773
5.84	IC50	1430	nM	CHEMBL1522300
5.64	IC50	2310	nM	CHEMBL3190268
5.62	IC50	2410	nM	CHEMBL1344772
5.58	IC50	2660	nM	CHEMBL3856090
5.56	IC50	2740	nM	CHEMBL1703699
5.53	IC50	2935	nM	CHEMBL1420111
5.37	IC50	4230	nM	CHEMBL1445700
5.33	IC50	4620	nM	CHEMBL1583797
5.32	IC50	4815	nM	CHEMBL1993780
5.30	IC50	4990	nM	CHEMBL1441794
5.29	IC50	5180	nM	CHEMBL1718734
5.27	IC50	5420	nM	CHEMBL1540272
5.26	IC50	5430	nM	CHEMBL1320897
5.24	IC50	5705	nM	CHEMBL1469858
5.24	IC50	5800	nM	CHEMBL1583019
5.21	IC50	6170	nM	CHEMBL1548422
5.21	IC50	6110	nM	CHEMBL1463019
5.19	IC50	6470	nM	CHEMBL1313635
5.14	IC50	7250	nM	CHEMBL1422657
5.14	IC50	7280	nM	CHEMBL1416302
5.11	IC50	7710	nM	CHEMBL1461216
5.08	IC50	8280	nM	CHEMBL1385494
5.08	IC50	8230	nM	CHEMBL1603147
5.08	IC50	8360	nM	CHEMBL1367248
5.04	IC50	9040	nM	CHEMBL1385027
5.03	IC50	9250	nM	CHEMBL1464460
5.02	IC50	9505	nM	CHEMBL1313635

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, decreases expression, increases expression	2
Fluorouracil	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
spautin-1	affects reaction, increases transport, affects cotreatment, decreases reaction, increases degradation (+1 more)	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
arsenite	affects binding, increases reaction	1
cupric oxide	increases expression	1
leupeptin	affects cotreatment, decreases reaction, increases degradation	1
diallyl trisulfide	decreases expression	1
chloropicrin	decreases expression	1
aloxistatin	affects cotreatment, decreases reaction, increases degradation	1
tanespimycin	affects cotreatment, decreases expression	1
corosolic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
quinocetone	decreases expression, increases expression	1
quizartinib	affects cotreatment, decreases reaction, increases degradation, affects localization, affects reaction (+1 more)	1
VER 155008	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Atrazine	increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Chloroquine	affects localization, affects reaction, increases transport, affects cotreatment, decreases reaction (+1 more)	1
Cytarabine	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 2 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613814	Binding	PUBCHEM_BIOASSAY: uHTS fluorescence polarization assay for the identification of translation initiation inhibitors (eIF4H). (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2014, AID2028, AID435011, AID435018, A	PubChem BioAssay data set
CHEMBL1737901	Functional	PUBCHEM_BIOASSAY: SAR analysis for the identification of translation initiation inhibitors (eIF4H). (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2012, AID2014, AID2028]	PubChem BioAssay data set

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2WH	Abcam HEK293T EIF4H KO	Transformed cell line	Female

Clinical trials (associated diseases)

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