EEF1D

Summary

EEF1D (eukaryotic translation elongation factor 1 delta, HGNC:3211) is a protein-coding gene on chromosome 8q24.3, encoding Elongation factor 1-delta (P29692). EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to the ribosome.

This gene encodes a subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This subunit, delta, functions as guanine nucleotide exchange factor. It is reported that following HIV-1 infection, this subunit interacts with HIV-1 Tat. This interaction results in repression of translation of host cell proteins and enhanced translation of viral proteins. Several alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. Related pseudogenes have been defined on chromosomes 1, 6, 7, 9, 11, 13, 17, 19.

Source: NCBI Gene 1936 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 215 total — 4 pathogenic, 5 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001130053

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3211
Approved symbol	EEF1D
Name	eukaryotic translation elongation factor 1 delta
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	EF-1D, FLJ20897
Ensembl gene	ENSG00000104529
Ensembl biotype	protein_coding
OMIM	130592
Entrez	1936

Gene structure

Transcript identifiers

Ensembl transcripts: 155 — 146 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay

ENST00000317198, ENST00000395119, ENST00000419152, ENST00000423316, ENST00000442189, ENST00000524397, ENST00000524624, ENST00000524883, ENST00000524900, ENST00000525223, ENST00000525261, ENST00000525695, ENST00000526133, ENST00000526135, ENST00000526340, ENST00000526710, ENST00000526786, ENST00000526838, ENST00000527741, ENST00000528303, ENST00000528382, ENST00000528519, ENST00000528610, ENST00000529007, ENST00000529272, ENST00000529516, ENST00000529576, ENST00000529832, ENST00000530109, ENST00000530191, ENST00000530306, ENST00000530445, ENST00000530545, ENST00000530616, ENST00000530848, ENST00000531218, ENST00000531281, ENST00000531621, ENST00000531670, ENST00000531931, ENST00000531953, ENST00000532400, ENST00000532543, ENST00000532596, ENST00000532741, ENST00000533494, ENST00000533749, ENST00000533833, ENST00000534232, ENST00000534377, ENST00000534380, ENST00000534475, ENST00000534804, ENST00000618139, ENST00000871803, ENST00000871804, ENST00000871805, ENST00000871806, ENST00000871807, ENST00000871808, ENST00000871809, ENST00000871810, ENST00000871811, ENST00000871812, ENST00000871813, ENST00000871814, ENST00000871815, ENST00000871816, ENST00000871817, ENST00000871818, ENST00000871819, ENST00000871820, ENST00000871821, ENST00000871822, ENST00000871823, ENST00000871824, ENST00000871825, ENST00000871826, ENST00000871827, ENST00000871828, ENST00000871829, ENST00000925953, ENST00000925954, ENST00000925955, ENST00000925956, ENST00000972259, ENST00000972260, ENST00000972261, ENST00000972262, ENST00000972263, ENST00000972264, ENST00000972265, ENST00000972266, ENST00000972267, ENST00000972268, ENST00000972269, ENST00000972270, ENST00000972271, ENST00000972272, ENST00000972273, ENST00000972274, ENST00000972275, ENST00000972276, ENST00000972277, ENST00000972278, ENST00000972279, ENST00000972280, ENST00000972281, ENST00000972282, ENST00000972283, ENST00000972284, ENST00000972285, ENST00000972286, ENST00000972287, ENST00000972288, ENST00000972289, ENST00000972290, ENST00000972291, ENST00000972292, ENST00000972293, ENST00000972294, ENST00000972295, ENST00000972296, ENST00000972297, ENST00000972298, ENST00000972299, ENST00000972300, ENST00000972301, ENST00000972302, ENST00000972303, ENST00000972304, ENST00000972305, ENST00000972306, ENST00000972307, ENST00000972308, ENST00000972309, ENST00000972310, ENST00000972311, ENST00000972312, ENST00000972313, ENST00000972314, ENST00000972315, ENST00000972316, ENST00000972317, ENST00000972318, ENST00000972319, ENST00000972320, ENST00000972321, ENST00000972322, ENST00000972323, ENST00000972324, ENST00000972325, ENST00000972326, ENST00000972327, ENST00000972328

RefSeq mRNA: 10 — MANE Select: NM_001130053 NM_001130053, NM_001130055, NM_001130056, NM_001130057, NM_001195203, NM_001289950, NM_001317743, NM_001330646, NM_001960, NM_032378

CCDS: CCDS47930, CCDS56559, CCDS6404, CCDS6405

Canonical transcript exons

ENST00000618139 — 10 exons

Exon	Start	End
ENSE00002181487	143597348	143597415
ENSE00002217578	143592647	143592660
ENSE00003513042	143586729	143586852
ENSE00003563181	143581054	143581154
ENSE00003582032	143581229	143581328
ENSE00003606924	143580012	143580206
ENSE00003612046	143579728	143579830
ENSE00003759730	143588991	143590081
ENSE00003787539	143586219	143586290
ENSE00003790282	143580506	143580727

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 99.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 140.8885 / max 1194.6495, expressed in 1825 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95500	126.7376	1824
95501	8.2323	1757
95499	1.9838	1166
95498	1.8713	1112
95503	1.1588	715
95502	0.8474	522
95497	0.0574	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.75	gold quality
apex of heart	UBERON:0002098	99.74	gold quality
left ovary	UBERON:0002119	99.70	gold quality
ovary	UBERON:0000992	99.69	gold quality
right ovary	UBERON:0002118	99.68	gold quality
right lobe of thyroid gland	UBERON:0001119	99.65	gold quality
body of pancreas	UBERON:0001150	99.65	gold quality
endocervix	UBERON:0000458	99.64	gold quality
prostate gland	UBERON:0002367	99.64	gold quality
body of uterus	UBERON:0009853	99.64	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.64	gold quality
granulocyte	CL:0000094	99.63	gold quality
left lobe of thyroid gland	UBERON:0001120	99.62	gold quality
thyroid gland	UBERON:0002046	99.62	gold quality
fundus of stomach	UBERON:0001160	99.61	gold quality
lower esophagus	UBERON:0013473	99.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.61	gold quality
body of stomach	UBERON:0001161	99.60	gold quality
zone of skin	UBERON:0000014	99.59	gold quality
myometrium	UBERON:0001296	99.59	gold quality
skin of abdomen	UBERON:0001416	99.59	gold quality
skin of leg	UBERON:0001511	99.59	gold quality
lymph node	UBERON:0000029	99.58	gold quality
spleen	UBERON:0002106	99.58	gold quality
thoracic mammary gland	UBERON:0005200	99.58	gold quality
ectocervix	UBERON:0012249	99.58	gold quality
uterine cervix	UBERON:0000002	99.56	gold quality
vagina	UBERON:0000996	99.55	gold quality
saliva-secreting gland	UBERON:0001044	99.55	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	93.62
E-HCAD-5	yes	36.59
E-MTAB-6678	yes	35.49
E-HCAD-9	yes	23.19
E-HCAD-31	yes	20.53
E-MTAB-10596	no	1345.52
E-HCAD-8	no	914.26
E-GEOD-111727	no	412.69
E-CURD-46	no	46.99
E-HCAD-1	no	42.44
E-MTAB-8410	no	13.37
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ITGA7	Repression

Literature-anchored findings (GeneRIF, showing 15)

• These results further confirm that overexpression of TEF-1 delta is oncogenic and the antisense TEF-1 delta mRNA expression reverses its oncogenic potential. (PMID:12210501)
• Interaction between HrHRF and EF-1delta taken with some of the recently published information concerning the TCTP (HrHRF) mentioned above suggest a possible intracellular role for TCTP/HrHRF. (PMID:15062873)
• Increased EF-1 delta mRNA expression is associated with lymph node metastases and advanced disease stages in esophageal carcinoma (PMID:15199388)
• Gain of 8q-mapped EF-1 delta is associated with adverse outcome in Medulloblastoma. (PMID:16968546)
• Repression of deltaEF1 plays a key role in mediating BMP-6-induced transcriptional activation of E-cadherin in breast cancer cells. (PMID:17997862)
• overexpression is positively correlated with malignant transformation of 16HBE cells induced by CdC12, but is not correlated with DNA mutations (PMID:20514991)
• Taken together, our data suggest EFF1D functions as a novel negative regulator of SIAH-1 (PMID:21633900)
• our results demonstrate that EEF1D is a bona fide physiological CK2 substrate for CK2 phosphorylation (PMID:21936567)
• eukaryotic translation elongation factor 1delta knockdown in oral squamous cell carcinoma reduced cell proliferation and induced EMT (epithelial-mesenchymal transition) phenotypes (PMID:26823560)
• EEF1D is upregulated in osteosarcoma and plays a tumor promoting role by facilitating Akt-mTOR and Akt-Bad signaling pathways. Accordingly, EEF1D is a potential target for cancer therapy. (PMID:29510727)
• the loss of function variants exclusively targeting the long EEF1D isoform may explicate the ARID phenotype through the heat shock response pathway, rather than interfering with the canonical translational elongation. (PMID:30787422)
• EEF1D Promotes Glioma Proliferation, Migration, and Invasion through EMT and PI3K/Akt Pathway. (PMID:33029523)
• Eukaryotic Translation Elongation Factor 1 Delta Inhibits the Nuclear Import of the Nucleoprotein and PA-PB1 Heterodimer of Influenza A Virus. (PMID:33087462)
• Autoantibodies against eukaryotic translation elongation factor 1 delta in two patients with autoimmune cerebellar ataxia. (PMID:38332912)
• EEF1D stabilized by SRSF9 promotes colorectal cancer via enhancing the proliferation and metastasis. (PMID:38771720)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	eef1db	ENSDARG00000030053
danio_rerio	eef1da	ENSDARG00000102291
mus_musculus	Eef1d	ENSMUSG00000055762
rattus_norvegicus	Eef1d	ENSRNOG00000021638
drosophila_melanogaster	eEF1beta	FBGN0028737
drosophila_melanogaster	eEF1delta	FBGN0032198
caenorhabditis_elegans		WBGENE00018846

Paralogs (2): EFCC1 (ENSG00000114654), EEF1B2 (ENSG00000114942)

Protein

Protein identifiers

Elongation factor 1-delta — P29692 (reviewed: P29692)

Alternative names: Antigen NY-CO-4

All UniProt accessions (39): A0A087X1X7, A0A8C8L741, E9PI39, E9PI93, E9PIP5, E9PIZ1, E9PJ84, E9PJD0, E9PJV8, E9PK01, E9PK06, E9PK72, P29692, E9PKH7, E9PKK3, E9PL12, E9PL21, E9PL71, E9PLA1, E9PLL8, E9PLS6, E9PLT8, E9PM66, E9PMW7, E9PN56, E9PN71, E9PN91, E9PNC8, E9PNW6, E9PPR1, E9PPY1, E9PQ49, E9PQC9, E9PQR8, E9PQZ1, E9PRL0, E9PRY8, H0YCK7, H0YE58

UniProt curated annotations — full annotation on UniProt →

Function. EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to the ribosome. Regulates induction of heat-shock-responsive genes through association with heat shock transcription factors and direct DNA-binding at heat shock promoter elements (HSE).

Subunit / interactions. EF-1 is composed of 4 subunits: alpha, beta, delta isoform 1, and gamma. Isoform 2 interacts with HSF1 and NFE2L2.

Subcellular location. Nucleus.

Tissue specificity. Isoform 2 is specifically expressed in brain, cerebellum and testis.

Disease relevance. Neurodevelopmental disorder with thin corpus callosum, hypotonia, and absent language (NEDTCHAL) [MIM:621150] An autosomal recessive disorder characterized by severe developmental delay with intellectual disability and absent language, microcephaly, and spasticity in addition to thin corpus callosum and hypotonia. Other features include failure to thrive, poor feeding, and optic atrophy. The disease is caused by variants affecting the gene represented in this entry.

Induction. By homocysteine (HC), may mediate accelerated synthesis of free thiol-containing proteins in response to HC-induced oxidative stress. Also induced following exposure to ionizing radiation.

Similarity. Belongs to the EF-1-beta/EF-1-delta family.

Isoforms (4)

UniProt ID	Names	Canonical?
P29692-1	1	yes
P29692-2	2, eEF1BdeltaL
P29692-3	3
P29692-4	4

RefSeq proteins (10): NP_001123525, NP_001123527, NP_001123528, NP_001123529, NP_001182132, NP_001276879, NP_001304672, NP_001317575, NP_001951, NP_115754 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001326	Transl_elong_EF1B_B/D_CS	Conserved_site
IPR014038	EF1B_bsu/dsu_GNE	Domain
IPR014717	Transl_elong_EF1B/ribsomal_bS6	Homologous_superfamily
IPR018940	EF-1_beta_acid_region_euk	Domain
IPR036219	eEF-1beta-like_sf	Homologous_superfamily
IPR049720	EF1B_bsu/dsu	Family

Pfam: PF00736, PF10587

UniProt features (51 total): modified residue 19, strand 8, helix 6, sequence conflict 4, region of interest 3, splice variant 3, sequence variant 3, turn 2, initiator methionine 1, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5JPO	X-RAY DIFFRACTION	2
2MVM	SOLUTION NMR
2MVN	SOLUTION NMR
2N51	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29692-F1	73.66	0.21

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 (19): 60, 73, 86, 106, 107, 117, 117, 119, 129, 133, 147, 162, 91, 94, 40, 2, 17, 37, 44

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-156842	Eukaryotic Translation Elongation

MSigDB gene sets: 332 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RESPONSE_TO_IONIZING_RADIATION, SWEET_KRAS_ONCOGENIC_SIGNATURE, MODULE_255, MODULE_151, MORF_UBE2I, MODULE_150, MORF_RAD21, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, MODULE_317, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP

GO Biological Process (6): cytoplasmic translational elongation (GO:0002182), translational elongation (GO:0006414), cellular response to heat (GO:0034605), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to ionizing radiation (GO:0071479), translation (GO:0006412)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), translation elongation factor activity (GO:0003746), guanyl-nucleotide exchange factor activity (GO:0005085), translation factor activity, RNA binding (GO:0008135), heat shock protein binding (GO:0031072), cadherin binding (GO:0045296), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515)

GO Cellular Component (7): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), eukaryotic translation elongation factor 1 complex (GO:0005853), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Translation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
translational elongation	3
cytoplasm	3
translation	2
macromolecule biosynthetic process	2
translation factor activity	2
intracellular membrane-bounded organelle	2
cytoplasmic translation	1
response to heat	1
cellular response to stress	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
response to ionizing radiation	1
cellular response to radiation	1
peptidyltransferase activity	1
translational initiation	1
translational termination	1
protein metabolic process	1
protein biosynthetic process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
nucleic acid binding	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
RNA binding	1
protein binding	1
cell adhesion molecule binding	1
transcription factor binding	1
binding	1
nucleolus	1
nuclear lumen	1
intracellular anatomical structure	1
protein-containing complex	1
endomembrane system	1

Protein interactions and networks

STRING

3098 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EEF1D	EEF1G	P26641	999
EEF1D	EEF1B2	P24534	982
EEF1D	KTN1	Q86UP2	920
EEF1D	EEF1A1	P04719	911
EEF1D	VARS1	P26640	732
EEF1D	EEF1A2	P54266	695
EEF1D	EEF1E1	O43324	651
EEF1D	RPL28	P46779	640
EEF1D	RPS14	P06366	612
EEF1D	EEF2	P13639	595
EEF1D	VARS2	Q5ST30	583
EEF1D	ARHGAP26	Q9UNA1	534
EEF1D	DTNA	Q9Y4J8	528
EEF1D	NPM1	P06748	513
EEF1D	CNTNAP1	P78357	502

IntAct

249 interactions, top by confidence:

A	B	Type	Score
FOSL2	JUN	psi-mi:“MI:0914”(association)	0.930
EEF1G	EEF1B2	psi-mi:“MI:0914”(association)	0.890
EEF1G	EEF1D	psi-mi:“MI:0915”(physical association)	0.810
EEF1D	ERP27	psi-mi:“MI:0915”(physical association)	0.740
EEF1D	HTT	psi-mi:“MI:0915”(physical association)	0.740
EEF1A2	EEF1B2	psi-mi:“MI:0914”(association)	0.740
SIAH1	EEF1D	psi-mi:“MI:0915”(physical association)	0.670
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
TPT1	EEF1D	psi-mi:“MI:0915”(physical association)	0.560
EEF1G	EEF1D	psi-mi:“MI:0915”(physical association)	0.560
EEF1D	TPT1	psi-mi:“MI:0915”(physical association)	0.560
EEF1D	EEF1G	psi-mi:“MI:0915”(physical association)	0.560
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
EEF1D	EEF1D	psi-mi:“MI:0915”(physical association)	0.550
EEF1D	ABTB1	psi-mi:“MI:0915”(physical association)	0.550
MLLT6	RGPD8	psi-mi:“MI:0914”(association)	0.530
EEF1G	INPPL1	psi-mi:“MI:0914”(association)	0.530
FOSL2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
EEF1A1	ZPR1	psi-mi:“MI:0914”(association)	0.530

BioGRID (519): EEF1D (Affinity Capture-MS), EEF1D (Two-hybrid), EEF1G (Two-hybrid), SIAH1 (Two-hybrid), TPT1 (Two-hybrid), ERP27 (Two-hybrid), EEF1D (Affinity Capture-MS), EEF1D (Affinity Capture-MS), EEF1D (Affinity Capture-MS), EEF1D (Affinity Capture-MS), EEF1D (Affinity Capture-MS), EEF1G (Two-hybrid), ACLY (Co-fractionation), AHNAK (Co-fractionation), AKAP8 (Co-fractionation)

ESM2 similar proteins: A1DLW4, A2R4I6, A3AYR1, A5D989, A6YRN9, A7T395, B0XPE7, C8VP82, F4IAE9, G0S5S6, O62305, P0C7L7, P0CN68, P0CN69, P29692, P48017, P53787, P54362, P57776, Q0CH70, Q0CJV3, Q0CS96, Q0UQJ8, Q0V4C4, Q1E3S4, Q2GXZ7, Q2H0S9, Q2H988, Q2U9E2, Q4I624, Q4IB50, Q4P5R8, Q4P7F2, Q4PA25, Q4R3D4, Q4WDH3, Q4WJI7, Q5AYT7, Q5B4Z3, Q5S7T7

Diamond homologs: A5D989, A6IPG1, O70251, O74173, O81918, O96827, P12262, P24534, P29412, P29522, P29545, P29546, P29692, P29693, P30151, P32192, P32471, P34460, P34826, P34827, P48006, P53787, P57776, P78590, P93447, Q40680, Q40682, Q4R3D4, Q5E983, Q658K8, Q68FR9, Q69BZ7, Q6DET9, Q717R8, Q84WM9, Q9GRF8, Q9SCX3, Q9SI20, Q9U2H9, Q9VL18

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CSNK2A1	unknown	EEF1D	phosphorylation
EEF1D	“form complex”	“EEF1B complex”	binding
CDK1	unknown	EEF1D	phosphorylation
EEF1D	“down-regulates quantity by repression”	ITGA7	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 194 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
Eukaryotic Translation Elongation	5	11.7×	9e-03
SARS-CoV-1 activates/modulates innate immune responses	5	11.4×	9e-03
CLEC7A (Dectin-1) signaling	7	8.4×	4e-03
Cellular responses to stress	12	3.7×	9e-03
Cellular responses to stimuli	13	3.4×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
response to muscle stretch	5	23.4×	1e-03
amyloid fibril formation	5	18.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	5
Uncertain significance	134
Likely benign	19
Benign	13

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
3775019	NM_001130053.5(EEF1D):c.69del (p.Glu24fs)	Pathogenic
3775021	NM_001130053.5(EEF1D):c.1780T>C (p.Trp594Arg)	Pathogenic
4292322	NM_001130053.5(EEF1D):c.966C>A (p.Tyr322Ter)	Pathogenic
599374	NM_001130053.5(EEF1D):c.948G>A (p.Trp316Ter)	Pathogenic
1805560	NM_001130053.5(EEF1D):c.1114del (p.Phe371_Leu372insTer)	Likely pathogenic
3064445	NM_001130053.5(EEF1D):c.1488+1G>A	Likely pathogenic
3775231	NM_001130053.5(EEF1D):c.1828C>T (p.Gln610Ter)	Likely pathogenic
3775457	NM_001130053.5(EEF1D):c.874C>T (p.Arg292Ter)	Likely pathogenic
982218	NM_001130053.5(EEF1D):c.1099A>G (p.Met367Val)	Likely pathogenic

SpliceAI

2121 predictions. Top by Δscore:

Variant	Effect	Δscore
8:143580005:CACT:C	donor_loss	1.0000
8:143580006:A:AC	donor_gain	1.0000
8:143580007:C:CC	donor_gain	1.0000
8:143580007:CT:C	donor_gain	1.0000
8:143580007:CTCA:C	donor_gain	1.0000
8:143580008:TCACG:T	donor_loss	1.0000
8:143580009:CAC:C	donor_loss	1.0000
8:143580010:A:AC	donor_gain	1.0000
8:143580010:ACGTG:A	donor_gain	1.0000
8:143580011:C:CC	donor_gain	1.0000
8:143580011:CGTG:C	donor_gain	1.0000
8:143580011:CGTGC:C	donor_gain	1.0000
8:143580202:TCCCA:T	acceptor_gain	1.0000
8:143580203:CCCA:C	acceptor_gain	1.0000
8:143580203:CCCAC:C	acceptor_gain	1.0000
8:143580204:CCA:C	acceptor_gain	1.0000
8:143580204:CCAC:C	acceptor_gain	1.0000
8:143580205:CA:C	acceptor_gain	1.0000
8:143580205:CAC:C	acceptor_gain	1.0000
8:143580206:ACTG:A	acceptor_loss	1.0000
8:143580207:C:CC	acceptor_gain	1.0000
8:143580209:G:C	acceptor_gain	1.0000
8:143580209:G:GC	acceptor_gain	1.0000
8:143580502:TCA:T	donor_loss	1.0000
8:143580503:CAC:C	donor_loss	1.0000
8:143580504:A:AC	donor_gain	1.0000
8:143580504:ACAGG:A	donor_gain	1.0000
8:143580505:C:CT	donor_gain	1.0000
8:143580505:CAG:C	donor_gain	1.0000
8:143580505:CAGG:C	donor_gain	1.0000

AlphaMissense

4081 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:143580068:C:G	D251H	1.000
8:143580137:A:G	W228R	1.000
8:143580137:A:T	W228R	1.000
8:143580507:G:T	P204H	1.000
8:143580509:C:A	K203N	1.000
8:143580509:C:G	K203N	1.000
8:143580511:T:C	K203E	1.000
8:143580513:A:T	V202D	1.000
8:143580525:A:T	I198N	1.000
8:143580531:G:A	S196F	1.000
8:143580078:A:C	C247W	0.999
8:143580080:A:G	C247R	0.999
8:143580085:A:T	I245N	0.999
8:143580091:A:G	L243P	0.999
8:143580093:C:A	K242N	0.999
8:143580093:C:G	K242N	0.999
8:143580095:T:C	K242E	0.999
8:143580109:C:T	G237D	0.999
8:143580135:C:A	W228C	0.999
8:143580135:C:G	W228C	0.999
8:143580142:A:G	L226P	0.999
8:143580145:C:T	G225E	0.999
8:143580204:C:A	W205C	0.999
8:143580204:C:G	W205C	0.999
8:143580206:A:G	W205R	0.999
8:143580206:A:T	W205R	0.999
8:143580507:G:C	P204R	0.999
8:143580519:A:G	L200P	0.999
8:143580525:A:C	I198S	0.999
8:143580525:A:G	I198T	0.999

dbSNP variants (sampled 300 via entrez): RS1000194917 (8:143586019 G>A), RS1000483257 (8:143585232 G>A), RS1000524089 (8:143585005 T>C), RS1000551410 (8:143597910 C>A), RS1000556740 (8:143585286 G>A), RS1000621666 (8:143580807 T>A), RS1000698438 (8:143581651 G>A), RS1000939598 (8:143594015 C>T), RS1000959145 (8:143593927 A>G), RS1001054047 (8:143593623 CGAG>C), RS1001156173 (8:143598513 A>C,G), RS1001197121 (8:143586989 C>G,T), RS1001267482 (8:143594407 G>A,C,T), RS1001505088 (8:143595932 C>T), RS1001517810 (8:143580747 A>C,G)

Disease associations

OMIM: gene MIM:130592 | disease phenotypes: MIM:621150, MIM:153550, MIM:249500

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal recessive

Mondo (4): neurodevelopmental disorder (MONDO:0700092), neurodevelopmental disorder with thin corpus callosum, hypotonia, and absent language (MONDO:0976263), myelodysplastic syndrome associated with isolated del(5q) (MONDO:0007925), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (3): Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (Orphanet:86841), Autosomal recessive non-syndromic intellectual disability (Orphanet:88616), Moyamoya angiopathy (Orphanet:477768)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008459_52	Schizophrenia	4.000000e-08
GCST008459_53	Schizophrenia	1.000000e-09

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C535323	Chromosome 5q Deletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295739 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.27	Kd	53.79	nM	CHEMBL5653589
7.27	ED50	53.79	nM	CHEMBL5653589
5.76	Kd	1737	nM	CHEMBL3752910
5.76	ED50	1737	nM	CHEMBL3752910
5.25	IC50	5680	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 11 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148286: Binding affinity to human EEF1D incubated for 45 mins by Kinobead based pull down assay	kd	0.0538	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148286: Binding affinity to human EEF1D incubated for 45 mins by Kinobead based pull down assay	kd	1.7374	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178794: Inhibition of EEF1D (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	5.6800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, decreases reaction, decreases expression, affects cotreatment, increases abundance (+1 more)	3
Arsenic Trioxide	affects binding, decreases reaction, decreases expression, affects cotreatment	3
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation, affects expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	3
Valproic Acid	increases methylation, affects cotreatment, increases expression, decreases expression	3
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Arsenic	decreases methylation, increases abundance, affects cotreatment, increases expression	2
Caffeine	affects phosphorylation, decreases expression	2
Doxorubicin	affects expression, increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
perfluorooctanoic acid	decreases expression	1
lead chloride	decreases expression	1
coumarin	affects phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
N-benzyloxycarbonylprolylprolinal	increases expression	1
isobutyl alcohol	increases abundance, increases expression, affects cotreatment	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4270829	Binding	Binding affinity to elongation factor 1-delta in human Hela cells lysates assessed as protein enrichment by measuring normalized heavy/light ratio at by nano-LC-ESIMS/MS analysis	Determination of Gymnemic Acid I as a Protein Biosynthesis Inhibitor Using Chemical Proteomics. — J Nat Prod

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9DZ	Ubigene HEK293 EEF1D KO	Transformed cell line	Female

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