EEFSEC

Summary

EEFSEC (eukaryotic elongation factor, selenocysteine-tRNA specific, HGNC:24614) is a protein-coding gene on chromosome 3q21.3, encoding Selenocysteine-specific elongation factor (P57772). Translation factor required for the incorporation of the rare amino acid selenocysteine encoded by UGA codons. It is a selective cancer dependency (DepMap: 48.8% of cell lines).

Enables GTPase activity. Involved in selenocysteine incorporation. Predicted to be located in cytoplasm and nucleus. Predicted to be part of ribonucleoprotein complex.

Source: NCBI Gene 60678 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 139
• Clinical variants (ClinVar): 129 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 80
• Cancer dependency (DepMap): dependent in 48.8% of screened cell lines
• MANE Select transcript: NM_021937

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24614
Approved symbol	EEFSEC
Name	eukaryotic elongation factor, selenocysteine-tRNA specific
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	SELB, EFSEC
Ensembl gene	ENSG00000132394
Ensembl biotype	protein_coding
OMIM	607695
Entrez	60678

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000254730, ENST00000483457, ENST00000483569, ENST00000484438, ENST00000868106, ENST00000868107, ENST00000868108, ENST00000868109, ENST00000934138, ENST00000945661

RefSeq mRNA: 1 — MANE Select: NM_021937 NM_021937

CCDS: CCDS33849

Canonical transcript exons

ENST00000254730 — 7 exons

Exon	Start	End
ENSE00000903888	128153481	128153823
ENSE00000903893	128358217	128358373
ENSE00001047553	128262128	128262224
ENSE00001177853	128341233	128341889
ENSE00001313311	128264617	128264781
ENSE00003573560	128408069	128408646
ENSE00003628405	128246836	128247043

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 89.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9112 / max 107.6742, expressed in 1762 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38436	8.9112	1762

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	89.30	gold quality
heart left ventricle	UBERON:0002084	88.25	gold quality
gastrocnemius	UBERON:0001388	87.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.75	gold quality
muscle of leg	UBERON:0001383	86.60	gold quality
granulocyte	CL:0000094	85.97	gold quality
heart	UBERON:0000948	85.54	gold quality
right lobe of liver	UBERON:0001114	85.52	gold quality
skeletal muscle tissue	UBERON:0001134	84.36	gold quality
left uterine tube	UBERON:0001303	84.36	gold quality
right atrium auricular region	UBERON:0006631	83.96	gold quality
popliteal artery	UBERON:0002250	83.84	gold quality
tibial artery	UBERON:0007610	83.82	gold quality
skin of leg	UBERON:0001511	83.65	gold quality
body of uterus	UBERON:0009853	83.47	gold quality
right testis	UBERON:0004534	83.46	gold quality
left testis	UBERON:0004533	83.25	gold quality
zone of skin	UBERON:0000014	83.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.21	gold quality
adult mammalian kidney	UBERON:0000082	83.21	gold quality
testis	UBERON:0000473	83.06	gold quality
ectocervix	UBERON:0012249	83.00	gold quality
tibial nerve	UBERON:0001323	82.95	gold quality
cortical plate	UBERON:0005343	82.93	gold quality
skin of abdomen	UBERON:0001416	82.88	gold quality
ganglionic eminence	UBERON:0004023	82.81	gold quality
left coronary artery	UBERON:0001626	82.73	gold quality
liver	UBERON:0002107	82.70	gold quality
muscle tissue	UBERON:0002385	82.67	gold quality
ascending aorta	UBERON:0001496	82.46	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF143

miRNA regulators (miRDB)

38 targeting EEFSEC, 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-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-384	98.71	67.34	1229
HSA-MIR-4463	98.56	66.05	1071

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 48.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• SECIS binding induces a conformational change in SBP2 that recruits eEFSec, which in concert with the Sec incorporation domain gains access to the ribosomal A site (PMID:18948268)
• eEFSec employs a non-canonical mechanism involving the distinct C-terminal domain 4 for the release of the selenocysteinyl-tRNA during decoding on the ribosome (PMID:27708257)
• EEFSEC, which encodes selenocysteine-tRNA specific eukaryotic elongation factor, participates in the incorporation of selenocysteine into selenoproteins. Selenoproteins serve critical cellular homeostatic functions in maintaining redox status and antioxidant defenses, as well as modulating inflammatory responses. These physiologic functions have been linked to the parturition process and preterm birth. (PMID:28877031)
• In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. (PMID:28877031)
• [EEFSEC knockdown inhibits proliferation, migration and invasion of prostate cancer cells in vitro]. (PMID:35012909)
• Association of rs142548867 (EEFSEC) and periodontitis Grade C in a young Brazilian population. (PMID:37466550)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eefsec	ENSDARG00000004696
mus_musculus	Eefsec	ENSMUSG00000033216
rattus_norvegicus	Eefsec	ENSRNOG00000012954
drosophila_melanogaster	eEFSec	FBGN0034627
caenorhabditis_elegans	efsc-1	WBGENE00008133

Paralogs (18): MTIF2 (ENSG00000085760), GTPBP1 (ENSG00000100226), EEF1A2 (ENSG00000101210), GSPT1 (ENSG00000103342), EFTUD2 (ENSG00000108883), HBS1L (ENSG00000112339), EIF2S3 (ENSG00000130741), EFL1 (ENSG00000140598), GUF1 (ENSG00000151806), EEF1A1 (ENSG00000156508), EIF5B (ENSG00000158417), GFM2 (ENSG00000164347), EEF2 (ENSG00000167658), GFM1 (ENSG00000168827), GTPBP2 (ENSG00000172432), TUFM (ENSG00000178952), EIF2S3B (ENSG00000180574), GSPT2 (ENSG00000189369)

Protein

Protein identifiers

Selenocysteine-specific elongation factor — P57772 (reviewed: P57772)

Alternative names: Elongation factor sec, Eukaryotic elongation factor, selenocysteine-tRNA-specific

All UniProt accessions (2): P57772, C9J8T0

UniProt curated annotations — full annotation on UniProt →

Function. Translation factor required for the incorporation of the rare amino acid selenocysteine encoded by UGA codons. Replaces the eRF1-eRF3-GTP ternary complex for the insertion of selenocysteine directed by the UGA codon. Insertion of selenocysteine at UGA codons is mediated by SECISBP2 and EEFSEC: SECISBP2 (1) specifically binds the SECIS sequence once the 80S ribosome encounters an in-frame UGA codon and (2) contacts the RPS27A/eS31 of the 40S ribosome before ribosome stalling. (3) GTP-bound EEFSEC then delivers selenocysteinyl-tRNA(Sec) to the 80S ribosome and adopts a preaccommodated state conformation. (4) After GTP hydrolysis, EEFSEC dissociates from the assembly, selenocysteinyl-tRNA(Sec) accommodates, and peptide bond synthesis and selenoprotein elongation occur.

Subcellular location. Cytoplasm. Nucleus.

Disease relevance. Neurodevelopmental disorder with progressive spasticity and brain abnormalities (NEDPSB) [MIM:621102] An autosomal recessive disorder with onset in infancy or early childhood, and characterized by global developmental delay with intellectual disability, poor or absent speech, progressive spasticity, ataxia, and seizures. Brain imaging primarily shows cerebral and/or cerebellar hypoplasia with delayed myelination, and progressive cerebellar atrophy in about half of patients. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. SelB subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P57772-1	1	yes
P57772-2	2

RefSeq proteins (1): NP_068756* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000795	T_Tr_GTP-bd_dom	Domain
IPR004161	EFTu-like_2	Domain
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR049393	eEFSec_III	Domain
IPR049394	eEFSec_C	Domain
IPR050055	EF-Tu_GTPase	Family

Pfam: PF00009, PF03144, PF21131, PF21208

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (93 total): strand 35, helix 14, binding site 13, region of interest 6, sequence variant 6, mutagenesis site 6, turn 4, modified residue 3, chain 1, domain 1, splice variant 1, sequence conflict 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5IZL	X-RAY DIFFRACTION	2.72
7ZJW	ELECTRON MICROSCOPY	2.8
5IZK	X-RAY DIFFRACTION	3.25
5IZM	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P57772-F1	79.98	0.28

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (13): 19; 19; 21; 21; 21; 22; 22; 48; 92; 149; 149; 187 …

Post-translational modifications (3): 537, 545, 556

Mutagenesis-validated functional residues (6):

Position	Phenotype
96	abolished gtpase activity.
229	abolished ability to mediate insertion of selenocysteine.
230	abolished ability to mediate insertion of selenocysteine.
285	abolished ability to mediate insertion of selenocysteine.
583–584	does not affect ability to mediate insertion of selenocysteine.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2408557	Selenocysteine synthesis
R-HSA-1430728	Metabolism
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 269 (showing top): GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_TRANSLATIONAL_ELONGATION, chr3q21, GOBP_REGULATION_OF_TRANSLATION, GOCC_RIBONUCLEOPROTEIN_COMPLEX, SCGGAAGY_ELK1_02, GOMF_GTPASE_ACTIVITY, GOMF_MRNA_BINDING, GOMF_TRNA_BINDING, GOMF_TRANSLATION_ELONGATION_FACTOR_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOMF_RIBONUCLEOPROTEIN_COMPLEX_BINDING, HSF2_01, GOBP_REGULATION_OF_PROTEIN_METABOLIC_PROCESS

GO Biological Process (2): selenocysteine incorporation (GO:0001514), translation (GO:0006412)

GO Molecular Function (8): tRNA binding (GO:0000049), translation elongation factor activity (GO:0003746), GTPase activity (GO:0003924), GTP binding (GO:0005525), selenocysteine insertion sequence binding (GO:0035368), ribonucleoprotein complex binding (GO:0043021), nucleotide binding (GO:0000166), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Selenoamino acid metabolism	1
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational elongation	2
translational readthrough	1
peptidyltransferase activity	1
translational initiation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
RNA binding	1
translation factor activity	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
mRNA binding	1
protein-containing complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

2184 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EEFSEC	SECISBP2	Q96T21	998
EEFSEC	PSTK	Q8IV42	993
EEFSEC	SEPHS1	P49903	931
EEFSEC	SEPSECS	Q9HD40	912
EEFSEC	TRNAU1AP	Q9NX07	901
EEFSEC	SEPHS2	Q99611	845
EEFSEC	SARS1	P49591	833
EEFSEC	M0R2C6	M0R2C6	798
EEFSEC	SARS2	Q9NP81	798
EEFSEC	SELENOS	Q9BQE4	783
EEFSEC	SELENOT	P62341	719
EEFSEC	SELENOO	Q9BVL4	717
EEFSEC	SELENOF	O60613	686
EEFSEC	SELENOP	P49908	686
EEFSEC	SELENOW	P63302	666

IntAct

29 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
PARD6B	PARD3	psi-mi:“MI:0914”(association)	0.350
Gspt1	MRPL27	psi-mi:“MI:0914”(association)	0.350
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
SOX17	EEFSEC	psi-mi:“MI:0914”(association)	0.350
HNRNPU		psi-mi:“MI:0914”(association)	0.350
KIE-2	SIAH2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
EEFSEC	HSPA8	psi-mi:“MI:0914”(association)	0.350
SNW1		psi-mi:“MI:0914”(association)	0.350
DGCR8	VWA8	psi-mi:“MI:2364”(proximity)	0.270
FASTKD2	MED19	psi-mi:“MI:2364”(proximity)	0.270
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ILF3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
LIN28B	MEX3A	psi-mi:“MI:2364”(proximity)	0.270
NONO	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
PPIL4	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
QKI	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SBDS	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
SF3B4	MED19	psi-mi:“MI:2364”(proximity)	0.270
SRSF7	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
TBRG4	VWA8	psi-mi:“MI:2364”(proximity)	0.270
XRCC6	PSMD11	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (66): EEFSEC (Affinity Capture-RNA), EEFSEC (Co-fractionation), EEFSEC (Co-fractionation), EEFSEC (Co-fractionation), EEFSEC (Co-fractionation), EEFSEC (Co-fractionation), EFTUD2 (Co-fractionation), POLR2A (Co-fractionation), RPS3 (Co-fractionation), TFAP2A (Co-fractionation), EEFSEC (Affinity Capture-MS), EEFSEC (Affinity Capture-MS), EEFSEC (Affinity Capture-MS), EEFSEC (Affinity Capture-MS), EEFSEC (Affinity Capture-MS)

ESM2 similar proteins: D2XV59, O00178, O08582, O43242, P11029, P11497, P14685, P42694, P54198, P57772, P79987, P97570, P97819, Q0J035, Q13085, Q15139, Q28559, Q2KJ46, Q3ZBE1, Q4FZT2, Q4R4U1, Q58DC5, Q58DN4, Q5R4F9, Q5R8Q7, Q5RCR8, Q5SWU9, Q5XGS8, Q61666, Q62101, Q6DFV5, Q6NYU2, Q6P9R2, Q7L5D6, Q80YV4, Q8BVQ5, Q8K2D3, Q8L5Y9, Q8R418, Q91V93

Diamond homologs: A0QL35, A0T0K6, A0T100, A1AVJ8, A1AX82, A1B002, A1KGG5, A4FWW9, A4IJI7, A5CW32, A5U071, A5VJ92, A6UPK8, A6UTL4, A6VGE8, A8F982, A9AAA4, B0R6Y7, B0RB36, B0RU84, B0RU96, B2G6R2, B3DT29, B6YW69, B9L7I8, B9LSM6, C1AL18, C4LL63, C5C0J3, C9WPN6, F1QGW6, J9VR81, O26361, O29663, O36041, O50306, O59410, O96719, P02992, P0A559

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 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
mRNA Splicing - Major Pathway	7	15.3×	7e-05
Dengue Virus-Host Interactions	7	12.8×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	5	14.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	103
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3764735	NM_021937.5(EEFSEC):c.1A>G (p.Met1Val)	Pathogenic
3764738	NM_021937.5(EEFSEC):c.1278C>A (p.Cys426Ter)	Pathogenic
3067138	NM_021937.5(EEFSEC):c.1169A>C (p.Asp390Ala)	Likely pathogenic
3067139	NM_021937.5(EEFSEC):c.1751_1752dup (p.Val585fs)	Likely pathogenic

SpliceAI

3179 predictions. Top by Δscore:

Variant	Effect	Δscore
3:128246834:A:AG	acceptor_gain	1.0000
3:128246834:AG:A	acceptor_gain	1.0000
3:128246834:AGG:A	acceptor_gain	1.0000
3:128246834:AGGG:A	acceptor_gain	1.0000
3:128246835:G:GT	acceptor_gain	1.0000
3:128246835:GG:G	acceptor_gain	1.0000
3:128246835:GGG:G	acceptor_gain	1.0000
3:128246835:GGGG:G	acceptor_gain	1.0000
3:128246835:GGGGC:G	acceptor_gain	1.0000
3:128246981:A:T	donor_gain	1.0000
3:128247044:G:GG	donor_gain	1.0000
3:128262220:TTGAG:T	donor_loss	1.0000
3:128262221:TGAGG:T	donor_loss	1.0000
3:128262222:GAGG:G	donor_loss	1.0000
3:128262223:AG:A	donor_loss	1.0000
3:128262224:GG:G	donor_loss	1.0000
3:128262225:GT:G	donor_loss	1.0000
3:128341230:CAGGT:C	acceptor_loss	1.0000
3:128341232:G:A	acceptor_loss	1.0000
3:128341886:GCGG:G	donor_gain	1.0000
3:128358201:G:A	acceptor_gain	1.0000
3:128358370:CCAGG:C	donor_loss	1.0000
3:128358371:CAGGT:C	donor_loss	1.0000
3:128358372:AGG:A	donor_loss	1.0000
3:128358373:GGT:G	donor_loss	1.0000
3:128358374:G:GG	donor_gain	1.0000
3:128358374:GTAA:G	donor_loss	1.0000
3:128358375:T:A	donor_loss	1.0000
3:128408064:TGCAG:T	acceptor_loss	1.0000
3:128408066:CA:C	acceptor_loss	1.0000

AlphaMissense

3898 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:128153664:T:C	F53L	1.000
3:128153666:C:A	F53L	1.000
3:128153666:C:G	F53L	1.000
3:128153790:G:T	G95W	1.000
3:128153795:C:A	H96Q	1.000
3:128153795:C:G	H96Q	1.000
3:128153803:T:C	L99P	1.000
3:128264689:T:C	F232L	1.000
3:128264691:C:A	F232L	1.000
3:128264691:C:G	F232L	1.000
3:128153539:G:A	G11D	0.999
3:128153547:G:C	G14R	0.999
3:128153548:G:A	G14D	0.999
3:128153563:G:A	G19D	0.999
3:128153565:A:C	K20Q	0.999
3:128153566:A:T	K20M	0.999
3:128153665:T:C	F53S	0.999
3:128153779:T:A	V91D	0.999
3:128153781:G:C	D92H	0.999
3:128153782:A:G	D92G	0.999
3:128153783:C:A	D92E	0.999
3:128153783:C:G	D92E	0.999
3:128153784:T:C	C93R	0.999
3:128153786:C:G	C93W	0.999
3:128153788:C:A	P94H	0.999
3:128153790:G:A	G95R	0.999
3:128153790:G:C	G95R	0.999
3:128153791:G:A	G95E	0.999
3:128153793:C:G	H96D	0.999
3:128153794:A:G	H96R	0.999

dbSNP variants (sampled 300 via entrez): RS1000004336 (3:128386526 A>G), RS1000011705 (3:128345292 G>C), RS1000014546 (3:128380755 G>A), RS1000024729 (3:128422371 G>A), RS1000028182 (3:128176875 C>G), RS1000033014 (3:128313801 G>A,T), RS1000036957 (3:128386270 A>C), RS1000039877 (3:128300713 G>A,T), RS1000043836 (3:128192156 T>C), RS1000049750 (3:128307176 A>G,T), RS1000050146 (3:128268638 G>A), RS1000053588 (3:128293380 T>A,G), RS1000072435 (3:128300396 G>A,T), RS1000092111 (3:128212505 G>A), RS1000092415 (3:128256603 C>G,T)

Disease associations

OMIM: gene MIM:607695 | disease phenotypes: MIM:621102, MIM:249500, MIM:613668

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal recessive
neurodevelopmental disorder with progressive spasticity and brain abnormalities	Limited	Autosomal recessive

Mondo (4): neurodevelopmental disorder with progressive spasticity and brain abnormalities (MONDO:0976233), autosomal recessive non-syndromic intellectual disability (MONDO:0019502), infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly (MONDO:0013351), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Autosomal recessive non-syndromic intellectual disability (Orphanet:88616), Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly (Orphanet:402364)

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000400	Macrotia
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000568	Microphthalmia
HP:0000609	Optic nerve hypoplasia
HP:0000639	Nystagmus
HP:0000641	Dysmetric saccades
HP:0000657	Oculomotor apraxia
HP:0000666	Horizontal nystagmus
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0001159	Syndactyly
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001317	Abnormal cerebellum morphology
HP:0001321	Cerebellar hypoplasia
HP:0001347	Hyperreflexia
HP:0001382	Joint hypermobility

GWAS associations

139 associations (top):

Study	Trait	p-value
GCST000880_4	Menarche (age at onset)	1.000000e-07
GCST002541_2	Menarche (age at onset)	1.000000e-10
GCST002563_5	Hypospadias	1.000000e-26
GCST003262_123	Post bronchodilator FEV1	1.000000e-06
GCST003262_124	Post bronchodilator FEV1	1.000000e-06
GCST003262_136	Post bronchodilator FEV1	6.000000e-07
GCST003262_141	Post bronchodilator FEV1	6.000000e-07
GCST003262_142	Post bronchodilator FEV1	6.000000e-07
GCST003262_144	Post bronchodilator FEV1	7.000000e-07
GCST003262_190	Post bronchodilator FEV1	1.000000e-06
GCST003262_191	Post bronchodilator FEV1	1.000000e-06
GCST003262_192	Post bronchodilator FEV1	1.000000e-06
GCST003262_193	Post bronchodilator FEV1	1.000000e-06
GCST003262_194	Post bronchodilator FEV1	1.000000e-06
GCST003262_195	Post bronchodilator FEV1	1.000000e-06
GCST003262_196	Post bronchodilator FEV1	1.000000e-06
GCST003262_197	Post bronchodilator FEV1	1.000000e-06
GCST003262_198	Post bronchodilator FEV1	1.000000e-06
GCST003262_199	Post bronchodilator FEV1	1.000000e-06
GCST003262_200	Post bronchodilator FEV1	1.000000e-06
GCST003262_201	Post bronchodilator FEV1	1.000000e-06
GCST003262_202	Post bronchodilator FEV1	1.000000e-06
GCST003262_203	Post bronchodilator FEV1	1.000000e-06
GCST003262_204	Post bronchodilator FEV1	1.000000e-06
GCST003262_205	Post bronchodilator FEV1	1.000000e-06
GCST003262_222	Post bronchodilator FEV1	7.000000e-07
GCST003262_223	Post bronchodilator FEV1	9.000000e-07
GCST003262_224	Post bronchodilator FEV1	1.000000e-06
GCST003262_225	Post bronchodilator FEV1	1.000000e-06
GCST003262_435	Post bronchodilator FEV1	2.000000e-07

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0003917	premature birth
EFO:0005939	parental genotype effect measurement
EFO:0005112	gestational age
EFO:0004847	age at onset
EFO:0003892	pulmonary function measurement
EFO:0005091	monocyte count
EFO:0007984	platelet component distribution width
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	3
Valproic Acid	decreases methylation, increases expression, affects expression	3
sodium arsenite	decreases expression, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
potassium perchlorate	decreases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
beta-lapachone	increases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
(+)-JQ1 compound	increases expression	1
Arsenic Trioxide	decreases response to substance	1
Arsenic	affects methylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

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