EFTUD2

elongation factor Tu GTP binding domain containing 2, the group of Spliceosomal C complex|U5 small nuclear ribonucleoprotein|Spliceosomal Bact complex|Spliceosomal P complex

Basic information

Region (hg38): 17:44849948-44899445

Links

ENSG00000108883

∙ NCBI:9343 ∙ OMIM:603892 ∙ HGNC:30858 ∙ Uniprot:Q15029 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

mandibulofacial dysostosis-microcephaly syndrome (Definitive), mode of inheritance: AD
mandibulofacial dysostosis-microcephaly syndrome (Strong), mode of inheritance: AD
mandibulofacial dysostosis-microcephaly syndrome (Supportive), mode of inheritance: AD
mandibulofacial dysostosis-microcephaly syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mandibulofacial dysostosis, Guion-Almeida type	AD	Audiologic/Otolaryngologic; Cardiovascular	Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Recognition of potential GI manifestations (eg, Hirschsprung disease) may allow prompt treatment; The condition can involve congenital cardiac anomalies, and awareness may allow early management	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	16760738; 19334086; 22541558; 22305528; 23188108; 25790162

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EFTUD2 gene.

not_provided (577 variants)
Mandibulofacial_dysostosis-microcephaly_syndrome (118 variants)
Inborn_genetic_diseases (69 variants)
EFTUD2-related_disorder (29 variants)
not_specified (24 variants)
See_cases (4 variants)
Global_developmental_delay (2 variants)
Neurodevelopmental_disorder (1 variants)
Cleft_lip/palate (1 variants)
Hereditary_syndromic_Pierre_Robin_syndrome (1 variants)
Esophageal_atresia/tracheoesophageal_fistula (1 variants)
Chromatinopathy (1 variants)
Congenital_anomaly_of_kidney_and_urinary_tract (1 variants)
Mandibulofacial_dysostosis (1 variants)
Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EFTUD2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004247.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar	1 clinvar	8 clinvar	113 clinvar	9 clinvar	132
missense	7 clinvar	19 clinvar	217 clinvar	28 clinvar	3 clinvar	274
nonsense	18 clinvar	8 clinvar				26
start loss	1					1
frameshift	41 clinvar	23 clinvar				64
splice donor/acceptor (+/-2bp)	22 clinvar	19 clinvar	1 clinvar			42
Total	90	70	226	141	12

Highest pathogenic variant AF is 0.00000657004

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EFTUD2	protein_coding	protein_coding	ENST00000426333	27	49720

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.08e-8	125713	0	1	125714	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.03	293	561	0.522	0.0000314	6417
Missense in Polyphen		75	243.93	0.30746		2766
Synonymous	0.545	212	222	0.954	0.0000135	1870
Loss of Function	6.45	1	50.4	0.0198	0.00000247	610

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex required for pre-mRNA splicing. Binds GTP.;
Disease: DISEASE: Mandibulofacial dysostosis with microcephaly (MFDM) [MIM:610536]: A rare syndrome characterized by progressive microcephaly, midface and malar hypoplasia, micrognathia, microtia, dysplastic ears, preauricular skin tags, significant developmental delay, and speech delay. Many patients have major sequelae, including choanal atresia that results in respiratory difficulties, conductive hearing loss, and cleft palate. {ECO:0000269|PubMed:22305528}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Spliceosome - Homo sapiens (human);mRNA Processing;Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

pRec: 0.337

Intolerance Scores

loftool: 0.0218
rvis_EVS: -1.15
rvis_percentile_EVS: 6.23

Haploinsufficiency Scores

pHI: 0.237
hipred: Y
hipred_score: 0.717
ghis: 0.659

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.989

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Eftud2
Phenotype: homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Zebrafish Information Network

Gene name: eftud2
Affected structure: neuroblast (sensu Vertebrata)
Phenotype tag: abnormal
Phenotype quality: increased occurrence

Gene ontology

Biological process: mRNA splicing, via spliceosome;mRNA processing;RNA splicing;cellular response to drug;response to cocaine
Cellular component: nucleoplasm;spliceosomal complex;cytosol;Cajal body;membrane;nuclear speck;U4/U6 x U5 tri-snRNP complex;U2-type catalytic step 2 spliceosome;catalytic step 2 spliceosome;ribonucleoprotein complex
Molecular function: RNA binding;GTPase activity;protein binding;GTP binding;U5 snRNA binding