EFTUD2

Chr 17AD

elongation factor Tu GTP binding domain containing 2

Also known as: MFDGA, MFDM, SNRNP116, Snrp116, Snu114, U5-116KD

NCBI Gene: 9343ENSG00000108883UniProt: Q15029

This gene encodes a GTPase which is a component of the spliceosome complex which processes precursor mRNAs to produce mature mRNAs. Mutations in this gene are associated with mandibulofacial dysostosis with microcephaly. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

Primary Disease Associations & Inheritance

Mandibulofacial dysostosis, Guion-Almeida typeMIM #610536
AD
338
ClinVar variants
65
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— EFTUD2
🧬
Gene-Disease Validity (ClinGen)
mandibulofacial dysostosis-microcephaly syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 157 VUS of 338 total submissions
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.09LOEUF
pLI 1.000
Z-score 6.45
OE 0.02 (0.01–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.03Z-score
OE missense 0.52 (0.47–0.57)
293 obs / 561.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.02 (0.01–0.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.47–0.57)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 1 / 50.4Missense obs/exp: 293 / 561.5Syn Z: 0.55

ClinVar Variant Classifications

338 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic27
VUS157
Likely Benign99
Benign10
Conflicting7
38
Pathogenic
27
Likely Pathogenic
157
VUS
99
Likely Benign
10
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
25
2
11
0
38
Likely Pathogenic
14
7
6
0
27
VUS
1
138
16
2
157
Likely Benign
0
6
40
53
99
Benign
0
0
10
0
10
Conflicting
—7
Total401538355338

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EFTUD2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

EFTUD2-related mandibulofacial dysostosis with microcephaly

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mandibulofacial dysostosis, Guion-Almeida type

MIM #610536

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — EFTUD2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Recurrent mandibulofacial dysostosis, Guion-Almeida type in consecutive pregnancies due to maternal mosaicism of a novel EFTUD2 variant: a case report and review of the literature.
Wang B et al.·J Med Case Rep
2026🔓 Open AccessReview
Whole-Exome Sequencing Revealed a Novel De Novo Pathogenic EFTUD2 Variant in Mandibulofacial Dysostosis, Guion-Almeida Type: Reinforcing Links to Choanal and Oesophageal Atresia.
Jazayeri O et al.·Int J Dev Neurosci
2025
LncRNA DGUOK-AS1 Promotes Bladder Cancer Progression by Enhancing EFTUD2 Stability.
Ying W et al.·Cancer Res Treat
2025
PROM1 and EFTUD2 Expression in High-Grade Clear Cell Renal Cell Carcinoma as a Molecular Marker for Survival Rate.
Kasperczak M et al.·Int J Mol Sci
2025🔓 Open Access
A novel EFTUD2 splicing variant causing mandibulofacial dysostosis with microcephaly: a case report.
Xu Y et al.·Transl Pediatr
2025🔓 Open AccessCase report
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools