EFTUD2

Chr 17AD

elongation factor Tu GTP binding domain containing 2

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

The protein is a GTPase component of the spliceosome complex required for pre-mRNA splicing, functioning in both major and minor spliceosomes including U5 snRNP and U4/U6-U5 tri-snRNP complexes. Mutations cause mandibulofacial dysostosis with microcephaly (Guion-Almeida type), inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.094), reflecting its essential role in RNA processing.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.091 OMIM phenotype
Clinical SummaryEFTUD2
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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.
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GeneReview available — EFTUD2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.09LOEUF
pLI 1.000
Z-score 6.45
OE 0.02 (0.010.09)
Highly constrained

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

Missense Constraint
4.03Z-score
OE missense 0.52 (0.470.57)
293 obs / 561.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.010.09)
00.351.4
Missense OE0.52 (0.470.57)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 1 / 50.4Missense obs/exp: 293 / 561.5Syn Z: 0.55
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEFTUD2-related mandibulofacial dysostosis with microcephalyLOFAD
DN
0.4488th %ile
GOF
0.5661th %ile
LOF
0.64top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOF1 literature citation · LOEUF 0.09

Literature Evidence

LOFTogether, these data support a model in which EFTUD2 haploinsufficiency leads to the mis-splicing of a distinct subset of pre-mRNAs with a widespread effect on gene expression, including altering the expression of ER stress response genes and genes involved in the development of the craniofacial regPMID:31304552

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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