EFTUD2

Chr 17

elongation factor Tu GTP binding domain containing 2

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

NCBI Gene: 9343 ENSG00000108883 UniProt: Q15029

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.09

Clinical Summary— EFTUD2

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Gene-Disease Validity (ClinGen)

mandibulofacial dysostosis-microcephaly syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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ClinVar Variants

183 unique Pathogenic / Likely Pathogenic· 296 VUS of 961 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — EFTUD2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.02 (0.01–0.09)

0≤0.351.4

Missense OE?0.52 (0.47–0.57)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

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

This gene — mechanism propensity

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 · 81% of P/LP variants are LoF · LOEUF 0.09 · ClinGen HI: Sufficient evidence for dosage pathogenicity

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 reg1

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

References

1.PMID 31304552 ↗

ClinVar Variant Classifications

961 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic100

Likely Pathogenic83

VUS296

Likely Benign296

Benign98

Conflicting26

100

Pathogenic

Likely Pathogenic

296

VUS

296

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	90	7	2	1	100
Likely Pathogenic	58	18	6	1	83
VUS	1	254	34	7	296
Likely Benign	1	13	147	135	296
Benign	0	3	86	9	98
Conflicting	—				26
Total	150	295	275	153	899

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap EFTUD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →