EIF2S3

Chr XXLR

eukaryotic translation initiation factor 2 subunit gamma

Also known as: EIF2, EIF2G, EIF2gamma, MEHMO, MRXSBRK, eIF-2gA, eIF2gX

The gamma subunit of eukaryotic initiation factor 2 (eIF2) forms a ternary complex with GTP and initiator tRNA that binds to the 40S ribosomal subunit during the early steps of protein synthesis. X-linked recessive mutations cause MEHMO syndrome, a severe neurodevelopmental disorder characterized by intellectual disability, epilepsy, hypogonadism, microcephaly, and obesity. This gene is highly constrained against loss-of-function variants (pLI 0.96), reflecting the critical nature of protein synthesis initiation in cellular function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.321 OMIM phenotype
Clinical SummaryEIF2S3
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Gene-Disease Validity (ClinGen)
MEHMO 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 0.96). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.32LOEUF
pLI 0.964
Z-score 3.32
OE 0.07 (0.020.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.61Z-score
OE missense 0.24 (0.180.31)
42 obs / 177.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.07 (0.020.32)
00.351.4
Missense OE0.24 (0.180.31)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 1 / 14.7Missense obs/exp: 42 / 177.1Syn Z: -0.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongEIF2S3-related syndromic intellectual disability with severe microcephalyLOFXLR
DN
0.3793th %ile
GOF
0.4085th %ile
LOF
0.75top 10%

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

LOFprediction above median · LOEUF 0.32

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

EIF2S3 · 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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