EIF4ENIF1

Chr 22

eukaryotic translation initiation factor 4E nuclear import factor 1

Also known as: 4E-T, Clast4

NCBI Gene: 56478ENSG00000184708UniProt: Q9NRA8

The protein encoded by this gene is a nucleocytoplasmic shuttle protein for the translation initiation factor eIF4E. This shuttle protein interacts with the importin alpha-beta complex to mediate nuclear import of eIF4E. It is predominantly cytoplasmic; its own nuclear import is regulated by a nuclear localization signal and nuclear export signals. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— EIF4ENIF1
⚡
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.
Some data sources returned errors (1)

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.18LOEUF
pLI 1.000
Z-score 6.15
OE 0.08 (0.04–0.18)
Highly constrained

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

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.
1.99Z-score
OE missense 0.76 (0.70–0.83)
428 obs / 560.3 exp
Tolerant

Mild missense constraint

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.0.08 (0.04–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.70–0.83)
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.1.00
0≤1.21.6
LoF obs/exp: 4 / 51.7Missense obs/exp: 428 / 560.3Syn Z: -0.01

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

EIF4ENIF1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Eif4enif1 haploinsufficiency disrupts oocyte mitochondrial dynamics and leads to subfertility.
Ding Y et al.·Development
2023
EIF4ENIF1 variants in two patients with non-syndromic premature ovarian insufficiency.
Shang L et al.·Eur J Med Genet
2022Case report
POI-associated EIF4ENIF1 mutations exhibit impaired translation regulation abilities.
Ding Y et al.·Gene
2024
Mutations in eIF4ENIF1 are associated with primary ovarian insufficiency.
Kasippillai T et al.·J Clin Endocrinol Metab
2013
A novel EIF4ENIF1 mutation associated with a diminished ovarian reserve and premature ovarian insufficiency identified by whole-exome sequencing.
Zhao M et al.·J Ovarian Res
2019Case report
A homozygous stop codon in HORMAD2 in a patient with recurrent digynic triploid miscarriage.
Liang M et al.·Mol Genet Genomic Med
2024
Screening of targeted panel genes in Brazilian patients with primary ovarian insufficiency.
França MM et al.·PLoS One
2020Cohort
Heterozygous Eif4nif1 Stop-Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women.
Moriwaki M et al.·Endocrinology
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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