NEMF

Chr 14AR

nuclear export mediator factor

Also known as: IDDSAPN, NY-CO-1, RQC2, SDCCAG1

The protein is a key component of the ribosome quality control complex that recognizes stalled ribosomes and facilitates the extraction and degradation of incompletely synthesized protein chains to prevent cellular toxicity. Biallelic mutations cause autosomal recessive intellectual developmental disorder with speech delay and axonal peripheral neuropathy. The gene is highly constrained against loss-of-function variants (LOEUF 0.415), indicating intolerance to protein disruption.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.411 OMIM phenotype
Clinical SummaryNEMF
🧬
Gene-Disease Validity (ClinGen)
intellectual developmental disorder with speech delay and axonal peripheral neuropathy · ARStrong

Strong evidence — appropriate for clinical testing

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.000
Z-score 5.63
OE 0.29 (0.200.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.19Z-score
OE missense 0.86 (0.790.93)
470 obs / 548.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.200.41)
00.351.4
Missense OE0.86 (0.790.93)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 21 / 72.9Missense obs/exp: 470 / 548.1Syn Z: -1.13
DN
0.6260th %ile
GOF
0.4777th %ile
LOF
0.3261th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NEMF · 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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