NEMF

Chr 14

nuclear export mediator factor

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

NCBI Gene: 9147 ENSG00000165525 UniProt: O60524

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a component of the ribosome quality control complex. The encoded protein facilitates the recognition and ubiquitination of stalled 60S subunits by the ubiquitin ligase listerin. A similar protein in fly functions as a tumor suppressor. [provided by RefSeq, Jul 2016]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.41

Clinical Summary— NEMF

🧬

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.

📋

ClinVar Variants

29 unique Pathogenic / Likely Pathogenic· 145 VUS of 242 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.000

Z-score 5.63

OE 0.29 (0.20–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.19Z-score

OE missense 0.86 (0.79–0.93)

470 obs / 548.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.20–0.41)

0≤0.351.4

Missense OE?0.86 (0.79–0.93)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 21 / 72.9Missense obs/exp: 470 / 548.1Syn Z: -1.13

This gene — mechanism propensity

0.6260th %ile

GOF

0.4777th %ile

LOF

0.3261th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

LOF93% of P/LP variants are LoF · LOEUF 0.41

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

242 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19

Likely Pathogenic10

VUS145

Likely Benign28

Benign7

Pathogenic

Likely Pathogenic

145

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	18	1	0	0	19
Likely Pathogenic	9	1	0	0	10
VUS	2	142	1	0	145
Likely Benign	0	6	3	19	28
Benign	0	0	4	3	7
Total	29	150	8	22	209

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap NEMF — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →