NELFE

Chr 6

negative elongation factor complex member E

Also known as: D6S45, NELF-E, RD, RDBP, RDP

NCBI Gene: 7936ENSG00000204356UniProt: P18615

The protein encoded by this gene is part of a complex termed negative elongation factor (NELF) which represses RNA polymerase II transcript elongation. This protein bears similarity to nuclear RNA-binding proteins; however, it has not been demonstrated that this protein binds RNA. The protein contains a tract of alternating basic and acidic residues, largely arginine (R) and aspartic acid (D). The gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. [provided by RefSeq, Jul 2008]

69
ClinVar variants
5
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— NELFE
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 54 VUS of 69 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.56LOEUF
pLI 0.007
Z-score 3.32
OE 0.32 (0.19–0.56)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.57Z-score
OE missense 0.72 (0.64–0.81)
177 obs / 246.3 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.0.32 (0.19–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.64–0.81)
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.0.86
0≤1.21.6
LoF obs/exp: 9 / 27.9Missense obs/exp: 177 / 246.3Syn Z: 1.00

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS54
Likely Benign6
Benign4
4
Pathogenic
1
Likely Pathogenic
54
VUS
6
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
49
5
0
54
Likely Benign
0
3
2
1
6
Benign
0
0
4
0
4
Total05216169

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

View in ClinVar →

Protein Context — Lollipop Plot

NELFE · 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
Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis.
Zhang J et al.·Nat Commun
2023
Oncogenic Activation of the RNA Binding Protein NELFE and MYC Signaling in Hepatocellular Carcinoma.
Dang H et al.·Cancer Cell
2017
NELFE promoted pancreatic cancer metastasis and the epithelial‑to‑mesenchymal transition by decreasing the stabilization of NDRG2 mRNA.
Han L et al.·Int J Oncol
2019
Identification of metabolic pathways contributing to ER(+) breast cancer disparities using a machine-learning pipeline.
Santaliz-Casiano A et al.·Sci Rep
2023
Integrated Analysis Identifies Novel Fusion Transcripts in Laterally Spreading Tumors Suggestive of Distinct Etiology Than Colorectal Cancers.
Rai S et al.·J Gastrointest Cancer
2023
Integrated multi-omics analysis of the clinical relevance and potential regulatory mechanisms of splicing factors in hepatocellular carcinoma.
Zhao YJ et al.·Bioengineered
2021Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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