NELFB

Chr 9

negative elongation factor complex member B

Also known as: COBRA1, NELF-B

NCBI Gene: 25920ENSG00000188986UniProt: Q8WX92OMIM: 611180

NELFB encodes an essential component of the negative elongation factor (NELF) complex that regulates RNA polymerase II transcriptional pausing and is critical for maintaining embryonic stem cell pluripotency and facilitating cell fate decisions during development. The gene is highly constrained against loss-of-function variants (LOEUF 0.603), but no specific Mendelian disorders have been definitively associated with NELFB mutations in humans to date.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.60
Clinical Summary— NELFB
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
99 unique Pathogenic / Likely Pathogenic· 86 VUS of 210 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.60LOEUF
pLI 0.003
Z-score 3.09
OE 0.35 (0.21–0.60)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.66Z-score
OE missense 0.75 (0.68–0.83)
271 obs / 359.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.21–0.60)
0≤0.351.4
Missense OE0.75 (0.68–0.83)
0≤0.61.4
Synonymous OE1.14
0≤1.21.6
LoF obs/exp: 9 / 26.0Missense obs/exp: 271 / 359.7Syn Z: -1.41
DN
0.6455th %ile
GOF
0.6834th %ile
LOF
0.3454th %ile

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

GOFprediction above median
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

210 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic7
VUS86
Likely Benign1
Benign1
Conflicting3
92
Pathogenic
7
Likely Pathogenic
86
VUS
1
Likely Benign
1
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
92
0
92
Likely Pathogenic
0
0
7
0
7
VUS
0
79
7
0
86
Likely Benign
0
0
0
1
1
Benign
0
0
1
0
1
Conflicting
—3
Total0791071190

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

View in ClinVar →

Protein Context — Lollipop Plot

NELFB · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients