NELFB

Chr 9

negative elongation factor complex member B

Also known as: COBRA1, NELF-B

NCBI Gene: 25920ENSG00000188986UniProt: Q8WX92

NELFB is a subunit of negative elongation factor (NELF), which also includes NELFA (WHSC2; MIM 606026), either NELFC or NELFD (TH1L; MIM 605297), and NELFE (RDBP; MIM 154040). NELF acts with DRB sensitivity-inducing factor (DSIF), a heterodimer of SPT4 (SUPT4H1; MIM 603555) and SPT5 (SUPT5H; MIM 602102), to cause transcriptional pausing of RNA polymerase II (see MIM 180660) (Narita et al., 2003 [PubMed 12612062]).[supplied by OMIM, Mar 2008]

189
ClinVar variants
98
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NELFB
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
98 Pathogenic / Likely Pathogenic· 86 VUS of 189 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

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

Typical tolerance to LoF variation

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.
1.66Z-score
OE missense 0.75 (0.68–0.83)
271 obs / 359.7 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.0.35 (0.21–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.68–0.83)
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.1.14
0≤1.21.6
LoF obs/exp: 9 / 26.0Missense obs/exp: 271 / 359.7Syn Z: -1.41

ClinVar Variant Classifications

189 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic91
Likely Pathogenic7
VUS86
Likely Benign1
Benign1
Conflicting3
91
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
91
0
91
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
Total0791061189

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Stress-induced nuclear condensation of NELF drives transcriptional downregulation.
Rawat P et al.·Mol Cell
2021
SPT5 stabilizes RNA polymerase II, orchestrates transcription cycles, and maintains the enhancer landscape.
Hu S et al.·Mol Cell
2021
P-TEFb goes viral.
Zaborowska J et al.·Bioessays
2016Review
Chromatin protein complexes involved in gene repression in lamina-associated domains.
Manzo SG et al.·EMBO J
2024
Structural basis of Integrator-dependent RNA polymerase II termination.
Fianu I et al.·Nature
2024
Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis.
Zhang J et al.·Nat Commun
2023
Disrupting the RNA polymerase II transcription cycle through CDK7 inhibition ameliorates inflammatory arthritis.
Chen X et al.·Sci Transl Med
2024
NELF focuses sites of initiation and maintains promoter architecture.
Santana JF et al.·Nucleic Acids Res
2024
NSUN6, an RNA methyltransferase of 5-mC controls glioblastoma response to temozolomide (TMZ) via NELFB and RPS6KB2 interaction.
Awah CU et al.·Cancer Biol Ther
2021
Transcription quality control at the promoter-proximal checkpoint.
Blears D et al.·Genes Dev
2025Review
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