NELFA

Chr 4

negative elongation factor complex member A

Also known as: NELF-A, P/OKcl.15, WHSC2

NELFA encodes an essential component of the NELF complex that negatively regulates RNA polymerase II transcription elongation. Mutations cause Wolf-Hirschhorn syndrome, a malformation syndrome that follows an autosomal dominant inheritance pattern due to hemizygous deletions of chromosome 4p16.3. The gene is highly constrained against loss-of-function variants (LOEUF 0.514), consistent with its essential role in transcriptional regulation.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
143
P/LP submissions
0%
P/LP missense
0.51
LOEUF
Mechanism
Clinical SummaryNELFA
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
143 unique Pathogenic / Likely Pathogenic· 85 VUS of 287 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.135
Z-score 3.29
OE 0.26 (0.140.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.82Z-score
OE missense 0.73 (0.660.81)
256 obs / 352.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.140.51)
00.351.4
Missense OE0.73 (0.660.81)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 6 / 23.0Missense obs/exp: 256 / 352.2Syn Z: -2.17

ClinVar Variant Classifications

287 submitted variants in ClinVar

Classification Summary

Pathogenic136
Likely Pathogenic7
VUS85
Likely Benign39
Benign10
136
Pathogenic
7
Likely Pathogenic
85
VUS
39
Likely Benign
10
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
136
0
136
Likely Pathogenic
0
0
7
0
7
VUS
0
65
20
0
85
Likely Benign
0
5
6
28
39
Benign
0
3
2
5
10
Total07317133277

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

View in ClinVar →

Protein Context — Lollipop Plot

NELFA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

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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