EAF1 encodes a transcriptional transactivator that enhances the elongation activities of ELL and ELL2 transcription factors, functioning as part of the transcription elongation factor complex. Mutations cause autosomal recessive intellectual disability with speech delay and behavioral abnormalities, typically manifesting in early childhood. The gene shows moderate tolerance to loss-of-function variants based on population genetics data.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.77
Clinical SummaryEAF1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 34 VUS of 74 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.061
Z-score 2.13
OE 0.33 (0.160.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.01Z-score
OE missense 0.77 (0.660.90)
114 obs / 148.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.160.77)
00.351.4
Missense OE0.77 (0.660.90)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 4 / 11.9Missense obs/exp: 114 / 148.7Syn Z: -0.04
DN
0.6453th %ile
GOF
0.3986th %ile
LOF
0.4331th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

74 submitted variants in ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic1
VUS34
Likely Benign2
Benign2
23
Pathogenic
1
Likely Pathogenic
34
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
1
0
1
VUS
0
33
1
0
34
Likely Benign
0
1
1
0
2
Benign
0
0
0
2
2
Total03426262

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

View in ClinVar →

Protein Context — Lollipop Plot

EAF1 · 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

No active trials found for this gene.

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Clinical Literature
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