EAF1

Chr 3

ELL associated factor 1

NCBI Gene: 85403 ENSG00000144597 UniProt: Q96JC9 OMIM: 608315

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables transcription elongation factor activity. Involved in regulation of transcription elongation by RNA polymerase II. Located in intercellular bridge and nuclear body. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.77

Clinical Summary— EAF1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

33 VUS of 48 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?

0.77LOEUF

pLI 0.061

Z-score 2.13

OE 0.33 (0.16–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.01Z-score

OE missense 0.77 (0.66–0.90)

114 obs / 148.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.16–0.77)

0≤0.351.4

Missense OE?0.77 (0.66–0.90)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 4 / 11.9Missense obs/exp: 114 / 148.7Syn Z: -0.04

This gene — mechanism propensity

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

48 submitted variants in ClinVar

ClinVar

Classification Summary

VUS33

Likely Benign1

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	33	0	33
Likely Benign	1	0	1
Benign	0	2	2
Total	34	2	36

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap EAF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →