ELF5

Chr 11

E74 like ETS transcription factor 5

Also known as: ESE2

ELF5 encodes an epithelium-specific ETS family transcription factor that regulates terminal differentiation of keratinocytes and controls expression of genes in glandular epithelial tissues including salivary gland and prostate. Pathogenic variants cause autosomal dominant hypohidrotic ectodermal dysplasia with distinctive facial features, sparse hair, reduced sweating, and dental abnormalities. The gene shows low constraint against loss-of-function variants, suggesting tolerance to haploinsufficiency in most contexts.

Summary from RefSeq, UniProt
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1
Active trials
14
Pubs (1 yr)
18
P/LP submissions
0%
P/LP missense
0.80
LOEUF
DN
Mechanism· predicted
Clinical SummaryELF5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 45 VUS of 68 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.001
Z-score 2.19
OE 0.44 (0.260.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.02Z-score
OE missense 1.00 (0.871.14)
145 obs / 145.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.260.80)
00.351.4
Missense OE1.00 (0.871.14)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 8 / 18.0Missense obs/exp: 145 / 145.5Syn Z: -0.45
DN
0.6550th %ile
GOF
0.5562th %ile
LOF
0.3745th %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

68 submitted variants in ClinVar

Classification Summary

Pathogenic18
VUS45
18
Pathogenic
45
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
0
0
0
VUS
0
38
7
0
45
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total03825063

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

View in ClinVar →

Protein Context — Lollipop Plot

ELF5 · protein map & ClinVar variants

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

Clinical Literature
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