EPS8L2

Chr 11AR

EPS8 signaling adaptor L2

Also known as: DFNB106, EPS8R2

NCBI Gene: 64787ENSG00000177106UniProt: Q9H6S3

This gene encodes a member of the EPS8 gene family. The encoded protein, like other members of the family, is thought to link growth factor stimulation to actin organization, generating functional redundancy in the pathways that regulate actin cytoskeletal remodeling. [provided by RefSeq, Dec 2008]

Primary Disease Associations & Inheritance

Deafness autosomal recessive 106MIM #617637
AR
UniProtDeafness, autosomal recessive, 106
463
ClinVar variants
52
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EPS8L2
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 222 VUS of 463 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.
0.63LOEUF
pLI 0.000
Z-score 3.44
OE 0.42 (0.28–0.63)
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.
-0.80Z-score
OE missense 1.11 (1.03–1.20)
451 obs / 405.7 exp
Tolerant

Tolerant to missense variation

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.0.42 (0.28–0.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (1.03–1.20)
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.1.18
0≤1.21.6
LoF obs/exp: 17 / 40.6Missense obs/exp: 451 / 405.7Syn Z: -1.94

ClinVar Variant Classifications

463 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic8
VUS222
Likely Benign147
Benign37
Conflicting5
44
Pathogenic
8
Likely Pathogenic
222
VUS
147
Likely Benign
37
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
31
0
44
Likely Pathogenic
4
1
3
0
8
VUS
0
193
28
1
222
Likely Benign
1
7
66
73
147
Benign
0
2
30
5
37
Conflicting
—5
Total1820315879463

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

View in ClinVar →

Protein Context — Lollipop Plot

EPS8L2 · 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

Deafness autosomal recessive 106

MIM #617637

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expansion of Molecular and Clinical Aspects of EPS8L2 (DFNB106)-Associated Hearing Loss Emphasizes a Potential Therapeutic Window.
Owrang D et al.·Mol Neurobiol
2026
The eps8 family of proteins links growth factor stimulation to actin reorganization generating functional redundancy in the Ras/Rac pathway.
Offenhäuser N et al.·Mol Biol Cell
2004Functional
Comprehensive analysis of biological landscape of oxidative stress-related genes in diabetic erectile dysfunction.
Meng Q et al.·Int J Impot Res
2024
Searching for prognostic biomarkers for small renal masses in the urinary proteome.
Di Meo A et al.·Int J Cancer
2020
EPS8L2 is a new causal gene for childhood onset autosomal recessive progressive hearing loss.
Dahmani M et al.·Orphanet J Rare Dis
2015Case report
Identification and phased de novo mutation of the EPS8L2 gene in a patient with progressive hearing loss: A case report.
Gan H et al.·Medicine (Baltimore)
2026Case report
Molecular Analysis of Twelve Pakistani Families with Nonsyndromic or Syndromic Hearing Loss.
Wang R et al.·Genet Test Mol Biomarkers
2017
Re-examination of MAGE-A3 as a T-cell Therapeutic Target.
Martin AD et al.·J Immunother
2021
A novel disulfidptosis-related mRNA signature predicts prognosis and therapeutic response in lung squamous cell carcinoma.
Bai W et al.·BMC Pulm Med
2025
Predictive Biomarker Panel in Proliferative Lupus Nephritis- Two-Dimensional Shotgun Proteomics.
Ghasemi M et al.·Iran J Kidney Dis
2021
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