EPS8L2
protein-codingEPS8 like 2
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~33.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0019588
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0019497
Submitter: ClinGen
EPS8L2 has been reported in relation to autosomal recessive nonsyndromic hearing loss. At least 2 unique loss of function variants have been reported in humans (26282398, 28281779). Variants in this gene segregated with disease in additional family members. This gene-disease association is supported by a knock-out mouse model and relevant expression studies. In summary, there is moderate evidence to support this gene-disease association. While more evidence is needed to establish this association definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Hearing Loss Working Group on 2/5/2020.
Inheritance Pattern: AR
Disease ID:MONDO:0033198
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0033198
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic
Intervention: Audiologic/Otolaryngologic
Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development
Comments: Prelingual hearing loss has been described in some (but not all) individuals
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EPS8L2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022772.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 85 | 1 | 91 | ||
| missense | 2 | 211 | 11 | 224 | ||
| nonsense | 4 | 5 | 9 | |||
| start loss | 0 | |||||
| frameshift | 13 | 8 | 21 | |||
| splice donor/acceptor (+/-2bp) | 1 | 4 | 1 | 6 | ||
| Total | 17 | 16 | 220 | 97 | 1 | 351 |
Highest pathogenic variant AF is 0.00037884997
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_073609.2 | 20 | MANE Select | |
| Ensembl | ENSP00000320828.8 | 20 | MANE Select | |
| RefSeq | NP_001428121.1 | 20 | Standard | |
| RefSeq | NP_001428122.1 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- Rho protein signal transduction
- sensory perception of sound
- regulation of Rho protein signal transduction
- positive regulation of ruffle assembly
Molecular Function
- actin binding
- Rho guanyl-nucleotide exchange factor activity
- protein binding
- Rac guanyl-nucleotide exchange factor activity
- cadherin binding
Cellular Component
- cytosol
- plasma membrane
- vesicle
- stereocilium bundle
- stereocilium tip
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000533256
- Coding exons
- 20
- Length
- 33290
- Individuals with no LoFs
- 125560
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 107
- Defined
- 125667
- p
- 0.000426
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.799 | 451 | 406 | 1.11 | 0.0000242 | 4584 |
| Missense (PolyPhen) | 139 | 130.46 | 1.0654 | 1546 | ||
| Synonymous | -1.94 | 214 | 181 | 1.18 | 0.0000118 | 1355 |
| Loss of Function | 3.44 | 17 | 40.6 | 0.418 | 0.00000199 | 454 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.00099 | notable |
| Latino/Admixed American | 0.00033 | 0.00029 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.00048 | 0.00044 | rare |
| Finnish | 0.00029 | 0.00028 | rare |
| European (Non-Finnish) | 0.00050 | 0.00047 | rare |
| South Asian | 0.00034 | 0.00033 | rare |
| Other | 0.00052 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Stimulates guanine exchange activity of SOS1. May play a role in membrane ruffling and remodeling of the actin cytoskeleton. In the cochlea, is required for stereocilia maintenance in adult hair cells (By similarity). {ECO:0000250|UniProtKB:Q99K30, ECO:0000269|PubMed:14565974}.;
Recessive Scores
- pRec
- 0.135
Intolerance Scores
- LoFtool
- 0.602
- RVIS EVS
- -1.26
- RVIS percentile EVS
- 5.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.749
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |