EPS8L3

protein-coding

EPS8 like 3

Gene summary

This gene encodes a protein that is related to epidermal growth factor receptor pathway substrate 8 (EPS8), a substrate for the epidermal growth factor receptor. The function of this protein is unknown. Alternatively spliced transcript variants encoding different isoforms exist. [provided by RefSeq, Jul 2008]

MANE transcript

NM_133181.4

Inheritance

ClinVar variants

U:90B:18

Top phenotype

Hypotrichosis 5

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr1:109,750,080-109,764,027

External References & Databases

Ensembl (ENSG00000198758)

Transcript & Mutation Effects

hg38 • Region Span ~13.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypotrichosis 5LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013017

Submitter: G2P

Marie Unna hereditary hypotrichosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018631

Submitter: Orphanet

Clinical Genomic Database (CGD)

Hypotrichosis 5AD

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 15347323; 23099647

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EPS8L3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 94

not providedTotal: 10

Hypotrichosis 5Total: 2

EPS8L3-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_133181.4. 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			1 clinvar	4 clinvar	2 clinvar	7
missense			86 clinvar	11 clinvar	1 clinvar	98
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	90	15	3	108

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_133181.4	RefSeq	NP_573444.2	18	MANE Select
ENST00000361965.9	Ensembl	ENSP00000355255.4	18	MANE Select
NM_001319952.2	RefSeq	NP_001306881.1	16	Standard
NM_024526.4	RefSeq	NP_078802.2	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

Rho protein signal transduction
regulation of Rho protein signal transduction
regulation of hair cycle
positive regulation of ruffle assembly

Molecular Function

actin binding
protein binding
Rac guanyl-nucleotide exchange factor activity
actin filament binding

Cellular Component

cytoplasm
plasma membrane
ruffle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369805
Coding exons: 18
Length: 13948
Individuals with no LoFs: 125585
Homozygous LoFs: 0
Heterozygous LoFs: 163
Defined: 125748
p: 0.000648

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0944	335	340	0.986	0.0000191	3828
Missense (PolyPhen)		103	110.21	0.93455		1382
Synonymous	0.00277	137	137	1.00	0.00000759	1185
Loss of Function	1.99	27	40.7	0.663	0.00000226	402

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00055	0.00054	rare
Finnish	0.0034	0.0034	notable
European (Non-Finnish)	0.00052	0.00051	rare
South Asian	0.000098	0.000098	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0889

Intolerance Scores

LoFtool: 0.946
RVIS EVS: 0.87
RVIS percentile EVS: 88.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.525

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High