EPS8L1

Summary

EPS8L1 (EPS8 signaling adaptor L1, HGNC:21295) is a protein-coding gene on chromosome 19q13.42, encoding Epidermal growth factor receptor kinase substrate 8-like protein 1 (Q8TE68). Stimulates guanine exchange activity of SOS1.

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. At least two alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 54869 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 198 total
• MANE Select transcript: NM_133180

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21295
Approved symbol	EPS8L1
Name	EPS8 signaling adaptor L1
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20258, DRC3, MGC23164, MGC4642
Ensembl gene	ENSG00000131037
Ensembl biotype	protein_coding
OMIM	614987
Entrez	54869

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 13 protein_coding, 10 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000201647, ENST00000245618, ENST00000540810, ENST00000585347, ENST00000586329, ENST00000587715, ENST00000587786, ENST00000587901, ENST00000588359, ENST00000589362, ENST00000589694, ENST00000590232, ENST00000590610, ENST00000591219, ENST00000592044, ENST00000592102, ENST00000592284, ENST00000592318, ENST00000592824, ENST00000908398, ENST00000908399, ENST00000908400, ENST00000908401, ENST00000908402, ENST00000918679, ENST00000918680, ENST00000959601

RefSeq mRNA: 2 — MANE Select: NM_133180 NM_017729, NM_133180

CCDS: CCDS12914, CCDS12915

Canonical transcript exons

ENST00000201647 — 20 exons

Exon	Start	End
ENSE00002766638	55075869	55075919
ENSE00003464681	55086392	55086518
ENSE00003488093	55087303	55087435
ENSE00003500320	55078999	55079057
ENSE00003502163	55081773	55081899
ENSE00003517826	55086714	55086888
ENSE00003530873	55080772	55080854
ENSE00003562826	55079690	55079851
ENSE00003589695	55082454	55082602
ENSE00003605072	55086061	55086192
ENSE00003605495	55076408	55076461
ENSE00003607266	55082092	55082180
ENSE00003612161	55081231	55081492
ENSE00003614964	55080129	55080278
ENSE00003627167	55083378	55083519
ENSE00003635058	55085841	55085973
ENSE00003655578	55082275	55082349
ENSE00003656781	55087528	55087923
ENSE00003662676	55083616	55083644
ENSE00003678159	55078088	55078128

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 99.91.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1601 / max 45.5812, expressed in 861 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177587	1.2221	435
177579	0.9833	304
177583	0.3567	209
177586	0.2101	108
177584	0.1247	44
177582	0.1210	69
177581	0.0754	42
177580	0.0419	20
177578	0.0248	9

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.91	gold quality
right uterine tube	UBERON:0001302	99.43	gold quality
buccal mucosa cell	CL:0002336	99.14	gold quality
esophagus mucosa	UBERON:0002469	98.93	gold quality
skin of abdomen	UBERON:0001416	98.77	gold quality
skin of leg	UBERON:0001511	98.67	gold quality
amniotic fluid	UBERON:0000173	98.13	gold quality
right lobe of thyroid gland	UBERON:0001119	97.95	gold quality
esophagus squamous epithelium	UBERON:0006920	97.75	gold quality
left lobe of thyroid gland	UBERON:0001120	97.67	gold quality
pancreatic ductal cell	CL:0002079	97.60	gold quality
epithelium of esophagus	UBERON:0001976	97.41	gold quality
zone of skin	UBERON:0000014	97.22	gold quality
metanephros cortex	UBERON:0010533	97.21	gold quality
oral cavity	UBERON:0000167	96.60	gold quality
thyroid gland	UBERON:0002046	96.40	gold quality
minor salivary gland	UBERON:0001830	96.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.61	gold quality
mouth mucosa	UBERON:0003729	95.50	gold quality
pharyngeal mucosa	UBERON:0000355	94.65	gold quality
placenta	UBERON:0001987	94.57	gold quality
saliva-secreting gland	UBERON:0001044	94.25	gold quality
squamous epithelium	UBERON:0006914	94.01	gold quality
cervix squamous epithelium	UBERON:0006922	93.90	gold quality
nasal cavity epithelium	UBERON:0005384	93.84	gold quality
gall bladder	UBERON:0002110	93.20	gold quality
mucosa of transverse colon	UBERON:0004991	92.62	gold quality
upper leg skin	UBERON:0004262	92.38	gold quality
vagina	UBERON:0000996	92.23	gold quality
tongue squamous epithelium	UBERON:0006919	92.00	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	2438.33
E-CURD-114	yes	51.59
E-MTAB-6701	yes	42.58
E-ANND-3	yes	4.97
E-HCAD-30	no	34.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting EPS8L1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6781-5P	94.61	59.49	155

Literature-anchored findings (GeneRIF, showing 1)

• Comparative immunohistochemical analysis suggests a conserved role of EPS8L1 in epidermal and hair follicle barriers of mammals. (PMID:37889356)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	eps8l1b	ENSDARG00000003313
danio_rerio	eps8l1a	ENSDARG00000057984
mus_musculus	Eps8l1	ENSMUSG00000006154
rattus_norvegicus	Eps8l1	ENSRNOG00000027942
drosophila_melanogaster	aru	FBGN0029095
drosophila_melanogaster	CG8907	FBGN0038466
caenorhabditis_elegans		WBGENE00001330

Paralogs (3): EPS8 (ENSG00000151491), EPS8L2 (ENSG00000177106), EPS8L3 (ENSG00000198758)

Protein

Protein identifiers

Epidermal growth factor receptor kinase substrate 8-like protein 1 — Q8TE68 (reviewed: Q8TE68)

Alternative names: Epidermal growth factor receptor pathway substrate 8-related protein 1

All UniProt accessions (5): Q8TE68, B4DKV7, K7EKX9, K7ELW3, K7EN83

UniProt curated annotations — full annotation on UniProt →

Function. Stimulates guanine exchange activity of SOS1. May play a role in membrane ruffling and remodeling of the actin cytoskeleton.

Subunit / interactions. Interacts with ABI1. Part of a complex that contains SOS1, ABI1 and EPS8L2. Associates with F-actin.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in placenta.

Similarity. Belongs to the EPS8 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8TE68-1	1, A	yes
Q8TE68-2	2, B
Q8TE68-3	3, C
Q8TE68-4	4

RefSeq proteins (2): NP_060199, NP_573441* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013625	PTB	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR033928	EPS8_PTB	Domain
IPR035462	Eps8_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR039801	EPS8-like	Family
IPR041418	SAM_3	Domain
IPR055093	EPS8_2nd	Domain

Pfam: PF00018, PF08416, PF18016, PF22975

UniProt features (38 total): splice variant 8, strand 6, sequence variant 5, compositionally biased region 4, sequence conflict 4, region of interest 4, domain 2, modified residue 2, chain 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2K2M	SOLUTION NMR
2ROL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TE68-F1	75.86	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 182, 187

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 325 (showing top): MORF_FLT1, MORF_MSH3, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_RUFFLE_ASSEMBLY, AREB6_01, KYNG_DNA_DAMAGE_DN, GOCC_RUFFLE, MORF_ESR1, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, MORF_RAD51L3, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (3): Rho protein signal transduction (GO:0007266), regulation of Rho protein signal transduction (GO:0035023), positive regulation of ruffle assembly (GO:1900029)

GO Molecular Function (6): actin binding (GO:0003779), T cell receptor binding (GO:0042608), cadherin binding (GO:0045296), guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (6): cytosol (GO:0005829), plasma membrane (GO:0005886), ruffle membrane (GO:0032587), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
small GTPase-mediated signal transduction	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
ruffle assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
regulation of ruffle assembly	1
cytoskeletal protein binding	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
cytoplasm	1
membrane	1
cell periphery	1
ruffle	1
cell projection membrane	1
leading edge membrane	1
cellular_component	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

798 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPS8L1	ESPN	B1AK53	585
EPS8L1	TSPO2	Q5TGU0	516
EPS8L1	ANKRD54	Q6NXT1	469
EPS8L1	SLC26A10P	Q8NG04	414
EPS8L1	KPRP	Q5T749	407
EPS8L1	CLCNKA	P51800	388
EPS8L1	NCK2	O43639	380
EPS8L1	CCDC166	P0CW27	378
EPS8L1	EGFR	P00533	376
EPS8L1	ZNF518A	Q6AHZ1	372
EPS8L1	ABI1	Q8IZP0	370
EPS8L1	ARHGEF39	Q8N4T4	360
EPS8L1	SIPA1	Q96FS4	358
EPS8L1	SNX33	Q8WV41	356
EPS8L1	TWF2	Q6IBS0	351

IntAct

33 interactions, top by confidence:

A	B	Type	Score
EPS8L1	CD3E	psi-mi:“MI:0915”(physical association)	0.750
CD3E	EPS8L1	psi-mi:“MI:0915”(physical association)	0.750
CD3E	EPS8L1	psi-mi:“MI:0407”(direct interaction)	0.750
EPS8L1	CD3E	psi-mi:“MI:0407”(direct interaction)	0.750
ADAM19	EPS8L1	psi-mi:“MI:0407”(direct interaction)	0.560
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
EPS8L1	DHPS	psi-mi:“MI:0914”(association)	0.530
EPS8L1	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
ATG16L1		psi-mi:“MI:0914”(association)	0.350
DYRK2	RBM47	psi-mi:“MI:0914”(association)	0.350
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
C18orf21	A2ML1	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350
MMTAG2	A2ML1	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
ZC3HC1	SULT2B1	psi-mi:“MI:0914”(association)	0.350
EPS8L1	IDE	psi-mi:“MI:0914”(association)	0.350
RSRP1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (52): EPS8L1 (Biochemical Activity), EPS8L1 (Proximity Label-MS), EPS8L1 (Affinity Capture-MS), EPS8L1 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), ABI1 (Affinity Capture-Western), SOS1 (Affinity Capture-Western), ACTG1 (Affinity Capture-Western), EPS8L1 (Affinity Capture-MS), CD3E (Affinity Capture-Western), CD3E (Protein-peptide), ABI2 (Two-hybrid), CYSRT1 (Two-hybrid), EPS8L1 (Affinity Capture-MS), ABI1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8P0N4K0, A2AB59, B4F7F3, D3YZU1, D3ZD05, O35681, O75427, O95382, P22455, P22607, P40748, P55144, P70218, Q06418, Q14160, Q1LZH7, Q2PS20, Q32P44, Q495M9, Q4ACU6, Q4H4B6, Q505F5, Q5F488, Q61851, Q63ZY3, Q6P9K8, Q6TLK4, Q6ZUM4, Q7KRY7, Q80T11, Q80U72, Q8BH60, Q8BX02, Q8N1G4, Q8TE68, Q8VC03, Q8VHK1, Q8VHK2, Q8WXD9, Q8WXE0

Diamond homologs: A1CAL7, A1DEZ0, A2QGW1, A5DR93, A5E1V8, A6QTM4, A6ZR73, A7F1F4, A7TI28, B0Y3Z4, B2ANF9, B2VV00, B3LRN4, B5VHP4, B6HR44, B6QEE0, B8MD74, B8NEM4, B8R1V5, C0S7Q7, C1GJ63, C4JLG3, C4QVD6, C4Y1G1, C5DE38, C5DQY5, C5FH98, C5GIQ8, C5JGE5, C5MB30, C6HFQ7, C7GKW5, C7Z504, C9SA05, D1ZRK4, D4ARB8, D4DA58, D6PVB4, D6PVB5, D8PSG0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

198 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	168
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

5828 predictions. Top by Δscore:

Variant	Effect	Δscore
17:17977728:G:GT	donor_gain	1.0000
17:17977754:TCGGA:T	donor_gain	1.0000
17:17977756:GGA:G	donor_gain	1.0000
17:17977757:GA:G	donor_gain	1.0000
17:17977757:GAG:G	donor_gain	1.0000
17:17977759:G:GG	donor_gain	1.0000
17:17983821:A:AG	acceptor_gain	1.0000
17:17983823:TTCA:T	acceptor_loss	1.0000
17:17983824:TCA:T	acceptor_loss	1.0000
17:17983826:A:AG	acceptor_gain	1.0000
17:17983826:AG:A	acceptor_loss	1.0000
17:17983827:G:GT	acceptor_gain	1.0000
17:17983827:GA:G	acceptor_gain	1.0000
17:17983827:GAC:G	acceptor_gain	1.0000
17:17983827:GACA:G	acceptor_gain	1.0000
17:17983827:GACAT:G	acceptor_gain	1.0000
17:17983940:GCTGG:G	donor_gain	1.0000
17:17983943:GG:G	donor_gain	1.0000
17:17983944:GG:G	donor_gain	1.0000
17:17983945:G:GG	donor_gain	1.0000
17:17983945:G:T	donor_loss	1.0000
17:17983946:TAA:T	donor_loss	1.0000
17:17987927:CCCAG:C	acceptor_loss	1.0000
17:17987928:CCA:C	acceptor_loss	1.0000
17:17987930:A:AG	acceptor_gain	1.0000
17:17987931:G:GA	acceptor_gain	1.0000
17:17987931:GAT:G	acceptor_gain	1.0000
17:17987931:GATC:G	acceptor_gain	1.0000
17:17987931:GATCT:G	acceptor_gain	1.0000
17:17988094:TGAAC:T	donor_gain	1.0000

AlphaMissense

4635 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:55082589:T:A	W401R	0.997
19:55082589:T:C	W401R	0.997
19:55086084:G:C	W514C	0.997
19:55086084:G:T	W514C	0.997
19:55079006:G:C	R22S	0.996
19:55079006:G:T	R22S	0.996
19:55079826:T:A	V85D	0.996
19:55085920:T:C	F489L	0.996
19:55085922:C:A	F489L	0.996
19:55085922:C:G	F489L	0.996
19:55082162:G:C	K324N	0.995
19:55082162:G:T	K324N	0.995
19:55082591:G:C	W401C	0.995
19:55082591:G:T	W401C	0.995
19:55086082:T:A	W514R	0.995
19:55086082:T:C	W514R	0.995
19:55079005:G:C	R22T	0.994
19:55079053:T:A	V38D	0.994
19:55079690:C:G	H40D	0.994
19:55079692:C:A	H40Q	0.994
19:55079692:C:G	H40Q	0.994
19:55079005:G:T	R22M	0.993
19:55079832:T:C	L87P	0.993
19:55080259:T:C	F137S	0.993
19:55079805:T:C	L78P	0.992
19:55082568:T:A	W394R	0.992
19:55082568:T:C	W394R	0.992
19:55085943:G:C	E496D	0.992
19:55085943:G:T	E496D	0.992
19:55079788:G:C	W72C	0.991

dbSNP variants (sampled 300 via entrez): RS1000031194 (19:55077635 C>T), RS1000425571 (19:55080277 G>A), RS1000469249 (19:55082095 G>A), RS1000579466 (19:55076027 G>C), RS1000654353 (19:55084468 C>A,G), RS1000779622 (19:55079210 A>T), RS1001193164 (19:55084279 G>A,C), RS1001762791 (19:55074004 G>T), RS1001776630 (19:55074902 C>A,T), RS1001941260 (19:55085477 T>C), RS1001982734 (19:55079540 G>A,T), RS1002050310 (19:55080547 G>T), RS1002108899 (19:55074005 C>T), RS1002200600 (19:55082818 G>A), RS1002392786 (19:55085280 C>T)

Disease associations

OMIM: gene MIM:614987 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression, affects expression	3
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases methylation	1
tetrabromobisphenol A	decreases expression	1
hydroquinone	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
M-VAC protocol	decreases response to substance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
3-nitrobenzanthrone	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	decreases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression, affects cotreatment	1
Ethinyl Estradiol	decreases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.