ERAS

Summary

ERAS (ES cell expressed Ras, HGNC:5174) is a protein-coding gene on chromosome Xp11.23, encoding GTPase ERas (Q7Z444). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

This gene encodes a constitutively active member of the small GTPase Ras protein family. The encoded protein activates the phosphatidylinositol 3-kinase signal transduction pathway in undifferentiated stem cells, but is not expressed in differentiated cells. This gene may be involved in cancer and chemotherapy resistance.

Source: NCBI Gene 3266 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total — 1 pathogenic
• MANE Select transcript: NM_181532

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5174
Approved symbol	ERAS
Name	ES cell expressed Ras
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187682
Ensembl biotype	protein_coding
OMIM	300437
Entrez	3266

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000338270, ENST00000636362

RefSeq mRNA: 1 — MANE Select: NM_181532 NM_181532

CCDS: CCDS35246

Canonical transcript exons

ENST00000636362 — 2 exons

Exon	Start	End
ENSE00003794218	48829081	48829869
ENSE00003799498	48826513	48826549

Expression profiles

Bgee: expression breadth broad, 95 present calls, max score 94.45.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.48	gold quality
hypothalamus	UBERON:0001898	65.49	gold quality
cerebellar hemisphere	UBERON:0002245	65.26	gold quality
cerebellar cortex	UBERON:0002129	65.25	gold quality
cerebellum	UBERON:0002037	65.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	64.91	gold quality
temporal lobe	UBERON:0001871	58.74	gold quality
amygdala	UBERON:0001876	58.72	gold quality
anterior cingulate cortex	UBERON:0009835	57.17	gold quality
nucleus accumbens	UBERON:0001882	57.16	gold quality
caudate nucleus	UBERON:0001873	57.12	gold quality
substantia nigra	UBERON:0002038	56.92	gold quality
putamen	UBERON:0001874	56.79	gold quality
right frontal lobe	UBERON:0002810	56.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	56.32	gold quality
brain	UBERON:0000955	55.58	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	55.06	gold quality
stromal cell of endometrium	CL:0002255	54.97	gold quality
pituitary gland	UBERON:0000007	54.78	gold quality
adenohypophysis	UBERON:0002196	54.56	gold quality
Ammon’s horn	UBERON:0001954	54.55	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	53.70	gold quality
lower esophagus mucosa	UBERON:0035834	53.21	gold quality
primary visual cortex	UBERON:0002436	53.06	gold quality
granulocyte	CL:0000094	52.42	gold quality
superior frontal gyrus	UBERON:0002661	51.07	gold quality
cerebral cortex	UBERON:0000956	50.87	gold quality
right lobe of liver	UBERON:0001114	50.17	gold quality
mucosa of transverse colon	UBERON:0004991	49.99	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.46

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 16)

• transforming oncogene ERas is important in the tumour-like growth properties of embryonic stem cells (PMID:12774123)
• Studies on ERas gene expression. (PMID:16081664)
• rasH2 may have a role in susceptibility to chemically-induced tongue and esophageal neoplasms (PMID:18174262)
• High ERas is associated with the tumorigenic process of gastric carcinomas. (PMID:19528480)
• Loss of methylation in the promoter of ERas might be one of mechanisms responsible for the re-expression of an embryonic oncogene in gastric cancer. (PMID:19787253)
• These data suggest that ERas is activated in a significant population of gastric cancer, where it may play a crucial role in gastric cancer cell survival and metastases to liver via down-regulation of E-cadherin. (PMID:20566745)
• ERas/PI3K pathway may provide resistance to chemotherapy and promote transforming activity in neuroblastoma. (PMID:20811723)
• ERas may be a potential biomarker for gastric cancer, but advanced studies are wanted. (PMID:21151392)
• Data indicate that expression of ERAS, LHX1, and CCRK is increased in aggressive subgroups of medulloblastomas. (PMID:22875024)
• After knocking down the ERas gene by siRNA, we observed that there was a significant decrease in proliferation, metastasis as well as clonality in gastric carcinoma. (PMID:23612786)
• Expression of ERAS in human melanoma cell lines conferred resistance to PLX4720 and induced hyperphosphorylation of AKT. (PMID:25624498)
• N-terminal extension of E-RAS is important for E-RAS signaling activity. (PMID:25940089)
• ERAS may serve as a novel clinical biomarker for PI3K/AKT pathway hyperactivation and HER2-targeted therapy resistance in breast cancer. (PMID:29326437)
• Epithelial-mesenchymal transition suppresses ERas to activate autophagy in retinal pigment epithelial cells in proliferative vitreoretinopathy. (PMID:32432726)
• ERas regulates cell proliferation and epithelial-mesenchymal transition by affecting Erk/Akt signaling pathway in pancreatic cancer. (PMID:32700262)
• Physical Interaction between Embryonic Stem Cell-Expressed Ras (ERas) and Arginase-1 in Quiescent Hepatic Stellate Cells. (PMID:35159317)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Eras	ENSMUSG00000031160
rattus_norvegicus	Eras	ENSRNOG00000042470

Paralogs (35): RALA (ENSG00000006451), REM1 (ENSG00000088320), RASL10A (ENSG00000100276), RASD2 (ENSG00000100302), RASL12 (ENSG00000103710), RHEB (ENSG00000106615), RASD1 (ENSG00000108551), RERGL (ENSG00000111404), RAP1A (ENSG00000116473), RASL11A (ENSG00000122035), RAP2C (ENSG00000123728), RAP2A (ENSG00000125249), RRAS (ENSG00000126458), RAP1B (ENSG00000127314), RASL11B (ENSG00000128045), KRAS (ENSG00000133703), RRAS2 (ENSG00000133818), RERG (ENSG00000134533), REM2 (ENSG00000139890), RIT1 (ENSG00000143622), RALB (ENSG00000144118), RIT2 (ENSG00000152214), MRAS (ENSG00000158186), DIRAS3 (ENSG00000162595), GEM (ENSG00000164949), DIRAS2 (ENSG00000165023), RRAD (ENSG00000166592), RHEBL1 (ENSG00000167550), NKIRAS2 (ENSG00000168256), HRAS (ENSG00000174775), DIRAS1 (ENSG00000176490), RAP2B (ENSG00000181467), NKIRAS1 (ENSG00000197885), NRAS (ENSG00000213281), RASL10B (ENSG00000270885)

Protein

Protein identifiers

GTPase ERas — Q7Z444 (reviewed: Q7Z444)

Alternative names: Embryonic stem cell-expressed Ras

All UniProt accessions (1): Q7Z444

UniProt curated annotations — full annotation on UniProt →

Function. Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Plays an important role in the tumor-like growth properties of embryonic stem cells.

Subunit / interactions. Interacts with PIK3CD.

Subcellular location. Cell membrane.

Activity regulation. Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).

Similarity. Belongs to the small GTPase superfamily. Ras family.

RefSeq proteins (1): NP_853510* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR020849	Small_GTPase_Ras-type	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (10 total): binding site 3, lipid moiety-binding region 3, chain 1, propeptide 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z444-F1	79.71	0.56

Functional residue map

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

Ligand- & substrate-binding residues (3): 48–55; 95–99; 151–154

Post-translational modifications (4): 230, 226, 228, 230

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 38 (showing top): THEODOROU_MAMMARY_TUMORIGENESIS, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, chrXp11, GOBP_POSITIVE_REGULATION_OF_CELL_POPULATION_PROLIFERATION, DELACROIX_RAR_BOUND_ES, ESC_J1_UP_EARLY.V1_DN, ESC_J1_UP_LATE.V1_DN, ESC_V6.5_UP_LATE.V1_DN, ZNF92_TARGET_GENES, GSE16522_MEMORY_VS_NAIVE_ANTI_CD3CD28_STIM_CD8_TCELL_DN, GSE16522_ANTI_CD3CD28_STIM_VS_UNSTIM_NAIVE_CD8_TCELL_UP, GSE17721_CTRL_VS_PAM3CSK4_24H_BMDC_DN

GO Biological Process (2): Ras protein signal transduction (GO:0007265), signal transduction (GO:0007165)

GO Molecular Function (7): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
guanyl ribonucleotide binding	2
small GTPase-mediated signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2013 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERAS	UTF1	Q5T230	581
ERAS	NANOG	Q9H9S0	545
ERAS	ZNF296	Q8WUU4	543
ERAS	MAZ	P56270	509
ERAS	EPM2A	O95278	482
ERAS	SOX2	P48431	479
ERAS	CRIPTO	P13385	478
ERAS	PDGFRB	P09619	467
ERAS	OPTN	Q96CV9	464
ERAS	KLF4	P78338	456
ERAS	ZFP42	Q96MM3	446
ERAS	POU5F1	P31359	442
ERAS	RALGDS	Q12967	439
ERAS	DPPA5	A6NC42	437
ERAS	FBXO15	Q8NCQ5	436

IntAct

7 interactions, top by confidence:

A	B	Type	Score
MYO15B	ERAS	psi-mi:“MI:0915”(physical association)	0.560
TLX3	ERAS	psi-mi:“MI:0915”(physical association)	0.560
TLX3	ERAS	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): PIK3CG (Affinity Capture-Western), RAF1 (Affinity Capture-Western), ERAS (Two-hybrid), MYO15B (Two-hybrid)

ESM2 similar proteins: A2YEQ6, O35963, O74536, O95661, O95755, P25378, P35283, P35284, P51156, P52198, P97950, Q00246, Q02723, Q06AU4, Q08AT1, Q08E00, Q09178, Q14088, Q20365, Q29RR0, Q3SXC5, Q3UHC2, Q504M8, Q53S08, Q5H913, Q5JT25, Q5R615, Q5U1Y1, Q5ZHV1, Q62120, Q62689, Q64008, Q69XM7, Q6IQ22, Q75R65, Q7SZ59, Q7TN89, Q7Z444, Q8C0V7, Q8CAM5

Diamond homologs: A1DZY4, A6QP66, A8NU18, G4MZY8, O35929, O35963, O42277, O42785, O76742, O88667, P01116, P01117, P01119, P01120, P03967, P05774, P08644, P08647, P0CQ42, P0CQ43, P15064, P22278, P22279, P22280, P25378, P28775, P32254, P32883, P34143, P35288, P55043, P62070, P62071, P79800, P87018, P97950, Q01387, Q05058, Q08AT1, Q08E00

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	16
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1808658	GRCh37/hg19 Xp11.4-11.22(chrX:39525562-52832596)x3	Pathogenic

SpliceAI

156 predictions. Top by Δscore:

Variant	Effect	Δscore
X:48829079:A:AG	acceptor_gain	0.7200
X:48829080:G:GG	acceptor_gain	0.7200
X:48828960:A:AG	donor_gain	0.6400
X:48828911:G:GT	donor_gain	0.6300
X:48828883:G:T	donor_gain	0.6200
X:48829080:GA:G	acceptor_gain	0.6000
X:48828959:GATC:G	donor_gain	0.5800
X:48829080:GAGCC:G	acceptor_gain	0.5600
X:48829073:A:AG	acceptor_gain	0.5500
X:48829360:G:GT	donor_gain	0.5300
X:48829078:CAG:C	acceptor_gain	0.4800
X:48829079:AGA:A	acceptor_gain	0.4800
X:48829080:GAG:G	acceptor_gain	0.4800
X:48829364:G:GT	donor_gain	0.4800
X:48829987:G:GT	donor_gain	0.4800
X:48829075:TTGCA:T	acceptor_loss	0.4700
X:48829076:TGCA:T	acceptor_loss	0.4700
X:48829077:GCA:G	acceptor_loss	0.4700
X:48829078:CAGA:C	acceptor_loss	0.4700
X:48829079:A:C	acceptor_loss	0.4700
X:48829080:G:GT	acceptor_loss	0.4700
X:48829223:G:T	donor_gain	0.4700
X:48829076:TGCAG:T	acceptor_gain	0.4500
X:48829074:C:G	acceptor_gain	0.4300
X:48829363:G:GT	donor_gain	0.4300
X:48828899:G:T	donor_gain	0.4200
X:48828961:T:G	donor_gain	0.4100
X:48829417:G:T	donor_gain	0.4100
X:48829080:GAGC:G	acceptor_gain	0.4000
X:48829442:GACC:G	donor_gain	0.4000

AlphaMissense

1518 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:48829319:T:C	F66L	0.995
X:48829321:C:A	F66L	0.995
X:48829321:C:G	F66L	0.995
X:48829481:T:C	F120L	0.991
X:48829483:C:A	F120L	0.991
X:48829483:C:G	F120L	0.991
X:48829579:G:C	K152N	0.988
X:48829579:G:T	K152N	0.988
X:48829697:T:C	F192L	0.988
X:48829699:T:A	F192L	0.988
X:48829699:T:G	F192L	0.988
X:48829285:G:C	K54N	0.986
X:48829285:G:T	K54N	0.986
X:48829284:A:T	K54M	0.985
X:48829577:A:G	K152E	0.985
X:48829286:A:C	S55R	0.982
X:48829288:T:A	S55R	0.982
X:48829288:T:G	S55R	0.982
X:48829320:T:G	F66C	0.982
X:48829407:A:C	D95A	0.982
X:48829576:C:A	N151K	0.982
X:48829576:C:G	N151K	0.982
X:48829407:A:T	D95V	0.980
X:48829281:G:T	G53V	0.979
X:48829482:T:C	F120S	0.979
X:48829283:A:G	K54E	0.976
X:48829408:C:A	D95E	0.976
X:48829408:C:G	D95E	0.976
X:48829287:G:T	S55I	0.975
X:48829283:A:C	K54Q	0.974

dbSNP variants (sampled 300 via entrez): RS1000010574 (X:48827180 C>A), RS1002558535 (X:48824625 G>A,T), RS1003481965 (X:48826803 G>A), RS1004120579 (X:48826450 T>C), RS1005125974 (X:48828539 A>G), RS1007966229 (X:48825575 C>G,T), RS1008569024 (X:48827223 G>T), RS1009098516 (X:48827851 A>G), RS1012149195 (X:48824715 C>T), RS1012760472 (X:48826854 G>A), RS1013287419 (X:48827120 C>A), RS1013874251 (X:48829723 G>A), RS1014176841 (X:48829168 C>T), RS1015086008 (X:48828024 T>G), RS1015161900 (X:48828566 C>A,T)

Disease associations

OMIM: gene MIM:300437 | disease phenotypes: MIM:300896

GenCC curated gene-disease

Mondo (1): SLC35A2-congenital disorder of glycosylation (MONDO:0010478)

Orphanet (1): SLC35A2-CDG (Orphanet:356961)

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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aminomethylphosphonic acid (AMPA)	decreases expression	1
CGP 52608	affects binding, increases reaction	1
licochalcone B	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Valproic Acid	increases methylation	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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