KRAS KRAS proto-oncogene, GTPase [Homo sapiens (human)] - Gene

Summary

Official Symbol: KRASprovided by HGNC
Official Full Name: KRAS proto-oncogene, GTPaseprovided by HGNC
Primary source: HGNC:HGNC:6407
See related: Ensembl:ENSG00000133703 MIM:190070; AllianceGenome:HGNC:6407
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NS; NS3; OES; CFC2; RALD; K-Ras; KRAS1; KRAS2; RASK2; KI-RAS; C-K-RAS; K-RAS2A; K-RAS2B; K-RAS4A; K-RAS4B; K-Ras 2; 'C-K-RAS; c-Ki-ras; c-Ki-ras2
Summary: This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in colon (RPKM 7.8), brain (RPKM 7.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12p12.1

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (25205246..25250929, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (25076496..25122152, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (25358180..25403863, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The prominent pervasive oncogenic role and tissue specific permissiveness of RAS gene mutations.
Title: The prominent pervasive oncogenic role and tissue specific permissiveness of RAS gene mutations.
PARP-1 selectively impairs KRAS-driven phenotypic and molecular features in intrahepatic cholangiocarcinoma.
Title: PARP-1 selectively impairs KRAS-driven phenotypic and molecular features in intrahepatic cholangiocarcinoma.
Oncogenic KRAS drives immunosuppression of colorectal cancer by impairing DDX60-mediated dsRNA accumulation and viral mimicry.
Title: Oncogenic KRAS drives immunosuppression of colorectal cancer by impairing DDX60-mediated dsRNA accumulation and viral mimicry.
Crosstalk between FTH1 and PYCR1 dysregulates proline metabolism and mediates cell growth in KRAS-mutant pancreatic cancer cells.
Title: Crosstalk between FTH1 and PYCR1 dysregulates proline metabolism and mediates cell growth in KRAS-mutant pancreatic cancer cells.
The TRIM4 E3 ubiquitin ligase degrades TPL2 and is modulated by oncogenic KRAS.
Title: The TRIM4 E3 ubiquitin ligase degrades TPL2 and is modulated by oncogenic KRAS.
Prevalence of KRAS amplification in patients with metastatic cancer: Real-world next-generation sequencing analysis.
Title: Prevalence of KRAS amplification in patients with metastatic cancer: Real-world next-generation sequencing analysis.
Oncogenic KRAS Induces Arginine Auxotrophy and Confers a Therapeutic Vulnerability to SLC7A1 Inhibition in Non-Small Cell Lung Cancer.
Title: Oncogenic KRAS Induces Arginine Auxotrophy and Confers a Therapeutic Vulnerability to SLC7A1 Inhibition in Non-Small Cell Lung Cancer.
Combined KRAS and TP53 mutation in patients with colorectal cancer enhance chemoresistance to promote postoperative recurrence and metastasis.
Title: Combined KRAS and TP53 mutation in patients with colorectal cancer enhance chemoresistance to promote postoperative recurrence and metastasis.
Association of KRAS Mutation and Gene Pathways in Colorectal Carcinoma: A Transcriptome- and Methylome-Wide Study and Potential Implications for Therapy.
Title: Association of KRAS Mutation and Gene Pathways in Colorectal Carcinoma: A Transcriptome- and Methylome-Wide Study and Potential Implications for Therapy.
Conformations of KRAS4B Affected by Its Partner Binding and G12C Mutation: Insights from GaMD Trajectory-Image Transformation-Based Deep Learning.
Title: Conformations of KRAS4B Affected by Its Partner Binding and G12C Mutation: Insights from GaMD Trajectory-Image Transformation-Based Deep Learning.

Submit: New GeneRIF Correction See all GeneRIFs (2696)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Acute myeloid leukemia MedGen: C0023467 OMIM: 601626 GeneReviews: CEBPA-Associated Familial Acute Myeloid Leukemia (AML), ETV6 Thrombocytopenia and Predisposition to Leukemia, RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancies, DDX41-Associated Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia	not available
Autoimmune lymphoproliferative syndrome type 4 MedGen: C2674723 OMIM: 614470 GeneReviews: Not available	not available
Carcinoma of pancreas MedGen: C0235974 GeneReviews: Not available	not available
Cardiofaciocutaneous syndrome 2 MedGen: C3809005 OMIM: 615278 GeneReviews: Cardiofaciocutaneous Syndrome	not available
Cerebral arteriovenous malformation MedGen: C0917804 OMIM: 108010 GeneReviews: Not available	not available
Cetuximab response MedGen: CN077967 GeneReviews: Not available	not available
Familial cancer of breast MedGen: C0346153 OMIM: 114480 GeneReviews: BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer	not available
Gastric cancer MedGen: C0024623 OMIM: 613659 GeneReviews: Not available	not available
Linear nevus sebaceous syndrome MedGen: C4552097 OMIM: 163200 GeneReviews: Not available	not available
Lung cancer MedGen: C0242379 OMIM: 211980 GeneReviews: Not available	not available
Malignant tumor of urinary bladder MedGen: C0005684 OMIM: 109800 GeneReviews: Not available	not available
Noonan syndrome 3 MedGen: C1860991 OMIM: 609942 GeneReviews: Noonan Syndrome	not available
Panitumumab response MedGen: CN077999 GeneReviews: Not available	not available
Toriello-Lacassie-Droste syndrome MedGen: C1838329 OMIM: 600268 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of Kirsten rat sarcoma viral oncogene homolog (KRAS) in human B cells	PubMed
Envelope surface glycoprotein gp160, precursor	env	Pretreatment of cells with HIV-1 gp160 results in marked inhibition of tyrosine phosphorylation of p59(fyn), PLC-gamma1, ras activation, and TNF-alpha secretion in anti-CD3 mAb activated CD4+ T cells	PubMed
	env	HIV-1 gp160 alone or CD4/gp160 cross-linking induces tyrosine phosphorylation of intracellular substrates p59fyn, zap 70, and p95vav and also leads to ras activation	PubMed
Tat	tat	Treatment with HIV-1 Tat and cocaine activates Ras/Erk pathway in human pulmonary artery endothelial cells	PubMed
	tat	NOX4-mediated K-Ras activation on the ER endomembrane results in Tat-induced unfolded-protein response	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:374084 (e-PCR)
- UniSTS:156940

GDB:177517 (e-PCR)
- UniSTS:154905

PMC130963P3 (e-PCR)
- UniSTS:270618

PMC17763P1 (e-PCR)
- UniSTS:271647

SHGC-33831 (e-PCR)
- UniSTS:32288

GDB:177536 (e-PCR)
- UniSTS:154916

GDB:177540 (e-PCR)
- UniSTS:154919

GDB:177541 (e-PCR)
- UniSTS:154920

GDB:177572 (e-PCR)
- UniSTS:154931

GDB:178532 (e-PCR)
- UniSTS:155016

GDB:181550 (e-PCR)
- UniSTS:155276

GDB:625317 (e-PCR)
- UniSTS:158364

GDB:581120 (e-PCR)
- UniSTS:157854

GDB:384734 (e-PCR)
- UniSTS:157091

RH65999 (e-PCR)
- UniSTS:85156

G44377 (e-PCR)
- UniSTS:95161

G62075 (e-PCR)
- UniSTS:139200

KRAS2_909 (e-PCR)
- UniSTS:277443

KRAS2_V192 (e-PCR)
- UniSTS:277443

Bda12d09 (e-PCR)
- UniSTS:86214

GDB:182132 (e-PCR)
- UniSTS:155355

RH80031 (e-PCR)
- UniSTS:91103

GDB:177365 (e-PCR)
- UniSTS:154863

SHGC-64023 (e-PCR)
- UniSTS:44527

GDB:182546 (e-PCR)
- UniSTS:155389

GDB:182559 (e-PCR)
- UniSTS:155390

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G protein activity	IEA Inferred from Electronic Annotation more info
enables GDP binding	IBA Inferred from Biological aspect of Ancestor more info
enables GTP binding	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables GTPase activity	TAS Traceable Author Statement more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed
enables protein-membrane adaptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in MAPK cascade	TAS Traceable Author Statement more info
involved_in Rac protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in Ras protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in actin cytoskeleton organization	IEA Inferred from Electronic Annotation more info
involved_in epithelial tube branching involved in lung morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in forebrain astrocyte development	IEA Inferred from Electronic Annotation more info
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in glial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in homeostasis of number of cells within a tissue	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of epithelial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of Rac protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of long-term neuronal synaptic plasticity	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic transmission, GABAergic	IEA Inferred from Electronic Annotation more info
involved_in skeletal muscle cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in striated muscle cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in type I pneumocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in visual learning	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi membrane	TAS Traceable Author Statement more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in focal adhesion	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
located_in mitochondrial outer membrane	TAS Traceable Author Statement more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: GTPase KRas

Names: K-ras p21 protein; KRAS-ENOPH fusion; Kirsten rat sarcoma viral oncogene homolog; Kirsten rat sarcoma viral proto-oncogene; Kras-Enoph1 fusion protein; PR310 c-K-ras oncogene; c-Kirsten-ras protein; cellular c-Ki-ras2 proto-oncogene; cellular transforming proto-oncogene; oncogene KRAS2; proto-oncogene GTPase; transforming protein p21; v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog

NP_001356715.1

EC 3.6.5.2

NP_001356716.1

EC 3.6.5.2

NP_004976.2

EC 3.6.5.2

NP_203524.1

EC 3.6.5.2

XP_047284782.1

EC 3.6.5.2

XP_054227990.1

EC 3.6.5.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007524.2 RefSeqGene

Range

5075..50758

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_344

mRNA and Protein(s)

NM_001369786.1 → NP_001356715.1 GTPase KRas isoform a

Status: REVIEWED

Source sequence(s)

AC087239, AC092794, KF459678

Consensus CDS

CCDS8703.1

UniProtKB/Swiss-Prot

A8K8Z5, B0LPF9, P01116, P01118, Q96D10

UniProtKB/TrEMBL

L7RSL8

Conserved Domains (1) summary

cd04138
Location:3 → 164

H_N_K_Ras_like; Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B
NM_001369787.1 → NP_001356716.1 GTPase KRas isoform b

Status: REVIEWED

Source sequence(s)

AC087239, AC092794

Consensus CDS

CCDS8702.1

UniProtKB/TrEMBL

A0A3G1LBH1

Related

ENSP00000508921.1, ENST00000685328.1

Conserved Domains (1) summary

cd04138
Location:3 → 164

H_N_K_Ras_like; Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B
NM_004985.5 → NP_004976.2 GTPase KRas isoform b

See identical proteins and their annotated locations for NP_004976.2

Status: REVIEWED

Description

Transcript Variant: This variant (b) is composed of five exons and lacks exon 4a which the longer transcript variant (a) includes. This predominant variant (b) has a cds that terminates in exon 4b and encodes isoform b.

Source sequence(s)

AC092794, AK292510, M54968

Consensus CDS

CCDS8702.1

UniProtKB/TrEMBL

A0A3G1LBH1

Related

ENSP00000308495.3, ENST00000311936.8

Conserved Domains (1) summary

cd04138
Location:3 → 164

H_N_K_Ras_like; Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B
NM_033360.4 → NP_203524.1 GTPase KRas isoform a

See identical proteins and their annotated locations for NP_203524.1

Status: REVIEWED

Description

Transcript Variant: This variant (a) is composed of six exons, including exon 4a, which the shorter transcript variant (b) lacks. This rare variant (a) has a cds that terminates in exon 4a and encodes a unique C-terminus, compared to isoform a.

Source sequence(s)

AC087239, AC092794, KF459678

Consensus CDS

CCDS8703.1

UniProtKB/Swiss-Prot

A8K8Z5, B0LPF9, P01116, P01118, Q96D10

UniProtKB/TrEMBL

L7RSL8

Related

ENSP00000256078.5, ENST00000256078.10

Conserved Domains (1) summary

cd04138
Location:3 → 164

H_N_K_Ras_like; Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B