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FLASH GENE

Symbol

RNF43

contributors: mct/pgu - updated : 20-04-2022

HGNC name	ring finger protein 43
HGNC id	18505

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	SSPCS sessile serrated polyposis cancer syndrome
Location	17q22      Physical location : 56.431.039 - 56.494.931
Synonym symbol(s)	RNF124, FLJ20315, DKFZp781H0392, URCC, DKFZp781H02126, FLJ77466, FLJ99338, MGC125630, SSPCS
EC.number	2.3.2.27

DNA

TYPE	functioning gene
STRUCTURE	65.03 kb     10 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_017763 10 - 4573 NP_060233 - 783 - 2021 34390652 NM_001305544 10 - 5543 NP_001292473 - 783 - 2021 34390652 NM_001305545 9 - 4625 NP_001292474 - 656 - 2021 34390652

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine         Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Digestive enterocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	low levels of expression in fetal kidney and lung

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	RING zinc finger motif
	two C-terminal nuclear localization

conjugated

MetalloP

HOMOLOGY

intraspecies

homolog to ZNRF3

Homologene

FAMILY

RING zinc finger ptoein family

CATEGORY

transcription factor , tumor suppressor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nucleus
	intracellular,nuclear envelope
text	resident protein of the ER and, at least partially, the nuclear membrane

basic FUNCTION	acts as a ubiquitin ligase with autoubiquitylating activity
	oncogenic RING finger protein
	promotes cell growth
	likely plays a crucial role for regulating wild-type TP53-associated apoptotic cell death
	RNF43 and ZNRF3 reduce Wnt signals by selectively ubiquitinating frizzled receptors, thereby targeting these Wnt receptors for degradation
	is a regulator of the DNA damage response and associated nonsense variants in this gene with a high risk of developing sessile serrated adenomas (SSAs)
	molecular role of RNF43 in canonical and noncanonical Wnt signaling
	plays important roles in tumor formation progression, and might act as a tumor suppressor in gastric carcinoma
	E3 ubiquitin ligase originally found in stem cells, and inhibiting the Wnt pathway downstream of oncogenic mutations that activate the pathway
	is a tumor suppressor, by exerting a predominant negative feedback mechanism in the Wnt/CTNNB1 signaling pathway
	RNF43 plays a tumour suppressive role in gastric and colorectal cancer cells and the loss of its function alters gastric tissue homeostasis
	novel function for RNF43 in the stomach as a regulator of DNA damage response (DDR)
	expressed in response to injury and is essential to promote remyelination
	important but distinct functions of RNF43/ZNRF3 in regulating taste versus lingual epithelial tissue homeostasis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	Zn2+

protein	AKAP8L, a chromatin-associated protein interfacing the nuclear envelope, is an RNF43-interacting protein
	SFPQ is a binding partner
	binds to NEDD-4-like ubiquitin-protein ligase-1 (HECW1), which enhances pro-apoptotic activity by TP53
	associated with TP53-mediated apoptosis in collaboration with HECW1 in colorectal carcinogenesis
	RNF43 binds to NEDD-4-like ubiquitin-protein ligase-1 (HECW1), which enhances pro-apoptotic activity by TP53
	membrane-located tumourigenesis inhibitors RNF43 and ZNRF3 mediating the degradation of the Wnt receptor components FZDS and LRP5/6
	LGR5 does not contact RNF43 but increases the affinity of RSPO1 to RNF43, supporting LGR5 as an engagement receptor and RNF43 as an effector receptor
	DVL1 is a dual function adaptor to recruit negative regulators ZNRF3/RNF43 to Wnt receptors to ensure proper control of pathway activity
	ZNRF3/RNF43--a direct linkage of extracellular recognition and E3 ligase activity to modulate cell surface signalling
	RNF43 physically interacted with T cell factor 4 (TCF4) in cells and tethered TCF4 to the nuclear membrane, thus silencing TCF4 transcriptional activity even in the presence of constitutively active mutants of CTNNB1
	DDB2 is critical for CTNNB1-mediated activation of RNF43, which restricts WNT signaling by removing WNT receptors from the cell surface
	RSPO2, serves as a direct antagonistic ligand to RNF43 and ZNRF3, which together constitute a master switch that governs limb specification
	ZNRF3 and RNF43 cooperate to safeguard liver homeostasis by spatially and temporally restricting WNT/CTNNB activity, balancing metabolic function and hepatocyte proliferation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

SSPCS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in colorectal cancer ( tumoral somatic mutation       frequent in gastric cancer5) tumoral     --low   increases membrane expression of frizzled receptor in pancreatic ductal adenocarcinoma tumoral     --low   in clear cell renal cell carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	may be a novel diagnostic marker for colorectal cancer
	might be a potential indicator for the clinical assessment of gastric cancer prognosis
	presence of RNF43 mutations could be used as a predictive biomarker for patient selection supporting the clinical development of Wnt inhibitors in subtypes of cancer
	RNF43 is a possible biomarker for therapy selection in gastric cancer
Therapy target
	System Type Disorder Pubmed cancer     harnessing phospho-regulation of RNF43 might be a potential therapeutic strategy for tumours with RNF43 mutations

ANIMAL & CELL MODELS