ZNRF4 (zinc and ring finger 4)

Gene

• Entrez ID: 148066
• Gene name: Zinc and ring finger 4
• Gene symbol: ZNRF4
• Synonyms (NCBI Gene): RNF204, SPERIZIN, Ssrzf1, spzn
• Chromosome: 19
• Chromosome location: 19p13.3

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	21205830, 32296183
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005783	Component	Endoplasmic reticulum	IDA	28656966
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IDA	28656966
GO:0005789	Component	Endoplasmic reticulum membrane	IDA	21205830
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0006511	Process	Ubiquitin-dependent protein catabolic process	IBA
GO:0006511	Process	Ubiquitin-dependent protein catabolic process	IDA	21205830
GO:0006511	Process	Ubiquitin-dependent protein catabolic process	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0012505	Component	Endomembrane system	IEA
GO:0016020	Component	Membrane	IEA
GO:0016567	Process	Protein ubiquitination	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0031090	Component	Organelle membrane	IEA
GO:0042742	Process	Defense response to bacterium	IDA	16824733
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	IDA	28656966
GO:0045786	Process	Negative regulation of cell cycle	IBA
GO:0046872	Function	Metal ion binding	IEA
GO:0061630	Function	Ubiquitin protein ligase activity	IBA
GO:0061630	Function	Ubiquitin protein ligase activity	IDA	28656966
GO:0061630	Function	Ubiquitin protein ligase activity	IEA
GO:0070431	Process	Nucleotide-binding oligomerization domain containing 2 signaling pathway	IDA	16824733
GO:0070433	Process	Negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	IDA	28656966
GO:1902532	Process	Negative regulation of intracellular signal transduction	IEA

Other IDs

• MIM: 612063
• HGNC: 17726
• e!Ensembl: ENSG00000105428

Protein

• UniProt ID: Q8WWF5
• Protein name: E3 ubiquitin-protein ligase ZNRF4 (EC 2.3.2.27) (Nixin) (RING finger protein 204) (RING-type E3 ubiquitin transferase ZNRF4) (Zinc/RING finger protein 4)
• Protein function: E3 ubiquitin-protein ligase that acts as a negative regulator of NOD2 signaling by mediating ubiquitination and degradation of RIPK2 (PubMed:28656966). Also catalyzes ubiquitination and proteasomal degradation of CANX within the endoplasmic reti
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02225	PA	123 → 222	PA domain	Family
  PF13639	zf-RING_2	307 → 352	Ring finger domain	Domain

• Sequence:

  MPLCRPEHLMPRASRVPVAASLPLSHAVIPTQLPSRPGHRPPGRPRRCPKASCLPPPVGP
  SSTQTAKRVTMGWPRPGRALVAVKALLVLSLLQVPAQAVVRAVLEDNSSSVDFADLPALF
  GVPLAPEGIRGYLMEVKPANACHPIEAPRLGNRSLGAIVLIRRYDCTFDLKVLNAQRAGF
  EAAIVHNVHSDDLVSMTHVYEDLRGQIAIPSVFVSEAASQDLRVILGCNKSAHALLLPDD
  PPCHDLGCHPVLTVSWVLGCTLALVVSAFFVLNHLWLWAQACCSHRRPVKTSTCQKAQVR
  TFTWHNDLCAICLDEYEEGDQLKILPCSHTYHCKCIDPWFSQAPRRSCPVCKQSVAATED
  SFDSTTYSFRDEDPSLPGHRPPIWAIQVQLRSRRLELLGRASPHCHCSTTSLEAEYTTVS
  SAPPEAPGQ

• Sequence length: 429

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LATE-ONSET ALZHEIMER'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METACHRONOUS COLORECTAL ADENOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OCULAR HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RHEUMATIC HEART DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations