ZNRF3

zinc and ring finger 3, the group of Ring finger proteins

Basic information

Region (hg38): 22:28883572-29057488

Links

ENSG00000183579 ∙ NCBI:84133 ∙ OMIM:612062 ∙ HGNC:18126 ∙ Uniprot:Q9ULT6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZNRF3 gene.

• not_specified (114 variants)
• not_provided (10 variants)
• ZNRF3-related_disorder (10 variants)
• ZNRF3-associated_neurodevelopmental_disorder (1 variants)
• Male_pseudohermaphroditism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZNRF3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001206998.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	2	5
missense	7	1	111	7		126
nonsense			3			3
start loss						0
frameshift			2			2
splice donor/acceptor (+/-2bp)			2			2
Total	7	1	118	10	2

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZNRF3	protein_coding	protein_coding	ENST00000544604	9	173896

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.989	0.0112	124748	0	47	124795	0.000188

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.975	482	546	0.883	0.0000357	5977
Missense in Polyphen		123	192.39	0.63933		2060
Synonymous	-1.97	280	241	1.16	0.0000170	1990
Loss of Function	4.51	4	31.2	0.128	0.00000163	357

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000289	0.000159
Middle Eastern	0.00	0.00
South Asian	0.00159	0.000883
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components Frizzled and LRP6. Acts on both canonical and non- canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone. {ECO:0000269|PubMed:22575959}.
• Pathway: Signaling by WNT;Signal Transduction;Regulation of FZD by ubiquitination;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.134
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.49

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.662
• ghis: 0.509

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.764

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Znrf3
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; vision/eye phenotype; endocrine/exocrine gland phenotype; cellular phenotype

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;Wnt signaling pathway;protein ubiquitination;Wnt receptor catabolic process;limb development;stem cell proliferation;negative regulation of canonical Wnt signaling pathway;negative regulation of non-canonical Wnt signaling pathway;regulation of Wnt signaling pathway, planar cell polarity pathway
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: ubiquitin-protein transferase activity;frizzled binding;protein binding;metal ion binding;ubiquitin protein ligase activity