ZNRF1

zinc and ring finger 1, the group of Ring finger proteins

Basic information

Region (hg38): 16:74999024-75110994

Links

ENSG00000186187 ∙ NCBI:84937 ∙ OMIM:612060 ∙ HGNC:18452 ∙ Uniprot:Q8ND25 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZNRF1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZNRF1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			15	1		16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					5	5
Total	0	0	15	2	5

Variants in ZNRF1

This is a list of pathogenic ClinVar variants found in the ZNRF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-74999399-C-T			Benign (Nov 13, 2018)
16-74999754-C-T		not specified	Uncertain significance (May 22, 2023)
16-74999786-A-G		not specified	Likely benign (Apr 07, 2023)
16-74999792-G-A		not specified	Uncertain significance (Jun 11, 2024)
16-74999801-A-G		not specified	Uncertain significance (Jun 10, 2024)
16-74999818-C-T		not specified	Likely benign (Jul 07, 2024)
16-74999820-C-G		not specified	Uncertain significance (Jun 22, 2021)
16-74999831-G-A		not specified	Uncertain significance (Dec 20, 2023)
16-74999851-C-G		not specified	Uncertain significance (Jun 18, 2021)
16-74999870-G-T		not specified	Uncertain significance (Jan 01, 2025)
16-74999933-G-C		not specified	Uncertain significance (Jun 24, 2022)
16-74999961-A-G		not specified	Uncertain significance (Feb 27, 2024)
16-74999973-A-G		not specified	Uncertain significance (May 04, 2022)
16-74999994-G-C		not specified	Uncertain significance (Feb 09, 2025)
16-75000050-G-C		not specified	Uncertain significance (Apr 24, 2024)
16-75000084-G-C		not specified	Uncertain significance (Dec 13, 2022)
16-75000235-A-G			Benign (Jun 19, 2021)
16-75000316-C-A			Benign (Jun 19, 2021)
16-75093363-C-T			Benign (Jun 19, 2021)
16-75093576-C-G		not specified	Uncertain significance (Feb 13, 2024)
16-75093578-A-C		not specified	Uncertain significance (Aug 01, 2023)
16-75104805-C-T		not specified	Uncertain significance (Dec 13, 2023)
16-75105029-A-G			Benign (Nov 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZNRF1	protein_coding	protein_coding	ENST00000335325	4	111965

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.906	0.0934	103722	0	3	103725	0.0000145

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.924	79	106	0.747	0.00000544	1442
Missense in Polyphen		3	18.828	0.15933		355
Synonymous	0.459	43	47.0	0.915	0.00000273	471
Loss of Function	2.56	0	7.62	0.00	3.28e-7	92

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000668	0.0000330
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase that mediates the ubiquitination of AKT1 and GLUL, thereby playing a role in neuron cells differentiation. Plays a role in the establishment and maintenance of neuronal transmission and plasticity. Regulates Schwann cells differentiation by mediating ubiquitination of GLUL. Promotes neurodegeneration by mediating 'Lys-48'-linked polyubiquitination and subsequent degradation of AKT1 in axons: degradation of AKT1 prevents AKT1-mediated phosphorylation of GSK3B, leading to GSK3B activation and phosphorylation of DPYSL2/CRMP2 followed by destabilization of microtubule assembly in axons (Probable). {ECO:0000305|PubMed:14561866}.
• Pathway: Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.111

Haploinsufficiency Scores

• pHI: 0.192
• hipred: N
• hipred_score: 0.401
• ghis: 0.497

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.601

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Znrf1

Gene ontology

• Biological process: protein polyubiquitination;proteasome-mediated ubiquitin-dependent protein catabolic process;protein K48-linked ubiquitination
• Cellular component: lysosome;endosome;cytosol;membrane;cell junction;synaptic vesicle membrane
• Molecular function: ubiquitin-protein transferase activity;protein binding;metal ion binding;ubiquitin protein ligase activity