ZNRF2
protein-codingzinc and ring finger 2, the group of MicroRNA protein coding host genes|Ring finger proteins
Gene summary
Enables ubiquitin protein ligase activity. Involved in positive regulation of autophagosome-lysosome fusion. Located in cytoplasmic vesicle membrane and plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~83.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ZNRF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_147128.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 53 | 53 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 55 | 1 | 0 | 56 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_667339.1 | 4 | MANE Select | |
| Ensembl | ENSP00000323879.4 | 4 | MANE Select | |
| Ensembl | ENSP00000607845.1 | 3 | Standard | |
| Ensembl | ENSP00000607845.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Immune System
- Adaptive Immune System
- Antigen processing: Ubiquitination & Proteasome degradation
- Class I MHC mediated antigen processing & presentation
Biological Process
- protein polyubiquitination
Molecular Function
- ubiquitin-protein transferase activity
- metal ion binding
- ubiquitin protein ligase activity
Cellular Component
- cytoplasm
- lysosomal membrane
- cytosol
- plasma membrane
- endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000323037
- Coding exons
- 4
- Length
- 128196
- Individuals with no LoFs
- 125710
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125714
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.07 | 42 | 66.5 | 0.632 | 0.00000309 | 1512 |
| Missense (PolyPhen) | 9 | 25.774 | 0.34919 | 393 | ||
| Synonymous | -1.19 | 32 | 24.5 | 1.31 | 0.00000109 | 510 |
| Loss of Function | 1.66 | 3 | 8.10 | 0.370 | 5.38e-7 | 101 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May play a role in the establishment and maintenance of neuronal transmission and plasticity via its ubiquitin ligase activity. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. {ECO:0000269|PubMed:14561866}.;
Recessive Scores
- pRec
- 0.114
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.542
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |