ZFP91
protein-codingZFP91 zinc finger protein, atypical E3 ubiquitin ligase, the group of Zinc fingers C2H2-type
Gene summary
The protein encoded by this gene is a member of the zinc finger family of proteins. The gene product contains C2H2-type domains, which are the classical zinc finger domains found in numerous nucleic acid-binding proteins. This protein functions as a regulator of the non-canonical NF-kappaB pathway in lymphotoxin-beta receptor signaling. Alternative splicing results in multiple transcript variants. A read-through transcript variant composed of ZFP91 and the downstream CNTF gene sequence has been identified, but it is thought to be non-coding. Read-through transcription of ZFP91 and CNTF has also been observed in mouse. A ZFP91-related pseudogene has also been identified on chromosome 2. [provided by RefSeq, Oct 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~42.5 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 ZFP91 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_053023.5. 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 | 0 | |||||
| missense | 81 | 81 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 81 | 0 | 0 | 81 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_444251.1 | 11 | MANE Select | |
| Ensembl | ENSP00000339030.5 | 11 | MANE Select | |
| RefSeq | NP_001183980.1 | 11 | Standard | |
| Ensembl | ENSP00000540425.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of transcription by RNA polymerase II
- activation of NF-kappaB-inducing kinase activity
- protein K63-linked ubiquitination
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- nucleic acid binding
- ubiquitin-protein transferase activity
- metal ion binding
Cellular Component
- nucleus
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000316059
- Coding exons
- 11
- Length
- 41932
- Individuals with no LoFs
- 124508
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 124513
- p
- 0.0000201
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.63 | 215 | 294 | 0.732 | 0.0000159 | 3659 |
| Missense (PolyPhen) | 60 | 128.59 | 0.46659 | 1523 | ||
| Synonymous | -0.917 | 119 | 107 | 1.11 | 0.00000554 | 1104 |
| Loss of Function | 4.69 | 1 | 27.6 | 0.0362 | 0.00000160 | 352 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000090 | 0.0000090 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Atypical E3 ubiquitin-protein ligase that mediates 'Lys- 63'-linked ubiquitination of MAP3K14/NIK, leading to stabilize and activate MAP3K14/NIK. It thereby acts as an activator of the non- canonical NF-kappa-B2/NFKB2 pathway. May also play an important role in cell proliferation and/or anti-apoptosis. {ECO:0000269|PubMed:12738986, ECO:0000269|PubMed:20682767}.;
Recessive Scores
- pRec
- 0.281
Intolerance Scores
- LoFtool
- 0.213
- RVIS EVS
- 0.37
- RVIS percentile EVS
- 75.29
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.925
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |