PNN
protein-codingpinin, desmosome associated protein
Gene summary
Enables RNA binding activity. Predicted to be involved in several processes, including mRNA splicing, via spliceosome; positive regulation of apoptotic process; and regulation of mRNA metabolic process. Predicted to act upstream of or within cell-cell adhesion. Located in exon-exon junction complex and nuclear speck. Part of catalytic step 2 spliceosome. [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 ~8.0 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 PNN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002687.4. 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 | 2 | |||
| missense | 83 | 1 | 1 | 85 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 87 | 2 | 2 | 91 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002678.3 | 9 | MANE Select | |
| Ensembl | ENSP00000216832.4 | 9 | MANE Select | |
| Ensembl | ENSP00000452217.1 | 5 | Standard | |
| Ensembl | ENSP00000452217.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| pnn | Danio rerio | Structure: neural crest cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mRNA surveillance pathway - Homo sapiens (human)
- RNA transport - Homo sapiens (human)
Biological Process
- mRNA splicing, via spliceosome
- cell adhesion
Molecular Function
- DNA binding
- RNA binding
- structural molecule activity
- protein binding
Cellular Component
- intermediate filament
- plasma membrane
- cell-cell junction
- membrane
- nuclear speck
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000216832
- Coding exons
- 9
- Length
- 8036
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125747
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.926 | 344 | 396 | 0.869 | 0.0000214 | 4767 |
| Missense (PolyPhen) | 46 | 86.852 | 0.52964 | 1059 | ||
| Synonymous | -1.36 | 148 | 128 | 1.15 | 0.00000625 | 1278 |
| Loss of Function | 4.14 | 9 | 35.7 | 0.252 | 0.00000204 | 426 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.000098 | 0.000092 | rare |
| European (Non-Finnish) | 0.000098 | 0.000097 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional activator binding to the E-box 1 core sequence of the E-cadherin promoter gene; the core-binding sequence is 5'CAGGTG-3'. Capable of reversing CTBP1-mediated transcription repression. Auxiliary component of the splicing- dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Participates in the regulation of alternative pre-mRNA splicing. Associates to spliced mRNA within 60 nt upstream of the 5'-splice sites. Component of the PSAP complex which binds RNA in a sequence-independent manner and is proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. Involved in the establishment and maintenance of epithelia cell- cell adhesion. Potential tumor suppressor for renal cell carcinoma. {ECO:0000269|PubMed:12051732, ECO:0000269|PubMed:14517304, ECO:0000269|PubMed:15542832, ECO:0000269|PubMed:15735603, ECO:0000269|PubMed:22388736}.;
Recessive Scores
- pRec
- 0.259
Intolerance Scores
- LoFtool
- 0.559
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.78
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |