NPNT
protein-codingnephronectin
Gene summary
Predicted to enable integrin binding activity. Predicted to be involved in several processes, including cell-cell adhesion mediated by integrin; positive regulation of ERK1 and ERK2 cascade; and positive regulation of osteoblast differentiation. Predicted to act upstream of or within positive regulation of transforming growth factor beta receptor signaling pathway. Located in extracellular exosome and extracellular matrix. [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 ~109.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0018470
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NPNT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001033047.3. 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 | 3 | 1 | 4 | |||
| missense | 87 | 13 | 100 | |||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 1 | 99 | 16 | 1 | 117 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001028219.1 | 12 | MANE Select | |
| Ensembl | ENSP00000369323.2 | 12 | MANE Select | |
| RefSeq | NP_001171619.1 | 13 | Standard | |
| RefSeq | NP_001171620.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| npnt | Danio rerio | Structure: atrioventricular valve Quality: increased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Beta1 integrin cell surface interactions
Biological Process
- ureteric bud development
- branching involved in ureteric bud morphogenesis
- cell-matrix adhesion
- positive regulation of alkaline phosphatase activity
- positive regulation of cell-substrate adhesion
Molecular Function
- integrin binding
- extracellular matrix structural constituent
- calcium ion binding
Cellular Component
- extracellular region
- basement membrane
- smooth muscle contractile fiber
- integrin alpha8-beta1 complex
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000427316
- Coding exons
- 13
- Length
- 109253
- Individuals with no LoFs
- 125697
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 51
- Defined
- 125748
- p
- 0.000203
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0940 | 341 | 336 | 1.01 | 0.0000175 | 3851 |
| Missense (PolyPhen) | 116 | 132.97 | 0.87237 | 1581 | ||
| Synonymous | 0.610 | 111 | 119 | 0.929 | 0.00000638 | 1168 |
| Loss of Function | 1.85 | 20 | 31.1 | 0.642 | 0.00000156 | 368 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00025 | 0.00025 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functional ligand of integrin alpha-8/beta-1 in kidney development. Regulates the expression of GDNF with integrin alpha- 8/beta-1 which is essential for kidney development. May also play a role in the development and function of various tissues, regulating cell adhesion, spreading and survival through the binding of several integrins (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.100
Intolerance Scores
- LoFtool
- 0.124
- RVIS EVS
- 1.8
- RVIS percentile EVS
- 96.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.419
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |