NCLN
protein-codingnicalin, the group of M28 metallopeptidases
Gene summary
Enables ribosome binding activity. Involved in several processes, including multi-pass transmembrane protein insertion into ER membrane; protein stabilization; and regulation of protein complex stability. Located in endoplasmic reticulum membrane. Part of multi-pass translocon complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.0 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 NCLN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020170.4. 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 | 2 | 1 | 3 | |||
| missense | 85 | 3 | 88 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 1 | 91 | 3 | 1 | 96 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_064555.2 | 15 | MANE Select | |
| Ensembl | ENSP00000246117.3 | 15 | MANE Select | |
| RefSeq | NP_001308392.1 | 15 | Standard | |
| Ensembl | ENSP00000467693.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ncln | Danio rerio | Structure: intestine Quality: lacks all parts of type abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of signal transduction
- regulation of protein complex assembly
- protein stabilization
- regulation of protein complex stability
Molecular Function
- protein binding
Cellular Component
- endoplasmic reticulum membrane
- membrane
- integral component of membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000246117
- Coding exons
- 15
- Length
- 24013
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125735
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.66 | 255 | 341 | 0.748 | 0.0000239 | 3547 |
| Missense (PolyPhen) | 44 | 86.494 | 0.50871 | 870 | ||
| Synonymous | -0.891 | 172 | 158 | 1.09 | 0.0000123 | 1138 |
| Loss of Function | 3.88 | 5 | 26.6 | 0.188 | 0.00000136 | 297 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000049 | 0.000046 | rare |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.000035 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May antagonize Nodal signaling and subsequent organization of axial structures during mesodermal patterning. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- LoFtool
- 0.345
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 18.14
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.837
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |