CSN2
protein-codingcasein beta
Gene summary
This gene is a member of the beta casein family. There are two types of casein protein, beta (encoded by this gene) and kappa, both of which are secreted in human milk. Beta casein is the principal protein in human milk and the primary source of essential amino acids for a suckling infant. Beta and kappa casein proteins acting together form spherical micelles which bind within them important dietary minerals, such as calcium and phosphorous. In addition, the C-terminal 14 aa of the protein has antimicrobial activity, especially in preterm milk, displaying antibacterial activity against S. aureus and Y. enterocolitica. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2020]
- CASB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.5 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 CSN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001891.4. 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 | 37 | 7 | 44 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 37 | 8 | 0 | 45 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001882.1 | 6 | MANE Select | |
| Ensembl | ENSP00000341030.3 | 6 | MANE Select | |
| RefSeq | NP_001289699.1 | 6 | Standard | |
| RefSeq | NP_001372660.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Prolactin signaling pathway - Homo sapiens (human)
- Signaling by ERBB4
- Signal Transduction
- Glucocorticoid receptor regulatory network
- Nuclear signaling by ERBB4
Biological Process
- calcium ion transport
- lactation
- negative regulation of lactation
- negative regulation of cysteine-type endopeptidase activity
Molecular Function
- enzyme inhibitor activity
- cysteine-type endopeptidase inhibitor activity
- calcium ion binding
Cellular Component
- extracellular region
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000353151
- Coding exons
- 6
- Length
- 5752
- Individuals with no LoFs
- 125472
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125477
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.47 | 158 | 114 | 1.39 | 0.00000516 | 1449 |
| Missense (PolyPhen) | 35 | 22.008 | 1.5903 | 272 | ||
| Synonymous | -2.41 | 62 | 42.1 | 1.47 | 0.00000202 | 470 |
| Loss of Function | 0.659 | 9 | 11.4 | 0.789 | 4.88e-7 | 132 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000064 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Important role in determination of the surface properties of the casein micelles.;
Recessive Scores
- pRec
- 0.388
Intolerance Scores
- LoFtool
- 0.319
- RVIS EVS
- 0.1
- RVIS percentile EVS
- 61.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0477
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |