NKX2-2
protein-codingNK2 homeobox 2, the group of NKL subclass homeoboxes and pseudogenes
Gene summary
The protein encoded by this gene contains a homeobox domain and may be involved in the morphogenesis of the central nervous system. This gene is found on chromosome 20 near NKX2-4, and these two genes appear to be duplicated on chromosome 14 in the form of TITF1 and NKX2-8. The encoded protein is likely to be a nuclear transcription factor. [provided by RefSeq, Jul 2008]
- NKX2B
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0015967
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0016391
Submitter: Genomics England PanelApp
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NKX2-2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002509.4. 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 | 25 | 1 | 27 | ||
| missense | 10 | 3 | 2 | 15 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 12 | 28 | 3 | 44 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002500.1 | 2 | MANE Select | |
| Ensembl | ENSP00000366347.4 | 2 | MANE Select | |
| RefSeq | NP_001411340.1 | 2 | Standard | |
| RefSeq | NP_001411341.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| nkx2.2a | Danio rerio | Structure: myelinating Schwann cell Quality: mislocalised abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Maturity onset diabetes of the young - Homo sapiens (human)
- Dopaminergic Neurogenesis
- Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
Biological Process
- type B pancreatic cell development
- pancreatic A cell fate commitment
- type B pancreatic cell fate commitment
- pancreatic PP cell fate commitment
- smoothened signaling pathway
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- proximal promoter sequence-specific DNA binding
- chromatin binding
- DNA-binding transcription factor activity
Cellular Component
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377142
- Coding exons
- 2
- Length
- 3017
- Individuals with no LoFs
- 125711
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125715
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.00371 | 161 | 161 | 0.999 | 0.00000724 | 1734 |
| Missense (PolyPhen) | 29 | 53.303 | 0.54406 | 556 | ||
| Synonymous | -2.38 | 100 | 73.9 | 1.35 | 0.00000349 | 568 |
| Loss of Function | 2.25 | 2 | 9.47 | 0.211 | 4.11e-7 | 101 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional activator involved in the development of insulin-producting beta cells in the endocrine pancreas (By similarity). May also be involved in specifying diencephalic neuromeric boundaries, and in controlling the expression of genes that play a role in axonal guidance. Binds to elements within the NEUROD1 promoter (By similarity). {ECO:0000250|UniProtKB:P42586}.;
Recessive Scores
- pRec
- 0.250
Intolerance Scores
- LoFtool
- 0.199
- RVIS EVS
- 0.51
- RVIS percentile EVS
- 80.01
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.942
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |