NKX2-8
protein-codingNK2 homeobox 8, the group of NKL subclass homeoboxes and pseudogenes
Gene summary
The protein encoded by this gene is a homeobox-containing developmental regulator associated with liver development. The encoded protein binds to the alpha-fetoprotein (AFP) gene promoter and increases the expression of AFP. This gene is overexpressed in some lung cancers and is linked to poor patient survival, possibly due to its resistance to cisplatin. This gene is aberrantly methylated in pancreatic cancer, deleted in squamous cell lung carcinomas, and acts as a tumor suppressor in esophageal cancer. Mutations in this gene may also be a cause of neural tube defects. [provided by RefSeq, Dec 2015]
- NKX2H
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.6 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 NKX2-8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014360.4. 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 | 2 | ||||
| missense | 49 | 49 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 49 | 0 | 2 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055175.2 | 2 | MANE Select | |
| Ensembl | ENSP00000258829.4 | 2 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- liver development
- transcription, DNA-templated
- transcription by RNA polymerase II
- axonogenesis
- cell differentiation
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- double-stranded DNA binding
- DNA-binding transcription factor activity
Cellular Component
- cellular_component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000258829
- Coding exons
- 2
- Length
- 2029
- Individuals with no LoFs
- 122493
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 122503
- p
- 0.0000408
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.500 | 119 | 105 | 1.14 | 0.00000488 | 1453 |
| Missense (PolyPhen) | 35 | 34.352 | 1.0189 | 433 | ||
| Synonymous | -1.75 | 66 | 50.2 | 1.32 | 0.00000246 | 537 |
| Loss of Function | 0.716 | 4 | 5.87 | 0.681 | 2.53e-7 | 73 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000068 | 0.000066 | rare |
| Latino/Admixed American | 0.000067 | 0.000059 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000062 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000030 | 0.000027 | rare |
| South Asian | 0.00010 | 0.000099 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.108
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.145
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |