FOXN4
protein-codingforkhead box N4, the group of Forkhead boxes
Gene summary
Members of the winged-helix/forkhead family of transcription factors, such as FOXN4, are characterized by a 110-amino acid DNA-binding domain that can fold into a variant of the helix-turn-helix motif consisting of 3 alpha helices flanked by 2 large loops or wings. These transcription factors are involved in a variety of biologic processes as key regulators in development and metabolism (Li et al., 2004 [PubMed 15363391]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.3 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 FOXN4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_213596.3. 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 | 0 | |||||
| missense | 76 | 76 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 76 | 0 | 0 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_998761.2 | 9 | MANE Select | |
| Ensembl | ENSP00000299162.5 | 9 | MANE Select | |
| Ensembl | ENSP00000347354.1 | 4 | Standard | |
| Ensembl | ENSP00000347354.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| foxn4 | Danio rerio | Structure: heart valve Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- heart looping
- regulation of transcription, DNA-templated
- regulation of transcription by RNA polymerase II
- regulation of heart contraction
- retina layer formation
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- enhancer sequence-specific DNA binding
- chromatin binding
- DNA-binding transcription factor activity
- protein binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000299162
- Coding exons
- 9
- Length
- 31242
- Individuals with no LoFs
- 125681
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125690
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.23 | 242 | 302 | 0.801 | 0.0000182 | 3312 |
| Missense (PolyPhen) | 82 | 100.66 | 0.81461 | 1053 | ||
| Synonymous | 1.05 | 120 | 136 | 0.885 | 0.00000945 | 1082 |
| Loss of Function | 3.48 | 3 | 19.6 | 0.153 | 0.00000106 | 220 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor essential for neural and some non- neural tissues development, such as retina and lung respectively. Binds to an 11-bp consensus sequence containing the invariant tetranucleotide 5'-ACGC-3'. During development of the central nervous system, is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating DLL4- NOTCH signaling. Also acts synergistically with ASCL1/MASH1 to activate DLL4-NOTCH signaling and drive commitment of p2 progenitors to the V2b interneuron fates during spinal cord neurogenesis. In development of non-neural tissues, plays an essential role in the specification of the atrioventricular canal and is indirectly required for patterning the distal airway during lung development (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.152
Intolerance Scores
- LoFtool
- 0.255
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.77
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.204
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |