NKD1
protein-codingNKD inhibitor of WNT signaling pathway 1, the group of EF-hand domain containing
Gene summary
In the mouse, Nkd is a Dishevelled (see DVL1; MIM 601365)-binding protein that functions as a negative regulator of the Wnt (see WNT1; MIM 164820)-beta-catenin (see MIM 116806)-Tcf (see MIM 602272) signaling pathway.[supplied by OMIM, Jun 2003]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~100.9 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 NKD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_033119.5. 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 | 2 | |||
| missense | 82 | 3 | 85 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 82 | 4 | 1 | 87 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_149110.1 | 10 | MANE Select | |
| Ensembl | ENSP00000268459.3 | 10 | MANE Select | |
| Ensembl | ENSP00000657864.1 | 6 | Standard | |
| Ensembl | ENSP00000788058.1 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| nkd1 | Danio rerio | Structure: organizer inducing center Quality: increased width abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Hippo signaling pathway - Homo sapiens (human)
- Wnt signaling pathway - Homo sapiens (human)
- WNT-Ncore
- Wnt Signaling Pathway and Pluripotency
- Wnt Signaling Pathway
Biological Process
- eye photoreceptor cell differentiation
- somatic muscle development
- Wnt signaling pathway
- negative regulation of Wnt signaling pathway
- positive regulation of protein catabolic process
Molecular Function
- calcium ion binding
- protein binding
- PDZ domain binding
Cellular Component
- protein phosphatase type 2A complex
- cytoplasm
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000268459
- Coding exons
- 10
- Length
- 88407
- Individuals with no LoFs
- 125018
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125021
- p
- 0.0000120
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.826 | 245 | 284 | 0.862 | 0.0000181 | 3025 |
| Missense (PolyPhen) | 78 | 108.31 | 0.72018 | 1169 | ||
| Synonymous | -0.265 | 129 | 125 | 1.03 | 0.00000865 | 944 |
| Loss of Function | 4.14 | 2 | 23.8 | 0.0841 | 0.00000150 | 247 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000090 | 0.0000089 | rare |
| South Asian | 0.000038 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cell autonomous antagonist of the canonical Wnt signaling pathway. May activate a second Wnt signaling pathway that controls planar cell polarity. {ECO:0000269|PubMed:11752446, ECO:0000269|PubMed:15687260, ECO:0000269|PubMed:16567647}.;
Recessive Scores
- pRec
- 0.170
Intolerance Scores
- LoFtool
- 0.0705
- RVIS EVS
- -0.82
- RVIS percentile EVS
- 11.77
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.934
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |