NDFIP1
Nedd4 family interacting protein 1
Basic information
Region (hg38): 5:142108779-142154440
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDFIP1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 4 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 4 | 0 | 1 |
Variants in NDFIP1
This is a list of pathogenic ClinVar variants found in the NDFIP1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-142109003-C-T | not specified | Uncertain significance (Nov 22, 2021) | ||
| 5-142109025-C-G | not specified | Uncertain significance (Dec 03, 2024) | ||
| 5-142131892-G-A | not specified | Uncertain significance (Mar 01, 2023) | ||
| 5-142135730-G-A | not specified | Uncertain significance (May 14, 2024) | ||
| 5-142137793-G-T | not specified | Uncertain significance (Nov 22, 2022) | ||
| 5-142140592-T-C | Benign (Dec 11, 2018) | |||
| 5-142144616-G-T | not specified | Uncertain significance (Nov 10, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NDFIP1 | protein_coding | protein_coding | ENST00000253814 | 7 | 45936 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.977 | 0.0225 | 125689 | 0 | 3 | 125692 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.50 | 65 | 109 | 0.597 | 0.00000512 | 1439 |
| Missense in Polyphen | 22 | 56.145 | 0.39184 | 729 | ||
| Synonymous | -0.0775 | 40 | 39.4 | 1.02 | 0.00000188 | 426 |
| Loss of Function | 3.16 | 0 | 11.6 | 0.00 | 4.91e-7 | 155 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000181 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets. As a result, controls many cellular processes. Prevents chronic T-helper cell-mediated inflammation by activating ITCH and thus controlling JUNB degradation (By similarity). Promotes pancreatic beta cell death through degradation of JUNB and inhibition of the unfolded protein response, leading to reduction of insulin secretion (PubMed:26319551). Restricts the production of proinflammatory cytokines in effector Th17 T-cells by promoting ITCH-mediated ubiquitination and degradation of RORC (By similarity). Together with NDFIP2, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination (By similarity). Regulates peripheral T-cell tolerance to self and foreign antigens, forcing the exit of naive CD4+ T-cells from the cell cycle before they become effector T-cells (By similarity). Negatively regulates RLR-mediated antiviral response by promoting SMURF1-mediated ubiquitination and subsequent degradation of MAVS (PubMed:23087404). Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus where it mediates KCNH2 degradation (PubMed:26363003). In cortical neurons, mediates the ubiquitination of the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its down- regulation and protection of the cells from cobalt and iron toxicity (PubMed:19706893). Important for normal development of dendrites and dendritic spines in cortex (By similarity). Enhances the ubiquitination of BRAT1 mediated by: NEDD4, NEDD4L and ITCH and is required for the nuclear localization of ubiquitinated BRAT1 (PubMed:25631046). Enhances the ITCH-mediated ubiquitination of MAP3K7 by recruiting E2 ubiquitin-conjugating enzyme UBE2L3 to ITCH (By similarity). Modulates EGFR signaling through multiple pathways. In particular, may regulate the ratio of AKT1-to-MAPK8 signaling in response to EGF, acting on AKT1 probably through PTEN destabilization and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result, may control cell growth rate (PubMed:20534535). Inhibits cell proliferation by promoting PTEN nuclear localization and changing its signaling specificity (PubMed:25801959). {ECO:0000250|UniProtKB:Q8R0W6, ECO:0000269|PubMed:19343052, ECO:0000269|PubMed:19706893, ECO:0000269|PubMed:20534535, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:25801959, ECO:0000269|PubMed:26319551, ECO:0000269|PubMed:26363003}.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- loftool
- 0.232
- rvis_EVS
- -0.16
- rvis_percentile_EVS
- 41.25
Haploinsufficiency Scores
- pHI
- 0.205
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.561
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.731
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ndfip1
- Phenotype
- immune system phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; respiratory system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);
Gene ontology
- Biological process
- regulation of myeloid leukocyte differentiation;negative regulation of type 2 immune response;cellular iron ion homeostasis;vacuolar transport;negative regulation of gene expression;metal ion transport;positive regulation of protein ubiquitination;negative regulation of transporter activity;negative regulation of interleukin-4 production;negative regulation of T cell proliferation;positive regulation of I-kappaB kinase/NF-kappaB signaling;regulation of lymphocyte differentiation;positive regulation of protein catabolic process;negative regulation of isotype switching to IgE isotypes;regulation of isotype switching to IgG isotypes;negative regulation of inflammatory response;negative regulation of protein transport
- Cellular component
- Golgi membrane;extracellular region;Golgi apparatus;cell cortex;endosome membrane;integral component of membrane;cell junction;dendrite;synapse;perinuclear region of cytoplasm
- Molecular function
- protein binding;WW domain binding