POFUT1
protein O-fucosyltransferase 1, the group of Fucosyltransferases|MicroRNA protein coding host genes
Basic information
Region (hg38): 20:32207855-32238658
Links
Phenotypes
GenCC
Source:
- Dowling-Degos disease 2 (Moderate), mode of inheritance: AD
- Dowling-Degos disease 2 (Strong), mode of inheritance: AD
- Dowling-Degos disease (Supportive), mode of inheritance: AD
- complex neurodevelopmental disorder (Limited), mode of inheritance: AR
- Dowling-Degos disease 2 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Dowling-Degos disease 2 | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Dermatologic | 23684010 |
ClinVar
This is a list of variants' phenotypes submitted to
- Dowling-Degos_disease_2 (73 variants)
- Inborn_genetic_diseases (36 variants)
- not_provided (25 variants)
- POFUT1-related_disorder (7 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the POFUT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015352.2. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 20 | 26 | ||||
| missense | 57 | 63 | ||||
| nonsense | 4 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 5 | 0 | 59 | 24 | 7 |
Highest pathogenic variant AF is 0.0000020530733
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| POFUT1 | protein_coding | protein_coding | ENST00000375749 | 7 | 30788 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.963 | 0.0370 | 125744 | 0 | 4 | 125748 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.952 | 190 | 231 | 0.824 | 0.0000134 | 2528 |
| Missense in Polyphen | 88 | 106.99 | 0.82253 | 1097 | ||
| Synonymous | 0.333 | 94 | 98.2 | 0.957 | 0.00000624 | 772 |
| Loss of Function | 3.62 | 2 | 19.1 | 0.105 | 9.71e-7 | 200 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000880 | 0.00000879 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs). {ECO:0000269|PubMed:11524432, ECO:0000269|PubMed:28334865, ECO:0000269|PubMed:8358148}.;
- Disease
- DISEASE: Dowling-Degos disease 2 (DDD2) [MIM:615327]: An autosomal dominant genodermatosis. Affected individuals develop a postpubertal reticulate hyperpigmentation that is progressive and disfiguring, and small hyperkeratotic dark brown papules that affect mainly the flexures and great skin folds. Patients usually show no abnormalities of the hair or nails. {ECO:0000269|PubMed:23684010}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Other types of O-glycan biosynthesis - Homo sapiens (human);NOTCH-Ncore;Notch;Signal Transduction;Pre-NOTCH Processing in the Endoplasmic Reticulum;Pre-NOTCH Expression and Processing;Signaling by NOTCH
(Consensus)
Recessive Scores
- pRec
- 0.132
Intolerance Scores
- loftool
- 0.447
- rvis_EVS
- -0.09
- rvis_percentile_EVS
- 46.92
Haploinsufficiency Scores
- pHI
- 0.718
- hipred
- Y
- hipred_score
- 0.714
- ghis
- 0.523
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pofut1
- 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); limbs/digits/tail phenotype; skeleton phenotype; immune system phenotype; respiratory system phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; reproductive 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); 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); muscle phenotype; endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- pofut1
- Affected structure
- whole organism
- Phenotype tag
- abnormal
- Phenotype quality
- decreased pigmentation
Gene ontology
- Biological process
- angiogenesis;somitogenesis;fucose metabolic process;regulation of transcription, DNA-templated;protein O-linked glycosylation;Notch signaling pathway;nervous system development;heart development;regulation of Notch signaling pathway;O-glycan processing;protein O-linked fucosylation
- Cellular component
- endoplasmic reticulum;membrane
- Molecular function
- fucosyltransferase activity;peptide-O-fucosyltransferase activity