MFNG
protein-codingMFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase, the group of Beta 3-glycosyltransferases
Gene summary
This gene is a member of the glycosyltransferase 31 gene family. Members of this gene family, which also includes the LFNG (GeneID: 3955) and RFNG (GeneID: 5986) genes, encode evolutionarily conserved glycosyltransferases that act in the Notch signaling pathway to define boundaries during embryonic development. While their genomic structure is distinct from other glycosyltransferases, these proteins have a fucose-specific beta-1,3-N-acetylglucosaminyltransferase activity that leads to elongation of O-linked fucose residues on Notch, which alters Notch signaling. The protein encoded by this gene may control Notch signaling in claudin-low breast cancer. [provided by RefSeq, May 2018]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.3 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 MFNG variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002405.4. 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 | 1 | 3 | |||
| missense | 55 | 55 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 59 | 1 | 0 | 60 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002396.2 | 8 | MANE Select | |
| Ensembl | ENSP00000349490.3 | 8 | MANE Select | |
| RefSeq | NP_001159815.1 | 7 | Standard | |
| Ensembl | ENSP00000413855.3 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Other types of O-glycan biosynthesis - Homo sapiens (human)
- Notch signaling pathway - Homo sapiens (human)
- Human papillomavirus infection - Homo sapiens (human)
- NOTCH-Ncore
- Notch Signaling Pathway
Biological Process
- blastocyst formation
- marginal zone B cell differentiation
- pattern specification process
- regulation of Notch signaling pathway
- positive regulation of protein binding
Molecular Function
- acetylglucosaminyltransferase activity
- O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity
- metal ion binding
Cellular Component
- extracellular space
- integral component of Golgi membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000356998
- Coding exons
- 8
- Length
- 17339
- Individuals with no LoFs
- 125641
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 99
- Defined
- 125742
- p
- 0.000402
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.301 | 187 | 199 | 0.940 | 0.0000123 | 2061 |
| Missense (PolyPhen) | 67 | 82.808 | 0.8091 | 942 | ||
| Synonymous | 0.0257 | 86 | 86.3 | 0.996 | 0.00000538 | 675 |
| Loss of Function | -0.0102 | 14 | 14.0 | 1.00 | 5.95e-7 | 153 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00052 | 0.00049 | rare |
| Latino/Admixed American | 0.0011 | 0.0011 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00039 | 0.00037 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Glycosyltransferase that initiates the elongation of O- linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules (PubMed:10935626). Modulates NOTCH1 activity by modifying O-fucose residues at specific EGF-like domains resulting in inhibition of NOTCH1 activation by JAG1 and enhancement of NOTCH1 activation by DLL1 via an increase in its binding to DLL1 (By similarity). {ECO:0000250|UniProtKB:O09008, ECO:0000269|PubMed:10935626}.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.716
- RVIS EVS
- -0.42
- RVIS percentile EVS
- 25.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.683
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |