MFNG

Summary

MFNG (MFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase, HGNC:7038) is a protein-coding gene on chromosome 22q13.1, encoding Beta-1,3-N-acetylglucosaminyltransferase manic fringe (O00587). Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules.

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.

Source: NCBI Gene 4242 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_002405

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7038
Approved symbol	MFNG
Name	MFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100060
Ensembl biotype	protein_coding
OMIM	602577
Entrez	4242

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000356998, ENST00000416983, ENST00000424765, ENST00000430411, ENST00000436341, ENST00000438891, ENST00000442496, ENST00000454291, ENST00000466943, ENST00000489515, ENST00000903589, ENST00000968702, ENST00000968703, ENST00000968704

RefSeq mRNA: 2 — MANE Select: NM_002405 NM_001166343, NM_002405

CCDS: CCDS13947, CCDS54525

Canonical transcript exons

ENST00000356998 — 8 exons

Exon	Start	End
ENSE00001712318	37472443	37472528
ENSE00001736266	37469063	37470029
ENSE00002239277	37485923	37486384
ENSE00003459998	37480721	37480769
ENSE00003491943	37479345	37479498
ENSE00003523054	37474512	37474677
ENSE00003566024	37476896	37476981
ENSE00003638302	37480197	37480299

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 97.69.

FANTOM5 (CAGE): breadth broad, TPM avg 10.6197 / max 220.3464, expressed in 726 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194062	10.2187	722
194064	0.2614	123
194063	0.0871	43
194061	0.0525	23

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.69	gold quality
monocyte	CL:0000576	96.29	gold quality
leukocyte	CL:0000738	96.25	gold quality
mononuclear cell	CL:0000842	96.19	gold quality
blood	UBERON:0000178	95.33	gold quality
lymph node	UBERON:0000029	95.32	gold quality
spleen	UBERON:0002106	95.05	gold quality
vermiform appendix	UBERON:0001154	92.85	gold quality
apex of heart	UBERON:0002098	92.11	gold quality
bone marrow cell	CL:0002092	91.56	gold quality
caecum	UBERON:0001153	90.95	gold quality
bone marrow	UBERON:0002371	90.52	gold quality
right lung	UBERON:0002167	90.27	gold quality
upper lobe of left lung	UBERON:0008952	90.11	gold quality
upper lobe of lung	UBERON:0008948	89.61	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.58	gold quality
thymus	UBERON:0002370	88.36	gold quality
omental fat pad	UBERON:0010414	87.62	gold quality
peritoneum	UBERON:0002358	87.58	gold quality
small intestine	UBERON:0002108	87.49	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.27	gold quality
gall bladder	UBERON:0002110	87.16	gold quality
type B pancreatic cell	CL:0000169	86.82	gold quality
olfactory bulb	UBERON:0002264	86.43	gold quality
lung	UBERON:0002048	86.13	gold quality
trabecular bone tissue	UBERON:0002483	85.55	gold quality
colonic epithelium	UBERON:0000397	85.22	gold quality
mucosa of transverse colon	UBERON:0004991	84.71	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.48	gold quality
left uterine tube	UBERON:0001303	84.25	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	11.83
E-GEOD-93593	yes	9.39
E-ANND-3	yes	6.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting MFNG, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-204-3P	97.80	66.84	1656

Literature-anchored findings (GeneRIF, showing 5)

• down regulated in Papillomavirus-mediated cervical neoplasia. (PMID:15280477)
• Mfng is an oncogene acting through Notch-mediated induction of Pik3cg. (PMID:25808869)
• MFNG imposes a negative correlation between Jag1 and Notch, being high Jag1 in the absence of MFNG predictive of poor prognosis. (PMID:30065304)
• Nuclear and stromal expression of Manic fringe in renal cell carcinoma. (PMID:34371013)
• MFNG is an independent prognostic marker for osteosarcoma. (PMID:37496053)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfng	ENSDARG00000042925
mus_musculus	Mfng	ENSMUSG00000018169
rattus_norvegicus	Mfng	ENSRNOG00000008133
drosophila_melanogaster	fng	FBGN0011591

Paralogs (3): LFNG (ENSG00000106003), RFNG (ENSG00000169733), B3GLCT (ENSG00000187676)

Protein

Protein identifiers

Beta-1,3-N-acetylglucosaminyltransferase manic fringe — O00587 (reviewed: O00587)

Alternative names: O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase

All UniProt accessions (7): A0A1B0GX02, A9UJP9, A9UJQ1, O00587, F8WE05, F8WE21, H0Y6Q9

UniProt curated annotations — full annotation on UniProt →

Function. Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules. 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.

Subcellular location. Golgi apparatus membrane.

Cofactor. Has some activity with cobalt, magnesium and calcium, but not zinc.

Similarity. Belongs to the glycosyltransferase 31 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00587-1	1	yes
O00587-2	2

RefSeq proteins (2): NP_001159815, NP_002396* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003378	Fringe-like_glycosylTrfase	Domain
IPR017374	Fringe	Family

Pfam: PF02434

Enzyme classification (BRENDA):

• EC 2.4.1.222 — O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase (BRENDA: 8 organisms, 66 substrates, 5 inhibitors, 20 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
P-NITROPHENYL-ALPHA-L-FUCOSE	0.0012–0.129	15
UDP-BETA-D-GLCNAC	0.0343–0.0707	5

Catalyzed reactions (Rhea), 2 shown:

• 3-O-(alpha-L-fucosyl)-L-seryl-[EGF-like domain protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl-beta-D-glucosaminyl-(1->3)-alpha-L-fucosyl)-L-seryl-[EGF-like domain protein] + UDP + H(+) (RHEA:70511)
• 3-O-(alpha-L-fucosyl)-L-threonyl-[EGF-like domain protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl-beta-D-glucosaminyl-(1->3)-alpha-L-fucosyl)-L-threonyl-[EGF-like domain protein] + UDP + H(+) (RHEA:70531)

UniProt features (17 total): binding site 4, disulfide bond 3, topological domain 2, glycosylation site 2, chain 1, splice variant 1, sequence variant 1, sequence conflict 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00587-F1	90.56	0.82

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 232

Ligand- & substrate-binding residues (4): 70; 143; 144; 256

Disulfide bonds (3): 110–121, 139–202, 306–315

Glycosylation sites (2): 185, 109

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1912420	Pre-NOTCH Processing in Golgi
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-1912422	Pre-NOTCH Expression and Processing

MSigDB gene sets: 202 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GSE45365_NK_CELL_VS_BCELL_DN, REACTOME_SIGNALING_BY_NOTCH, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_B_CELL_ACTIVATION, GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, GOBP_BLASTOCYST_FORMATION, CAGCTG_AP4_Q5, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_UP, GOBP_BLASTOCYST_DEVELOPMENT, SHIN_B_CELL_LYMPHOMA_CLUSTER_8

GO Biological Process (5): blastocyst formation (GO:0001825), marginal zone B cell differentiation (GO:0002315), pattern specification process (GO:0007389), regulation of Notch signaling pathway (GO:0008593), positive regulation of Notch signaling pathway (GO:0045747)

GO Molecular Function (4): O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity (GO:0033829), metal ion binding (GO:0046872), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (5): Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Pre-NOTCH Expression and Processing	1
Signal Transduction	1
Signaling by NOTCH	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
Notch signaling pathway	2
cellular anatomical structure	2
blastocyst development	1
anatomical structure formation involved in morphogenesis	1
mature B cell differentiation involved in immune response	1
multicellular organism development	1
multicellular organismal process	1
regulation of signal transduction	1
regulation of Notch signaling pathway	1
positive regulation of signal transduction	1
acetylglucosaminyltransferase activity	1
cation binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFNG	POFUT1	Q9H488	670
MFNG	DLL3	Q9NYJ7	631
MFNG	EGF	P01133	579
MFNG	HES5	Q5TA89	566
MFNG	DLL1	O00548	563
MFNG	NOTCH3	Q9UM47	534
MFNG	JAG1	P78504	531
MFNG	MAML1	Q92585	524
MFNG	DTX1	Q86Y01	487
MFNG	DLL4	Q9NR61	475
MFNG	PSEN1	P49768	466
MFNG	ST3GAL5	Q9UNP4	460
MFNG	FUT9	Q9Y231	443
MFNG	DNER	Q8NFT8	442
MFNG	JAG2	Q9Y219	441

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MFNG	PLSCR1	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): KDM8 (Affinity Capture-MS), ITIH2 (Affinity Capture-MS), SAMD8 (Affinity Capture-MS), HS6ST1 (Affinity Capture-MS), PLSCR1 (Affinity Capture-MS), GLMN (Affinity Capture-MS), HAPLN3 (Affinity Capture-MS), EIF2B4 (Affinity Capture-MS), SPAG4 (Affinity Capture-MS), TNPO3 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), MAN2A2 (Affinity Capture-MS), B4GALT3 (Affinity Capture-MS), CLPTM1 (Affinity Capture-MS), CANT1 (Affinity Capture-MS)

ESM2 similar proteins: A4FV98, A5PK51, A6NDG6, E1BE10, O00587, O35595, O95294, P60487, Q12788, Q17QS4, Q1JPJ0, Q2T9S4, Q2TBI8, Q32NY4, Q3T063, Q3ZBF9, Q501J2, Q5E9V4, Q5F4B1, Q5IS64, Q5SUV1, Q5T9C9, Q6AYG0, Q6AYR8, Q6XQN1, Q6XQN6, Q6ZMM2, Q80US4, Q8BNV1, Q8BZG5, Q8CC86, Q8IZ69, Q8N9H8, Q8NE01, Q8R2H9, Q8TCT1, Q8VCA8, Q8VD52, Q969S8, Q96AZ1

Diamond homologs: O00587, O09008, O09009, O09010, O12971, O12972, P79948, P79949, Q24342, Q2KJ92, Q5IS64, Q5YB40, Q6KFX9, Q8JHF2, Q8NES3, Q924T4, Q9R1U9, Q9Y644, Q9YHB3, Q5F3G7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MFNG	up-regulates	NOTCH2	binding
MFNG	up-regulates	NOTCH1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

65 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1520 predictions. Top by Δscore:

Variant	Effect	Δscore
22:37472438:CCCA:C	donor_loss	1.0000
22:37472439:CCA:C	donor_loss	1.0000
22:37472440:CAC:C	donor_loss	1.0000
22:37472441:ACCTG:A	donor_loss	1.0000
22:37474642:C:CT	acceptor_gain	1.0000
22:37474675:CCA:C	acceptor_gain	1.0000
22:37474676:CAC:C	acceptor_gain	1.0000
22:37476890:GCTTA:G	donor_loss	1.0000
22:37476891:CTTAC:C	donor_loss	1.0000
22:37476892:TTACC:T	donor_loss	1.0000
22:37476893:TA:T	donor_loss	1.0000
22:37476894:A:AC	donor_gain	1.0000
22:37476894:A:AG	donor_loss	1.0000
22:37476895:C:CC	donor_gain	1.0000
22:37476895:C:T	donor_loss	1.0000
22:37476895:CCTGG:C	donor_gain	1.0000
22:37476977:AGCCT:A	acceptor_gain	1.0000
22:37476978:GCCT:G	acceptor_gain	1.0000
22:37476979:CCTC:C	acceptor_gain	1.0000
22:37476980:CT:C	acceptor_gain	1.0000
22:37476982:C:CC	acceptor_gain	1.0000
22:37476982:C:CG	acceptor_loss	1.0000
22:37476983:T:C	acceptor_loss	1.0000
22:37479340:CCCA:C	donor_loss	1.0000
22:37479341:CCAC:C	donor_loss	1.0000
22:37479342:CA:C	donor_loss	1.0000
22:37479343:A:AC	donor_gain	1.0000
22:37479344:C:CC	donor_gain	1.0000
22:37479344:CCGTG:C	donor_gain	1.0000
22:37479494:ACCAC:A	acceptor_gain	1.0000

AlphaMissense

2078 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:37476961:A:C	F194L	0.997
22:37476961:A:T	F194L	0.997
22:37476963:A:G	F194L	0.997
22:37472517:G:C	S275R	0.991
22:37472517:G:T	S275R	0.991
22:37472519:T:G	S275R	0.991
22:37476967:G:C	F192L	0.991
22:37476967:G:T	F192L	0.991
22:37476969:A:G	F192L	0.991
22:37485946:A:G	W78R	0.991
22:37485946:A:T	W78R	0.991
22:37479475:T:A	D144V	0.990
22:37476937:G:C	C202W	0.989
22:37479481:T:A	D142V	0.989
22:37479478:T:A	D143V	0.988
22:37485944:C:A	W78C	0.987
22:37485944:C:G	W78C	0.987
22:37485995:C:A	K61N	0.987
22:37485995:C:G	K61N	0.987
22:37476962:A:G	F194S	0.986
22:37479497:A:G	W137R	0.986
22:37479497:A:T	W137R	0.986
22:37472518:C:A	S275I	0.985
22:37474567:A:G	F253S	0.985
22:37479475:T:G	D144A	0.985
22:37480238:C:A	K122N	0.985
22:37480238:C:G	K122N	0.985
22:37474619:C:G	G236R	0.984
22:37476962:A:C	F194C	0.984
22:37479479:C:G	D143H	0.984

dbSNP variants (sampled 300 via entrez): RS1000180139 (22:37472483 T>C), RS1000340869 (22:37469594 A>G), RS1000463680 (22:37472777 C>A,T), RS1000623917 (22:37469298 T>G), RS1000630885 (22:37481256 C>T), RS1000675963 (22:37478377 T>C), RS1000681683 (22:37484047 G>A,C), RS1000814653 (22:37475033 T>C), RS1000954889 (22:37475312 C>G), RS1001203879 (22:37480416 A>G), RS1001279153 (22:37480756 G>A), RS1001338338 (22:37486353 C>G,T), RS1001808263 (22:37485305 C>T), RS1001962854 (22:37477018 G>C), RS1002005788 (22:37475696 C>A)

Disease associations

OMIM: gene MIM:602577 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	6
trichostatin A	affects cotreatment, decreases expression	3
mercuric bromide	affects cotreatment, decreases expression	2
belinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cisplatin	affects expression, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	affects methylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
MRK 003	increases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Bortezomib	decreases expression	1
Decitabine	affects expression	1
Curcumin	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	increases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7V1	Ubigene A-549 MFNG KO	Cancer cell line	Male
CVCL_D8QK	Ubigene HCT 116 MFNG KO	Cancer cell line	Male
CVCL_D9K8	Ubigene HEK293 MFNG KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.