LFNG

LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase, the group of Beta 3-glycosyltransferases|MicroRNA protein coding host genes

Basic information

Region (hg38): 7:2512529-2529177

Links

ENSG00000106003

∙ NCBI:3955 ∙ OMIM:602576 ∙ HGNC:6560 ∙ Uniprot:Q8NES3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

spondylocostal dysostosis 3, autosomal recessive (Definitive), mode of inheritance: AR
spondylocostal dysostosis 3, autosomal recessive (Moderate), mode of inheritance: AR
autosomal recessive spondylocostal dysostosis (Supportive), mode of inheritance: AR
spondylocostal dysostosis 3, autosomal recessive (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondylocostal dysostosis 3, autosomal recessive	AR	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	Musculoskeletal	16385447; 20301771

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LFNG gene.

Spondylocostal_dysostosis_3,_autosomal_recessive (217 variants)
Inborn_genetic_diseases (50 variants)
not_provided (28 variants)
LFNG-related_disorder (10 variants)
not_specified (3 variants)
Spondylocostal_dysostosis_2,_autosomal_recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LFNG gene is commonly pathogenic or not. These statistics are base on transcript: NM_001040167.2. 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			3 clinvar	78 clinvar	1 clinvar	82
missense	2 clinvar	1 clinvar	106 clinvar	7 clinvar	1 clinvar	117
nonsense						0
start loss						0
frameshift	3 clinvar					3
splice donor/acceptor (+/-2bp)		2 clinvar				2
Total	5	3	109	85	2

Highest pathogenic variant AF is 0.00000547629

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LFNG	protein_coding	protein_coding	ENST00000222725	8	16649

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0976	0.895	125369	0	7	125376	0.0000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.616	172	196	0.876	0.0000140	2380
Missense in Polyphen		38	77.38	0.49108		805
Synonymous	-1.32	105	89.1	1.18	0.00000694	829
Loss of Function	2.36	4	13.3	0.302	5.75e-7	151

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000927	0.0000908
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000968	0.0000924
European (Non-Finnish)	0.0000289	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: 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 (By similarity). Decreases the binding of JAG1 to NOTCH2 but not that of DLL1 (PubMed:11346656). Essential mediator of somite segmentation and patterning (By similarity). {ECO:0000250|UniProtKB:O09010, ECO:0000269|PubMed:11346656}.;
Disease: DISEASE: Spondylocostal dysostosis 3, autosomal recessive (SCDO3) [MIM:609813]: A condition of variable severity associated with vertebral and rib segmentation defects. The main skeletal malformations include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and other rib malformations. Deformity of the chest and spine (severe scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the malformation and leads to a dwarf- like appearance. As the thorax is small, infants frequently have respiratory insufficiency and repeated respiratory infections resulting in life-threatening complications in the first year of life. {ECO:0000269|PubMed:16385447}. 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 signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);NOTCH-Ncore;Notch Signaling Pathway;Gene regulatory network modelling somitogenesis;Notch Signaling Pathway;Notch;Signal Transduction;segmentation clock;Notch;Pre-NOTCH Processing in Golgi;Pre-NOTCH Expression and Processing;Signaling by NOTCH (Consensus)

Recessive Scores

pRec: 0.189

Intolerance Scores

loftool: 0.907
rvis_EVS: -0.05
rvis_percentile_EVS: 50.34

Haploinsufficiency Scores

pHI: 0.270
hipred: Y
hipred_score: 0.775
ghis: 0.515

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.685

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Lfng
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); hearing/vestibular/ear phenotype; vision/eye phenotype; skeleton phenotype; embryo phenotype; respiratory 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); reproductive system 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); hematopoietic system phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype;

Zebrafish Information Network

Gene name: lfng
Affected structure: CiD
Phenotype tag: abnormal
Phenotype quality: increased amount

Gene ontology

Biological process: ovarian follicle development;somitogenesis;marginal zone B cell differentiation;compartment pattern specification;regulation of Notch signaling pathway;animal organ morphogenesis;regulation of somitogenesis;T cell differentiation;positive regulation of protein binding;protein O-linked fucosylation;positive regulation of Notch signaling pathway;positive regulation of meiotic cell cycle;negative regulation of Notch signaling pathway involved in somitogenesis
Cellular component: extracellular region;integral component of Golgi membrane;extracellular vesicle
Molecular function: molecular_function;acetylglucosaminyltransferase activity;O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity;metal ion binding