POFUT1

protein O-fucosyltransferase 1, the group of Fucosyltransferases|MicroRNA protein coding host genes

Basic information

Region (hg38): 20:32207855-32238658

Links

ENSG00000101346 ∙ NCBI:23509 ∙ OMIM:607491 ∙ HGNC:14988 ∙ Uniprot:Q9H488 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Dowling-Degos disease 2 (Moderate), mode of inheritance: AD
• complex neurodevelopmental disorder (Limited), mode of inheritance: AR
• Dowling-Degos disease 2 (Definitive), mode of inheritance: AD
• Dowling-Degos disease 2 (Strong), mode of inheritance: AD
• Dowling-Degos disease (Supportive), mode of inheritance: AD
• Dowling-Degos disease 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the POFUT1 gene.

• Dowling-Degos_disease_2 (82 variants)
• Inborn_genetic_diseases (41 variants)
• not_provided (25 variants)
• POFUT1-related_disorder (7 variants)
• not_specified (1 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	21	5	27
missense			66	4	2	72
nonsense	3		1			4
start loss						0
frameshift	2					2
splice donor/acceptor (+/-2bp)						0
Total	5	0	68	25	7

Highest pathogenic variant AF is 0.0000020530733

GnomAD

Source: gnomAD

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
		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: dbNSFP

• 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

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

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