POFUT2

protein-coding

protein O-fucosyltransferase 2, the group of Fucosyltransferases

Gene summary

Fucose is typically found as a terminal modification of branched chain glycoconjugates, but it also exists in direct O-linkage to serine or threonine residues within cystine knot motifs in epidermal growth factor (EGF; MIM 131530)-like repeats or thrombospondin (THBS; see MIM 188060) type-1 repeats. POFUT2 is an O-fucosyltransferase that use THBS type-1 repeats as substrates (Luo et al., 2006 [PubMed 16464857]).[supplied by OMIM, Mar 2008]

Previous symbols:

C21orf80

MANE transcript

NM_133635.6

Inheritance

—

ClinVar variants

U:58B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr21:45,263,928-45,287,898

External References & Databases

Ensembl (ENSG00000186866)

Transcript & Mutation Effects

hg38 • Region Span ~24.0 kb

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GenCC 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 POFUT2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 57

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_133635.6. 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 clinvar	1 clinvar	3
missense			55 clinvar	4 clinvar	2 clinvar	61
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	58	6	3	67

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_133635.6	RefSeq	NP_598368.2	9	MANE Select
ENST00000349485.10	Ensembl	ENSP00000339613.5	9	MANE Select
NM_015227.6	RefSeq	NP_056042.1	8	Standard
ENST00000331343.11	Ensembl	ENSP00000329682.7	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
pofut2	Danio rerio	Structure: cranial nerve X Quality: position abnormal

Gene / Model

Organism

Observed Phenotype

pofut2

Danio rerio

Structure: cranial nerve X

Quality: position

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Other types of O-glycan biosynthesis - Homo sapiens (human)
Post-translational protein modification
Metabolism of proteins
O-glycosylation of TSR domain-containing proteins
O-linked glycosylation

Biological Process

mesoderm formation
fucose metabolic process
regulation of gene expression
regulation of epithelial to mesenchymal transition
protein O-linked fucosylation

Molecular Function

peptide-O-fucosyltransferase activity

Cellular Component

endoplasmic reticulum membrane
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000349485
Coding exons: 9
Length: 23971
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.16	204	256	0.796	0.0000160	2775
Missense (PolyPhen)		67	99.591	0.67275		1083
Synonymous	-1.65	134	112	1.20	0.00000816	827
Loss of Function	2.52	10	23.1	0.433	0.00000107	256

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.00014	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue in the consensus sequence C1-X(2,3)-S/T-C2-X(2)-G of thrombospondin type 1 repeats where C1 and C2 are the first and second cysteines, respectively. O-fucosylates members of several protein families including the ADAMTS family, the thrombosporin (TSP) and spondin families. The O-fucosylation of TSRs is also required for restricting epithelial to mesenchymal transition (EMT), maintaining the correct patterning of mesoderm and localization of the definite endoderm (By similarity). Required for the proper secretion of ADAMTS family members such as ADAMSL1 and ADAMST13. {ECO:0000250, ECO:0000269|PubMed:11067851, ECO:0000269|PubMed:16464858, ECO:0000269|PubMed:17395588, ECO:0000269|PubMed:17395589, ECO:0000269|PubMed:22588082}.;

Recessive Scores

pRec: 0.151

Intolerance Scores

LoFtool: 0.275
RVIS EVS: -0.11
RVIS percentile EVS: 45.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.696

Gene Damage Prediction

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