POGLUT1

protein O-glucosyltransferase 1, the group of Glycosyltransferase family 90

Basic information

Region (hg38): 3:119468963-119494708

Previous symbols: [ "C3orf9", "KTELC1" ]

Links

ENSG00000163389 ∙ NCBI:56983 ∙ OMIM:615618 ∙ HGNC:22954 ∙ Uniprot:Q8NBL1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Dowling-Degos disease 4 (Moderate), mode of inheritance: AD
• Dowling-Degos disease (Supportive), mode of inheritance: AD
• autosomal recessive limb-girdle muscular dystrophy type 2R1 (Supportive), mode of inheritance: AR
• Dowling-Degos disease 4 (Strong), mode of inheritance: AD
• autosomal recessive limb-girdle muscular dystrophy type 2R1 (Strong), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dowling-Degos disease 4; Muscular dystrophy, limb-girdle, autosomal recessive 21	AD/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	Dermatologic; Musculoskeletal	21971768; 24387993; 27807076

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POGLUT1 gene.

• not provided (7 variants)
• Dowling-Degos disease 4 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POGLUT1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				27	4	31
missense		1	88	5	1	95
nonsense	2	4				6
start loss						0
frameshift	5		1			6
inframe indel						0
splice donor/acceptor (+/-2bp)		1	2			3
splice region			5	9	4	18
non coding			1	35	25	61
Total	7	6	92	67	30

Highest pathogenic variant AF is 0.0000263

Variants in POGLUT1

This is a list of pathogenic ClinVar variants found in the POGLUT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-119469032-G-A		Dowling-Degos disease 4	Pathogenic/Likely pathogenic (Sep 20, 2022)
3-119469038-G-C		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
3-119469038-G-T		POGLUT1-related disorder	Uncertain significance (Jan 11, 2023)
3-119469042-G-A			Likely benign (Jan 20, 2023)
3-119469044-C-T			Uncertain significance (Dec 28, 2023)
3-119469048-T-A			Likely benign (Nov 12, 2023)
3-119469059-T-G			Uncertain significance (May 16, 2023)
3-119469064-T-G		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
3-119469066-G-T		Inborn genetic diseases	Uncertain significance (Aug 08, 2023)
3-119469072-C-T			Likely benign (Mar 18, 2022)
3-119469077-C-T		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
3-119469086-A-G		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
3-119469088-G-A			Uncertain significance (May 20, 2023)
3-119469092-G-A			Uncertain significance (Dec 01, 2023)
3-119469099-G-A			Likely benign (Dec 03, 2021)
3-119469114-C-G			Likely benign (Dec 09, 2022)
3-119469123-GCCGAGCCTGCCCCTTGGGCTCGGGGTCTGGCCGGAGTCCCGAGGCGCTCC-G			Likely benign (Oct 04, 2021)
3-119469125-C-G			Likely benign (Jan 19, 2024)
3-119469126-G-A			Likely benign (Oct 30, 2023)
3-119469126-G-T			Benign/Likely benign (Jan 18, 2024)
3-119469238-C-T			Likely benign (May 01, 2023)
3-119469366-G-T			Benign (Jun 20, 2019)
3-119469800-A-G			Likely benign (Oct 22, 2023)
3-119469813-T-C			Likely benign (Oct 17, 2022)
3-119469830-G-C			Uncertain significance (Jan 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POGLUT1	protein_coding	protein_coding	ENST00000295588	11	25771

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.56e-8	0.956	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.15	164	211	0.777	0.0000107	2570
Missense in Polyphen		58	82.609	0.70211		963
Synonymous	-0.834	81	72.0	1.13	0.00000342	703
Loss of Function	2.00	17	28.6	0.595	0.00000165	297

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000630	0.000629
Ashkenazi Jewish	0.000203	0.000198
East Asian	0.000109	0.000109
Finnish	0.0000555	0.0000462
European (Non-Finnish)	0.000169	0.000167
Middle Eastern	0.000109	0.000109
South Asian	0.0000988	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Dual specificity glycosyltransferase that catalyzes the transfer of glucose and xylose from UDP-glucose and UDP-xylose, respectively, to a serine residue found in the consensus sequence of C-X-S-X-P-C (PubMed:21081508, PubMed:21490058, PubMed:21949356, PubMed:27807076, PubMed:28775322). Specifically targets extracellular EGF repeats of protein such as CRB2, F7, F9 and NOTCH2 (PubMed:21081508, PubMed:21490058, PubMed:21949356, PubMed:27807076, PubMed:28775322). Acts as a positive regulator of Notch signaling by mediating O-glucosylation of Notch, leading to regulate muscle development (PubMed:27807076). Notch glucosylation does not affect Notch ligand binding (PubMed:21490058). Required during early development to promote gastrulation: acts by mediating O-glucosylation of CRB2, which is required for CRB2 localization to the cell membrane (By similarity). {ECO:0000250|UniProtKB:Q8BYB9, ECO:0000269|PubMed:21081508, ECO:0000269|PubMed:21490058, ECO:0000269|PubMed:21949356, ECO:0000269|PubMed:27807076, ECO:0000269|PubMed:28775322}.
• Disease: DISEASE: Limb-girdle muscular dystrophy 2Z (LGMD2Z) [MIM:617232]: A form of autosomal recessive limb-girdle muscular dystrophy, a degenerative myopathy characterized by slowly progressive wasting and weakness of the proximal muscles of arms and legs around the pelvic or shoulder girdles, elevated creatine kinase levels and dystrophic features on muscle biopsy. LGMD2Z is characterized by young-adult onset. {ECO:0000269|PubMed:27807076}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Other types of O-glycan biosynthesis - Homo sapiens (human);Signal Transduction;Pre-NOTCH Processing in the Endoplasmic Reticulum;Pre-NOTCH Expression and Processing;Signaling by NOTCH (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.92

Haploinsufficiency Scores

• pHI: 0.128
• hipred: N
• hipred_score: 0.488
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Poglut1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; liver/biliary system phenotype; embryo 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); 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); 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)

Gene ontology

• Biological process: somitogenesis;protein O-linked glycosylation;gastrulation;regulation of gastrulation;protein O-linked glycosylation via serine;positive regulation of Notch signaling pathway;axial mesoderm development;paraxial mesoderm development;muscle tissue development;cardiovascular system development
• Cellular component: endoplasmic reticulum lumen
• Molecular function: protein xylosyltransferase activity;UDP-glucosyltransferase activity;UDP-xylosyltransferase activity;glucosyltransferase activity