POGLUT1

Summary

POGLUT1 (protein O-glucosyltransferase 1, HGNC:22954) is a protein-coding gene on chromosome 3q13.33, encoding Protein O-glucosyltransferase 1 (Q8NBL1). 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.

This gene encodes a protein with both O-glucosyltransferase and O-xylosyltransferase activity which localizes to the lumen of the endoplasmic reticulum. This protein has a carboxy-terminal KTEL motif which is predicted to function as an endoplasmic reticulum retention signal. This gene is an essential regulator of Notch signalling and likely plays a role in cell fate and tissue formation during development. It may also play a role in the pathogenesis of leukemia. Mutations in this gene have been associated with the autosomal dominant genodermatosis Dowling-Degos disease 4. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 56983 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive limb-girdle muscular dystrophy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 340 total — 15 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 45
• MANE Select transcript: NM_152305

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22954
Approved symbol	POGLUT1
Name	protein O-glucosyltransferase 1
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	MDS010, MGC32995, 9630046K23Rik, MDSRP, hCLP46, KDELCL1, Rumi
Ensembl gene	ENSG00000163389
Ensembl biotype	protein_coding
OMIM	615618
Entrez	56983

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000295588, ENST00000390401, ENST00000460339, ENST00000473648, ENST00000476573, ENST00000481043, ENST00000486607, ENST00000497447, ENST00000647766, ENST00000909528, ENST00000909529, ENST00000937492, ENST00000937493, ENST00000937494, ENST00000961894, ENST00000961895

RefSeq mRNA: 1 — MANE Select: NM_152305 NM_152305

CCDS: CCDS2988

Canonical transcript exons

ENST00000295588 — 11 exons

Exon	Start	End
ENSE00001238863	119480051	119480172
ENSE00001238870	119477313	119477448
ENSE00001238898	119492282	119494708
ENSE00001847914	119468963	119469106
ENSE00003504745	119486833	119486932
ENSE00003552754	119491518	119491574
ENSE00003613490	119490551	119490718
ENSE00003615585	119469820	119469910
ENSE00003641729	119471309	119471452
ENSE00003676002	119488929	119488987
ENSE00003692888	119485328	119485387

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 88.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.5055 / max 105.4209, expressed in 1795 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38102	10.5055	1795

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	88.56	gold quality
stromal cell of endometrium	CL:0002255	87.58	gold quality
monocyte	CL:0000576	86.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.72	gold quality
lymph node	UBERON:0000029	86.36	gold quality
mononuclear cell	CL:0000842	86.07	gold quality
leukocyte	CL:0000738	85.85	gold quality
adrenal tissue	UBERON:0018303	85.48	gold quality
body of pancreas	UBERON:0001150	84.97	gold quality
rectum	UBERON:0001052	84.80	gold quality
skin of abdomen	UBERON:0001416	84.22	gold quality
buccal mucosa cell	CL:0002336	83.82	silver quality
body of uterus	UBERON:0009853	83.70	gold quality
germinal epithelium of ovary	UBERON:0001304	83.62	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.60	gold quality
skin of leg	UBERON:0001511	83.51	gold quality
vermiform appendix	UBERON:0001154	83.44	gold quality
granulocyte	CL:0000094	83.36	gold quality
epithelium of nasopharynx	UBERON:0001951	83.27	gold quality
nasopharynx	UBERON:0001728	83.26	gold quality
right coronary artery	UBERON:0001625	83.13	gold quality
pancreas	UBERON:0001264	83.10	gold quality
left adrenal gland cortex	UBERON:0035825	83.02	gold quality
descending thoracic aorta	UBERON:0002345	82.94	gold quality
islet of Langerhans	UBERON:0000006	82.91	gold quality
caecum	UBERON:0001153	82.83	gold quality
left adrenal gland	UBERON:0001234	82.76	gold quality
right adrenal gland cortex	UBERON:0035827	82.69	gold quality
right adrenal gland	UBERON:0001233	82.68	gold quality
spleen	UBERON:0002106	82.64	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	10.23
E-ANND-3	yes	7.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

147 targeting POGLUT1, 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-3064-3P	100.00	70.09	1254
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-1229-3P	99.97	66.49	906
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4487	99.96	64.58	1252

Literature-anchored findings (GeneRIF, showing 16)

• Altered C3ORF9 expression in myelodysplastic syndrome was possibly due to different gene regulation in these patients and/or to the increased CD34+ cells. (PMID:19822096)
• CLP46 was overexpressed in AML, T-ALL, and leukemic cell lines. Considering that CLP46 has the capability of modifying the Notch pathway, our finding adds weight to the possible importance of Notch signaling in the pathogenesis of AML and T-ALL. (PMID:20143914)
• lack of hCLP46 results in impaired ligand induced Notch activation in mammalian cell, and hCLP46 regulates the proliferation of U937 cell through CDKI-RB signaling pathway, which may be important for the pathogenesis of leukemia. (PMID:21458412)
• overexpression of hCLP46 inhibited proliferation of 293TRexs and was correlated with increases in cyclin dependent kinase inhibitors p21 and p27, whereas reduced hCLP46 expression moderately increased cell proliferation. (PMID:23692084)
• Mutations in POFUT1, which encodes protein O-fucosyltransferase 1, were reported to be responsible for Dowling-Degos disease. (PMID:24387993)
• miR-134 inhibited human endometrial cancer stem cells proliferation and migration by targeting protein O-glucosyltransferase 1 (POGLUT1) expression (PMID:25528443)
• hCLP46 increases Smad3 protein stability via inhibiting its ubiquitin-proteasomal degradation (PMID:26058784)
• These findings expand the spectrum of mutations in POGLUT1 and confirm POGLUT1 as the third candidate gene, along with KRT5 and POFUT1, to consider in diagnosis of GGD/DDD. (PMID:27479915)
• These data suggest that a key pathomechanism for this novel form of muscular dystrophy with POGLUT1 mutation is Notch-dependent loss of satellite cells. (PMID:27807076)
• The data suggest that hCLP46(human CAP10-like protein 46 kDa) overexpression in colorectal cancer is associated with higher tumor-node-metastasis stage, lymph node metastasis, and shorter survival time. (PMID:28481732)
• Here we report the generation and characterization of an iPSC line (CSCRMi001-A) from a LGMD-2Z patient with missense mutation in POGLUT1 which can be used for in vitro disease modeling. (PMID:29034878)
• To conclude, we report a new heterozygous nonsense mutation in POGLUT1 predicted to result in a loss of function in two siblings with DD disease. (PMID:29569780)
• RUMI is a novel negative prognostic factor with significant therapeutic potential in non-small-cell lung cancer. (PMID:29953591)
• This is the first study to demonstrate that POGLUT1 and not CD80 is the effector gene regulated by the primary functional SNP rs2293370, and that increased expression of POGLUT1 might be involved in the pathogenesis of Primary biliary cholangitis. (PMID:30643196)
• Case Report: Japanese female with Galli-Galli Disease due to novel POGLUT1 mutation. (PMID:30653241)
• POGLUT1 biallelic mutations cause myopathy with reduced satellite cells, alpha-dystroglycan hypoglycosylation and a distinctive radiological pattern. (PMID:31897643)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	poglut1	ENSDARG00000053463
mus_musculus	Poglut1	ENSMUSG00000034064
rattus_norvegicus	Poglut1	ENSRNOG00000003014
drosophila_melanogaster	CG31139	FBGN0051139
drosophila_melanogaster	rumi	FBGN0086253

Paralogs (2): POGLUT2 (ENSG00000134901), POGLUT3 (ENSG00000178202)

Protein

Protein identifiers

Protein O-glucosyltransferase 1 — Q8NBL1 (reviewed: Q8NBL1)

Alternative names: CAP10-like 46 kDa protein, KTEL motif-containing protein 1, Myelodysplastic syndromes relative protein, O-glucosyltransferase Rumi homolog, Protein O-xylosyltransferase POGLUT1

All UniProt accessions (5): B4DVA9, Q8NBL1, F8WDC4, F8WEW4, H7C5H0

UniProt curated annotations — full annotation on UniProt →

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. Specifically targets extracellular EGF repeats of protein such as CRB2, F7, F9 and NOTCH2. Acts as a positive regulator of Notch signaling by mediating O-glucosylation of Notch, leading to regulate muscle development. Notch glucosylation does not affect Notch ligand binding. Required during early development to promote gastrulation: acts by mediating O-glucosylation of CRB2, which is required for CRB2 localization to the cell membrane.

Subcellular location. Endoplasmic reticulum lumen.

Tissue specificity. Expressed in most adult tissues at different intensities. Abundantly expressed in liver. Expressed also in brain, heart, skeletal muscle, spleen, kidney, placenta, lung and peripheral blood leukocyte. Not detectable in colon, thymus and small intestine. Expressed in the epidermis, especially in the upper parts, stratum spinosum and stratum granulosum (at protein level).

Disease relevance. Dowling-Degos disease 4 (DDD4) [MIM:615696] A form of Dowling-Degos disease, a genodermatosis manifesting with 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. DDD4 is characterized by prominent involvement of non-flexural skin areas. The disease is caused by variants affecting the gene represented in this entry. Muscular dystrophy, limb-girdle, autosomal recessive 21 (LGMDR21) [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. LGMDR21 is characterized by young-adult onset. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 90 family.

RefSeq proteins (1): NP_689518* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006598	CAP10	Domain
IPR051091	O-Glucosyltr/Glycosyltrsf_90	Family

Pfam: PF05686

Enzyme classification (BRENDA):

• EC 2.4.1.376 — EGF-domain serine glucosyltransferase (BRENDA: 3 organisms, 15 substrates, 1 inhibitors, 0 Km, 0 kcat entries)
• EC 2.4.2.63 — EGF-domain serine xylosyltransferase (BRENDA: 3 organisms, 10 substrates, 1 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[EGF-like domain protein] + UDP-alpha-D-glucose = 3-O-(beta-D-glucosyl)-L-seryl-[EGF-like domain protein] + UDP + H(+) (RHEA:58116)
• L-seryl-[EGF-like domain protein] + UDP-alpha-D-xylose = 3-O-(beta-D-xylosyl)-L-seryl-[EGF-like domain protein] + UDP + H(+) (RHEA:62016)

UniProt features (64 total): helix 19, strand 13, sequence variant 6, glycosylation site 4, disulfide bond 4, binding site 4, turn 3, site 2, region of interest 2, sequence conflict 2, signal peptide 1, chain 1, mutagenesis site 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5L0V	X-RAY DIFFRACTION	1.3
5L0T	X-RAY DIFFRACTION	1.43
5L0S	X-RAY DIFFRACTION	1.45
5L0R	X-RAY DIFFRACTION	1.5
5L0U	X-RAY DIFFRACTION	1.8
5UB5	X-RAY DIFFRACTION	2.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBL1-F1	93.11	0.90

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 (3): 132 (interaction with the consensus sequence c-x-s-x-[pa]-c in peptide substrates); 240 (interaction with the consensus sequence c-x-s-x-[pa]-c in peptide substrates); 133 (proton donor/acceptor)

Ligand- & substrate-binding residues (4): 177; 212; 218; 274–279

Disulfide bonds (4): 49–56, 54–357, 102–108, 263–286

Glycosylation sites (4): 40, 53, 204, 373

Mutagenesis-validated functional residues (1):

Position	Phenotype
169	loss of o-glucosyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1912399	Pre-NOTCH Processing in the Endoplasmic Reticulum

MSigDB gene sets: 280 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, REACTOME_SIGNALING_BY_NOTCH, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, SP3_Q3, GOBP_POSITIVE_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, YY1_Q6, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GTGCCTT_MIR506, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_SOMITOGENESIS

GO Biological Process (14): somitogenesis (GO:0001756), protein O-linked glycosylation (GO:0006493), gastrulation (GO:0007369), regulation of gastrulation (GO:0010470), positive regulation of Notch signaling pathway (GO:0045747), axial mesoderm development (GO:0048318), paraxial mesoderm development (GO:0048339), muscle tissue development (GO:0060537), circulatory system development (GO:0072359), protein O-linked glycosylation via glucose (GO:0180059), protein O-linked glycosylation via xylose (GO:0180064), obsolete protein glycosylation (GO:0006486), regulation of Notch signaling pathway (GO:0008593), obsolete protein O-linked glycosylation via serine (GO:0018242)

GO Molecular Function (7): UDP-glucosyltransferase activity (GO:0035251), UDP-xylosyltransferase activity (GO:0035252), glucosyltransferase activity (GO:0046527), EGF-domain serine glucosyltransferase activity (GO:0140561), EGF-domain serine xylosyltransferase activity (GO:0140562), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Pre-NOTCH Expression and Processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
Notch signaling pathway	2
mesoderm development	2
protein O-linked glycosylation	2
UDP-glycosyltransferase activity	2
anterior/posterior pattern specification	1
segmentation	1
chordate embryonic development	1
anatomical structure formation involved in morphogenesis	1
somite development	1
glycoprotein biosynthetic process	1
ectoderm formation	1
endoderm formation	1
mesoderm formation	1
embryonic morphogenesis	1
gastrulation	1
regulation of anatomical structure morphogenesis	1
regulation of embryonic development	1
regulation of Notch signaling pathway	1
positive regulation of signal transduction	1
mesenchyme development	1
tissue development	1
system development	1
regulation of signal transduction	1
glucosyltransferase activity	1
xylosyltransferase activity	1
hexosyltransferase activity	1
UDP-glucosyltransferase activity	1
UDP-xylosyltransferase activity	1
catalytic activity	1
transferase activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1
vacuole	1
plasma membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

552 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POGLUT1	POFUT1	Q9H488	860
POGLUT1	XXYLT1	Q8NBI6	805
POGLUT1	EOGT	Q5NDL2	772
POGLUT1	GXYLT1	Q4G148	725
POGLUT1	GXYLT2	A0PJZ3	723
POGLUT1	NOTCH1	P46531	585
POGLUT1	POFUT2	Q9Y2G5	523
POGLUT1	PSENEN	Q9NZ42	487
POGLUT1	RFNG	Q9Y644	462
POGLUT1	NOTCH2	Q04721	451
POGLUT1	EGF	P01133	430
POGLUT1	B4GAT1	O43505	429
POGLUT1	POMT1	Q9Y6A1	427
POGLUT1	ARHGAP31	Q2M1Z3	421
POGLUT1	TIMMDC1	Q9NPL8	418

IntAct

94 interactions, top by confidence:

A	B	Type	Score
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
POGLUT1	CANX	psi-mi:“MI:0914”(association)	0.640
PRG3	ZNF324	psi-mi:“MI:0914”(association)	0.530
POGLUT1	ZZEF1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
POGLUT1	CLGN	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
SUSD4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
F9	DDX11L8	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
PTPRK	MANBA	psi-mi:“MI:0914”(association)	0.350
TAZ	MANBA	psi-mi:“MI:0914”(association)	0.350
LYPD4	DPYSL4	psi-mi:“MI:0914”(association)	0.350
LYZL1	MANBA	psi-mi:“MI:0914”(association)	0.350
TMEM25	FUZ	psi-mi:“MI:0914”(association)	0.350
LYZL2	MANBA	psi-mi:“MI:0914”(association)	0.350
	HSPA12A	psi-mi:“MI:0914”(association)	0.350
DPEP2	KDELR3	psi-mi:“MI:0914”(association)	0.350
NAAA	NRP2	psi-mi:“MI:0914”(association)	0.350
A2M	PZP	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
BST1	GXYLT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (154): POGLUT1 (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS), UBR4 (Affinity Capture-MS), CANX (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), CSGALNACT2 (Affinity Capture-MS), PON2 (Affinity Capture-MS), KCMF1 (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS)

ESM2 similar proteins: A0NDG6, A9RGD8, B0X1Q4, G3V9D0, G5EDR5, G5EE06, G5EEE1, G5EFP5, L7YAI7, O35789, O48842, O48843, O97422, P83088, Q08C60, Q09363, Q16QY8, Q29AU6, Q33AH8, Q3V5L5, Q5CB03, Q5E9Q1, Q5F2N2, Q5F2N3, Q6A1G2, Q6DBG8, Q6H4N0, Q6NQ51, Q70AG8, Q765H6, Q7XLG3, Q7Z1Z1, Q8BYB9, Q8H038, Q8MVS5, Q8NBL1, Q8S1X7, Q8S1X8, Q8S1X9, Q8T045

Diamond homologs: A0NDG6, B0X1Q4, G3V9D0, Q16QY8, Q29AU6, Q5E9Q1, Q7ZVE6, Q8BYB9, Q8NBL1, Q8T045, G5E897, Q566E5, Q6UW63, Q7Z4H8, Q9JHP7, Q5K8R6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
POGLUT1	up-regulates	NOTCH1	glycosylation
POGLUT1	up-regulates	NOTCH2	binding
POGLUT1	up-regulates	NOTCH	glycosylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	6
Uncertain significance	152
Likely benign	106
Benign	35

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
126529	NM_152305.3(POGLUT1):c.652C>T (p.Arg218Ter)	Pathogenic
126530	NM_152305.3(POGLUT1):c.798-2A>C	Pathogenic
126531	NM_152305.3(POGLUT1):c.835dup (p.Arg279fs)	Pathogenic
2026258	NM_152305.3(POGLUT1):c.614_615del (p.Ser205fs)	Pathogenic
2052612	NM_152305.3(POGLUT1):c.183_192del (p.Ile61_Glu62insTer)	Pathogenic
2098854	NM_152305.3(POGLUT1):c.803del (p.Leu268fs)	Pathogenic
2118041	NM_152305.3(POGLUT1):c.347del (p.Leu116fs)	Pathogenic
2978970	NM_152305.3(POGLUT1):c.1006C>T (p.Gln336Ter)	Pathogenic
3027277	NM_152305.3(POGLUT1):c.320_321insA (p.Cys108fs)	Pathogenic
3622742	NM_152305.3(POGLUT1):c.891G>A (p.Trp297Ter)	Pathogenic
3631264	NM_152305.3(POGLUT1):c.572del (p.Leu191fs)	Pathogenic
3643343	NM_152305.3(POGLUT1):c.910C>T (p.Gln304Ter)	Pathogenic
3662911	NM_152305.3(POGLUT1):c.1007_1008del (p.Gln336fs)	Pathogenic
372263	NM_152305.3(POGLUT1):c.699T>G (p.Asp233Glu)	Pathogenic
4729449	NM_152305.3(POGLUT1):c.574dup (p.Val192fs)	Pathogenic
1708167	NM_152305.3(POGLUT1):c.292C>T (p.Arg98Trp)	Likely pathogenic
3247059	NC_000003.11:g.(?119198952)(119200618_?)del	Likely pathogenic
3659972	NM_152305.3(POGLUT1):c.798-2A>G	Likely pathogenic
4730038	NM_152305.3(POGLUT1):c.457-2A>G	Likely pathogenic
851736	NM_152305.3(POGLUT1):c.514_578+1602del	Likely pathogenic
988328	NM_152305.3(POGLUT1):c.205C>T (p.Arg69Ter)	Likely pathogenic

SpliceAI

1959 predictions. Top by Δscore:

Variant	Effect	Δscore
3:119471307:A:AG	acceptor_gain	1.0000
3:119471308:G:GG	acceptor_gain	1.0000
3:119471308:GT:G	acceptor_gain	1.0000
3:119477444:GTAAG:G	donor_gain	1.0000
3:119477446:AAGGT:A	donor_loss	1.0000
3:119477447:AGG:A	donor_loss	1.0000
3:119477448:GGT:G	donor_loss	1.0000
3:119477449:G:GA	donor_loss	1.0000
3:119477449:G:GG	donor_gain	1.0000
3:119477450:T:A	donor_loss	1.0000
3:119485323:CTTA:C	acceptor_loss	1.0000
3:119485327:G:GT	acceptor_loss	1.0000
3:119485384:CAAGG:C	donor_loss	1.0000
3:119485385:AAGG:A	donor_loss	1.0000
3:119485386:AGGTG:A	donor_loss	1.0000
3:119485387:GGTG:G	donor_loss	1.0000
3:119485388:G:GG	donor_gain	1.0000
3:119486930:A:T	donor_gain	1.0000
3:119486933:G:GG	donor_gain	1.0000
3:119488988:G:GG	donor_gain	1.0000
3:119490714:GTCCA:G	donor_gain	1.0000
3:119490719:G:GG	donor_gain	1.0000
3:119491517:GA:G	acceptor_gain	1.0000
3:119469007:G:GG	donor_gain	0.9900
3:119469298:A:T	donor_gain	0.9900
3:119469332:G:GT	donor_gain	0.9900
3:119469333:G:T	donor_gain	0.9900
3:119469363:G:GT	donor_gain	0.9900
3:119469908:TGGGT:T	donor_loss	0.9900
3:119469909:GG:G	donor_gain	0.9900

AlphaMissense

2585 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:119471452:G:T	R107M	1.000
3:119477389:G:C	D133H	1.000
3:119477390:A:C	D133A	1.000
3:119477390:A:T	D133V	1.000
3:119480084:T:A	W164R	1.000
3:119480084:T:C	W164R	1.000
3:119480144:T:A	W184R	1.000
3:119480144:T:C	W184R	1.000
3:119480146:G:C	W184C	1.000
3:119480146:G:T	W184C	1.000
3:119471397:T:G	Y89D	0.999
3:119471425:G:C	R98P	0.999
3:119471442:T:C	F104L	0.999
3:119471443:T:G	F104C	0.999
3:119471444:C:A	F104L	0.999
3:119471444:C:G	F104L	0.999
3:119471452:G:C	R107T	0.999
3:119477382:T:A	N130K	0.999
3:119477382:T:G	N130K	0.999
3:119477390:A:G	D133G	0.999
3:119477391:T:A	D133E	0.999
3:119477391:T:G	D133E	0.999
3:119477440:T:C	F150L	0.999
3:119477442:C:A	F150L	0.999
3:119477442:C:G	F150L	0.999
3:119477443:A:C	S151R	0.999
3:119477445:T:A	S151R	0.999
3:119477445:T:G	S151R	0.999
3:119480066:G:C	D158H	0.999
3:119480067:A:T	D158V	0.999

dbSNP variants (sampled 300 via entrez): RS1000044468 (3:119470936 G>C), RS1000333367 (3:119471339 A>C,G,T), RS1000581600 (3:119482466 G>A,T), RS1000750271 (3:119490681 C>T), RS1000903447 (3:119469221 A>G), RS1001026728 (3:119483487 G>A,C), RS1001222341 (3:119489317 G>A), RS1001425015 (3:119471343 G>A), RS1001485902 (3:119476307 A>G), RS1001614572 (3:119490319 C>T), RS1001898550 (3:119483567 T>C), RS1002130574 (3:119472693 G>A,C), RS1002298171 (3:119485198 C>T), RS1002322162 (3:119476693 T>C,G), RS1002383622 (3:119470253 T>G)

Disease associations

OMIM: gene MIM:615618 | disease phenotypes: MIM:615696, MIM:617232

GenCC curated gene-disease

Disease	Classification	Inheritance
Dowling-Degos disease 4	Strong	Autosomal dominant
autosomal recessive limb-girdle muscular dystrophy type 2R1	Strong	Autosomal recessive
Dowling-Degos disease	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy	Definitive	AR

Mondo (3): Dowling-Degos disease 4 (MONDO:0014307), autosomal recessive limb-girdle muscular dystrophy type 2R1 (MONDO:0014977), Dowling-Degos disease (MONDO:0008371)

Orphanet (2): POGLUT1-related limb-girdle muscular dystrophy R21 (Orphanet:480682), Dowling-Degos disease (Orphanet:79145)

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000464	Abnormality of the neck
HP:0000962	Hyperkeratosis
HP:0000989	Pruritus
HP:0001034	Hypermelanotic macule
HP:0001155	Abnormality of the hand
HP:0001231	Abnormal fingernail morphology
HP:0001369	Arthritis
HP:0002046	Heat intolerance
HP:0002091	Restrictive ventilatory defect
HP:0002093	Respiratory insufficiency
HP:0002505	Loss of ambulation
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003581	Adult onset
HP:0003677	Slowly progressive
HP:0003691	Scapular winging
HP:0006536	Airway obstruction
HP:0006785	Limb-girdle muscular dystrophy
HP:0007456	Progressive reticulate hyperpigmentation
HP:0008994	Proximal lower limb muscle weakness
HP:0009123	Mixed hypo- and hyperpigmentation of the skin
HP:0010610	Palmar pits
HP:0011354	Generalized abnormality of skin
HP:0011462	Young adult onset
HP:0012548	Fatty replacement of skeletal muscle
HP:0012855	Scrotal hyperpigmentation
HP:0020073	Hypopigmented macule
HP:0025092	Epidermal acanthosis

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000612_22	Celiac disease	8.000000e-09
GCST005581_44	Primary biliary cirrhosis	7.000000e-16
GCST006585_1606	Blood protein levels	8.000000e-68
GCST009131_7	Systemic sclerosis	2.000000e-10

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562924	Dowling-Degos Disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, affects expression, decreases expression	3
bisphenol F	increases expression, affects cotreatment	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
testosterone undecanoate	affects cotreatment, decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ferrous chloride	decreases expression	1
beta-methylcholine	affects expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Ethanol	decreases expression, increases abundance, affects cotreatment	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Gasoline	increases abundance, affects cotreatment, decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_E2H2	HAP1 POGLUT1 (-) 1	Cancer cell line	Male
CVCL_E2H3	HAP1 POGLUT1 (-) 2	Cancer cell line	Male
CVCL_QX93	CSCRMi001-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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