GALNT3

polypeptide N-acetylgalactosaminyltransferase 3, the group of Polypeptide N-acetylgalactosaminyltransferases

Basic information

Region (hg38): 2:165747588-165846201

Links

ENSG00000115339

∙ NCBI:2591 ∙ OMIM:601756 ∙ HGNC:4125 ∙ Uniprot:Q14435 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

tumoral calcinosis, hyperphosphatemic, familial, 1 (Strong), mode of inheritance: AR
tumoral calcinosis, hyperphosphatemic, familial, 1 (Strong), mode of inheritance: AR
tumoral calcinosis, hyperphosphatemic, familial, 1 (Strong), mode of inheritance: AR
tumoral calcinosis, hyperphosphatemic, familial, 1 (Supportive), mode of inheritance: AR
tumoral calcinosis, hyperphosphatemic, familial, 1 (Definitive), mode of inheritance: AR
tumoral calcinosis, hyperphosphatemic, familial, 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tumoral calcinosis, hyperphosphatemic, familial, 1	AR	Renal	Individuals may manifest with sequelae (ie, increased calcium phosphate deposition) of hyperphosphatemia due to increased renal phosphate absorption, and phosphate reduction (eg, with dietary means and phosphate-binding agents) can be beneficial, though families for whom treatment was not effective have been reported	Dermatologic; Musculoskeletal; Renal	3774168; 4538804; 3998061; 3839626; 3659264; 338191; 2777854; 12541190; 15133511; 15599692; 15687324; 16528452; 16528452; 16567474; 16940445; 17129170; 17311862; 17351710; 17853462; 18322299; 18618993; 18982401; 19255228; 20358599; 21347749; 22142751

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GALNT3 gene.

not_provided (372 variants)
Tumoral_calcinosis,_hyperphosphatemic,_familial,_1 (125 variants)
Inborn_genetic_diseases (60 variants)
GALNT3-related_disorder (10 variants)
not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GALNT3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004482.4. 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			2 clinvar	137 clinvar	1 clinvar	140
missense	5 clinvar	12 clinvar	164 clinvar	3 clinvar	3 clinvar	187
nonsense	13 clinvar	4 clinvar				17
start loss						0
frameshift	15 clinvar	4 clinvar				19
splice donor/acceptor (+/-2bp)	5 clinvar	10 clinvar	1 clinvar			16
Total	38	30	167	140	4

Highest pathogenic variant AF is 0.000053282514

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GALNT3	protein_coding	protein_coding	ENST00000392701	10	47092

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.41e-9	0.973	125648	0	98	125746	0.000390

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.386	317	337	0.941	0.0000173	4190
Missense in Polyphen		138	160.69	0.85879		1927
Synonymous	0.491	106	113	0.941	0.00000586	1161
Loss of Function	2.16	18	30.9	0.582	0.00000163	393

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00222	0.00217
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000489	0.000489
Finnish	0.000110	0.0000924
European (Non-Finnish)	0.000344	0.000343
Middle Eastern	0.000489	0.000489
South Asian	0.000197	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on the protein receptor. Has activity toward HIV envelope glycoprotein gp120, EA2, Muc2 and Muc5. Probably glycosylates fibronectin in vivo. Glycosylates FGF23. Plays a central role in phosphate homeostasis. {ECO:0000269|PubMed:16638743, ECO:0000269|PubMed:9295285}.;
Disease: DISEASE: Tumoral calcinosis, hyperphosphatemic, familial, 1 (HFTC1) [MIM:211900]: A form of hyperphosphatemic tumoral calcinosis, a rare autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Some patients have recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis and absence of skin involvement. {ECO:0000269|PubMed:15133511, ECO:0000269|PubMed:15599692}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Mucin type O-glycan biosynthesis - Homo sapiens (human);FGFR3c ligand binding and activation;Signaling by FGFR3;Signal Transduction;Signaling by FGFR;FGFR3 ligand binding and activation;Post-translational protein modification;Metabolism of proteins;mucin core 1 and core 2 <i>O</i>-glycosylation;O-Glycan biosynthesis;Signaling by Receptor Tyrosine Kinases;O-linked glycosylation of mucins;O-linked glycosylation (Consensus)

Intolerance Scores

loftool: 0.676
rvis_EVS: -0.38
rvis_percentile_EVS: 28.11

Haploinsufficiency Scores

pHI: 0.228
hipred: N
hipred_score: 0.394
ghis: 0.488

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.189

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Galnt3
Phenotype: craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); hematopoietic 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); growth/size/body region phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype;

Gene ontology

Biological process: carbohydrate metabolic process;fibroblast growth factor receptor signaling pathway;O-glycan processing;protein O-linked glycosylation via serine;protein O-linked glycosylation via threonine
Cellular component: Golgi membrane;Golgi apparatus;membrane;integral component of membrane;Golgi cisterna membrane;perinuclear region of cytoplasm;extracellular exosome
Molecular function: polypeptide N-acetylgalactosaminyltransferase activity;calcium ion binding;manganese ion binding;carbohydrate binding