ST3GAL3

ST3 beta-galactoside alpha-2,3-sialyltransferase 3, the group of Sialyltransferases|MicroRNA protein coding host genes

Basic information

Region (hg38): 1:43705823-43931165

Previous symbols: [ "SIAT6", "MRT12" ]

Links

ENSG00000126091 ∙ NCBI:6487 ∙ OMIM:606494 ∙ HGNC:10866 ∙ Uniprot:Q11203 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 12 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy, 15 (Limited), mode of inheritance: AR
• West syndrome (Supportive), mode of inheritance: AD
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• developmental and epileptic encephalopathy, 15 (Strong), mode of inheritance: AR
• complex neurodevelopmental disorder (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual development disorder, autosomal recessive 12; Developmental and epileptic encephalopathy 15	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	Neurologic	17120046; 21907012; 23252400
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ST3GAL3 gene.

• Early infantile epileptic encephalopathy with suppression bursts (264 variants)
• not provided (62 variants)
• Inborn genetic diseases (47 variants)
• not specified (25 variants)
• Developmental and epileptic encephalopathy, 15 (11 variants)
• Intellectual disability, autosomal recessive 12 (7 variants)
• Intellectual disability, autosomal recessive 12;Developmental and epileptic encephalopathy, 15 (4 variants)
• Intellectual disability (3 variants)
• Developmental and epileptic encephalopathy, 15;Intellectual disability, autosomal recessive 12 (2 variants)
• Prolonged neonatal jaundice;Intellectual disability, severe;Frequent falls;Difficulty walking;Aggressive behavior (1 variants)
• Epilepsy due to perinatal stroke (1 variants)
• Developmental and epileptic encephalopathy, 1 (1 variants)
• Generalized myoclonic seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ST3GAL3 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			5	61		66
missense		2	120	5	1	128
nonsense	3					3
start loss			2			2
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)	2	6				8
splice region			10	14	1	25
non coding		1	5	44	22	72
Total	5	9	134	110	23

Highest pathogenic variant AF is 0.00000658

Variants in ST3GAL3

This is a list of pathogenic ClinVar variants found in the ST3GAL3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-43717324-T-C		Developmental and epileptic encephalopathy, 15	Uncertain significance (Jun 18, 2020)
1-43717557-G-A			Uncertain significance (Feb 04, 2021)
1-43723677-T-G			Uncertain significance (Feb 04, 2021)
1-43736265-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jun 03, 2022)
1-43736274-G-A		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Mar 31, 2023)
1-43736277-A-G		Inborn genetic diseases	Likely benign (Jun 20, 2017)
1-43736285-G-A		not specified • Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Nov 07, 2023)
1-43736285-G-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (May 25, 2022)
1-43736287-A-C		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
1-43736288-A-G		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Aug 31, 2021)
1-43736300-C-A		Intellectual disability, autosomal recessive 12	Pathogenic (Sep 09, 2011)
1-43736320-C-G		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Mar 29, 2020)
1-43736342-C-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jul 05, 2020)
1-43736343-G-A		Early infantile epileptic encephalopathy with suppression bursts • Inborn genetic diseases	Likely benign (Oct 13, 2023)
1-43736349-G-A		Early infantile epileptic encephalopathy with suppression bursts • Inborn genetic diseases	Likely benign (Oct 10, 2023)
1-43736378-C-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jul 12, 2018)
1-43736380-A-G		Inborn genetic diseases	Uncertain significance (Mar 19, 2019)
1-43736381-G-A		Early infantile epileptic encephalopathy with suppression bursts	Likely pathogenic (Jul 21, 2021)
1-43736383-A-G		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Feb 11, 2022)
1-43736385-G-A		not specified • Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jul 19, 2022)
1-43736386-T-C		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Aug 16, 2022)
1-43736390-G-C		not specified • Early infantile epileptic encephalopathy with suppression bursts • ST3GAL3-related disorder	Conflicting classifications of pathogenicity (Jan 17, 2024)
1-43736396-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Aug 16, 2022)
1-43736416-C-G		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
1-43736419-G-T		Intellectual disability, autosomal recessive 12	Uncertain significance (Jul 11, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ST3GAL3	protein_coding	protein_coding	ENST00000262915	12	225337

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00256	0.997	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.50	188	255	0.736	0.0000172	2854
Missense in Polyphen		49	92.206	0.53142		1059
Synonymous	0.275	101	105	0.966	0.00000735	904
Loss of Function	3.00	9	25.3	0.356	0.00000144	301

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.0000615	0.0000615
Middle Eastern	0.000272	0.000272
South Asian	0.000392	0.000392
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the formation of the NeuAc-alpha-2,3-Gal-beta- 1,4-GlcNAc-, NeuAc-alpha-2,3-Gal-beta-1,3-GlcNAc- and NeuAc-alpha- 2,3-Gal-beta-1,3-GalNAc- sequences found in terminal carbohydrate groups of glycoproteins and glycolipids. The highest activity is toward Gal-beta-1,3-GlcNAc and the lowest toward Gal-beta-1,3- GalNAc. {ECO:0000250|UniProtKB:P97325}.
• Disease: DISEASE: Mental retardation, autosomal recessive 12 (MRT12) [MIM:611090]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:21907012}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epileptic encephalopathy, early infantile, 15 (EIEE15) [MIM:615006]: A form of epilepsy that manifests in the neonatal or the early infantile period as severely impaired cognitive and motor development, due to recurrent clinical seizures or prominent interictal epileptiform discharges. Patients develop infantile spasms, mainly of the flexor type, between 3 and 7 months of age, which are accompanied by hypsarrhythmia on EEG. Other features include poor eye contact, hypotonia, primitive reflexes, and irritability. Seizures evolve clinically to Lennox-Gastaut syndrome. {ECO:0000269|PubMed:23252400}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Other types of O-glycan biosynthesis - Homo sapiens (human);Mannose type O-glycan biosynthesis - Homo sapiens (human);Glycosphingolipid biosynthesis - lacto and neolacto series - Homo sapiens (human);Glycosaminoglycan biosynthesis - keratan sulfate - Homo sapiens (human);Glycosphingolipid biosynthesis - lactoseries;Signal Transduction;Metabolism of carbohydrates;Keratan sulfate biosynthesis;Keratan sulfate/keratin metabolism;Glycosaminoglycan metabolism;Post-translational protein modification;Metabolism of proteins;Metabolism;Pre-NOTCH Processing in Golgi;Pre-NOTCH Expression and Processing;Signaling by NOTCH;terminal <i>O</i>-glycans residues modification;Sialic acid metabolism;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation;Termination of O-glycan biosynthesis;O-linked glycosylation of mucins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.589
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.16

Haploinsufficiency Scores

• pHI: 0.351
• hipred: Y
• hipred_score: 0.625
• ghis: 0.667

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.871

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: St3gal3

Gene ontology

• Biological process: protein glycosylation;O-glycan processing;keratan sulfate biosynthetic process;sialylation
• Cellular component: Golgi membrane;extracellular region;integral component of membrane;Golgi cisterna membrane
• Molecular function: beta-galactoside (CMP) alpha-2,3-sialyltransferase activity;N-acetyllactosaminide alpha-2,3-sialyltransferase activity;sialyltransferase activity