ST3GAL5

ST3 beta-galactoside alpha-2,3-sialyltransferase 5, the group of Sialyltransferases

Basic information

Region (hg38): 2:85837119-85905199

Previous symbols: [ "SIAT9" ]

Links

ENSG00000115525 ∙ NCBI:8869 ∙ OMIM:604402 ∙ HGNC:10872 ∙ Uniprot:Q9UNP4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• GM3 synthase deficiency (Definitive), mode of inheritance: AR
• GM3 synthase deficiency (Strong), mode of inheritance: AR
• GM3 synthase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Salt and pepper developmental regression syndrome (Ganglioside GM3 synthase deficiency)	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; Neurologic; Ophthalmologic	4213132; 15502825; 22990144; 23436467
Treatment with ubiquinone has been described, but the overall efficacy is unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ST3GAL5 gene.

• GM3 synthase deficiency (341 variants)
• not provided (46 variants)
• Inborn genetic diseases (15 variants)
• not specified (6 variants)
• Intellectual disability (2 variants)
• Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ST3GAL5 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			4	69		73
missense	2	2	140		3	147
nonsense	10	1				11
start loss						0
frameshift	7	5	2			14
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	2				3
splice region			8	13	1	22
non coding		1	26	37	17	81
Total	20	11	175	106	20

Highest pathogenic variant AF is 0.0000525

Variants in ST3GAL5

This is a list of pathogenic ClinVar variants found in the ST3GAL5 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-85839143-C-T		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839168-C-A		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839194-C-T		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839200-G-A		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839388-C-T		GM3 synthase deficiency	Uncertain significance (Jan 12, 2018)
2-85839466-G-A		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839495-G-A		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839535-C-G		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839537-G-A		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839550-C-T		GM3 synthase deficiency	Benign (Jan 12, 2018)
2-85839662-C-T		GM3 synthase deficiency	Benign (Jan 12, 2018)
2-85839689-C-T		GM3 synthase deficiency	Uncertain significance (Jan 12, 2018)
2-85839712-C-T		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839729-A-G		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839732-G-A		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839781-T-G		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839789-C-T		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839800-G-A		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839821-G-C		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839884-C-T		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85839997-G-A		GM3 synthase deficiency	Uncertain significance (Jan 13, 2018)
2-85840003-AT-A		GM3 synthase deficiency	Uncertain significance (Jun 14, 2016)
2-85840004-T-A		GM3 synthase deficiency	Uncertain significance (Jan 12, 2018)
2-85840029-G-A		GM3 synthase deficiency	Likely benign (Jan 13, 2018)
2-85840075-T-C		GM3 synthase deficiency	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ST3GAL5	protein_coding	protein_coding	ENST00000377332	7	49871

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00131	0.991	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	168	211	0.797	0.0000117	2735
Missense in Polyphen		48	77.081	0.62272		960
Synonymous	1.23	65	78.9	0.824	0.00000462	785
Loss of Function	2.35	8	19.1	0.419	0.00000109	245

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000308	0.000308
Middle Eastern	0.000326	0.000326
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the formation of ganglioside GM3 (alpha-N- acetylneuraminyl-2,3-beta-D-galactosyl-1, 4-beta-D- glucosylceramide). {ECO:0000269|PubMed:16934889}.
• Disease: DISEASE: Salt and pepper developmental regression syndrome (SPDRS) [MIM:609056]: A rare autosomal recessive disorder characterized by infantile onset of severe, recurrent and refractory seizures, failure to thrive, psychomotor delay, developmental stagnation, and cortical blindness. Deafness is observed in some patients. Affected individuals have patches of skin hypo- or hyperpigmentation on the trunk, face, and extremities. {ECO:0000269|PubMed:15502825}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycosphingolipid biosynthesis - ganglio series - Homo sapiens (human);Ganglio Sphingolipid Metabolism;Post-translational protein modification;Metabolism of proteins;Glycosphingolipid biosynthesis - ganglioseries;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 (Consensus)

Recessive Scores

• pRec: 0.153

Intolerance Scores

• loftool: 0.713
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.69

Haploinsufficiency Scores

• pHI: 0.111
• hipred: N
• hipred_score: 0.385
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.324

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: St3gal5
• Phenotype: 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); homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: st3gal5
• Affected structure: midbrain
• Phenotype tag: abnormal
• Phenotype quality: increased occurrence

Gene ontology

• Biological process: ganglioside biosynthetic process;carbohydrate metabolic process;protein glycosylation;glycosphingolipid biosynthetic process;sialylation
• Cellular component: Golgi membrane;integral component of plasma membrane;integral component of membrane
• Molecular function: beta-galactoside (CMP) alpha-2,3-sialyltransferase activity;neolactotetraosylceramide alpha-2,3-sialyltransferase activity;sialyltransferase activity;lactosylceramide alpha-2,3-sialyltransferase activity