SLC35A3

solute carrier family 35 member A3, the group of Solute carrier family 35

Basic information

Region (hg38): 1:99969351-100035634

Links

ENSG00000117620 ∙ NCBI:23443 ∙ OMIM:605632 ∙ HGNC:11023 ∙ Uniprot:Q9Y2D2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder - epilepsy - arthrogryposis syndrome (Strong), mode of inheritance: AR
• autism spectrum disorder - epilepsy - arthrogryposis syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arthrogryposis, impaired intellectual development, and seizures	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	Musculoskeletal; Neurologic	24031089

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC35A3 gene.

• Autism spectrum disorder - epilepsy - arthrogryposis syndrome (25 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC35A3 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				111	2	113
missense	1		38	3	2	44
nonsense	11	1		1		13
start loss						0
frameshift	13	1	1			15
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3	1		1	5
splice region			4	14		18
non coding				40	29	69
Total	25	5	41	155	34

Highest pathogenic variant AF is 0.0000526

Variants in SLC35A3

This is a list of pathogenic ClinVar variants found in the SLC35A3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-99970124-C-T			Benign (Mar 20, 2020)
1-99970577-A-G		Autism spectrum disorder - epilepsy - arthrogryposis syndrome • SLC35A3-related disorder	Benign (Jul 10, 2021)
1-99970713-T-A			Likely benign (Oct 20, 2019)
1-99970859-T-C			Benign (Mar 20, 2020)
1-99993238-G-A			Likely benign (Sep 04, 2018)
1-99993465-C-T			Benign (Jul 27, 2018)
1-99993536-G-T		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Pathogenic (May 16, 2022)
1-99993560-C-T		Autism spectrum disorder - epilepsy - arthrogryposis syndrome • Arthrogryposis multiplex congenita	Benign (Jan 09, 2024)
1-99993565-A-C		Autism spectrum disorder - epilepsy - arthrogryposis syndrome • Arthrogryposis multiplex congenita	Uncertain significance (Aug 24, 2021)
1-99993566-C-T		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Likely benign (Jul 23, 2022)
1-99993575-C-G		Autism spectrum disorder - epilepsy - arthrogryposis syndrome • Inborn genetic diseases	Pathogenic/Likely pathogenic (Jan 09, 2023)
1-99993575-C-T		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Likely benign (Nov 13, 2023)
1-99993576-G-A		Autism spectrum disorder - epilepsy - arthrogryposis syndrome • Arthrogryposis multiplex congenita	Benign (Jan 31, 2024)
1-99993582-C-T		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Likely benign (Dec 05, 2022)
1-99993588-AT-A		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Pathogenic (Jul 03, 2021)
1-99993594-G-A		Autism spectrum disorder - epilepsy - arthrogryposis syndrome • Arthrogryposis multiplex congenita	Uncertain significance (Aug 24, 2021)
1-99993596-C-A		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Likely benign (Jul 06, 2023)
1-99993596-C-G		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Likely benign (Jan 02, 2024)
1-99993596-CT-C		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Pathogenic (Jun 25, 2023)
1-99993598-T-C		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Uncertain significance (Feb 04, 2022)
1-99993603-A-G		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Uncertain significance (Jul 25, 2022)
1-99993608-C-G		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Likely benign (Nov 17, 2023)
1-99993617-T-A		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Likely benign (Nov 15, 2020)
1-99993617-T-G		Autism spectrum disorder - epilepsy - arthrogryposis syndrome • Arthrogryposis multiplex congenita • SLC35A3-related disorder	Likely benign (Jan 31, 2024)
1-99993623-A-T		Autism spectrum disorder - epilepsy - arthrogryposis syndrome	Likely benign (Nov 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC35A3	protein_coding	protein_coding	ENST00000370155	7	57191

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00260	0.984	125700	0	33	125733	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.42	109	159	0.684	0.00000742	2059
Missense in Polyphen		19	34.353	0.55308		482
Synonymous	0.738	51	58.2	0.877	0.00000281	665
Loss of Function	2.17	7	16.5	0.423	8.45e-7	212

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000268	0.000268
Ashkenazi Jewish	0.00	0.00
East Asian	0.000281	0.000272
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000117	0.000114
Middle Eastern	0.000281	0.000272
South Asian	0.000141	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) transporter in the Golgi apparatus. May supply UDP-GlcNAc as substrate for Golgi-resident glycosyltransferases that generate branching of diantennary oligosaccharides. {ECO:0000269|PubMed:10393322}.
• Disease: DISEASE: Arthrogryposis, mental retardation, and seizures (AMRS) [MIM:615553]: A disease characterized by arthrogryposis, mental retardation, autism spectrum disorder, and epilepsy. Additional features include limb malformations, distal joint involvement, microcephaly, retromicrognathia, and general muscle hypotonia. {ECO:0000269|PubMed:24031089}. Note=The disease is caused by mutations affecting the gene represented in this entry. In Golgi vesicles isolated from patient fibroblasts the transport of the respective nucleotide sugar is significantly reduced causing a massive decrease in the content of cell surface expressed highly branched N-glycans and a concomitant sharp increase of lower branched glycoforms.
• Pathway: Transport of vitamins, nucleosides, and related molecules;SLC-mediated transmembrane transport;Transport of small molecules;Galactose metabolism;Transport of nucleotide sugars (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.680
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.4

Haploinsufficiency Scores

• pHI: 0.295
• hipred: N
• hipred_score: 0.439
• ghis: 0.565

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.245

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc35a3

Gene ontology

• Biological process: UDP-N-acetylglucosamine metabolic process;carbohydrate transport;UDP-N-acetylglucosamine transmembrane transport
• Cellular component: Golgi membrane;Golgi apparatus;integral component of Golgi membrane
• Molecular function: UDP-N-acetylglucosamine transmembrane transporter activity;protein binding