SLC19A3

solute carrier family 19 member 3, the group of Solute carrier family 19

Basic information

Region (hg38): 2:227683763-227718028

Links

ENSG00000135917 ∙ NCBI:80704 ∙ OMIM:606152 ∙ HGNC:16266 ∙ Uniprot:Q9BZV2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• biotin-responsive basal ganglia disease (Definitive), mode of inheritance: AR
• biotin-responsive basal ganglia disease (Strong), mode of inheritance: AR
• biotin-responsive basal ganglia disease (Strong), mode of inheritance: AR
• biotin-responsive basal ganglia disease (Supportive), mode of inheritance: AR
• thiamine-responsive encephalopathy (Supportive), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• infantile spams-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome (Supportive), mode of inheritance: AR
• Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Basal ganglia disease, biotin-thiamine responsive	AR	Biochemical	Medical management (with biotin and/or thiamine) has been reported as beneficial; During crises, medical management with biotin and/or thiamine has been reported as resulting in marked improvement within days, and untreated encephalopathies can result in permanent dystonia	Biochemical; Neurologic	9679779; 15871139; 19387023; 20065143; 21176162; 22777947; 23423671; 24878501; 24957181

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC19A3 gene.

• Biotin-responsive_basal_ganglia_disease (532 variants)
• not_provided (148 variants)
• Inborn_genetic_diseases (35 variants)
• not_specified (29 variants)
• SLC19A3-related_disorder (12 variants)
• Spastic_paraplegia (1 variants)
• Thiamine_metabolism_dysfunction_syndrome_2_(biotin/thiamine-responsive_basal_ganglia_disease_type) (1 variants)
• Intellectual_disability (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC19A3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000025243.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	177	4	182
missense	8	18	227	25	2	280
nonsense	14	6				20
start loss		1				1
frameshift	18	8	5			31
splice donor/acceptor (+/-2bp)	1	6				7
Total	41	39	233	202	6

Highest pathogenic variant AF is 0.000068765905

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC19A3	protein_coding	protein_coding	ENST00000258403	5	32803

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.104	0.895	125723	0	24	125747	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.365	283	266	1.06	0.0000141	3224
Missense in Polyphen		93	91.838	1.0127		1193
Synonymous	1.52	89	109	0.815	0.00000705	986
Loss of Function	2.82	5	17.8	0.280	7.66e-7	230

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.0000544	0.0000544
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates high affinity thiamine uptake, probably via a proton anti-port mechanism. Has no folate transport activity. {ECO:0000269|PubMed:11731220}.
• Pathway: Vitamin digestion and absorption - Homo sapiens (human);Vitamin B1 (thiamin) metabolism;Vitamin B1 (thiamin) metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Vitamin H (biotin) metabolism (Consensus)

Recessive Scores

• pRec: 0.143

Intolerance Scores

• loftool: 0.192
• rvis_EVS: -0.24
• rvis_percentile_EVS: 36.17

Haploinsufficiency Scores

• pHI: 0.0974
• hipred: N
• hipred_score: 0.144
• ghis: 0.458

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0259

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc19a3
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; immune system phenotype; renal/urinary system phenotype; 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); digestive/alimentary 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)

Gene ontology

• Biological process: thiamine transport;thiamine-containing compound metabolic process;transmembrane transport;thiamine transmembrane transport
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: thiamine transmembrane transporter activity