SLC19A2

solute carrier family 19 member 2, the group of Solute carrier family 19

Basic information

Region (hg38): 1:169463909-169485944

Previous symbols: [ "TRMA" ]

Links

ENSG00000117479 ∙ NCBI:10560 ∙ OMIM:603941 ∙ HGNC:10938 ∙ Uniprot:O60779 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thiamine-responsive megaloblastic anemia syndrome (Strong), mode of inheritance: AR
• thiamine-responsive megaloblastic anemia syndrome (Strong), mode of inheritance: AR
• thiamine-responsive megaloblastic anemia syndrome (Definitive), mode of inheritance: AR
• thiamine-responsive megaloblastic anemia syndrome (Supportive), mode of inheritance: AR
• thiamine-responsive megaloblastic anemia syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thiamine-responsive megaloblastic anemia syndrome	AR	Endocrine; Hematologic	High-dose thiamine can improve anemia and may ameliorate diabetes; Individuals may also have sensorineural hearing loss, but prelingual onset appears to have not been reported	Audiologic/Otolaryngologic; Endocrine; Hematologic	5767338; 671156; 6175336; 2540004; 1326679; 7707690; 10391221; 10391223; 10074490; 10978358; 19643445; 20301459; 22369132; 22576805; 22876572

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC19A2 gene.

• not_provided (345 variants)
• Megaloblastic_anemia,_thiamine-responsive,_with_diabetes_mellitus_and_sensorineural_deafness (132 variants)
• Inborn_genetic_diseases (70 variants)
• Thiamine-responsive_megaloblastic_anemia (18 variants)
• not_specified (18 variants)
• SLC19A2-related_disorder (6 variants)
• Monogenic_diabetes (5 variants)
• Ear_malformation (1 variants)
• Possible_mitochondrial_disorder_-_nuclear_genes (1 variants)
• Sensorineural_hearing_loss_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC19A2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006996.3. 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			4	148		152
missense	3	10	157	11	1	182
nonsense	19	1	2			22
start loss						0
frameshift	21	2	2			25
splice donor/acceptor (+/-2bp)	3	4				7
Total	46	17	165	159	1

Highest pathogenic variant AF is 0.000038418828

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC19A2	protein_coding	protein_coding	ENST00000236137	6	22095

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125710	0	38	125748	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.192	263	272	0.967	0.0000136	3165
Missense in Polyphen		123	117.07	1.0507		1440
Synonymous	0.302	104	108	0.963	0.00000539	1061
Loss of Function	2.36	9	20.6	0.438	0.00000105	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000111	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000186	0.000185
Middle Eastern	0.000111	0.000109
South Asian	0.000262	0.000261
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: High-affinity transporter for the intake of thiamine. {ECO:0000269|PubMed:10391222, ECO:0000269|PubMed:10542220}.
• Pathway: Vitamin digestion and absorption - Homo sapiens (human);Thiamine Metabolism;Glucocorticoid Receptor Pathway;Nuclear Receptors Meta-Pathway;Vitamin B1 (thiamin) metabolism;Vitamin B1 (thiamin) metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

• pRec: 0.159

Intolerance Scores

• loftool: 0.258
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.6

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.323

Gene Damage Prediction

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

Gene ontology

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