SLC19A1

solute carrier family 19 member 1, the group of Minor histocompatibility antigens|Solute carrier family 19

Basic information

Region (hg38): 21:45493572-45573365

Links

ENSG00000173638 ∙ NCBI:6573 ∙ OMIM:600424 ∙ HGNC:10937 ∙ Uniprot:P41440 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Megaloblastic anemia, folate-responsive; Immunodeficiency 114, folate-responsive	AR	Allergy/Immunology/Infectious; Biochemical	Immunodeficiency 114, folate-responsive can involve immunologic and infections manifestations, and awareness can enable early and aggressive treatment of infections and sequelae, including early treatment with folinic acid, which has been reported as beneficial; Megaloblastic anemia, folate-responsive can manifest with anemia, and managemement (with oral folate) has been reported as being beneficial; Immunodeficiency 114, folate-responsive	Allergy/Immunology/Infectious; Biochemical; Hematologic	32276275; 36517554; 36745868

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC19A1 gene.

• not provided (64 variants)
• Knobloch syndrome (8 variants)
• Knobloch syndrome 1 (3 variants)
• Retinal dystrophy (3 variants)
• COL18A1-related disorder (1 variants)
• Glaucoma, primary closed-angle (1 variants)
• Retinitis pigmentosa (1 variants)
• Macular dystrophy (1 variants)
• Knobloch syndrome 1;Glaucoma, primary closed-angle (1 variants)
• Cataract;Nystagmus;High myopia;Retinal dystrophy (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC19A1 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			1	48	9	58
missense			67	5	4	76
nonsense					1	1
start loss			1			1
frameshift			4		1	5
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			1	2		3
non coding	68	16	518	460	113	1175
Total	68	16	593	513	128

Highest pathogenic variant AF is 0.000952

Variants in SLC19A1

This is a list of pathogenic ClinVar variants found in the SLC19A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-45493577-T-C			Likely pathogenic (May 10, 2023)
21-45493580-G-A			Uncertain significance (Apr 06, 2021)
21-45493581-G-T			Uncertain significance (Feb 04, 2022)
21-45493582-G-C			Benign (Jan 29, 2024)
21-45493584-C-A			Likely benign (Oct 24, 2022)
21-45493584-C-T		COL18A1-related disorder	Likely benign (May 04, 2023)
21-45493585-G-A			Likely benign (Dec 13, 2022)
21-45493591-C-T			Uncertain significance (Mar 17, 2022)
21-45493594-C-T			Likely benign (Oct 03, 2023)
21-45493600-G-A			Benign (May 14, 2021)
21-45493603-A-G		not specified	Benign (May 10, 2021)
21-45493697-T-C			Benign (May 10, 2021)
21-45494347-G-A			Benign (May 10, 2021)
21-45494348-C-T			Benign (May 11, 2021)
21-45494349-T-C			Benign (May 11, 2021)
21-45494523-GTCT-G			Benign (Jan 17, 2024)
21-45494525-C-T			Likely benign (Nov 27, 2023)
21-45494526-T-G			Likely benign (Jan 27, 2023)
21-45494527-T-G			Likely benign (Feb 25, 2021)
21-45494528-C-T			Benign (Jan 27, 2024)
21-45494528-CTTGT-C			Likely benign (Feb 03, 2022)
21-45494529-T-C			Likely benign (Nov 28, 2023)
21-45494531-G-C			Likely benign (Mar 26, 2022)
21-45494531-G-GT			Likely benign (Aug 21, 2021)
21-45494536-T-A			Uncertain significance (May 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC19A1	protein_coding	protein_coding	ENST00000311124	5	50840

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000647	0.721	125616	0	56	125672	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.606	350	383	0.913	0.0000282	3676
Missense in Polyphen		103	132.77	0.7758		1355
Synonymous	-0.284	200	195	1.03	0.0000153	1339
Loss of Function	1.11	10	14.6	0.686	7.89e-7	146

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000486	0.000472
Ashkenazi Jewish	0.000522	0.000497
East Asian	0.0000693	0.0000544
Finnish	0.000103	0.0000924
European (Non-Finnish)	0.000227	0.000202
Middle Eastern	0.0000693	0.0000544
South Asian	0.000392	0.000392
Other	0.000185	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transporter for the intake of folate. Uptake of folate in human placental choriocarcinoma cells occurs by a novel mechanism called potocytosis which functionally couples three components, namely the folate receptor, the folate transporter, and a V-type H(+)-pump.
• Pathway: Methotrexate Pathway, Pharmacokinetics;Vitamin digestion and absorption - Homo sapiens (human);Folate Metabolism;Ethanol effects on histone modifications;Vitamin B1 (thiamin) metabolism;Metabolism;Metabolism of folate and pterines;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Histidine metabolism;Vitamin B9 (folate) metabolism (Consensus)

Recessive Scores

• pRec: 0.319

Intolerance Scores

• loftool: 0.187
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.47

Haploinsufficiency Scores

• pHI: 0.0749
• hipred: N
• hipred_score: 0.311
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.125

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc19a1
• Phenotype: homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; hematopoietic system phenotype; endocrine/exocrine gland phenotype; digestive/alimentary phenotype; immune system phenotype; renal/urinary system phenotype; embryo phenotype; liver/biliary system 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); reproductive system phenotype

Gene ontology

• Biological process: folic acid transport;folic acid metabolic process;methotrexate transport;transmembrane transport;folate transmembrane transport;folate import across plasma membrane
• Cellular component: plasma membrane;integral component of plasma membrane;basolateral plasma membrane;apical plasma membrane
• Molecular function: folic acid binding;folic acid transmembrane transporter activity;folate:anion antiporter activity;methotrexate transmembrane transporter activity