SLC46A1

solute carrier family 46 member 1, the group of Solute carrier family 46

Basic information

Region (hg38): 17:28394642-28407197

Links

ENSG00000076351 ∙ NCBI:113235 ∙ OMIM:611672 ∙ HGNC:30521 ∙ Uniprot:Q96NT5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary folate malabsorption (Strong), mode of inheritance: AR
• hereditary folate malabsorption (Strong), mode of inheritance: AR
• hereditary folate malabsorption (Supportive), mode of inheritance: AR
• hereditary folate malabsorption (Strong), mode of inheritance: AR
• hereditary folate malabsorption (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Folate malabsorption, hereditary	AR	Biochemical	Individuals may present in infancy with anemia, diarrhea, infections/immune deficiency, and cognitiive impairment, and treatment (eg, with folate/folinic acid supplementation) can be effective	Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Hematologic; Neurologic	5450108; 3987728; 2381546; 11804211; 11807405; 7129779; 17641272; 18559978; 17446347; 21333572; 21489556

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC46A1 gene.

• not_provided (264 variants)
• Congenital_defect_of_folate_absorption (52 variants)
• Inborn_genetic_diseases (44 variants)
• not_specified (16 variants)
• SLC46A1-related_disorder (12 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 SLC46A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000080669.6. 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	99		100
missense	5	4	140	13		162
nonsense	2	1				3
start loss		1				1
frameshift	12	3	1			16
splice donor/acceptor (+/-2bp)	1	2	1			4
Total	20	11	143	112	0

Highest pathogenic variant AF is 0.00007126038

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC46A1	protein_coding	protein_coding	ENST00000440501	6	12555

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		3989	120652	1	124642	0.821

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.24	201	257	0.782	0.0000143	2877
Missense in Polyphen		86	117.76	0.73029		1314
Synonymous	1.82	93	118	0.787	0.00000676	1020
Loss of Function	2.14	5	13.5	0.371	6.66e-7	156

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	2.00	1.77
Ashkenazi Jewish	1.00	0.867
East Asian	1.00	0.843
Finnish	1.00	0.864
European (Non-Finnish)	1.00	0.807
Middle Eastern	1.00	0.843
South Asian	1.00	0.826
Other	1.00	0.824

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has been shown to act both as an intestinal proton- coupled high-affinity folate transporter and as an intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithelial cells. The iron is then released from heme and may be transported into the bloodstream. Dietary heme iron is an important nutritional source of iron. Shows a higher affinity for folate than heme. {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17156779, ECO:0000269|PubMed:17446347, ECO:0000269|PubMed:17475902}.
• Pathway: Methotrexate Pathway, Pharmacokinetics;Vitamin digestion and absorption - Homo sapiens (human);Mineral absorption - Homo sapiens (human);Folate malabsorption, hereditary;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Methotrexate Action Pathway;Folate Metabolism;Folate Metabolism;Metabolism;Metabolism of folate and pterines;Transport of small molecules;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Porphyrin metabolism;Iron uptake and transport (Consensus)

Recessive Scores

• pRec: 0.156

Essentials

• essential_gene_CRISPR2: 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

Gene ontology

• Biological process: cellular iron ion homeostasis;folic acid transport;heme transport;folic acid metabolic process;methotrexate transport;intestinal folate absorption;proton transmembrane transport;folate import across plasma membrane
• Cellular component: cytoplasm;plasma membrane;cell surface;integral component of membrane;apical plasma membrane;brush border membrane
• Molecular function: folic acid binding;folic acid transmembrane transporter activity;proton transmembrane transporter activity;heme transporter activity;methotrexate transmembrane transporter activity