SLC40A1

solute carrier family 40 member 1, the group of Solute carrier family 40

Basic information

Region (hg38): 2:189560590-189583758

Previous symbols: [ "SLC11A3" ]

Links

ENSG00000138449 ∙ NCBI:30061 ∙ OMIM:604653 ∙ HGNC:10909 ∙ Uniprot:Q9NP59 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemochromatosis type 4 (Strong), mode of inheritance: AD
• hemochromatosis type 4 (Strong), mode of inheritance: AD
• hemochromatosis type 4 (Supportive), mode of inheritance: AD
• hemochromatosis type 4 (Strong), mode of inheritance: AD
• hemochromatosis type 4 (Definitive), mode of inheritance: AR
• hemochromatosis type 4 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hemochromatosis, type 4	AD	Biochemical; Gastrointestinal; Hematologic	Phlebotomy may be beneficial in some individuals, but genetic diagnosis may be useful to direct treatment regimens, as some indviduals may have reduced tolerance to phlebotomy and can become anemic on therapy despite persistently elevated serum ferritin	Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic	1518736; 11431687; 14752817; 14757427; 15030991; 16351644; 15831700; 17566043; 17383046; 19709084; 19342478; 19589941; 20230395; 21175851; 21411349; 22584997; 22890139
Biallelic variants (with other hemochromatosis-related genes, such as HFE) have been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC40A1 gene.

• Hemochromatosis_type_4 (250 variants)
• Inborn_genetic_diseases (47 variants)
• not_provided (22 variants)
• SLC40A1-related_disorder (15 variants)
• not_specified (7 variants)
• Hemochromatosis_type_1 (1 variants)
• Hereditary_hemochromatosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC40A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014585.6. 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	67	5	73
missense	17	22	109	16	4	168
nonsense		2	2			4
start loss						0
frameshift		2				2
splice donor/acceptor (+/-2bp)			6			6
Total	17	26	118	83	9

Highest pathogenic variant AF is 0.000097889184

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC40A1	protein_coding	protein_coding	ENST00000261024	8	23180

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.92	213	308	0.692	0.0000158	3698
Missense in Polyphen		33	93.106	0.35443		1174
Synonymous	1.17	100	116	0.862	0.00000635	1191
Loss of Function	4.25	3	26.7	0.113	0.00000167	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in iron export from duodenal epithelial cell and also in transfer of iron between maternal and fetal circulation. Mediates iron efflux in the presence of a ferroxidase (hephaestin and/or ceruloplasmin).
• Pathway: Mineral absorption - Homo sapiens (human);Ferroptosis - Homo sapiens (human);Iron metabolism in placenta;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Metal ion SLC transporters;Iron uptake and transport (Consensus)

Recessive Scores

• pRec: 0.258

Intolerance Scores

• loftool: 0.0890
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.41

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.812

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: slc40a1
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: lymphocyte homeostasis;endothelium development;cellular iron ion homeostasis;regulation of transcription from RNA polymerase II promoter in response to iron;iron ion transmembrane transport;negative regulation of apoptotic process;positive regulation of transcription by RNA polymerase II;spleen trabecula formation;multicellular organismal iron ion homeostasis;divalent inorganic cation transport;iron ion export across plasma membrane
• Cellular component: nucleoplasm;cytoplasm;cytosol;plasma membrane;integral component of plasma membrane;synaptic vesicle;integral component of membrane;basolateral plasma membrane
• Molecular function: iron ion transmembrane transporter activity;protein binding;ferrous iron transmembrane transporter activity;peptide hormone binding;identical protein binding;iron channel activity