SLC11A2

solute carrier family 11 member 2, the group of Solute carrier family 11

Basic information

Region (hg38): 12:50979400-51028566

Previous symbols: [ "NRAMP2" ]

Links

ENSG00000110911 ∙ NCBI:4891 ∙ OMIM:600523 ∙ HGNC:10908 ∙ Uniprot:P49281 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcytic anemia with liver iron overload (Strong), mode of inheritance: AR
• microcytic anemia with liver iron overload (Supportive), mode of inheritance: AR
• microcytic anemia with liver iron overload (Moderate), mode of inheritance: AR
• microcytic anemia with liver iron overload (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anemia, hypochromic microcytic, with iron overload	AR	Hematologic	Individuals can require RBC transfusions and erythropoietin treatment; As hepatic iron overload is common, awareness may allow monitoring and adjustment of treatments and surveillance accordingly	Hematologic	14135503; 15459009; 16439678; 16160008; 16584902; 21871825; 22313374

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC11A2 gene.

• Microcytic anemia with liver iron overload (93 variants)
• not provided (30 variants)
• Inborn genetic diseases (17 variants)
• SLC11A2-related condition (2 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC11A2 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			7	4	2	13
missense	1		30	2	5	38
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			6	1	2	9
non coding	1		36	6	17	60
Total	2	1	73	12	24

Variants in SLC11A2

This is a list of pathogenic ClinVar variants found in the SLC11A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-50985993-T-A		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)
12-50986004-AT-A		Microcytic anemia with liver iron overload	Uncertain significance (Jun 14, 2016)
12-50986036-C-A		Microcytic anemia with liver iron overload	Uncertain significance (Jan 12, 2018)
12-50986240-ACT-A		Microcytic anemia with liver iron overload	Uncertain significance (Jun 14, 2016)
12-50986376-T-C		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)
12-50986423-G-C		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)
12-50986449-A-G		Microcytic anemia with liver iron overload	Benign (Jan 13, 2018)
12-50986530-C-T		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)
12-50986572-A-AT		Microcytic anemia with liver iron overload	Uncertain significance (Jun 14, 2016)
12-50986586-G-A		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)
12-50986710-A-G		Microcytic anemia with liver iron overload	Uncertain significance (Jan 12, 2018)
12-50986726-G-A		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)
12-50986766-C-A		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)
12-50986839-C-A		Microcytic anemia with liver iron overload	Benign (Jan 12, 2018)
12-50986858-C-CA		Microcytic anemia with liver iron overload	Uncertain significance (Jun 14, 2016)
12-50986881-G-A		Microcytic anemia with liver iron overload	Uncertain significance (Jan 12, 2018)
12-50986958-A-G		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)
12-50986965-T-C		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)
12-50987052-C-T		Microcytic anemia with liver iron overload	Benign (Jan 13, 2018)
12-50987064-C-T		Microcytic anemia with liver iron overload	Benign (Jan 13, 2018)
12-50987110-T-G		Microcytic anemia with liver iron overload	Benign (Jan 13, 2018)
12-50987267-C-T		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)
12-50987268-G-A		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)
12-50987294-C-T		Microcytic anemia with liver iron overload	Benign (Jan 13, 2018)
12-50987318-T-C		Microcytic anemia with liver iron overload	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC11A2	protein_coding	protein_coding	ENST00000394904	16	49166

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00665	0.993	125722	0	25	125747	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.23	213	326	0.653	0.0000174	3806
Missense in Polyphen		46	106.96	0.43007		1240
Synonymous	-0.0107	119	119	1.00	0.00000615	1206
Loss of Function	3.63	10	32.3	0.310	0.00000163	371

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.00	0.00
South Asian	0.000133	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Important in metal transport, in particular iron. Can also transport manganese, cobalt, cadmium, nickel, vanadium and lead. Involved in apical iron uptake into duodenal enterocytes. Involved in iron transport from acidified endosomes into the cytoplasm of erythroid precursor cells. May play an important role in hepatic iron accumulation and tissue iron distribution. May serve to import iron into the mitochondria. {ECO:0000269|PubMed:17109629, ECO:0000269|PubMed:24448823, ECO:0000269|PubMed:25326704, ECO:0000269|PubMed:25491917}.
• Disease: DISEASE: Anemia, hypochromic microcytic, with iron overload 1 (AHMIO1) [MIM:206100]: A hematologic disease characterized by abnormal hemoglobin content in the erythrocytes which are reduced in size. The disorder is due to an error of iron metabolism that results in high serum iron, massive hepatic iron deposition, and absence of sideroblasts and stainable bone marrow iron store. Despite adequate transferrin-iron complex, delivery of iron to the erythroid bone marrow is apparently insufficient for the demands of hemoglobin synthesis. {ECO:0000269|PubMed:15459009, ECO:0000269|PubMed:16160008, ECO:0000269|PubMed:16439678}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Mineral absorption - Homo sapiens (human);Ferroptosis - Homo sapiens (human);Iron metabolism in placenta;Copper homeostasis;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;HIF-2-alpha transcription factor network;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: 0.382

Intolerance Scores

• loftool: 0.697
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.6

Haploinsufficiency Scores

• pHI: 0.557
• hipred: Y
• hipred_score: 0.696
• ghis: 0.466

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.795

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc11a2
• 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; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); renal/urinary system phenotype; cellular phenotype; immune system 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

Zebrafish Information Network

• Gene name: slc11a2
• Affected structure: erythroid lineage cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: response to hypoxia;heme biosynthetic process;cobalt ion transport;copper ion transport;iron ion transport;manganese ion transport;cellular iron ion homeostasis;learning or memory;response to iron ion;lead ion transport;iron import into cell;iron ion transmembrane transport;copper ion transmembrane transport;nickel cation transmembrane transport;dendrite morphogenesis;erythrocyte development;multicellular organismal iron ion homeostasis;cadmium ion transmembrane transport;manganese ion transmembrane transport;proton transmembrane transport
• Cellular component: nucleus;cytoplasm;mitochondrion;mitochondrial outer membrane;lysosomal membrane;early endosome;vacuole;plasma membrane;integral component of plasma membrane;cell surface;membrane;apical plasma membrane;cytoplasmic vesicle;brush border membrane;late endosome membrane;apical part of cell;basal part of cell;perinuclear region of cytoplasm;recycling endosome;paraferritin complex;extracellular vesicle
• Molecular function: copper ion transmembrane transporter activity;iron ion transmembrane transporter activity;manganese ion transmembrane transporter activity;iron ion binding;copper ion binding;protein binding;zinc ion binding;cadmium ion transmembrane transporter activity;cobalt ion transmembrane transporter activity;ferrous iron transmembrane transporter activity;lead ion transmembrane transporter activity;nickel cation transmembrane transporter activity;solute:proton symporter activity;nickel cation binding;manganese ion binding;cadmium ion binding;transition metal ion transmembrane transporter activity;cobalt ion binding