SLC11A1

protein-coding

solute carrier family 11 member 1, the group of Solute carrier family 11

Gene summary

This gene is a member of the solute carrier family 11 (proton-coupled divalent metal ion transporters) family and encodes a multi-pass membrane protein. The protein functions as a divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Mutations in this gene have been associated with susceptibility to infectious diseases such as tuberculosis and leprosy, and inflammatory diseases such as rheumatoid arthritis and Crohn disease. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

Previous symbols:

LSH
NRAMP
NRAMP1

MANE transcript

NM_000578.4

Inheritance

AR, AD

ClinVar variants

U:97B:21

Top phenotype

cystic fibrosis

gnomAD constraint

pLI —, LoF o/e 0.99

Max pathogenic AF

—

Genomic locus

chr2:218,382,029-218,396,894

External References & Databases

Ensembl (ENSG00000018280)

Transcript & Mutation Effects

hg38 • Region Span ~14.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cystic fibrosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009061

Submitter: Orphanet

Mycobacterium tuberculosis, susceptibilityLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0000070

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC11A1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 100

not providedTotal: 15

SLC11A1-related disorderTotal: 8

Mycobacterium tuberculosis, susceptibility toTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000578.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	5 clinvar	2 clinvar	8
missense			94 clinvar	10 clinvar	4 clinvar	108
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	97	15	6	118

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000578.4	RefSeq	NP_000569.3	15	MANE Select
ENST00000233202.11	Ensembl	ENSP00000233202.6	15	MANE Select
ENST00000354352.9	Ensembl	ENSP00000346320.5	6	Standard
ENST00000473367.5	Ensembl	ENSP00000484905.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysosome - Homo sapiens (human)
Ion influx/efflux at host-pathogen interface
Neutrophil degranulation
ROS, RNS production in phagocytes
Antimicrobial peptides

Biological Process

negative regulation of cytokine production
positive regulation of cytokine production
T cell proliferation involved in immune response
T cell cytokine production
positive regulation of dendritic cell antigen processing and presentation

Molecular Function

manganese ion transmembrane transporter activity
cadmium ion transmembrane transporter activity
protein homodimerization activity
transition metal ion transmembrane transporter activity
metal ion:proton antiporter activity

Cellular Component

lysosome
late endosome
plasma membrane
integral component of plasma membrane
phagocytic vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000233202
Coding exons: 15
Length: 14866
Individuals with no LoFs: 125643
Homozygous LoFs: 1
Heterozygous LoFs: 104
Defined: 125748
p: 0.000418

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.502	323	349	0.924	0.0000215	3513
Missense (PolyPhen)		124	136.64	0.90748		1391
Synonymous	0.0825	154	155	0.992	0.0000108	1157
Loss of Function	0.0345	29	29.2	0.993	0.00000157	290

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00082	0.00080	rare
Latino/Admixed American	0.0011	0.0010	notable
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00073	0.00071	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00040	0.00039	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Macrophage-specific membrane transport function. Controls natural resistance to infection with intracellular parasites. Pathogen resistance involves sequestration of Fe(2+) and Mn(2+), cofactors of both prokaryotic and eukaryotic catalases and superoxide dismutases, not only to protect the macrophage against its own generation of reactive oxygen species, but to deny the cations to the pathogen for synthesis of its protective enzymes.;

Recessive Scores

pRec: 0.339

Intolerance Scores

LoFtool: 0.911
RVIS EVS: -0.51
RVIS percentile EVS: 21.77

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.195

Gene Damage Prediction

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