SLC48A1

Summary

SLC48A1 (solute carrier family 48 member 1, HGNC:26035) is a protein-coding gene on chromosome 12q13.11, encoding Heme transporter HRG1 (Q6P1K1). Heme transporter that regulates intracellular heme availability through the endosomal or lysosomal compartment.

Enables heme binding activity and heme transmembrane transporter activity. Involved in heme transport. Located in endosome membrane; lysosomal membrane; and plasma membrane.

Source: NCBI Gene 55652 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_017842

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26035
Approved symbol	SLC48A1
Name	solute carrier family 48 member 1
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20489, hHRG-1, HRG1
Ensembl gene	ENSG00000211584
Ensembl biotype	protein_coding
OMIM	612187
Entrez	55652

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000442218, ENST00000442892, ENST00000461620, ENST00000476104, ENST00000547002, ENST00000548498, ENST00000549243, ENST00000551301, ENST00000552003, ENST00000911890

RefSeq mRNA: 1 — MANE Select: NM_017842 NM_017842

CCDS: CCDS8755

Canonical transcript exons

ENST00000442218 — 3 exons

Exon	Start	End
ENSE00001521454	47773238	47773440
ENSE00001624856	47780145	47782751
ENSE00003641037	47779028	47779195

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 97.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.4874 / max 1031.2089, expressed in 1803 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125230	25.8850	1798
125226	0.5172	270
206683	0.5147	271
125229	0.3695	154
125227	0.1765	86
125225	0.0244	8

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.59	gold quality
inferior vagus X ganglion	UBERON:0005363	97.49	gold quality
spinal cord	UBERON:0002240	97.23	gold quality
putamen	UBERON:0001874	96.02	gold quality
substantia nigra	UBERON:0002038	95.79	gold quality
midbrain	UBERON:0001891	95.72	gold quality
subthalamic nucleus	UBERON:0001906	95.65	gold quality
amygdala	UBERON:0001876	95.62	gold quality
caudate nucleus	UBERON:0001873	95.40	gold quality
right frontal lobe	UBERON:0002810	95.21	gold quality
right lobe of thyroid gland	UBERON:0001119	95.00	gold quality
metanephros cortex	UBERON:0010533	94.93	gold quality
ventral tegmental area	UBERON:0002691	94.89	gold quality
left lobe of thyroid gland	UBERON:0001120	94.74	gold quality
nucleus accumbens	UBERON:0001882	94.73	gold quality
left ovary	UBERON:0002119	94.62	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.55	gold quality
medulla oblongata	UBERON:0001896	94.53	gold quality
right ovary	UBERON:0002118	94.40	gold quality
hypothalamus	UBERON:0001898	94.25	gold quality
Ammon’s horn	UBERON:0001954	94.23	gold quality
anterior cingulate cortex	UBERON:0009835	94.15	gold quality
cingulate cortex	UBERON:0003027	94.14	gold quality
inferior olivary complex	UBERON:0002127	94.11	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.08	gold quality
corpus callosum	UBERON:0002336	94.06	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.95	gold quality
thyroid gland	UBERON:0002046	93.89	gold quality
CA1 field of hippocampus	UBERON:0003881	93.84	gold quality
prefrontal cortex	UBERON:0000451	93.74	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	9.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting SLC48A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6885-3P	99.75	70.36	3187

Literature-anchored findings (GeneRIF, showing 6)

• Human and worm proteins localize together, and bind and transport haem, thus establishing an evolutionarily conserved function for HRG-1. (PMID:18418376)
• HRG-1 regulates V-ATPase activity, which is essential for endosomal acidification, heme binding, and receptor trafficking in mammalian cells. (PMID:19875448)
• SLC48A1 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• a model in which heme is translocated across membranes facilitated by conserved amino acids positioned on the exoplasmic, cytoplasmic, and transmembrane regions of HRG-1-related proteins. (PMID:22174408)
• These results reveal HRG1 as the long-sought heme transporter for heme-iron recycling in macrophages and suggest that genetic variations in HRG1 could be modifiers of human iron metabolism. (PMID:23395172)
• HRG-1 may represent a novel target for selectively disrupting V-ATPase activity and the metastatic potential of cancer cells. (PMID:24141772)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc48a1b	ENSDARG00000026109
danio_rerio	slc48a1a	ENSDARG00000026907
mus_musculus	Slc48a1	ENSMUSG00000081534
rattus_norvegicus	Slc48a1	ENSRNOG00000053196
caenorhabditis_elegans		WBGENE00009493
caenorhabditis_elegans		WBGENE00009494
caenorhabditis_elegans		WBGENE00009495
caenorhabditis_elegans		WBGENE00019830

Protein

Protein identifiers

Heme transporter HRG1 — Q6P1K1 (reviewed: Q6P1K1)

Alternative names: Heme-responsive gene 1 protein homolog, Solute carrier family 48 member 1

All UniProt accessions (4): Q6P1K1, F8VQX9, F8VXV4, F8W1R8

UniProt curated annotations — full annotation on UniProt →

Function. Heme transporter that regulates intracellular heme availability through the endosomal or lysosomal compartment. In macrophages of the reticuloendothelial system, is the heme transporter for heme-iron recycling. Essential for macrophage iron homeostasis, transports heme from the phagolysosome to the cytoplasm during erythrophagocytosis (EP).

Subcellular location. Endosome membrane. Lysosome membrane. Cytoplasmic vesicle. Phagosome membrane.

Tissue specificity. Highly expressed in the brain, kidney, heart and skeletal muscle. Moderately expressed in the liver, lung, placenta and small intestine. Strongly expressed in macrophages of the reticuloendothelial system.

Induction. Induced by iron via heme and non-iron metalloporphyrins in macrophages as well as by erythrophagocytosis (at protein level). Also induced by hemolysis.

Similarity. Belongs to the HRG family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P1K1-1	1	yes
Q6P1K1-2	2

RefSeq proteins (1): NP_060312* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026218	HRG	Family

Pfam: PF16954

Catalyzed reactions (Rhea), 1 shown:

• heme b(in) = heme b(out) (RHEA:75443)

UniProt features (11 total): transmembrane region 4, mutagenesis site 4, chain 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P1K1-F1	86.46	0.45

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (4):

Position	Phenotype
115	slightly decreases heme transport.
36	strongly decreases heme transport.
73	no effect on heme transport.
82	no effect on heme transport.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 202 (showing top): GOBP_IRON_COORDINATION_ENTITY_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOBP_TRANSITION_METAL_ION_TRANSPORT, AREB6_03, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_IRON_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_PORPHYRIN_CONTAINING_COMPOUND_METABOLIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, KESHELAVA_MULTIPLE_DRUG_RESISTANCE, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, INGRAM_SHH_TARGETS_UP, GOBP_TETRAPYRROLE_METABOLIC_PROCESS, GOBP_PIGMENT_METABOLIC_PROCESS

GO Biological Process (8): phagocytosis (GO:0006909), lysosomal transport (GO:0007041), heme transport (GO:0015886), erythrocyte differentiation (GO:0030218), heme metabolic process (GO:0042168), localization of cell (GO:0051674), heme export (GO:0097037), heme export from vacuole to cytoplasm (GO:0140357)

GO Molecular Function (3): heme transmembrane transporter activity (GO:0015232), heme binding (GO:0020037), protein binding (GO:0005515)

GO Cellular Component (11): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), endosome membrane (GO:0010008), endolysosome (GO:0036019), phagolysosome membrane (GO:0061474), cytoplasm (GO:0005737), lysosome (GO:0005764), endosome (GO:0005768), membrane (GO:0016020), phagocytic vesicle membrane (GO:0030670), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
heme transport	2
lysosome	2
endosome	2
cellular anatomical structure	2
endocytosis	1
vacuolar transport	1
nitrogen compound transport	1
iron coordination entity transport	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
porphyrin-containing compound metabolic process	1
pigment metabolic process	1
cellular process	1
localization	1
intercellular transport	1
vacuolar transmembrane transport	1
heme transmembrane transport	1
transmembrane transporter activity	1
tetrapyrrole binding	1
binding	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
lysosomal membrane	1
phagocytic vesicle membrane	1
phagolysosome	1
intracellular anatomical structure	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1
endocytic vesicle membrane	1
phagocytic vesicle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

418 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC48A1	FLVCR1	Q9Y5Y0	724
SLC48A1	SLC46A1	Q96NT5	593
SLC48A1	FLVCR2	Q9UPI3	534
SLC48A1	ABCB6	Q9NP58	517
SLC48A1	FTL	P02792	510
SLC48A1	SLC40A1	Q9NP59	500
SLC48A1	FTH1	P02794	490
SLC48A1	FECH	P22830	481
SLC48A1	HMOX1	P09601	441
SLC48A1	SLC7A11	Q9UPY5	441
SLC48A1	SLC39A14	Q15043	436
SLC48A1	CTNNA3	Q9UI47	404
SLC48A1	SLC11A1	P49279	403
SLC48A1	HPX	P02790	403
SLC48A1	ALAS1	P13196	389

IntAct

27 interactions, top by confidence:

A	B	Type	Score
SLC48A1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	SLC48A1	psi-mi:“MI:0915”(physical association)	0.560
SLC48A1	EBP	psi-mi:“MI:0915”(physical association)	0.560
SLC48A1	UNC93A	psi-mi:“MI:0915”(physical association)	0.560
UNC93A	SLC48A1	psi-mi:“MI:0915”(physical association)	0.560
EBP	SLC48A1	psi-mi:“MI:0915”(physical association)	0.560
SLC48A1	LDAF1	psi-mi:“MI:0915”(physical association)	0.560
LAMP1	SLC48A1	psi-mi:“MI:0915”(physical association)	0.560
SLC48A1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
COMT	SLC48A1	psi-mi:“MI:0915”(physical association)	0.560
SLC48A1	NME2	psi-mi:“MI:0915”(physical association)	0.400
SLC48A1	FXR1	psi-mi:“MI:0915”(physical association)	0.370
SLC48A1	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
IGHG1	PDPK1	psi-mi:“MI:0914”(association)	0.350
SLC48A1	NME2	psi-mi:“MI:0914”(association)	0.350
SLC48A1	LDAF1	psi-mi:“MI:0915”(physical association)	0.000
SLC48A1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.000
SLC48A1	COMT	psi-mi:“MI:0915”(physical association)	0.000
SLC48A1	LAMP1	psi-mi:“MI:0915”(physical association)	0.000
TMEM14B	SLC48A1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): SLC48A1 (Two-hybrid), NME2 (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), SLC48A1 (Two-hybrid), SLC48A1 (Two-hybrid), SLC48A1 (Two-hybrid), SLC48A1 (Two-hybrid), SLC48A1 (Two-hybrid), SLC48A1 (Two-hybrid), SLC48A1 (Two-hybrid), SLC48A1 (Affinity Capture-RNA), NME2 (Affinity Capture-MS), SLC48A1 (Affinity Capture-RNA), APP (Reconstituted Complex)

ESM2 similar proteins: A0A1B4XBI5, A4S8B7, B0BNL4, C1EI34, F5HDD0, O10361, O36388, O48670, O48671, O94349, P03215, P04135, P04288, P09175, P09298, P0C655, P10204, P16733, P24412, P28948, P33464, P36299, P52373, P89433, P89443, P9WEK8, Q00134, Q00138, Q00U99, Q04569, Q1HVE9, Q20106, Q21642, Q3KSR7, Q4FZW7, Q54U35, Q5XJX0, Q63ZL3, Q6P1K1, Q6SW43

Diamond homologs: B0BNL4, Q4FZW7, Q5ZHU0, Q63ZL3, Q6P1K1, Q6ZM28, Q7T3B2, Q9D8M3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

29 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

750 predictions. Top by Δscore:

Variant	Effect	Δscore
12:47757864:AC:A	donor_gain	1.0000
12:47757865:CC:C	donor_gain	1.0000
12:47757865:CCCAG:C	donor_gain	1.0000
12:47779194:GA:G	donor_gain	1.0000
12:47779196:G:GG	donor_gain	1.0000
12:47779201:G:GT	donor_gain	1.0000
12:47780287:G:GT	donor_gain	1.0000
12:47757860:ACT:A	donor_loss	0.9900
12:47757861:CTCA:C	donor_loss	0.9900
12:47757863:CACCC:C	donor_loss	0.9900
12:47757864:A:AC	donor_gain	0.9900
12:47757864:A:C	donor_loss	0.9900
12:47757864:ACC:A	donor_gain	0.9900
12:47757865:C:CG	donor_gain	0.9900
12:47757865:CCC:C	donor_gain	0.9900
12:47757865:CCCA:C	donor_gain	0.9900
12:47758164:T:TA	donor_gain	0.9900
12:47773396:T:TA	donor_gain	0.9900
12:47773397:G:GA	donor_gain	0.9900
12:47773436:CGCAG:C	donor_loss	0.9900
12:47773437:GCAGG:G	donor_loss	0.9900
12:47773438:CAGGT:C	donor_loss	0.9900
12:47773439:AGGTA:A	donor_loss	0.9900
12:47773440:GGT:G	donor_loss	0.9900
12:47773441:G:C	donor_loss	0.9900
12:47773442:T:G	donor_loss	0.9900
12:47779022:CTGCA:C	acceptor_loss	0.9900
12:47779023:TGCA:T	acceptor_loss	0.9900
12:47779024:GCA:G	acceptor_loss	0.9900
12:47779025:CAGG:C	acceptor_loss	0.9900

AlphaMissense

946 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:47773389:T:A	W29R	0.996
12:47773389:T:C	W29R	0.996
12:47779042:T:A	W51R	0.996
12:47779042:T:C	W51R	0.996
12:47780183:T:A	W115R	0.996
12:47780183:T:C	W115R	0.996
12:47780186:A:C	S116R	0.996
12:47780188:C:A	S116R	0.996
12:47780188:C:G	S116R	0.996
12:47780250:T:C	F137S	0.996
12:47780276:T:C	F146L	0.996
12:47780278:C:A	F146L	0.996
12:47780278:C:G	F146L	0.996
12:47780204:T:A	W122R	0.995
12:47780204:T:C	W122R	0.995
12:47780249:T:C	F137L	0.995
12:47780251:T:A	F137L	0.995
12:47780251:T:G	F137L	0.995
12:47773428:G:A	G42R	0.994
12:47773428:G:C	G42R	0.994
12:47779081:T:A	W64R	0.994
12:47779081:T:C	W64R	0.994
12:47773368:G:C	G22R	0.993
12:47780250:T:G	F137C	0.993
12:47773440:G:A	G46R	0.992
12:47773440:G:C	G46R	0.992
12:47779065:G:A	M58I	0.992
12:47779065:G:C	M58I	0.992
12:47779065:G:T	M58I	0.992
12:47780268:T:A	L143H	0.992

dbSNP variants (sampled 300 via entrez): RS1000127889 (12:47770321 T>G), RS1000170554 (12:47752088 G>A), RS1000179536 (12:47755691 T>A,C,G), RS1000244351 (12:47770855 A>C), RS1000357575 (12:47764162 G>A), RS1000358554 (12:47770985 C>A), RS1000532101 (12:47758220 G>A,C,T), RS1000631303 (12:47777355 G>A), RS1000665818 (12:47752450 T>C), RS1000734345 (12:47782111 G>T), RS1000875369 (12:47764527 C>A,T), RS1000912191 (12:47775840 C>T), RS1000947526 (12:47781145 C>T), RS1001061765 (12:47781344 C>A), RS1001139695 (12:47770053 T>A)

Disease associations

OMIM: gene MIM:612187 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST007611_20	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	7.000000e-11
GCST007993_17	Asthma (adult onset)	2.000000e-10
GCST008103_172	Bipolar disorder	7.000000e-06
GCST90002385_226	High light scatter reticulocyte count	3.000000e-11
GCST90002386_321	High light scatter reticulocyte percentage of red cells	9.000000e-13
GCST90002387_120	Immature fraction of reticulocytes	2.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1002011	adult onset asthma
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC48 heme transporter

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	4
Arsenic Trioxide	increases expression, decreases response to substance	4
Valproic Acid	affects expression, increases expression	4
Benzo(a)pyrene	increases expression	3
Aflatoxin B1	affects expression, increases expression	3
bisphenol A	increases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Lead	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
dicrotophos	increases expression	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
clothianidin	increases expression	1
abrine	decreases expression	1
quinocetone	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Curcumin	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4PJ	HCT116-SLC48A1-KO-c10	Cancer cell line	Male
CVCL_D4PK	HCT116-SLC48A1-KO-c5	Cancer cell line	Male
CVCL_TN86	HAP1 SLC48A1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.