SLC40A1

Summary

SLC40A1 (solute carrier family 40 member 1, HGNC:10909) is a protein-coding gene on chromosome 2q32.2, encoding Ferroportin (Q9NP59). Transports Fe(2+) from the inside of a cell to the outside of the cell, playing a key role for maintaining systemic iron homeostasis.

The protein encoded by this gene is a cell membrane protein that may be involved in iron export from duodenal epithelial cells. Defects in this gene are a cause of hemochromatosis type 4 (HFE4).

Source: NCBI Gene 30061 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hemochromatosis type 4 (Definitive, GenCC)
• GWAS associations: 15
• Clinical variants (ClinVar): 334 total — 19 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014585

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10909
Approved symbol	SLC40A1
Name	solute carrier family 40 member 1
Location	2q32.2
Locus type	gene with protein product
Status	Approved
Aliases	MTP1, IREG1, FPN1, HFE4, FPN
Ensembl gene	ENSG00000138449
Ensembl biotype	protein_coding
OMIM	604653
Entrez	30061

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000261024, ENST00000418714, ENST00000427241, ENST00000427419, ENST00000440626, ENST00000455320, ENST00000479598, ENST00000852923, ENST00000852924, ENST00000852925, ENST00000852926, ENST00000852927, ENST00000852928, ENST00000852929, ENST00000972158, ENST00000972159, ENST00000972160

RefSeq mRNA: 1 — MANE Select: NM_014585 NM_014585

CCDS: CCDS2299

Canonical transcript exons

ENST00000261024 — 8 exons

Exon	Start	End
ENSE00000883209	189560590	189562191
ENSE00000883211	189580418	189580786
ENSE00002448333	189571715	189571841
ENSE00002485231	189565354	189565599
ENSE00002493640	189572846	189572961
ENSE00002504240	189563584	189564225
ENSE00003488856	189579813	189579880
ENSE00003587136	189575161	189575320

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 99.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.6565 / max 645.1802, expressed in 1145 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
32868	13.4454	1140
32871	0.5107	83
32870	0.4924	76
32875	0.1086	33
32876	0.0406	14
32869	0.0233	9
32873	0.0151	8
32874	0.0111	6
32872	0.0094	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.91	gold quality
epithelial cell of pancreas	CL:0000083	99.80	gold quality
oviduct epithelium	UBERON:0004804	99.78	gold quality
jejunal mucosa	UBERON:0000399	99.73	gold quality
ileal mucosa	UBERON:0000331	99.60	gold quality
germinal epithelium of ovary	UBERON:0001304	99.56	gold quality
ileum	UBERON:0002116	99.50	silver quality
trabecular bone tissue	UBERON:0002483	99.40	gold quality
decidua	UBERON:0002450	99.39	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.36	gold quality
superficial temporal artery	UBERON:0001614	99.30	gold quality
palpebral conjunctiva	UBERON:0001812	99.30	gold quality
placenta	UBERON:0001987	99.25	gold quality
duodenum	UBERON:0002114	99.24	gold quality
kidney epithelium	UBERON:0004819	99.15	gold quality
caput epididymis	UBERON:0004358	99.09	gold quality
parietal pleura	UBERON:0002400	98.96	gold quality
gall bladder	UBERON:0002110	98.93	gold quality
eye	UBERON:0000970	98.92	gold quality
epithelium of mammary gland	UBERON:0003244	98.90	gold quality
mammary duct	UBERON:0001765	98.89	gold quality
visceral pleura	UBERON:0002401	98.78	gold quality
jejunum	UBERON:0002115	98.65	gold quality
lower lobe of lung	UBERON:0008949	98.64	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.56	gold quality
right adrenal gland	UBERON:0001233	98.50	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.47	gold quality
pylorus	UBERON:0001166	98.46	gold quality
lymph node	UBERON:0000029	98.41	gold quality
colonic mucosa	UBERON:0000317	98.24	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 21.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	2332.74
E-MTAB-10553	yes	1982.64
E-CURD-6	yes	1029.85
E-ANND-5	yes	675.89
E-MTAB-9067	yes	519.98
E-MTAB-8884	yes	260.06
E-HCAD-6	yes	244.29
E-MTAB-10283	yes	234.33
E-MTAB-6075	yes	169.76
E-HCAD-10	yes	43.11
E-MTAB-6701	yes	41.55
E-CURD-46	yes	41.46
E-HCAD-9	yes	25.43
E-GEOD-125970	yes	23.02
E-MTAB-10287	yes	15.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APP, BACH1, BMP6, IFNG, MTF1, NFE2L2, NR1I2, PPARA, PSEN1, SMAD4

miRNA regulators (miRDB)

91 targeting SLC40A1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587

Literature-anchored findings (GeneRIF, showing 40)

• Hemochromatosis is caused by mutations in the iron-regulatory protein ferroportin. (PMID:11774199)
• gene coding and flanking regions were sequenced and examined for mutations that might modulate the iron burden of individuals harboring the common mutant hemochromatosis HFE genotype or cause hemochromatosis independent of mutations in the HFE gene (PMID:11783942)
• expression levels of human DCT1 mRNA, and to a lesser extent IREG1 mRNA, are regulated in an iron-dependent manner (PMID:11897618)
• A 3-base pair deletion in exon 5 of the ferroportin 1 gene predicting Val162 deletion was found in a family with autosomal dominant inheritance of increased body iron stores without hemochromatosis. (PMID:12091367)
• Iron increases expression of this iron-export protein in lung cells. (PMID:12376346)
• both L ferritin IRE and ferroportin mutations can account for isolated hyperferritinemia. (PMID:12730114)
• Q248H mutation is a common polymorphism in the ferroportin 1 gene in African populations that may be associated with mild anemia and a tendency to iron loading (PMID:14636642)
• variant is associated with increased ferritin levels in African-Americans and may play a role in their propensity to develop iron overload (PMID:14636643)
• review of a new inherited disorder of iron metabolism due to pathogenic mutations in the SLC40A1 gene (PMID:14757427)
• the presence of cirrhosis is an independent factor associated with increased expression of DMT1 but not Ireg1. (PMID:14768003)
• Neither HFE (C282Y and H63D) nor ferroportin(Val162del) mutations were determinants of total body iron status, as assessed by ferritin levels, in thalassemia intermedia and betas/betathal patients (PMID:15075083)
• In Africans with iron overload not related to the HFE gene, the possible involvement of the SLC40A1 and CYBRD1 genes was demonstrated for the first time. (PMID:15338274)
• ferroportin mutations A77D, V162delta, and G490D are associated with a typical pattern of hemochromatosis disease in vivo (PMID:15692071)
• Hereditary hemochromatosis associated with a previously unrecognized ferroportin mutation (Cys326Ser). (PMID:15727899)
• the Y64N and C326Y mutants of FPN are completely resistant to hepcidin inhibition and N144D and N144H are partially resistant. Hemochromatosis-associated FPN mutations, either reduce iron export or produce an FPN variant that is insensitive to hepcidin (PMID:15831700)
• Mutation in the ferroportin 1 may be related to hemochromatosis. (PMID:15897636)
• HFE4 mutations are heterogeneous in their effects on protein function; all mutants appear to be unresponsive to hepcidin and do not demonstrate the expected internalization on exposure to hepcidin. (PMID:15935710)
• ferroportin mutations A77D, V162delta, and G490D are associated with a typical pattern of hemochromatosis disease in vivo (PMID:15942076)
• The behavior of mutant ferroportin in cell culture and the ability of mutant Fpn to act as a dominant negative explain the dominant inheritance of hemochromaatois as well as the different patient phenotypes. (PMID:15956209)
• FPN1 is present in erythroid cells at all stages of differentiation. The existence of multiple FPN1 transcripts indicates a complex regulation of the FPN1 gene in erythroid cells. (PMID:16330432)
• Iron mobilization by alveolar macrophages can be affected by iron and LPS via several pathways, including HAMP-mediated degradation of FPN1, and that these cells may use unique regulatory mechanisms to cope with iron imbalance in the lung. (PMID:16648237)
• Fpn amino acid substitution represents a class of Fpn mutants whose behavior in vitro does not explain the phenotype of patients with iron overload. (PMID:16885049)
• findings conclude that the frequency of the FPN1 Q248H polymorphism is greater in African American men with elevated serum ferritin than in those with normal serum ferritin (PMID:17276706)
• the S338R mutation results in a mutated ferroportin associated with iron overload and is predicted insensitive to regulation by the iron regulatory hormone hepcidin (PMID:17383046)
• After binding of hepcidin, Fpn is tyrosine phosphorylated at the plasma membrane. (PMID:17475779)
• Results suggest the possibility that FPN-1 might associate and interact with Heph in the process of iron exit across the basolateral membrane of intestinal absorptive cell. (PMID:17486601)
• frequency of SLC40A1 Q248H is significantly lower in African-Americans than Native Africans; OR estimates of iron overload in African-Americans & Native Africans with Q248H were greater than unity, increased OR were not statistically significant (PMID:17490902)
• analysis of the SLC40A1 gene at the mRNA level in 2 patients with hyperferritinemia, normal transferrin saturation & iron accumulation predominantly in macrophages & Kupffer cells; first displayed V162 Delta; the second a novel mutation (R178G) (PMID:17997113)
• ferroportin was investigated as a candidate gene in 2 pedigrees with hyperferritinaemia and siderosis in mononuclear phagocytes; A77D mutation was detected in patient 1, his father & brother; V162del mutation was detected in patient 4 (PMID:18160317)
• A new SLC40A1 exon 7 mutation c.1402G–>A results in aberrant splicing to a cryptic upstream splice site at nt 990 in the same exon. The truncated protein, missing its C-terminal 241 AAs, lacks all structural motifs beyond transmembrane region 7. (PMID:18160816)
• We identified two novel mutations (D157N and V72F) at the heterozygous state of SLC40A1 in two probands. Phenotype heterogeneity was observed in both families, suggesting variable penetrance and expression (PMID:18177470)
• No significant change in placental expression of either protein or mRNA ferroportin 1 (FP1) was observed in the maternal anemia groups (PMID:18586377)
• The expression of both protein and mRNA of FP1 of term placentas was not influenced by different degree of iron status of pregnant women. (PMID:18646536)
• Ther is a higher prevalence of ferroportin Q248H with greater alcohol consumption, and this higher prevalence raises the possibility that the allele might ameliorate the toxicity of alcohol. (PMID:18782341)
• Multi-organ iron overload in an African-American man with ALAS2 R452S and SLC40A1 R561G. (PMID:19066423)
• Hepcidin addition resulted in a redistribution of ferroportin to intracellular compartments that labeled with early endosomal and lysosomal, but not Golgi, markers and that trafficked along microtubules. (PMID:19150361)
• These results show that cooperativity between the ferroportin monomers is required for hepcidin-mediated Jak2 activation and ferroportin down-regulation. (PMID:19234114)
• These relatively high hepcidin levels are probably a consequence of patients’ elevated transferrin saturation (PMID:19589941)
• the functional relevance of a novel ferroportin variant: the c.1502 A>G transition, which changes amino acid 501 from tyrosine to cysteine (p.Y501C);the p.Y501C mutant protein reached the plasma membrane and retained a full iron export ability (PMID:19709084)
• None of the individuals in this cohort of Brazilian patients with the classical phenotype of HH had any of the aforementioned non-C282Y mutations in the HFE gene or any mutations in the TfR2 and SCL40A1 genes. (PMID:19759876)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc40a1	ENSDARG00000000241
mus_musculus	Slc40a1	ENSMUSG00000025993
rattus_norvegicus	Slc40a1	ENSRNOG00000003872
caenorhabditis_elegans		WBGENE00019977

Protein

Protein identifiers

Ferroportin — Q9NP59 (reviewed: Q9NP59)

Alternative names: Ferroportin-1, Iron-regulated transporter 1, Solute carrier family 40 member 1

All UniProt accessions (4): Q9NP59, E7EQF8, E7ES28, Q4PNE6

UniProt curated annotations — full annotation on UniProt →

Function. Transports Fe(2+) from the inside of a cell to the outside of the cell, playing a key role for maintaining systemic iron homeostasis. Transports iron from intestinal, splenic, hepatic cells, macrophages and erythrocytes into the blood to provide iron to other tissues. Controls therefore dietary iron uptake, iron recycling by macrophages and erythrocytes, and release of iron stores in hepatocytes. When iron is in excess in serum, circulating HAMP/hepcidin levels increase resulting in a degradation of SLC40A1, thus limiting the iron efflux to plasma.

Subunit / interactions. Identified in a complex with STOM. Interacts with HAMP; affinity of the peptide hormone HAMP for SLC40A1 increases by 80-fold in the presence of iron and the interaction promotes SLC40A1 ubiquitination and degradation. Part of a complex composed of SLC40A1/ferroportin, TF/transferrin and HEPH/hephaestin that transfers iron from cells to transferrin.

Subcellular location. Cell membrane. Basolateral cell membrane.

Tissue specificity. Detected in erythrocytes (at protein level). Expressed in placenta, intestine, muscle and spleen. Highly expressed in mature red blood.

Post-translational modifications. Polyubiquitinated by RNF217; leading to proteasomal degradation. Under conditions of high systemic iron levels, both the hormone peptide hepcidin/HAMP and holo(iron bound)-transferrin/TF induce the ubiquitination, internalization and proteasomal degradation of SLC40A1 to control iron release from cells.

Disease relevance. Hemochromatosis 4 (HFE4) [MIM:606069] A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A subfamily.

RefSeq proteins (1): NP_055400* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009716	Ferroportin-1	Family
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF06963

Catalyzed reactions (Rhea), 1 shown:

• Fe(2+)(in) = Fe(2+)(out) (RHEA:28486)

UniProt features (90 total): sequence variant 21, helix 19, topological domain 13, transmembrane region 12, mutagenesis site 10, binding site 4, sequence conflict 3, turn 3, strand 3, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6WBV	ELECTRON MICROSCOPY	2.5
8DL7	ELECTRON MICROSCOPY	2.7
8DL6	ELECTRON MICROSCOPY	3
8DL8	ELECTRON MICROSCOPY	3
6W4S	ELECTRON MICROSCOPY	3.2
8BZY	ELECTRON MICROSCOPY	3.24
8C03	ELECTRON MICROSCOPY	3.89
8C02	ELECTRON MICROSCOPY	4.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP59-F1	80.26	0.54

Antibody-complex structures (SAbDab): 7 — 6W4S, 6WBV, 8BZY, 8C02, 8DL6, 8DL7, 8DL8

Functional residue map

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

Ligand- & substrate-binding residues (4): 39; 43; 326; 507

Glycosylation sites (1): 434

Mutagenesis-validated functional residues (10):

Position	Phenotype
88	reduces protein stability. loss of cell surface localization. loss of iron export activity. increases intracellular mang
157	loss of iron export activity. loss of cell surface localization. increases intracellular manganese.
170	loss of iron export activity.
236	no loss of ubiquitination; when associated with r-253.
240	loss of hamp-induced endocytosis.
253	no loss of ubiquitination; when associated with r-236.
326	complete loss of hamp-dependent ubiquitination. does not affect protein stability. does not affect cell surface localiza
338	reduces protein stability.
501	about 90% loss of hamp binding.
504	about 95% loss of hamp binding.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-425410	Metal ion SLC transporters
R-HSA-5619049	Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages)
R-HSA-5619060	Defective CP causes aceruloplasminemia (ACERULOP)
R-HSA-5655799	Defective SLC40A1 causes hemochromatosis 4 (HFE4) (duodenum)
R-HSA-917937	Iron uptake and transport
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 315 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_TRANSITION_METAL_ION_TRANSPORT, CHUNG_BLISTER_CYTOTOXICITY_DN, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_IRON_ION_TRANSPORT, WOTTON_RUNX_TARGETS_UP, GOBP_MONOATOMIC_CATION_TRANSPORT, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, FINAK_BREAST_CANCER_SDPP_SIGNATURE, GOBP_TRABECULA_MORPHOGENESIS

GO Biological Process (16): lymphocyte homeostasis (GO:0002260), endothelium development (GO:0003158), transcription by RNA polymerase II (GO:0006366), intracellular iron ion homeostasis (GO:0006879), apoptotic process (GO:0006915), iron ion transmembrane transport (GO:0034755), negative regulation of apoptotic process (GO:0043066), positive regulation of transcription by RNA polymerase II (GO:0045944), establishment of localization in cell (GO:0051649), spleen trabecula formation (GO:0060345), multicellular organismal-level iron ion homeostasis (GO:0060586), iron ion export across plasma membrane (GO:1903988), monoatomic ion transport (GO:0006811), iron ion transport (GO:0006826), spleen development (GO:0048536), transmembrane transport (GO:0055085)

GO Molecular Function (6): iron ion transmembrane transporter activity (GO:0005381), ferrous iron transmembrane transporter activity (GO:0015093), peptide hormone binding (GO:0017046), identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), membrane (GO:0016020), basolateral plasma membrane (GO:0016323)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SLC transporter disorders	3
Transport of small molecules	2
SLC-mediated transmembrane transport	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
inorganic ion homeostasis	2
iron ion transmembrane transport	2
transport	2
leukocyte homeostasis	1
epithelium development	1
DNA-templated transcription	1
intracellular monoatomic cation homeostasis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
iron ion transport	1
monoatomic cation transmembrane transport	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
establishment of localization	1
cellular localization	1
spleen development	1
trabecula formation	1
monoatomic cation homeostasis	1
multicellular organismal-level chemical homeostasis	1
export across plasma membrane	1
transition metal ion transport	1
hematopoietic or lymphoid organ development	1
cellular process	1
transition metal ion transmembrane transporter activity	1
iron ion transmembrane transporter activity	1
hormone binding	1
protein binding	1
cation binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1326 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC40A1	HAMP	P81172	999
SLC40A1	SLC11A2	P49281	987
SLC40A1	TFR2	Q9UP52	959
SLC40A1	CYBRD1	Q53TN4	941
SLC40A1	TFRC	P02786	937
SLC40A1	FTL	P02792	929
SLC40A1	HEPH	Q9BQS7	925
SLC40A1	HFE	Q30201	921
SLC40A1	HJV	Q6ZVN8	904
SLC40A1	FTH1	P02794	893
SLC40A1	PCBP2	Q15366	867
SLC40A1	SLC39A1	Q9NY26	832
SLC40A1	IREB2	P48200	830
SLC40A1	ACO1	P21399	825
SLC40A1	SLC39A14	Q15043	786

IntAct

17 interactions, top by confidence:

A	B	Type	Score
APP	SLC40A1	psi-mi:“MI:0915”(physical association)	0.590
SLC40A1	APP	psi-mi:“MI:0915”(physical association)	0.590
SLC4A1	FLOT1	psi-mi:“MI:0914”(association)	0.530
SLC40A1	APP	psi-mi:“MI:0915”(physical association)	0.400
SLC40A1	CP	psi-mi:“MI:0915”(physical association)	0.400
SLC40A1	Rps27a	psi-mi:“MI:0915”(physical association)	0.400
ALDOA	SLC4A1	psi-mi:“MI:0914”(association)	0.350
AQP1	FLOT1	psi-mi:“MI:0914”(association)	0.350
SLC40A1	UBR5	psi-mi:“MI:0914”(association)	0.350
SLC40A1		psi-mi:“MI:0915”(physical association)	0.000
GOLM1	SLC40A1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (44): SLC40A1 (PCA), SLC40A1 (Affinity Capture-MS), RNF217 (Two-hybrid), RNF217 (Affinity Capture-Western), SLC40A1 (Affinity Capture-Western), FAM189A2 (Affinity Capture-Western), FAM189A2 (Co-fractionation), SLC40A1 (Affinity Capture-Western), SLC40A1 (Cross-Linking-MS (XL-MS)), SLC40A1 (Cross-Linking-MS (XL-MS)), ADAM9 (Affinity Capture-MS), ATAD3B (Affinity Capture-MS), ATP1B1 (Affinity Capture-MS), CLINT1 (Affinity Capture-MS), CRYZ (Affinity Capture-MS)

ESM2 similar proteins: A0A2K2AIF4, A0A2K2BF92, A0A6P3HVI0, A1L272, A2SWM2, B8AF63, B9H7I1, B9N9Y7, E2RFJ3, E7EXX2, O02228, O54902, O77741, O80605, P41251, P49279, P49280, P49281, P49282, P51027, P56436, P57057, P70553, Q0D7E4, Q27946, Q27981, Q5M7K3, Q5R6B8, Q5R839, Q653V6, Q6DIV6, Q6PF45, Q6YK44, Q86UD5, Q8AVC3, Q8BJA2, Q8CH36, Q8H4H5, Q8IVJ1, Q8L4X4

Diamond homologs: E2RFJ3, Q923U9, Q9I9R3, Q9JHI9, Q9NP59, Q5Z922

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
iron(3+)	“down-regulates quantity”	SLC40A1	relocalization
NFE2L2	“up-regulates quantity by expression”	SLC40A1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	17
Uncertain significance	130
Likely benign	102
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
208986	NP_055400.1(SLC40A1):p.Gln248His	Pathogenic
240918	NM_014585.6(SLC40A1):c.430A>T (p.Asn144Tyr)	Pathogenic
2580954	NM_014585.6(SLC40A1):c.977G>A (p.Cys326Tyr)	Pathogenic
406376	NM_014585.6(SLC40A1):c.1469G>A (p.Gly490Asp)	Pathogenic
488151	NM_014585.6(SLC40A1):c.479T>C (p.Val160Ala)	Pathogenic
488152	NM_014585.6(SLC40A1):c.541G>A (p.Asp181Asn)	Pathogenic
488154	NM_014585.6(SLC40A1):c.1049C>A (p.Ala350Asp)	Pathogenic
488155	NM_014585.6(SLC40A1):c.544C>G (p.Gln182Glu)	Pathogenic
488156	NM_014585.6(SLC40A1):c.-205A>C	Pathogenic
5410	NM_014585.6(SLC40A1):c.430A>C (p.Asn144His)	Pathogenic
5411	NM_014585.6(SLC40A1):c.230C>A (p.Ala77Asp)	Pathogenic
5413	NM_014585.6(SLC40A1):c.546G>T (p.Gln182His)	Pathogenic
5415	NM_014585.6(SLC40A1):c.968G>T (p.Gly323Val)	Pathogenic
5416	NM_014585.6(SLC40A1):c.542A>T (p.Asp181Val)	Pathogenic
5417	NM_014585.6(SLC40A1):c.239G>T (p.Gly80Val)	Pathogenic
5418	NM_014585.6(SLC40A1):c.800G>A (p.Gly267Asp)	Pathogenic
568628	NM_014585.6(SLC40A1):c.474G>T (p.Trp158Cys)	Pathogenic
801843	NM_014585.6(SLC40A1):c.430A>G (p.Asn144Asp)	Pathogenic
917398	NM_014585.6(SLC40A1):c.1592T>C (p.Val531Ala)	Pathogenic
1209853	NM_014585.6(SLC40A1):c.1250_1251insGACAAGAACAGTTTGACAGTCAGAAGGTGCCACAAATCCTGCATTCAAGGAGAGTC (p.Ser417_Ile418insThrArgThrValTer)	Likely pathogenic
1209854	NM_014585.6(SLC40A1):c.1263_1264insGTGAGATTGACAAGAACAGTTTGACAGTCAGAAGGTGCCACAAATCCTGCATTCAAGGAGAGTCAATTACACCTACC (p.Lys422delinsValArgLeuThrArgThrValTer)	Likely pathogenic
2203235	NM_014585.6(SLC40A1):c.977G>T (p.Cys326Phe)	Likely pathogenic
406375	NM_014585.6(SLC40A1):c.524C>A (p.Ala175Asp)	Likely pathogenic
5412	NM_014585.6(SLC40A1):c.470A>G (p.Asp157Gly)	Likely pathogenic
986322	NM_014585.6(SLC40A1):c.188T>C (p.Val63Ala)	Likely pathogenic
986323	NM_014585.6(SLC40A1):c.212C>T (p.Ser71Phe)	Likely pathogenic
986325	NM_014585.6(SLC40A1):c.442A>G (p.Thr148Ala)	Likely pathogenic
986326	NM_014585.6(SLC40A1):c.536G>C (p.Arg179Thr)	Likely pathogenic
986327	NM_014585.6(SLC40A1):c.554A>C (p.Asn185Thr)	Likely pathogenic
986328	NM_014585.6(SLC40A1):c.611G>T (p.Gly204Val)	Likely pathogenic

SpliceAI

1197 predictions. Top by Δscore:

Variant	Effect	Δscore
2:189562189:GACC:G	acceptor_loss	1.0000
2:189562192:C:CA	acceptor_loss	1.0000
2:189563578:TCTTA:T	donor_loss	1.0000
2:189563579:CTTAC:C	donor_loss	1.0000
2:189563580:TTA:T	donor_loss	1.0000
2:189563581:TACC:T	donor_loss	1.0000
2:189563582:A:AC	donor_gain	1.0000
2:189563582:A:AT	donor_loss	1.0000
2:189563583:C:CC	donor_gain	1.0000
2:189564222:GTAT:G	acceptor_gain	1.0000
2:189564223:TATC:T	acceptor_loss	1.0000
2:189564224:AT:A	acceptor_gain	1.0000
2:189564224:ATC:A	acceptor_loss	1.0000
2:189564225:TC:T	acceptor_loss	1.0000
2:189564226:C:CC	acceptor_gain	1.0000
2:189564227:T:A	acceptor_loss	1.0000
2:189565350:TTACC:T	donor_loss	1.0000
2:189565351:TA:T	donor_loss	1.0000
2:189565352:A:AT	donor_loss	1.0000
2:189565595:CATAT:C	acceptor_gain	1.0000
2:189565596:ATAT:A	acceptor_gain	1.0000
2:189565597:TAT:T	acceptor_gain	1.0000
2:189565599:TC:T	acceptor_loss	1.0000
2:189565600:C:CC	acceptor_gain	1.0000
2:189571710:ATTAC:A	donor_loss	1.0000
2:189571711:TTA:T	donor_loss	1.0000
2:189571712:TACT:T	donor_loss	1.0000
2:189571713:A:AC	donor_gain	1.0000
2:189571714:C:A	donor_loss	1.0000
2:189571714:C:CC	donor_gain	1.0000

AlphaMissense

3708 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:189565483:A:G	W211R	1.000
2:189565483:A:T	W211R	1.000
2:189571757:A:G	W158R	1.000
2:189571757:A:T	W158R	1.000
2:189575235:A:G	L66P	1.000
2:189575300:A:C	F44L	1.000
2:189575300:A:T	F44L	1.000
2:189575302:A:G	F44L	1.000
2:189575308:A:G	W42R	1.000
2:189575308:A:T	W42R	1.000
2:189562034:A:C	F520L	0.999
2:189562034:A:T	F520L	0.999
2:189562035:A:C	F520C	0.999
2:189562036:A:G	F520L	0.999
2:189562062:A:T	V511D	0.999
2:189562070:G:C	F508L	0.999
2:189562070:G:T	F508L	0.999
2:189562072:A:G	F508L	0.999
2:189562080:A:G	L505P	0.999
2:189562188:A:G	L469P	0.999
2:189563920:C:G	G356R	0.999
2:189563920:C:T	G356R	0.999
2:189563957:A:C	S343R	0.999
2:189563957:A:T	S343R	0.999
2:189563959:T:G	S343R	0.999
2:189563991:G:T	A332D	0.999
2:189563998:C:A	G330W	0.999
2:189564014:A:C	F324L	0.999
2:189564014:A:T	F324L	0.999
2:189564016:A:G	F324L	0.999

dbSNP variants (sampled 300 via entrez): RS1000075400 (2:189565791 C>A,G), RS1000184613 (2:189567374 A>G,T), RS1000214695 (2:189561000 T>C), RS1000228230 (2:189569473 T>C,G), RS1000244159 (2:189561596 T>A,C,G), RS1000600240 (2:189569104 G>C), RS1000617482 (2:189578287 A>C,G), RS1000691723 (2:189580080 C>T), RS1001036414 (2:189568263 T>G), RS1001203382 (2:189567644 C>A,T), RS1001241666 (2:189581117 G>A), RS1001633074 (2:189568072 G>A), RS1001809472 (2:189563409 A>G), RS1001845074 (2:189579557 C>A), RS1002183279 (2:189576441 A>C)

Disease associations

OMIM: gene MIM:604653 | disease phenotypes: MIM:606069, MIM:235200

GenCC curated gene-disease

Disease	Classification	Inheritance
hemochromatosis type 4	Definitive	Autosomal dominant

Mondo (2): hemochromatosis type 4 (MONDO:0011631), hemochromatosis type 1 (MONDO:0021001)

Orphanet (5): OBSOLETE: Hemochromatosis type 4 (Orphanet:139491), Symptomatic form of HFE-related hemochromatosis (Orphanet:465508), SLC40A1-related hemochromatosis (Orphanet:647834), Ferroportin disease (Orphanet:648562), NON RARE IN EUROPE: Hemochromatosis type 1 (Orphanet:139498)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000518	Cataract
HP:0000802	Impotence
HP:0000819	Diabetes mellitus
HP:0000953	Hyperpigmentation of the skin
HP:0001394	Cirrhosis
HP:0001397	Hepatic steatosis
HP:0001638	Cardiomyopathy
HP:0001903	Anemia
HP:0001952	Glucose intolerance
HP:0002240	Hepatomegaly
HP:0002758	Osteoarthritis
HP:0002829	Arthralgia
HP:0003281	Increased circulating ferritin concentration
HP:0011675	Arrhythmia
HP:0012378	Fatigue
HP:0012463	Elevated transferrin saturation
HP:0040270	Impaired glucose tolerance

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002677_1	Iron status biomarkers (ferritin levels)	8.000000e-19
GCST002678_1	Iron status biomarkers (transferrin levels)	1.000000e-11
GCST004403_3	Bone fracture in osteoporosis	3.000000e-06
GCST004571_22	Iron status biomarkers (total iron binding capacity)	8.000000e-07
GCST004572_3	Iron status biomarkers (transferrin saturation)	8.000000e-07
GCST004601_36	Red blood cell count	6.000000e-09
GCST004605_60	Mean corpuscular hemoglobin concentration	8.000000e-09
GCST004630_108	Mean corpuscular hemoglobin	1.000000e-09
GCST011368_6	Iron status biomarkers (total iron binding capacity)	3.000000e-11
GCST011369_29	Iron status biomarkers (ferritin levels)	2.000000e-48
GCST011995_1	Restless legs syndrome	5.000000e-08
GCST90002383_196	Hematocrit	3.000000e-09
GCST90002390_383	Mean corpuscular hemoglobin	3.000000e-11
GCST90002404_32	Red cell distribution width	3.000000e-09
GCST90016674_4	Liver iron content	3.000000e-12

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004459	ferritin measurement
EFO:0004461	iron biomarker measurement
EFO:0006341	transferrin measurement
EFO:0006334	total iron binding capacity
EFO:0004305	erythrocyte count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004527	mean corpuscular hemoglobin
EFO:0004348	hematocrit
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537249	Hemochromatosis, type 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3392948 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 15 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL4475199	VAMIFEPORT HYDROCHLORIDE	1	15

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC40 iron transporter

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
vamifeport	Antagonist	8.05	pIC50

ChEMBL bioactivities

546 potent at pChembl≥5 of 706 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.96	EC50	1.1	nM	CHEMBL3393878
8.38	EC50	4.2	nM	CHEMBL3393870
8.38	EC50	4.2	nM	CHEMBL3623057
8.22	EC50	6	nM	CHEMBL4564862
8.20	EC50	6.3	nM	CHEMBL3393871
8.08	EC50	8.4	nM	CHEMBL3393877
8.00	EC50	10	nM	CHEMBL3393876
7.98	EC50	10.4	nM	CHEMBL3393872
7.90	EC50	12.6	nM	CHEMBL3393873
7.80	IC50	16	nM	CHEMBL4587045
7.77	IC50	17	nM	CHEMBL4462224
7.72	IC50	19	nM	CHEMBL4442485
7.72	IC50	19	nM	CHEMBL4565338
7.68	IC50	21	nM	CHEMBL4468502
7.68	EC50	21	nM	CHEMBL4527595
7.66	EC50	22	nM	CHEMBL4455858
7.64	IC50	23	nM	CHEMBL4575243
7.64	IC50	23	nM	VAMIFEPORT HYDROCHLORIDE
7.58	IC50	26	nM	CHEMBL4581730
7.52	IC50	30	nM	CHEMBL4470632
7.51	IC50	31	nM	CHEMBL4456285
7.47	EC50	34	nM	CHEMBL3393875
7.47	IC50	34	nM	CHEMBL4589376
7.46	IC50	35	nM	CHEMBL4441062
7.44	IC50	36	nM	CHEMBL4459067
7.44	IC50	36	nM	CHEMBL4564862
7.42	IC50	38	nM	CHEMBL4445738
7.42	IC50	38	nM	CHEMBL4520569
7.42	IC50	38	nM	CHEMBL4473202
7.39	IC50	41	nM	CHEMBL4573733
7.37	EC50	43	nM	CHEMBL4476775
7.36	EC50	44.2	nM	CHEMBL3623073
7.36	IC50	44	nM	CHEMBL4579471
7.36	IC50	44	nM	CHEMBL4539480
7.34	IC50	46	nM	CHEMBL4456611
7.33	IC50	47	nM	CHEMBL4462521
7.33	IC50	47	nM	CHEMBL4536483
7.31	IC50	49	nM	CHEMBL4518192
7.29	IC50	51	nM	CHEMBL4585912
7.29	IC50	51.1	nM	CHEMBL4585288
7.28	EC50	52.3	nM	CHEMBL3621378
7.26	EC50	54.3	nM	CHEMBL3623071
7.24	IC50	58	nM	CHEMBL4580803
7.24	IC50	58	nM	CHEMBL4562191
7.21	IC50	61	nM	CHEMBL4440019
7.18	IC50	66	nM	CHEMBL4442719
7.17	IC50	68	nM	CHEMBL4593358
7.16	EC50	69	nM	CHEMBL4528718
7.15	EC50	71	nM	CHEMBL4456285
7.15	EC50	71	nM	CHEMBL4575243

PubChem BioAssay actives

29 with measured affinity, of 39 total; 29 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(2-amino-2-oxoethyl)-6-[[(2S)-2-[[(2S)-2-[[(2R)-3-[(Z)-1,2-bis(diethoxyphosphoryl)ethenyl]sulfanyl-2-[[(2S)-5-carbamimidamido-2-[[2-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[2-[(2-hydroxyacetyl)amino]acetyl]amino]butanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3,3-diphenylpropanoyl]pyrrolidin-2-yl]acetyl]amino]pentanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-phenylpropanoyl]amino]-N-[2-(hexadecylamino)-2-oxoethyl]hexanamide	1190850: Induction of human ferroportin degradation expressed in HEK293 cells after 24 hrs by flow cytometry	ec50	0.0011	uM
N-(2-amino-2-oxoethyl)-6-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2R)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[2-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[2-[(2-hydroxyacetyl)amino]acetyl]amino]butanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3,3-diphenylpropanoyl]pyrrolidin-2-yl]acetyl]amino]pentanoyl]amino]-3-sulfanylpropanoyl]amino]pentanoyl]amino]-3-phenylpropanoyl]amino]-N-[2-(hexadecylamino)-2-oxoethyl]hexanamide	1190850: Induction of human ferroportin degradation expressed in HEK293 cells after 24 hrs by flow cytometry	ec50	0.0042	uM
2-[[2-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[2-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-4-[[6-[(2-amino-2-oxoethyl)-[2-(hexadecylamino)-2-oxoethyl]amino]-6-oxohexyl]amino]-4-oxo-1-phenylbutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]acetic acid	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.0042	uM
ditert-butyl (Z)-2-[(2R)-3-[[(2S)-1-[[(2S)-1-[[6-[(2-amino-2-oxoethyl)-[2-(hexadecylamino)-2-oxoethyl]amino]-6-oxohexyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-2-[[(2S)-5-carbamimidamido-2-[[2-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[2-[(2-hydroxyacetyl)amino]acetyl]amino]butanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3,3-diphenylpropanoyl]pyrrolidin-2-yl]acetyl]amino]pentanoyl]amino]-3-oxopropyl]sulfanylbut-2-enedioate	1190850: Induction of human ferroportin degradation expressed in HEK293 cells after 24 hrs by flow cytometry	ec50	0.0063	uM
(Z)-2-[(2R)-3-[[(2S)-1-[[(2S)-1-[[6-[(2-amino-2-oxoethyl)-[2-(hexadecylamino)-2-oxoethyl]amino]-6-oxohexyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-2-[[(2S)-5-carbamimidamido-2-[[2-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[2-[(2-hydroxyacetyl)amino]acetyl]amino]butanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3,3-diphenylpropanoyl]pyrrolidin-2-yl]acetyl]amino]pentanoyl]amino]-3-oxopropyl]sulfanylbut-2-enediamide	1190850: Induction of human ferroportin degradation expressed in HEK293 cells after 24 hrs by flow cytometry	ec50	0.0084	uM
N-(2-amino-2-oxoethyl)-6-[[(2S)-2-[[(2S)-2-[[(2R)-3-[(E)-1,2-bis(tert-butylsulfonyl)ethenyl]sulfanyl-2-[[(2S)-5-carbamimidamido-2-[[2-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[2-[(2-hydroxyacetyl)amino]acetyl]amino]butanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3,3-diphenylpropanoyl]pyrrolidin-2-yl]acetyl]amino]pentanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-phenylpropanoyl]amino]-N-[2-(hexadecylamino)-2-oxoethyl]hexanamide	1190850: Induction of human ferroportin degradation expressed in HEK293 cells after 24 hrs by flow cytometry	ec50	0.0100	uM
diethyl (Z)-2-[(2R)-3-[[(2S)-1-[[(2S)-1-[[6-[(2-amino-2-oxoethyl)-[2-(hexadecylamino)-2-oxoethyl]amino]-6-oxohexyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-2-[[(2S)-5-carbamimidamido-2-[[2-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[2-[(2-hydroxyacetyl)amino]acetyl]amino]butanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3,3-diphenylpropanoyl]pyrrolidin-2-yl]acetyl]amino]pentanoyl]amino]-3-oxopropyl]sulfanylbut-2-enedioate	1190850: Induction of human ferroportin degradation expressed in HEK293 cells after 24 hrs by flow cytometry	ec50	0.0104	uM
dimethyl (Z)-2-[(2R)-3-[[(2S)-1-[[(2S)-1-[[6-[(2-amino-2-oxoethyl)-[2-(hexadecylamino)-2-oxoethyl]amino]-6-oxohexyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-2-[[(2S)-5-carbamimidamido-2-[[2-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[2-[(2-hydroxyacetyl)amino]acetyl]amino]butanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3,3-diphenylpropanoyl]pyrrolidin-2-yl]acetyl]amino]pentanoyl]amino]-3-oxopropyl]sulfanylbut-2-enedioate	1190850: Induction of human ferroportin degradation expressed in HEK293 cells after 24 hrs by flow cytometry	ec50	0.0126	uM
N-(2-amino-2-oxoethyl)-6-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2R)-2-[[(2S)-5-carbamimidamido-2-[[2-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[2-[(2-hydroxyacetyl)amino]acetyl]amino]butanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3,3-diphenylpropanoyl]pyrrolidin-2-yl]acetyl]amino]pentanoyl]amino]-3-[(Z)-1-phenyl-2-sulfamoylethenyl]sulfanylpropanoyl]amino]pentanoyl]amino]-3-phenylpropanoyl]amino]-N-[2-(hexadecylamino)-2-oxoethyl]hexanamide	1190850: Induction of human ferroportin degradation expressed in HEK293 cells after 24 hrs by flow cytometry	ec50	0.0340	uM
(5R,8S,14S,17S,20R,23S,26S,29R)-5-acetamido-N-[6-[(2-amino-2-oxoethyl)-[2-(hexadecylamino)-2-oxoethyl]amino]-6-oxohexyl]-8-benzhydryl-26-benzyl-17,23-bis[3-(diaminomethylideneamino)propyl]-6,9,15,18,21,24,27-heptaoxo-20-(sulfanylmethyl)-3,31-dithia-7,10,16,19,22,25,28-heptazatricyclo[31.3.1.010,14]heptatriaconta-1(37),33,35-triene-29-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.0442	uM
(5R,8S,11S,14R,17S,20R)-8-benzyl-11,17-bis[3-(diaminomethylideneamino)propyl]-20-(3,3-diphenylpropanoylamino)-N-[2-[2-[2-(hexadecanoylamino)ethoxy]ethoxy]ethyl]-7,10,13,16,19-pentaoxo-14-(sulfanylmethyl)-3,22-dithia-6,9,12,15,18-pentazabicyclo[22.3.1]octacosa-1(27),24(28),25-triene-5-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.0523	uM
(5R,8S,14S,17S,20R,23S,26S,29R)-5-acetamido-8-benzhydryl-26-benzyl-17,23-bis[3-(diaminomethylideneamino)propyl]-6,9,15,18,21,24,27-heptaoxo-20-(sulfanylmethyl)-3,31-dithia-7,10,16,19,22,25,28-heptazatricyclo[31.3.1.010,14]heptatriaconta-1(37),33,35-triene-29-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.0543	uM
2-[[2-[[(2S,3R)-1-[[(5R,8S,14S,17S,20R,23S,26S,29R)-8-benzhydryl-26-benzyl-29-carbamoyl-17,23-bis[3-(diaminomethylideneamino)propyl]-6,9,15,18,21,24,27-heptaoxo-20-(sulfanylmethyl)-3,31-dithia-7,10,16,19,22,25,28-heptazatricyclo[31.3.1.010,14]heptatriaconta-1(37),33,35-trien-5-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]acetic acid	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.0751	uM
(8S,14S,17S,20R,23S,26S,29R)-N-[2-[2-(2-aminoethoxy)ethoxy]ethyl]-8-benzhydryl-26-benzyl-17,23-bis[3-(diaminomethylideneamino)propyl]-6,9,15,18,21,24,27-heptaoxo-20-(sulfanylmethyl)-3,31-dithia-7,10,16,19,22,25,28-heptazatricyclo[31.3.1.010,14]heptatriaconta-1(37),33,35-triene-29-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.0923	uM
(5R,8S,11S,14R,17S,20R)-8-benzyl-11,17-bis[3-(diaminomethylideneamino)propyl]-20-(3,3-diphenylpropanoylamino)-7,10,13,16,19-pentaoxo-14-(sulfanylmethyl)-3,22-dithia-6,9,12,15,18-pentazabicyclo[22.3.1]octacosa-1(27),24(28),25-triene-5-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.1038	uM
(5R,8S,11S,14R,17S,20R)-8-benzyl-11,17-bis[3-(diaminomethylideneamino)propyl]-7,10,13,16,19-pentaoxo-14-(sulfanylmethyl)-20-(3,3,3-triphenylpropanoylamino)-3,22-dithia-6,9,12,15,18-pentazabicyclo[22.3.1]octacosa-1(27),24(28),25-triene-5-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.1127	uM
(5R,8S,14S,17S,20R,23S,26S,29R)-5-acetamido-N-[2-[2-(2-aminoethoxy)ethoxy]ethyl]-8-benzhydryl-26-benzyl-17,23-bis[3-(diaminomethylideneamino)propyl]-6,9,15,18,21,24,27-heptaoxo-20-(sulfanylmethyl)-3,31-dithia-7,10,16,19,22,25,28-heptazatricyclo[31.3.1.010,14]heptatriaconta-1(37),33,35-triene-29-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.1645	uM
(Z)-3-[(2R)-3-[[(2S)-1-[[(2S)-1-[[6-[(2-amino-2-oxoethyl)-[2-(hexadecylamino)-2-oxoethyl]amino]-6-oxohexyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-2-[[(2S)-5-carbamimidamido-2-[[2-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[2-[(2-hydroxyacetyl)amino]acetyl]amino]butanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3,3-diphenylpropanoyl]pyrrolidin-2-yl]acetyl]amino]pentanoyl]amino]-3-oxopropyl]sulfanylprop-2-enoic acid	1190850: Induction of human ferroportin degradation expressed in HEK293 cells after 24 hrs by flow cytometry	ec50	0.2181	uM
N-[(8S,11S,14R,17S,20S)-8-benzyl-11,17-bis[3-(diaminomethylideneamino)propyl]-7,10,13,16,19-pentaoxo-14-(sulfanylmethyl)-3,22-dithia-6,9,12,15,18-pentazabicyclo[22.3.1]octacosa-1(28),24,26-trien-20-yl]-3,3-diphenylpropanamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.2688	uM
(5R,8S,14S,17S,20R,23S,26S,29R)-5-acetamido-8,26-dibenzyl-17,23-bis[3-(diaminomethylideneamino)propyl]-6,9,15,18,21,24,27-heptaoxo-20-(sulfanylmethyl)-3,31-dithia-7,10,16,19,22,25,28-heptazatricyclo[31.3.1.010,14]heptatriaconta-1(37),33,35-triene-29-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.2722	uM
2-[(3S,6S,9S,12S,15R,20R,23S,26S)-15-amino-20-[[(2S,3S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]-3-benzyl-23-[(2S)-butan-2-yl]-9-[(1R)-1-hydroxyethyl]-6-(1H-imidazol-5-ylmethyl)-2,5,8,11,14,22,25-heptaoxo-17,18-dithia-1,4,7,10,13,21,24-heptazabicyclo[24.3.0]nonacosan-12-yl]acetic acid	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.3000	uM
(5R,8S,11S,14R,17S,20S)-8-benzyl-11,17-bis[3-(diaminomethylideneamino)propyl]-20-(3,3-diphenylpropanoylamino)-7,10,13,16,19-pentaoxo-14-(sulfanylmethyl)-3,22-dithia-6,9,12,15,18-pentazabicyclo[22.3.1]octacosa-1(27),24(28),25-triene-5-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.3353	uM
N-[(5R,8S,14S,17S,20R,23S,26S)-8-benzhydryl-26-benzyl-17,23-bis[3-(diaminomethylideneamino)propyl]-6,9,15,18,21,24,27-heptaoxo-20-(sulfanylmethyl)-3,31-dithia-7,10,16,19,22,25,28-heptazatricyclo[31.3.1.010,14]heptatriaconta-1(36),33(37),34-trien-5-yl]hexadecanamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.3690	uM
N-[(2R)-1-[[(8S,11S,14R,17S,20R)-8-benzyl-11,17-bis[3-(diaminomethylideneamino)propyl]-7,10,13,16,19-pentaoxo-14-(sulfanylmethyl)-3,22-dithia-6,9,12,15,18-pentazabicyclo[22.3.1]octacosa-1(28),24,26-trien-20-yl]amino]-1-oxo-3,3-diphenylpropan-2-yl]hexadecanamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.4583	uM
(10R,13S,19S,22S,25R,28S,31S,34R)-10-acetamido-13,31-dibenzyl-22,28-bis[3-(diaminomethylideneamino)propyl]-11,14,20,23,26,29,32-heptaoxo-25-(sulfanylmethyl)-2-oxa-8,36-dithia-12,15,21,24,27,30,33-heptazatetracyclo[36.2.2.23,6.015,19]tetratetraconta-1(40),3(44),4,6(43),38,41-hexaene-34-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.4774	uM
(11R,14S,20S,23S,26R,29S,32S,35R)-11-acetamido-14,32-dibenzyl-23,29-bis[3-(diaminomethylideneamino)propyl]-12,15,21,24,27,30,33-heptaoxo-26-(sulfanylmethyl)-9,37-dithia-13,16,22,25,28,31,34-heptazatetracyclo[37.3.1.13,7.016,20]tetratetraconta-1(43),3(44),4,6,39,41-hexaene-35-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.5169	uM
2-[[2-[[(2S,3R)-1-[[(5R,8S,14S,17S,20R,23S,26S,29R)-8,26-dibenzyl-29-carbamoyl-17,23-bis[3-(diaminomethylideneamino)propyl]-6,9,15,18,21,24,27-heptaoxo-20-(sulfanylmethyl)-3,31-dithia-7,10,16,19,22,25,28-heptazatricyclo[31.3.1.010,14]heptatriaconta-1(37),33,35-trien-5-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]acetic acid	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.5317	uM
(5R,8S,14S,17S,20R,23S,26S,29R)-5-acetamido-8,26-dibenzyl-17,23-bis[3-(diaminomethylideneamino)propyl]-6,9,15,18,21,24,27-heptaoxo-20-(sulfanylmethyl)-3,31-dithia-7,10,16,19,22,25,28-heptazatricyclo[31.2.2.010,14]heptatriaconta-1(36),33(37),34-triene-29-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.5856	uM
(5R,8S,14S,17S,20R,23S,26S,29R)-5-acetamido-8,26-dibenzyl-17,23-bis[3-(diaminomethylideneamino)propyl]-6,9,15,18,21,24,27-heptaoxo-20-(sulfanylmethyl)-3,31-dithia-7,10,16,19,22,25,28-heptazatricyclo[31.4.0.010,14]heptatriaconta-1(37),33,35-triene-29-carboxamide	1249412: Agonist activity at GFP-fused human FPN transfected in HEK293 cells assessed as protein degradation after 24 hrs by flow cytometric analysis	ec50	0.5989	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects reaction, decreases expression, affects cotreatment	7
Tobacco Smoke Pollution	decreases expression	6
sodium arsenite	increases expression, decreases expression, decreases reaction, increases abundance	5
Benzo(a)pyrene	affects cotreatment, decreases reaction, increases expression, decreases methylation	5
trichostatin A	increases expression, affects cotreatment	3
Panobinostat	affects cotreatment, affects expression, increases expression	3
Acetaminophen	decreases expression, increases expression	3
Cadmium	increases expression, increases response to substance, decreases expression, increases abundance	3
Nickel	decreases reaction, increases export, decreases expression	3
Tretinoin	increases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
bisphenol A	affects expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
ferrostatin-1	affects reaction, decreases expression, decreases reaction, increases abundance	2
Air Pollutants	decreases expression, increases abundance	2
Arsenic	increases abundance, increases expression, decreases expression, decreases reaction	2
Cisplatin	affects cotreatment, increases expression, affects expression	2
Copper	decreases expression, increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Iron	affects reaction, increases uptake, decreases reaction, increases export, increases oxidation (+1 more)	2
Lipopolysaccharides	decreases expression, decreases reaction, affects response to substance, increases expression	2
Paraquat	affects cotreatment, decreases expression, increases expression, increases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
N,N’-Bis(2-mercaptoethyl)isophthalamide	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3396798	Binding	Induction of human ferroportin degradation expressed in HEK293 cells after 24 hrs by flow cytometry	Thiol-derivatized minihepcidins retain biological activity. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4TP	HuH7-SLC40A1-KO-c3	Cancer cell line	Male
CVCL_D4TQ	HuH7-SLC40A1-KO-c5	Cancer cell line	Male
CVCL_TN64	HAP1 SLC40A1 (-) 1	Cancer cell line	Male
CVCL_TN65	HAP1 SLC40A1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00122980	PHASE3	TERMINATED	Stroke With Transfusions Changing to Hydroxyurea
NCT00202436	PHASE3	COMPLETED	Haemochromatosis:Phlebotomy Versus Erythrocytapheresis Therapy
NCT00350662	PHASE3	COMPLETED	Study With Deferiprone and/or Desferrioxamine in Iron Overloaded Patients
NCT01949467	PHASE2	COMPLETED	Analysis of the Modulation of Serum Hepcidin Level in Response to Iron Oral Intake: Potential Interest for the Differential Diagnosis Between Ferroportin Disease and Dysmetabolic Hepatosiderosis.
NCT00000595	PHASE2	COMPLETED	Evaluation of Subcutaneous Desferrioxamine as Treatment for Transfusional Hemochromatosis
NCT00007150	PHASE2	ACTIVE_NOT_RECRUITING	Treatment of Hemochromatosis
NCT00349453	PHASE2	COMPLETED	Study Using Deferiprone Alone or in Combination With Desferrioxamine in Iron Overloaded Transfusion-dependent Patients
NCT01892644	PHASE2	WITHDRAWN	Treatment of Iron Overload With Deferasirox (Exjade) in Hereditary Hemochromatosis and Myelodysplastic Syndrome
NCT00712738	PHASE1	COMPLETED	Oral Nifedipine to Treat Iron Overload
NCT00001203	Not specified	COMPLETED	Deferoxamine for the Treatment of Hemochromatosis
NCT00001455	Not specified	COMPLETED	Iron Overload in African Americans
NCT00005541	Not specified	COMPLETED	Hemochromatosis and Iron Overload Screening Study (HEIRS)
NCT00005559	Not specified	COMPLETED	Statistical Basis for Hemochromatosis Screening
NCT00006312	Not specified	COMPLETED	Hemochromatosis–Genetic Prevalence and Penetrance
NCT00199628	Not specified	COMPLETED	Research Network for Neonatal Diseases Induced by Tissular Fetomaternal Alloimmunization
NCT00509652	Not specified	UNKNOWN	Erythrocyte Apheresis Versus Phlebotomy in Hemochromatosis
NCT00587535	Not specified	COMPLETED	Evaluation of a New MR Pulse Sequence to Quantify Liver Iron Concentration
NCT01524757	Not specified	UNKNOWN	Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis
NCT01810965	Not specified	COMPLETED	Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis
NCT02025543	Not specified	COMPLETED	Confounder-Corrected Quantitative MRI Biomarker of Hepatic Iron Content
NCT02099214	Not specified	COMPLETED	Estimation of Myocardial Iron Overload by 3 Tesla MRI in HFE Hereditary Haemochromatosis
NCT03654794	Not specified	COMPLETED	Study of the Cellular Diffusion of Tacrolimus Across the Membrane of Mononuclear Cells
NCT03743272	Not specified	COMPLETED	Repeatability and Reproducibility of Multiparametric MRI
NCT04631718	Not specified	COMPLETED	MRI QSM Imaging for Iron Overload
NCT06137079	Not specified	UNKNOWN	Iron Overload and Endocrinological Diseases