ABCB6

Summary

ABCB6 (ATP binding cassette subfamily B member 6 (LAN blood group), HGNC:47) is a protein-coding gene on chromosome 2q35, encoding ATP-binding cassette sub-family B member 6 (Q9NP58). ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen.

This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ABC proteins transport various molecules across extra- and intra-cellular membranes. This protein is a member of the heavy metal importer subfamily and plays a role in porphyrin transport. This gene is the molecular basis of the Langereis (Lan) blood group antigen and mutations in this gene underlie familial pseudohyperkalemia and dyschromatosis universalis hereditaria.

Source: NCBI Gene 10058 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dyschromatosis universalis hereditaria 3 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 333 total — 10 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 27
• Druggable target: yes
• MANE Select transcript: NM_005689

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:47
Approved symbol	ABCB6
Name	ATP binding cassette subfamily B member 6 (LAN blood group)
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	EST45597, umat, MTABC3
Ensembl gene	ENSG00000115657
Ensembl biotype	protein_coding
OMIM	605452
Entrez	10058

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 12 protein_coding, 7 retained_intron, 4 nonsense_mediated_decay

ENST00000265316, ENST00000295750, ENST00000417678, ENST00000443805, ENST00000448398, ENST00000452545, ENST00000485773, ENST00000487380, ENST00000492543, ENST00000492953, ENST00000494639, ENST00000496984, ENST00000497882, ENST00000856959, ENST00000856960, ENST00000856961, ENST00000856962, ENST00000856963, ENST00000958199, ENST00000958200, ENST00000958201, ENST00000958202, ENST00000958203

RefSeq mRNA: 2 — MANE Select: NM_005689 NM_001349828, NM_005689

CCDS: CCDS2436, CCDS86920

Canonical transcript exons

ENST00000265316 — 19 exons

Exon	Start	End
ENSE00000786005	219216652	219216832
ENSE00001142630	219218125	219218958
ENSE00003479814	219210711	219210823
ENSE00003484735	219210381	219210475
ENSE00003485970	219212387	219212491
ENSE00003531941	219214389	219214498
ENSE00003585746	219210230	219210298
ENSE00003588841	219213008	219213065
ENSE00003602112	219213439	219213502
ENSE00003608587	219215997	219216180
ENSE00003616606	219216364	219216465
ENSE00003617329	219213826	219213951
ENSE00003617678	219213241	219213326
ENSE00003624577	219209772	219210046
ENSE00003651399	219210934	219211108
ENSE00003655022	219214121	219214186
ENSE00003655829	219213590	219213666
ENSE00003691860	219217670	219217807
ENSE00003694655	219214961	219215082

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 94.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0216 / max 96.2773, expressed in 1592 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34036	2.6970	1105
34035	1.6187	885
34034	0.8187	508
34037	0.6394	386
34033	0.2325	103
34032	0.0153	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right ovary	UBERON:0002118	94.95	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.57	gold quality
left ovary	UBERON:0002119	94.56	gold quality
cerebellar hemisphere	UBERON:0002245	94.39	gold quality
cerebellar cortex	UBERON:0002129	94.31	gold quality
cerebellum	UBERON:0002037	94.30	gold quality
right lobe of thyroid gland	UBERON:0001119	93.93	gold quality
nucleus accumbens	UBERON:0001882	93.90	gold quality
ovary	UBERON:0000992	93.78	gold quality
hypothalamus	UBERON:0001898	93.40	gold quality
right frontal lobe	UBERON:0002810	93.22	gold quality
left testis	UBERON:0004533	93.22	gold quality
left lobe of thyroid gland	UBERON:0001120	93.19	gold quality
caudate nucleus	UBERON:0001873	93.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.94	gold quality
right testis	UBERON:0004534	92.94	gold quality
putamen	UBERON:0001874	92.82	gold quality
testis	UBERON:0000473	92.61	gold quality
lower esophagus mucosa	UBERON:0035834	92.60	gold quality
brain	UBERON:0000955	92.56	gold quality
anterior cingulate cortex	UBERON:0009835	92.54	gold quality
adenohypophysis	UBERON:0002196	92.37	gold quality
frontal cortex	UBERON:0001870	92.34	gold quality
gastrocnemius	UBERON:0001388	92.33	gold quality
thyroid gland	UBERON:0002046	92.25	gold quality
Ammon’s horn	UBERON:0001954	92.23	gold quality
cerebral cortex	UBERON:0000956	92.22	gold quality
pituitary gland	UBERON:0000007	92.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	286.45
E-ANND-3	yes	6.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, HNF1B, HSF1, MYC

miRNA regulators (miRDB)

11 targeting ABCB6, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-6793-3P	97.66	65.78	1084

Literature-anchored findings (GeneRIF, showing 40)

• study of C-terminal nucleotide-binding domain of ABCB6 in nucleotide-free & ADP-bound states by NMR & homology modelling; results revealed localised dynamic cooperativity, which was proposed for a prokaryotic ABC MJ1267, also exists in a eukaryotic ABC (PMID:16791740)
• ABCB6 is uniquely located in the outer mitochondrial membrane and is required for mitochondrial porphyrin uptake (PMID:17006453)
• ABCB6 exists in two molecular weight forms, is localized to both the outer mitochondrial membrane and the plasma membrane, and plays a functional role in the plasma membrane. (PMID:17661442)
• ather, it localized in the ER-derived and brefeldin A-sensitive perinuclear compartments, mainly in the Golgi apparatus. (PMID:18279659)
• overall structure of ABCB6 is L-shaped and consists of two lobes, consistent with other reported nucleotide-binding domain structures (PMID:20823549)
• Conserved intramolecular disulfide bond is critical to trafficking and fate of ATP-binding cassette (ABC) transporters ABCB6 and sulfonylurea receptor 1 (SUR1)/ABCC8. (PMID:21199866)
• ABCB6 plays a role in cell growth and proliferation by targeting the cell cycle. (PMID:21849266)
• The results demonstrated that ABCB6 mutations cause ocular coloboma. (PMID:22226084)
• It was established that ABCB6 encodes a new blood group system (Langereis, Lan). Targeted sequencing of ABCB6 in 12 unrelated individuals of the Lan(-) blood type identified 10 different ABCB6 null mutations. (PMID:22246506)
• Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis in differentiating K562 cells, excluding this ABC transporter as a key regulator of porphyrin synthesis. (PMID:22655043)
• High expression levels of ABCB6 are associated with glioma. (PMID:22688660)
• Polycyclic aromatic hydrocarbons (PAHs) mediate transcriptional activation of the ATP binding cassette transporter ABCB6 gene via the aryl hydrocarbon receptor (AhR) (PMID:22761424)
• p.Arg192Trp is the first ABCB6 missense mutation causing the Lan- blood type and appears to be a relatively frequent cause of this rare blood type. (PMID:22958180)
• the two missense mutations in residue 375 of the ABCB6 polypeptide found in affected individuals of families with chromosome 2-linked FP could contribute to the red cell K(+) leak characteristic of this condition. (PMID:23180570)
• Aberrant mRNA and DNA methylation levels of ABCB6 may serve as useful predictive biomarkers for early intrahepatic recurrence of HCV-related hepatocellular carcinoma (PMID:23483087)
• These findings suggest that ABCB6 may be a physiological factor for skin pigmentation. (PMID:23519333)
• To date, 19 ABCB6 alleles that encode Lan- or Lan+(w) /-, or Lan+(w) phenotypes have been described. (PMID:23763549)
• results suggest a direct interaction between mitochondrial ABCB6 and its transport substrates that is critical for the activity of the transporter (PMID:23792964)
• Data suggest that expression of ABCB6 varies widely in bone marrow and blood samples from patients with acute myeloid leukemia. [LETTER] (PMID:23793916)
• No significant associations were detected for the ABCB6 or ABCG1 gene. (PMID:24192121)
• data add new variants to the repertoire of ABCB6 mutations with dyschromatosis universalis hereditaria. (PMID:24224009)
• We describe eight new mutations in ABCB6 of which seven, including three missense mutations, underlie the Lan- phenotype and determine that a complete gene deletion of ABCG2 or ABCB6 is not responsible for the Jr(a-) or Lan- phenotype, respectively. (PMID:24456066)
• Data indicate ATP-binding cassette sub-family B member 6 (ABCB6) as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val) that co-segregates with the dyschromatosis universalis hereditaria phenotype. (PMID:24498303)
• a heterozygous substitution Arg723Gln in the ATP-binding cassette, Subfamily B, Member 6 protein that segregated with FP in the Cardiff family and was also present in both blood donors. Arg723Gln is listed in human variation databases (PMID:24947683)
• Expression of ABCB6 is related to resistance to 5-FU, SN-38 and vincristine. (PMID:25202056)
• Identified two novel ABCB6 mutations in two Chinese families affected with dyschromatosis universalis hereditaria (DUH), underscoring the causative role of the ABCB6 mutations in the molecular pathogenesis of DUH. (PMID:25288164)
• genetic variants linked to lower or absent cell surface expression of ABCB6/Langereis may be more common than previously thought. (PMID:25360778)
• These data indicate that the expression of ABCB6 in plasma membrane is important for porphyrin accumulation after ALA administration, including hypoxic conditions. (PMID:25573285)
• Data suggest N-terminal transmembrane domain of ABCB6 functions as independent folding unit and plays crucial role in lysosomal (rather than plasma membrane) targeting of ABCB6; this domain is dispensable for dimerization and ATP binding/hydrolysis. (PMID:25627919)
• ABCB6 missense mutations in red blood cells from subjects with familial pseudohyperkalemia show elevated potassium ion efflux. (PMID:27151991)
• Severely affected porphyria patients harbor variant alleles in the ABCB6 gene. (PMID:27507172)
• The human ABCB6 protein is the functional homologue of HMT-1 proteins mediating cadmium detoxification in Schizosaccharomyces pombe and Caenorhabditis elegans. (PMID:31053883)
• Investigated whether 9 SNPs in ABCB1 (rs6946119, rs28401781, rs4148739, and rs3747802), ABCB6 (rs1109866, rs1109867, rs3731885, and rs3755047), and ABCG1 (rs182694); findings support an association between ABCG1 polymorphism and schizophrenia in a Han Chinese population; no association between schizophrenia and a specific allele or genotype among the SNPs of ABCB1 and ABCB6 was observed (PMID:31189171)
• UBE2L6 is Involved in Cisplatin Resistance by Regulating the Transcription of ABCB6. (PMID:32329696)
• Systematic analysis of the ABC transporter family in hepatocellular carcinoma reveals the importance of ABCB6 in regulating ferroptosis. (PMID:32710948)
• Cryo-electron microscopy structure of human ABCB6 transporter. (PMID:33007128)
• Substrate specificity of Chondroitinase ABC I based on analyses of biochemical reactions and crystal structures in complex with disaccharides. (PMID:34392362)
• ABCB6 polymorphisms are not overly represented in patients with porphyria. (PMID:34724702)
• ABCB6 knockdown suppresses melanogenesis through the GSK3-beta/beta-catenin signaling axis in human melanoma and melanocyte cell lines. (PMID:35461746)
• Association of UBE2L6 and ABCB6 Expression With Platinum Resistance in Serous Ovarian Carcinoma. (PMID:37500176)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	abcb6a	ENSDARG00000063297
danio_rerio	abcb6b	ENSDARG00000074254
mus_musculus	Abcb6	ENSMUSG00000026198
rattus_norvegicus	Abcb6	ENSRNOG00000018697
drosophila_melanogaster	Hmt-1	FBGN0038376
caenorhabditis_elegans		WBGENE00001815

Paralogs (10): ABCB5 (ENSG00000004846), ABCB4 (ENSG00000005471), ABCB11 (ENSG00000073734), ABCB1 (ENSG00000085563), ABCB7 (ENSG00000131269), ABCB10 (ENSG00000135776), ABCB9 (ENSG00000150967), TAP1 (ENSG00000168394), ABCB8 (ENSG00000197150), TAP2 (ENSG00000204267)

Protein

Protein identifiers

ATP-binding cassette sub-family B member 6 — Q9NP58 (reviewed: Q9NP58)

Alternative names: ABC-type heme transporter ABCB6, Mitochondrial ABC transporter 3, P-glycoprotein-related protein, Ubiquitously-expressed mammalian ABC half transporter

All UniProt accessions (5): Q9NP58, H7C049, H7C1R6, H7C245, H7C3Z0

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen. May also function as an ATP-dependent importer of porphyrins from the cytoplasm into the mitochondria, in turn may participate in the de novo heme biosynthesis regulation and in the coordination of heme and iron homeostasis during phenylhydrazine stress. May also play a key role in the early steps of melanogenesis producing PMEL amyloid fibrils. In vitro, it confers to cells a resistance to toxic metal such as arsenic and cadmium and against chemotherapeutics agent such as 5-fluorouracil, SN-38 and vincristin. In addition may play a role in the transition metal homeostasis.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane. Mitochondrion outer membrane. Endoplasmic reticulum membrane. Golgi apparatus membrane. Endosome membrane. Lysosome membrane. Late endosome membrane. Early endosome membrane. Secreted. Extracellular exosome. Mitochondrion. Endosome. Multivesicular body membrane. Melanosome membrane.

Tissue specificity. Widely expressed. High expression is detected in the retinal epithelium. Expressed in mature erythrocytes.

Post-translational modifications. N-glycosylated.

Disease relevance. Microphthalmia/Coloboma 7 (MCOPCB7) [MIM:614497] A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). The disease is caused by variants affecting the gene represented in this entry. Dyschromatosis universalis hereditaria 3 (DUH3) [MIM:615402] An autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body, that appear in infancy or early childhood. The trunk and extremities are the dominant sites of abnormal pigmentation. Facial lesions can be seen in 50% of affected individuals, but involvement of palms and soles is unusual. Abnormalities of hair and nails have also been reported. Dyschromatosis universalis hereditaria may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications. The disease is caused by variants affecting the gene represented in this entry. Pseudohyperkalemia, familial, 2, due to red cell leak (PSHK2) [MIM:609153] A dominantly inherited condition characterized by increased serum potassium levels, measured in whole-blood specimens stored at or below room temperature. This condition is not accompanied by clinical symptoms or biological signs except for borderline abnormalities of red cell shape. The disease is caused by variants affecting the gene represented in this entry. Defects in ABCB6 may be the cause of a severe porphyria. Affected individuals show higher urinary porphyrin concentrations.

Activity regulation. ATPase activity is inhibited by MgATP with an IC(50) of 1.03 mM and up-regulated by coporphyrin III> hemin > protoporphyrin IX. ATPase activity for hemin is up-regulated by glutathione. The ATPase activity is impaired by increasing copper concentrations (0-300 uM). The ATPase activity is stimulated in presence of glutathione for increasing copper concentrations (0-300 uM).

Domain organisation. Contains two independently folding units, the N-terminal transmembrane domain (residues 1-205) and the ABC-core domain (206-842) are respectively responsible for the lysosomal targeting and the ATPase activity.

Induction. Up-regulated by cellular porphyrins (at protein level). Up-regulated during erythroid differentiation (at protein level). Induced by sodium arsenite in a dose-dependent manner.

Polymorphism. Genetic variations in ABCB6 define the Langereis blood group system (LAN) [MIM:111600]. Individuals with Lan(-) blood group lack the Lan antigen on their red blood cells. These individuals may have anti-Lan antibodies in their serum, which can cause transfusion reactions or hemolytic disease of the fetus or newborn. The Lan(-) blood group is only clinically significant in transfusion settings or during pregnancy; otherwise Lan(-) individuals have no clinical features.

Similarity. Belongs to the ABC transporter superfamily. ABCB family. Heavy Metal importer (TC 3.A.1.210) subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NP58-1	1	yes
Q9NP58-4	2

RefSeq proteins (2): NP_001336757, NP_005680* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR011527	ABC1_TM_dom	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032410	ABCB6_N	Domain
IPR036640	ABC1_TM_sf	Homologous_superfamily
IPR039421	Type_1_exporter	Family

Pfam: PF00005, PF00664, PF16185

Catalyzed reactions (Rhea), 8 shown:

• heme b(in) + ATP + H2O = heme b(out) + ADP + phosphate + H(+) (RHEA:19261)
• protoporphyrin IX(in) + ATP + H2O = protoporphyrin IX(out) + ADP + phosphate + H(+) (RHEA:61336)
• pheophorbide a(in) + ATP + H2O = pheophorbide a(out) + ADP + phosphate + H(+) (RHEA:61360)
• coproporphyrin III(in) + ATP + H2O = coproporphyrin III(out) + ADP + phosphate + H(+) (RHEA:66664)
• coproporphyrinogen III(in) + ATP + H2O = coproporphyrinogen III(out) + ADP + phosphate + H(+) (RHEA:66680)
• coproporphyrin I(in) + ATP + H2O = coproporphyrin I(out) + ADP + phosphate + H(+) (RHEA:66768)
• uroporphyrin I(in) + ATP + H2O = uroporphyrin I(out) + ADP + phosphate + H(+) (RHEA:66772)
• uroporphyrin III(in) + ATP + H2O = uroporphyrin III(out) + ADP + phosphate + H(+) (RHEA:66776)

UniProt features (123 total): helix 27, sequence variant 22, mutagenesis site 19, strand 16, topological domain 12, transmembrane region 11, sequence conflict 5, domain 2, region of interest 2, binding site 2, chain 1, turn 1, glycosylation site 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
3NH6	X-RAY DIFFRACTION	2
3NH9	X-RAY DIFFRACTION	2.1
3NHA	X-RAY DIFFRACTION	2.1
3NHB	X-RAY DIFFRACTION	2.15
9DBQ	ELECTRON MICROSCOPY	2.9
8YR4	ELECTRON MICROSCOPY	3.1
8YR3	ELECTRON MICROSCOPY	3.2
7DNY	ELECTRON MICROSCOPY	3.4
7EKL	ELECTRON MICROSCOPY	3.5
8FWK	ELECTRON MICROSCOPY	3.5
7DNZ	ELECTRON MICROSCOPY	3.6
7EKM	ELECTRON MICROSCOPY	3.6
8K7B	ELECTRON MICROSCOPY	3.9
8K7C	ELECTRON MICROSCOPY	3.9
7D7R	ELECTRON MICROSCOPY	4
7D7N	ELECTRON MICROSCOPY	5.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP58-F1	83.17	0.43

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 (2): 599; 623–634

Disulfide bonds (1): 8–26

Glycosylation sites (1): 6

Mutagenesis-validated functional residues (19):

Position	Phenotype
6	loss of n-glycosylation. loss of n-glycosylation; when associated with q-447; q-498; q-677 and q-775. does not affect su
8	loss of n-glycosylation.
8	does not affect substrate binding. does not affect n-glycosylation. impairs endoplasmic reticulum exit. impairs endoplas
26	decreases protein expression. affects protein stability. loss of ability to stimulate porphyrin synthesis.
26	decreases protein expression. impairs endoplasmic reticulum exit; when associated with c-8. affects protein stability.
50	increases migration in the absence of dtt; when associated with a-120. reduces migration in with the presence of dtt; wh
120	increases migration in the absence of dtt; when associated with a-50. reduces migration in with the presence of dtt; whe
286	loss of substrate-stimulate atpase activity. impairs protein expression.
447	does not affect n-glycosylation. does not affect n-glycosylation; when associated with q-498; q-677 and q-775. does not
498	does not affect n-glycosylation. does not affect n-glycosylation; when associated with q-447; q-677 and q-775. does not
531	loss of substrate-stimulate atpase activity. impairs protein expression.
542	loss of substrate-stimulate atpase activity.
546	loss of substrate-stimulate atpase activity. impairs protein expression.
546	does not affect substrate-stimulate atpase activity.
629	abolishes atp hydrolysis. abolishes coproporphyrin iii transport.
629	does not affect subcellular location in early melanosome and lysosome. does not rescue the normal amyloid fibril formati
677	does not affect n-glycosylation. does not affect n-glycosylation; when associated with q-447; q-498; and q-775. does not
775	does not affect n-glycosylation. does not affect n-glycosylation; when associated with q-447; q-498 and q-677. does not

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1369007	Mitochondrial ABC transporters
R-HSA-5683371	Defective ABCB6 causes MCOPCB7
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-382556	ABC-family protein mediated transport
R-HSA-5619084	ABC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 263 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, AP1_01, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_IRON_COORDINATION_ENTITY_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_VESICLE_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_CADMIUM_ION, MENSE_HYPOXIA_UP, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_CELLULAR_PIGMENTATION, GOBP_TETRAPYRROLE_BIOSYNTHETIC_PROCESS, GOBP_IRON_ION_TRANSPORT

GO Biological Process (14): porphyrin-containing compound metabolic process (GO:0006778), porphyrin-containing compound biosynthetic process (GO:0006779), intracellular copper ion homeostasis (GO:0006878), intracellular iron ion homeostasis (GO:0006879), brain development (GO:0007420), heme transport (GO:0015886), tetrapyrrole metabolic process (GO:0033013), heme transmembrane transport (GO:0035351), heme metabolic process (GO:0042168), skin development (GO:0043588), transmembrane transport (GO:0055085), cellular detoxification of cadmium ion (GO:0098849), melanosome assembly (GO:1903232), iron ion transmembrane transport (GO:0034755)

GO Molecular Function (9): ATP binding (GO:0005524), ABC-type heme transporter activity (GO:0015439), efflux transmembrane transporter activity (GO:0015562), ATP hydrolysis activity (GO:0016887), heme binding (GO:0020037), tetrapyrrole binding (GO:0046906), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166), heme transmembrane transporter activity (GO:0015232)

GO Cellular Component (26): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial envelope (GO:0005740), mitochondrial outer membrane (GO:0005741), lysosomal membrane (GO:0005765), endosome (GO:0005768), vacuolar membrane (GO:0005774), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), early endosome membrane (GO:0031901), multivesicular body membrane (GO:0032585), melanosome membrane (GO:0033162), endolysosome membrane (GO:0036020), ATP-binding cassette (ABC) transporter complex (GO:0043190), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), extracellular region (GO:0005576), lysosome (GO:0005764), endosome membrane (GO:0010008), membrane (GO:0016020), late endosome membrane (GO:0031902)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
ABC-family protein mediated transport	1
ABC transporter disorders	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	3
intracellular membrane-bounded organelle	3
endomembrane system	3
porphyrin-containing compound metabolic process	2
intracellular monoatomic cation homeostasis	2
animal organ development	2
heme transport	2
transmembrane transporter activity	2
bounding membrane of organelle	2
endosome membrane	2
tetrapyrrole metabolic process	1
tetrapyrrole biosynthetic process	1
copper ion homeostasis	1
inorganic ion homeostasis	1
central nervous system development	1
head development	1
nitrogen compound transport	1
iron coordination entity transport	1
metabolic process	1
iron ion transmembrane transport	1
pigment metabolic process	1
transport	1
cellular process	1
cellular response to cadmium ion	1
detoxification of cadmium ion	1
cellular detoxification of metal ion	1
melanosome organization	1
organelle assembly	1
iron ion transport	1
monoatomic cation transmembrane transport	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
heme transmembrane transporter activity	1
heme transmembrane transport	1
ABC-type transporter activity	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
tetrapyrrole binding	1
binding	1

Protein interactions and networks

STRING

1302 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCB6	FECH	P22830	737
ABCB6	PPOX	P50336	666
ABCB6	SLC25A38	Q96DW6	664
ABCB6	TFRC	P02786	648
ABCB6	ABCF2	Q9UG63	643
ABCB6	CPOX	P36551	636
ABCB6	UROS	P10746	629
ABCB6	ABCE1	P61221	623
ABCB6	UROD	P06132	613
ABCB6	SLC25A37	Q9NYZ2	612
ABCB6	FLVCR1	Q9Y5Y0	609
ABCB6	ABCF3	Q9NUQ8	575
ABCB6	BCS1L	Q9Y276	569
ABCB6	ALAD	P13716	548
ABCB6	SLC48A1	Q6P1K1	517

IntAct

75 interactions, top by confidence:

A	B	Type	Score
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
AUP1	APOB	psi-mi:“MI:0914”(association)	0.610
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
MRAP2	PODXL	psi-mi:“MI:0914”(association)	0.530
HAX1	CHEK1	psi-mi:“MI:0914”(association)	0.530
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
SPCS3	ENTPD6	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
TOLLIP	IRAK2	psi-mi:“MI:0914”(association)	0.500
pipB2	SCD	psi-mi:“MI:0914”(association)	0.460
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
SDCBP	ABCB6	psi-mi:“MI:0407”(direct interaction)	0.440
TSG101	ABCB6	psi-mi:“MI:0915”(physical association)	0.370
	HAX1	psi-mi:“MI:0914”(association)	0.350
	TSPO	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
pipB2	PLOD2	psi-mi:“MI:0914”(association)	0.350
sseL	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
POMK	ESYT2	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
IGHM	ESYT2	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
RAMP2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
TMEM59	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (103): ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS)

ESM2 similar proteins: A0A125QXJ1, D3ZHR2, E7F6F7, G5EFD4, H2LNR5, O15440, O70595, O75027, P21441, P21958, P33897, P36370, P48410, P70170, P82451, P9WEL8, Q02592, Q08D64, Q09427, Q09428, Q09429, Q10185, Q2UPC0, Q42093, Q4WA92, Q4WPP6, Q61102, Q63120, Q63563, Q704E8, Q751N2, Q7DM58, Q8LPQ6, Q8RY46, Q92887, Q96J65, Q9C8G9, Q9C8H0, Q9C8H1, Q9DC29

Diamond homologs: A0A125QXJ1, E7F6F7, G5EFD4, H2LNR5, J9VWU3, O14286, O31707, O31708, O70595, O75027, P0C529, P0CL92, P0CL93, P0DKX5, P0DKX6, P40416, P45861, P54719, P55469, P60752, P60753, P63359, P63360, P63398, P71082, P9WQJ2, P9WQJ3, Q02592, Q08D64, Q142P6, Q1BUV6, Q1CA68, Q1CGH0, Q1QX69, Q21NS8, Q2FFM9, Q2G2M9, Q2G506, Q2HIE9, Q2J0F4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NFE2L2	“up-regulates quantity by expression”	ABCB6	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	4
Uncertain significance	203
Likely benign	53
Benign	23

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1180532	GRCh37/hg19 2q35-36.3(chr2:220056891-227164817)x1	Pathogenic
1526953	GRCh37/hg19 2q35-37.3(chr2:219606537-239217703)	Pathogenic
208249	NM_005689.4(ABCB6):c.1663C>A (p.Gln555Lys)	Pathogenic
218179	NM_005689.4(ABCB6):c.1124G>A (p.Arg375Gln)	Pathogenic
30482	NM_005689.4(ABCB6):c.2431C>G (p.Leu811Val)	Pathogenic
549857	Single allele	Pathogenic
562681	GRCh37/hg19 2q35-37.3(chr2:219225872-242016876)x3	Pathogenic
64646	NM_005689.4(ABCB6):c.1067T>C (p.Leu356Pro)	Pathogenic
64647	NM_005689.4(ABCB6):c.508A>G (p.Ser170Gly)	Pathogenic
64648	NM_005689.4(ABCB6):c.1736G>A (p.Gly579Glu)	Pathogenic
218180	NM_005689.4(ABCB6):c.1123C>T (p.Arg375Trp)	Likely pathogenic
3066330	NM_005689.4(ABCB6):c.1452+2T>A	Likely pathogenic
3357313	NM_005689.4(ABCB6):c.1589_1590del (p.Tyr530fs)	Likely pathogenic
4086262	NM_005689.4(ABCB6):c.1348C>T (p.Arg450Trp)	Likely pathogenic

SpliceAI

2348 predictions. Top by Δscore:

Variant	Effect	Δscore
2:219210047:C:CC	acceptor_gain	1.0000
2:219210299:C:CC	acceptor_gain	1.0000
2:219210706:CGCA:C	donor_loss	1.0000
2:219210707:GCAC:G	donor_loss	1.0000
2:219210708:CA:C	donor_loss	1.0000
2:219210710:CC:C	donor_loss	1.0000
2:219210851:T:C	acceptor_gain	1.0000
2:219210928:TCTCA:T	donor_loss	1.0000
2:219210929:CTCAC:C	donor_loss	1.0000
2:219210930:TCACC:T	donor_loss	1.0000
2:219210931:CA:C	donor_loss	1.0000
2:219210933:C:CG	donor_loss	1.0000
2:219210933:CCTT:C	donor_gain	1.0000
2:219211078:CAA:C	acceptor_gain	1.0000
2:219211106:CAC:C	acceptor_gain	1.0000
2:219211107:ACC:A	acceptor_loss	1.0000
2:219211109:CT:C	acceptor_loss	1.0000
2:219213239:AC:A	donor_gain	1.0000
2:219213240:CC:C	donor_gain	1.0000
2:219213427:C:CA	donor_gain	1.0000
2:219213437:A:AC	donor_gain	1.0000
2:219213438:C:CC	donor_gain	1.0000
2:219213438:CTT:C	donor_gain	1.0000
2:219213440:T:TA	donor_gain	1.0000
2:219213499:CATC:C	acceptor_gain	1.0000
2:219213503:C:CC	acceptor_gain	1.0000
2:219213503:CT:C	acceptor_loss	1.0000
2:219213666:CCTG:C	acceptor_loss	1.0000
2:219213667:C:CA	acceptor_loss	1.0000
2:219213668:T:A	acceptor_loss	1.0000

AlphaMissense

5408 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:219213614:A:T	L544H	0.999
2:219210754:G:T	A738D	0.998
2:219210766:C:G	R734P	0.998
2:219213626:A:G	L540P	0.998
2:219213882:C:G	G508R	0.998
2:219213882:C:T	G508R	0.998
2:219213901:C:A	Q501H	0.998
2:219213901:C:G	Q501H	0.998
2:219214398:G:C	N459K	0.998
2:219214398:G:T	N459K	0.998
2:219215036:C:G	G401R	0.998
2:219210761:C:G	A736P	0.997
2:219210768:C:A	Q733H	0.997
2:219210768:C:G	Q733H	0.997
2:219211028:A:C	N683K	0.997
2:219211028:A:T	N683K	0.997
2:219213614:A:G	L544P	0.997
2:219213870:C:G	G512R	0.997
2:219213878:A:G	L509P	0.997
2:219214405:A:G	L457P	0.997
2:219214979:A:G	C420R	0.997
2:219215048:C:G	D397H	0.997
2:219216027:C:G	R375P	0.997
2:219216672:G:T	P283H	0.997
2:219210755:C:G	A738P	0.996
2:219210783:G:C	S728R	0.996
2:219210783:G:T	S728R	0.996
2:219210785:T:G	S728R	0.996
2:219212465:G:C	S630R	0.996
2:219212465:G:T	S630R	0.996

dbSNP variants (sampled 300 via entrez): RS1000591910 (2:219214039 ACACTCGACTAT>A), RS1000818861 (2:219218043 T>C), RS1000917600 (2:219220667 C>G,T), RS1001045027 (2:219211384 G>T), RS1001081778 (2:219215781 G>A), RS1001416834 (2:219217177 G>A), RS1001427121 (2:219211976 G>A), RS1001918004 (2:219211122 A>T), RS1002065045 (2:219211690 G>A,C), RS1002346711 (2:219212653 G>T), RS1003074361 (2:219218491 C>A,T), RS1003087272 (2:219218730 T>A,C,G), RS1003375773 (2:219219246 A>G), RS1003429566 (2:219219460 C>A,G,T), RS1003907383 (2:219214776 C>T)

Disease associations

OMIM: gene MIM:605452 | disease phenotypes: MIM:176000, MIM:177000, MIM:609153, MIM:614497, MIM:615402, MIM:121300, MIM:176200, MIM:603596

GenCC curated gene-disease

Disease	Classification	Inheritance
dyschromatosis universalis hereditaria 3	Strong	Autosomal dominant
dyschromatosis universalis hereditaria	Supportive	Autosomal dominant
familial pseudohyperkalemia	Supportive	Autosomal dominant
microphthalmia, isolated, with coloboma	Supportive	Autosomal dominant
microphthalmia, isolated, with coloboma 7	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
microphthalmia, isolated, with coloboma 7	Limited	AD
dyschromatosis universalis hereditaria 3	Moderate	AD

Mondo (10): acute intermittent porphyria (MONDO:0008294), protoporphyria, erythropoietic, 1 (MONDO:0008319), familial pseudohyperkalemia (MONDO:0012204), microphthalmia, isolated, with coloboma 7 (MONDO:0013783), dyschromatosis universalis hereditaria 3 (MONDO:0014169), hereditary coproporphyria (MONDO:0007369), variegate porphyria (MONDO:0008297), polydactyly (MONDO:0021003), dyschromatosis universalis hereditaria (MONDO:0000736), microphthalmia, isolated, with coloboma (MONDO:0000170)

Orphanet (6): Acute intermittent porphyria (Orphanet:79276), Autosomal erythropoietic protoporphyria (Orphanet:79278), Familial pseudohyperkalemia (Orphanet:90044), Colobomatous microphthalmia (Orphanet:98938), Hereditary coproporphyria (Orphanet:79273), Variegate porphyria (Orphanet:79473)

HPO phenotypes

27 total (28 of 27 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000365	Hearing impairment
HP:0000568	Microphthalmia
HP:0000612	Iris coloboma
HP:0000822	Hypertension
HP:0000992	Cutaneous photosensitivity
HP:0001034	Hypermelanotic macule
HP:0001053	Hypopigmented skin patches
HP:0001480	Freckling
HP:0001878	Hemolytic anemia
HP:0001923	Reticulocytosis
HP:0002153	Hyperkalemia
HP:0002378	Hand tremor
HP:0003324	Generalized muscle weakness
HP:0003394	Muscle spasm
HP:0003577	Congenital onset
HP:0003768	Periodic paralysis
HP:0004322	Short stature
HP:0004446	Stomatocytosis
HP:0004802	Episodic hemolytic anemia
HP:0005518	Increased mean corpuscular volume
HP:0005590	Spotty hypopigmentation
HP:0007565	Multiple cafe-au-lait spots
HP:0011463	Childhood onset
HP:0012733	Macule
HP:0020073	Hypopigmented macule
HP:0031613	Inferior chorioretinal coloboma
HP:0010442	Polydactyly

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004619_68	Reticulocyte fraction of red cells	2.000000e-20
GCST004622_157	Reticulocyte count	1.000000e-21
GCST90002385_462	High light scatter reticulocyte count	4.000000e-44
GCST90002386_533	High light scatter reticulocyte percentage of red cells	8.000000e-43
GCST90002387_61	Immature fraction of reticulocytes	3.000000e-10
GCST90002404_35	Red cell distribution width	2.000000e-20
GCST90002405_3	Reticulocyte count	3.000000e-49
GCST90002406_70	Reticulocyte fraction of red cells	2.000000e-48

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D046349	Coproporphyria, Hereditary	C06.552.830.074; C16.320.850.742.074; C17.800.827.742.074; C18.452.811.400.074
D017689	Polydactyly	C05.660.585.600; C16.131.621.585.600
D017118	Porphyria, Acute Intermittent	C06.552.830.150; C16.320.850.742.150; C17.800.827.742.150; C18.452.811.400.150
D046350	Porphyria, Variegate	C06.552.830.625; C16.320.850.742.625; C17.800.827.742.625; C18.452.811.400.625
C535730	Dyschromatosis universalis hereditaria (supp.)
C537463	Microphthalmia associated with colobomatous cyst (supp.)
C563785	Pseudohyperkalemia, Familial, 2, due to Red Cell Leak (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2007630 (SINGLE PROTEIN)

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1109866	ABCB6		0.00	0
rs1109867	ABCB6		0.00	0
rs3731885	ABCB6, ATG9A		0.00	0
rs3755047	ABCB6, ATG9A		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — ABCB subfamily

Binding affinities (BindingDB)

8 measured of 8 human assays (8 total across all organisms); most potent 8 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
MLS001002340	EC50	210 nM
cid_360569	EC50	4140 nM
5-chloro-N-(3-methylphenyl)-2-(phenylmethyl)sulfonyl-4-pyrimidinecarboxamide	EC50	21500 nM
MLS001116165	EC50	34700 nM
MLS001116149	EC50	44200 nM
cid_16446684	EC50	62800 nM
MLS001116228	EC50	74500 nM
cid_16446988	EC50	80400 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	8
sodium arsenite	decreases activity, decreases reaction, increases response to substance, decreases response to substance, decreases expression (+3 more)	7
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Cisplatin	affects cotreatment, increases expression, decreases expression, affects response to substance	4
Tetrachlorodibenzodioxin	affects expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Cadmium Chloride	decreases reaction, increases response to substance, decreases response to substance, increases abundance, increases expression	3
bisphenol A	increases expression	2
cobaltous chloride	increases expression, decreases reaction	2
ochratoxin A	decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Zoledronic Acid	decreases expression	2
Leflunomide	decreases expression	2
Acetaminophen	decreases expression	2
Fluorouracil	decreases response to substance, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Vincristine	decreases response to substance, affects expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
tungsten carbide	affects cotreatment, increases expression	1
chloroacetaldehyde	affects expression	1
methylmercuric chloride	increases expression	1
deoxynivalenol	decreases expression	1
sulforaphane	increases expression	1
zinc chloride	decreases reaction, increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
glycidamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1963925	Functional	PUBCHEM_BIOASSAY: Dose Response of Flow Cytometric HTS Screen for inhibitors of the ABC transporter ABCB6 for Cherry Pick01. (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

1 cell lines: 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_ZM55	XP115KO	Finite cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03338816	PHASE3	COMPLETED	ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)
NCT00004940	PHASE3	COMPLETED	Phase III Study of L-Cysteine in Patients With Erythropoietic Protoporphyria
NCT00979745	PHASE3	COMPLETED	Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)
NCT01605136	PHASE3	COMPLETED	Phase III Confirmatory Study in Erythropoietic Protoporphyria
NCT04053270	PHASE3	COMPLETED	Multicentre Phase III Erythropoietic Protoporphyria Study
NCT04402489	PHASE3	COMPLETED	Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Subjects With Erythropoietic Protoporphyria or X-Linked Protoporphyria
NCT04578496	PHASE3	COMPLETED	A Safety Extension Study in Patients With Erythropoietic Protoporphyria (EPP)
NCT05005975	PHASE3	RECRUITING	Extension Study to Evaluate Safety and Tolerability of Oral Dersimelagon (MT-7117) in Subjects With Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)
NCT06144840	PHASE3	ACTIVE_NOT_RECRUITING	INcreased Sun Exposure Without Pain In Research Participants With EPP or XLP
NCT06910358	PHASE3	ACTIVE_NOT_RECRUITING	Study of Bitopertin in Participants With EPP or XLP (APOLLO)
NCT02922413	PHASE2	TERMINATED	Panhematin for Prevention of Acute Attacks of Porphyria
NCT01097044	PHASE2	COMPLETED	Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP)
NCT03520036	PHASE2	COMPLETED	Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Subjects With Erythropoietic Protoporphyria
NCT05020184	PHASE2	COMPLETED	Effect of Oral Cimetidine in the Protoporphyrias
NCT05308472	PHASE2	COMPLETED	Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and PPIX Concentrations in Participants With EPP
NCT06971900	PHASE2	ENROLLING_BY_INVITATION	GATEWAY: A Phase 2a Study of PORT-77 in Adults With Erythropoietic Protoporphyria
NCT05854784	PHASE2	COMPLETED	Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Variegate Porphyria (VP)
NCT02082860	PHASE1	COMPLETED	Phase I Gene Therapy Clinical Trial Using the Vector rAAV2/5-PBGD for the Treatment of Acute Intermittent Porphyria
NCT02452372	PHASE1	COMPLETED	A Phase 1 Study of Givosiran (ALN-AS1) in Patients With Acute Intermittent Porphyria (AIP)
NCT02943213	PHASE1	COMPLETED	Assessment of Intra-subject Variability in the Bioavailability of Chlorpromazine Hydrochloride
NCT03505853	PHASE1	COMPLETED	A Study to Investigate the Interaction Between Givosiran and a 5-probe Drug Cocktail in Patients With Acute Intermittent Porphyria (AIP)
NCT00418795	PHASE2/PHASE3	COMPLETED	Porphozym in the Treatment of Acute Attacks in AIP
NCT02949830	PHASE1/PHASE2	COMPLETED	A Study to Evaluate Long-term Safety and Clinical Activity of Givosiran (ALN-AS1) in Patient With Acute Intermittent Porphyria (AIP)
NCT01568554	Not specified	COMPLETED	Clinical Diagnosis of Acute Porphyria
NCT01617642	Not specified	ACTIVE_NOT_RECRUITING	Dental Health, Diet, Inflammation and Biomarkers in Patients With Acute Intermittent Porphyria(AIP)
NCT02076763	Not specified	COMPLETED	Observational Study of Acute Intermittent Porphyria Patients
NCT02935400	Not specified	ACTIVE_NOT_RECRUITING	Acute Porphyria Biomarkers for Disease Activity
NCT03547297	Not specified	TERMINATED	INSIGHT-AHP: A Study to Characterize the Prevalence of Acute Hepatic Porphyria (AHP) in Patients With Clinical Presentation and History Consistent With AHP
NCT05502133	Not specified	RECRUITING	Identification of Acute Intermittent Porphyria Modifying Genes
NCT06273644	Not specified	RECRUITING	Clinical Research on Acute Intermittent Porphyria and the Use of Carbohydrate-Rich Diet as a Treatment
NCT01422915	PHASE2/PHASE3	COMPLETED	Sorbent Therapy of the Cutaneous Porphyrias
NCT05883748	PHASE2/PHASE3	ENROLLING_BY_INVITATION	HELIOS: Open-Label, Long-Term Extension Study to Investigate the Safety, Tolerability, and Efficacy of DISC-1459 (Bitopertin) in Participants With EPP or XLP
NCT06388642	PHASE1/PHASE2	COMPLETED	Pharmacokinetics of Afamelanotide in Erythropoietic Protoporphyria Patients
NCT00004831	Not specified	COMPLETED	Study of Cysteine Hydrochloride for Erythropoietic Protoporphyria
NCT00206869	Not specified	UNKNOWN	Does Exercise and Heat Increase the Lightsensibility in Patients With Erythropoietic Protoporphyria
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