ABCB7

Summary

ABCB7 (ATP binding cassette subfamily B member 7, HGNC:48) is a protein-coding gene on chromosome Xq13.3, encoding Iron-sulfur clusters transporter ABCB7, mitochondrial (O75027). Exports glutathione-coordinated iron-sulfur clusters such as [2Fe-2S]-(GS)4 cluster from the mitochondria to the cytosol in an ATP-dependent manner allowing the assembly of the cytosolic iron-sulfur (Fe/S) cluster-containing proteins and participates in iron homeostasis. It is a common-essential gene (DepMap: required in 94.3% of cancer cell lines).

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This gene encodes a half-transporter involved in the transport of heme from the mitochondria to the cytosol. With iron/sulfur cluster precursors as its substrates, this protein may play a role in metal homeostasis. Mutations in this gene have been associated with mitochondrial iron accumulation and isodicentric (X)(q13) and sideroblastic anemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 22 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked sideroblastic anemia with ataxia (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 488 total — 68 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 64
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 94.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_001271696

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:48
Approved symbol	ABCB7
Name	ATP binding cassette subfamily B member 7
Location	Xq13.3
Locus type	gene with protein product
Status	Approved
Aliases	EST140535, Atm1p, ASAT
Ensembl gene	ENSG00000131269
Ensembl biotype	protein_coding
OMIM	300135
Entrez	22

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 19 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000253577, ENST00000339447, ENST00000373394, ENST00000469368, ENST00000490858, ENST00000526404, ENST00000529949, ENST00000534524, ENST00000534570, ENST00000620875, ENST00000643632, ENST00000644766, ENST00000645829, ENST00000663420, ENST00000666534, ENST00000669388, ENST00000669573, ENST00000864230, ENST00000864231, ENST00000864232, ENST00000864233, ENST00000928614, ENST00000928615, ENST00000943284, ENST00000943285, ENST00000943286

RefSeq mRNA: 5 — MANE Select: NM_001271696 NM_001271696, NM_001271697, NM_001271698, NM_001271699, NM_004299

CCDS: CCDS14428, CCDS65290, CCDS65291, CCDS75994

Canonical transcript exons

ENST00000373394 — 16 exons

Exon	Start	End
ENSE00000899005	75098942	75099061
ENSE00000899006	75076522	75076654
ENSE00001191680	75112886	75112972
ENSE00001191684	75114754	75114831
ENSE00001612197	75062328	75062431
ENSE00001680121	75073868	75073956
ENSE00001695130	75071509	75071683
ENSE00001713613	75065070	75065241
ENSE00002166202	75075362	75075630
ENSE00003508361	75073689	75073776
ENSE00003589600	75069291	75069454
ENSE00003606949	75069007	75069136
ENSE00003643155	75060223	75060330
ENSE00003683822	75070365	75070522
ENSE00003824915	75051048	75053585
ENSE00003844516	75156105	75156283

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 91.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.4239 / max 167.9062, expressed in 1800 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199774	18.3680	1800
199773	0.0559	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	91.72	gold quality
gluteal muscle	UBERON:0002000	91.37	silver quality
triceps brachii	UBERON:0001509	90.85	gold quality
gastrocnemius	UBERON:0001388	90.84	gold quality
muscle of leg	UBERON:0001383	90.79	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.46	gold quality
monocyte	CL:0000576	90.32	gold quality
muscle organ	UBERON:0001630	90.26	gold quality
mononuclear cell	CL:0000842	90.01	gold quality
heart left ventricle	UBERON:0002084	89.91	gold quality
cardiac ventricle	UBERON:0002082	89.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.80	gold quality
leukocyte	CL:0000738	89.73	gold quality
jejunal mucosa	UBERON:0000399	89.42	gold quality
calcaneal tendon	UBERON:0003701	89.31	gold quality
vastus lateralis	UBERON:0001379	88.89	gold quality
quadriceps femoris	UBERON:0001377	88.70	gold quality
heart right ventricle	UBERON:0002080	88.67	gold quality
bone marrow cell	CL:0002092	88.57	gold quality
duodenum	UBERON:0002114	88.53	gold quality
heart	UBERON:0000948	88.47	gold quality
left ventricle myocardium	UBERON:0006566	88.43	gold quality
skeletal muscle tissue	UBERON:0001134	88.24	gold quality
adrenal tissue	UBERON:0018303	88.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.08	gold quality
right atrium auricular region	UBERON:0006631	88.05	gold quality
apex of heart	UBERON:0002098	88.03	gold quality
tendon	UBERON:0000043	87.77	gold quality
cardiac atrium	UBERON:0002081	87.73	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.71	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.37
E-MTAB-6386	no	500.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting ABCB7, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-7852-3P	98.37	67.98	823
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-541-5P	98.24	67.77	1181

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 94.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 23)

• Hsp22 is a key player in cell-protection mechanisms against oxidative injuries and aging in Drosophila. (PMID:14734639)
• Drosophila that are not expressing this mitochondrial small Hsp22 have a 40% decrease in lifespan. (PMID:15331597)
• Life span alteration after irradiation in Drosophila melanogaster strains with mutations of Hsf and Hsps. (PMID:18551381)
• Expression of hsp22 and hsp70 transgenes is partially predictive of drosophila survival under normal and stress conditions. (PMID:19420297)
• Data show that the DmHsp22 interacts and inactivates wild type tumor suppressor protein p53, which may be one possible way of its functioning in human cells. (PMID:19948727)
• The up-regulation of genes of the OXPHOS system in Hsp22+ flies suggest that mitochondrial homeostasis is at the center of Hsp22 beneficial effects on lifespan. (PMID:20036725)
• Hsp22 and Hsp23 play important roles in the recovery from chill coma in adult males, and suggest that these contribute to adaptive responses to fluctuating thermal conditions. (PMID:21112994)
• hsp22 could play an important role in relation to stress resistance and adaptation. (PMID:22576832)
• Together the results are consistent with a role of Hsp22 in the UPR(MT) and in mitochondrial proteostasis. (PMID:26930296)
• This study shows that mutations of arginine to glycine in Hsp22 alpha-crystallin domain induce a number of structural changes, some of which differ from those described in mammalian small heat shock proteins. (PMID:28389817)
• 60 common DmHsp22-binding mitochondrial partners were detected via immunoaffinity conjugation with mass spectroscopy analysis of mitochondria from HeLa cells transfected with DmHsp22 in non-heat shock condition and after heat shock. Among the partners of DmHsp22, several ATP synthase subunits were found. (PMID:29509794)
• ABCB7 may have a role in refractory anemia with ring sideroblasts (PMID:18398482)
• loss of the ABCB7 gene may be a pathogenetic factor underlying mitochondrial iron accumulation in RARS patients with idicXq13. (PMID:21380928)
• We describe a fourth family with X-linked sideroblastic anemia and ataxia and a novel mutation in the ABCB7 gene (PMID:22398176)
• findings support that ABCB7 is implicated in the phenotype of acquired RARS and suggest a relation between SF3B1 mutations and ABCB7 downregulation (PMID:23070040)
• A missense mutation in the ABCB7 is a major causative factor of the cerebellar hypoplasia/atrophy found in affected individuals of a Buryat family who had no evidence of sideroblastic anemia. (PMID:26242992)
• data support a model in which cycloheximide -induced downregulation of the iron exporter ABCB7 mRNA transcript resulting from aberrant splicing caused by mutant SF3B1 underlies the increased mitochondrial iron accumulation found in MDS patients with ring sideroblasts (PMID:27211273)
• ABCB7 and ABCB10 homodimers form an architecturally defined molecular complex required for heme biosynthesis (PMID:30765471)
• ABCB7 simultaneously regulates apoptotic and non-apoptotic cell death by modulating mitochondrial ROS and HIF1alpha-driven NFkappaB signaling. (PMID:31772327)
• Evolution of the human mitochondrial ABCB7 2Fe-2S4 cluster exporter and the molecular mechanism of an E433K disease-causing mutation. (PMID:33157103)
• Expression, purification and microscopic characterization of human ATP-binding cassette sub-family B member 7 protein. (PMID:33689857)
• Coordinated missplicing of TMEM14C and ABCB7 causes ring sideroblast formation in SF3B1-mutant myelodysplastic syndrome. (PMID:34861039)
• Knockdown of ABCB7 inhibits esophageal cancer progression by inhibiting the TGF-beta/Smad signaling. (PMID:37142077)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	abcb7	ENSDARG00000062795
mus_musculus	Abcb7	ENSMUSG00000031333
rattus_norvegicus	Abcb7	ENSRNOG00000002790
drosophila_melanogaster	ABCB7	FBGN0035244
caenorhabditis_elegans	abtm-1	WBGENE00022281

Paralogs (10): ABCB5 (ENSG00000004846), ABCB4 (ENSG00000005471), ABCB11 (ENSG00000073734), ABCB1 (ENSG00000085563), ABCB6 (ENSG00000115657), ABCB10 (ENSG00000135776), ABCB9 (ENSG00000150967), TAP1 (ENSG00000168394), ABCB8 (ENSG00000197150), TAP2 (ENSG00000204267)

Protein

Protein identifiers

Iron-sulfur clusters transporter ABCB7, mitochondrial — O75027 (reviewed: O75027)

Alternative names: ATP-binding cassette sub-family B member 7, mitochondrial, ATP-binding cassette transporter 7

All UniProt accessions (11): A0A087WW65, A0A0S2Z2Z3, A0A2R8Y3N2, A0A2R8Y473, A0A2R8YF35, A0A590UJS8, A0A5F9ZA98, B4DGL8, E9PJR8, E9PNQ5, O75027

UniProt curated annotations — full annotation on UniProt →

Function. Exports glutathione-coordinated iron-sulfur clusters such as [2Fe-2S]-(GS)4 cluster from the mitochondria to the cytosol in an ATP-dependent manner allowing the assembly of the cytosolic iron-sulfur (Fe/S) cluster-containing proteins and participates in iron homeostasis. Moreover, through a functional complex formed of ABCB7, FECH and ABCB10, also plays a role in the cellular iron homeostasis, mitochondrial function and heme biosynthesis. In cardiomyocytes, regulates cellular iron homeostasis and cellular reactive oxygen species (ROS) levels through its interaction with COX4I1. May also play a role in hematopoiesis.

Subunit / interactions. Homodimer or heterodimer. Interacts with C10orf88/PAAT. Forms a complex with ABCB10 and FECH, where a dimeric FECH bridges ABCB7 and ABCB10 homodimers; this complex may be required for cellular iron homeostasis, mitochondrial function and heme biosynthesis. Interacts with FECH. Interacts with ATP5F1A. Interacts with COX4I1; this interaction allows the regulation of cellular iron homeostasis and cellular reactive oxygen species (ROS) levels in cardiomyocytes.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Spinocerebellar ataxia, X-linked 6, with or without sideroblastic anemia (SCAX6) [MIM:301310] An X-linked recessive disorder characterized by an infantile to early childhood onset of non-progressive cerebellar ataxia and mild anemia, with hypochromia and microcytosis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. ATPase activity is stimulated by glutathione.

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

Isoforms (3)

UniProt ID	Names	Canonical?
O75027-1	1	yes
O75027-2	2
O75027-3	3

RefSeq proteins (5): NP_001258625, NP_001258626, NP_001258627, NP_001258628, NP_004290 (=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
IPR036640	ABC1_TM_sf	Homologous_superfamily
IPR039421	Type_1_exporter	Family

Pfam: PF00005, PF00664

Catalyzed reactions (Rhea), 1 shown:

• (glutathione)4[2Fe(III)-2S] cluster(in) + ATP + H2O = (glutathione)4[2Fe(III)-2S] cluster(out) + ADP + phosphate + H(+) (RHEA:67028)

UniProt features (80 total): helix 20, strand 12, sequence variant 8, sequence conflict 8, topological domain 7, transmembrane region 6, binding site 5, modified residue 5, domain 2, splice variant 2, mutagenesis site 2, transit peptide 1, chain 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
23PI	ELECTRON MICROSCOPY	2.33
23PG	ELECTRON MICROSCOPY	2.87
23PH	ELECTRON MICROSCOPY	3.01
7VGF	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75027-F1	78.19	0.48

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 (5): 315–319; 378–381; 428; 481; 505–516

Post-translational modifications (5): 216, 251, 336, 340, 342

Mutagenesis-validated functional residues (2):

Position	Phenotype
433	significantly increases atpase activity by [2fe-2s]-(gs)4 cluster stimulation. increases affinity for mg-atp. does not a
433	loss of atpase activity stimulation by [2fe-2s]-(gs)4 cluster stimulation. loss of the ability to couple mgatp binding w

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1369007	Mitochondrial ABC transporters
R-HSA-2564830	Cytosolic iron-sulfur cluster assembly
R-HSA-1430728	Metabolism
R-HSA-382551	Transport of small molecules
R-HSA-382556	ABC-family protein mediated transport

MSigDB gene sets: 292 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_IRON_COORDINATION_ENTITY_TRANSPORT, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_TETRAPYRROLE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_IRON_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, KEGG_ABC_TRANSPORTERS, PUJANA_CHEK2_PCC_NETWORK, GOBP_PORPHYRIN_CONTAINING_COMPOUND_METABOLIC_PROCESS

GO Biological Process (9): intracellular iron ion homeostasis (GO:0006879), iron-sulfur cluster assembly (GO:0016226), iron ion transmembrane transport (GO:0034755), transmembrane transport (GO:0055085), positive regulation of heme biosynthetic process (GO:0070455), iron-sulfur cluster export from the mitochondrion (GO:0140466), positive regulation of iron-sulfur cluster assembly (GO:1903331), negative regulation of reactive oxygen species biosynthetic process (GO:1903427), heme transport (GO:0015886)

GO Molecular Function (10): ATP binding (GO:0005524), heme transmembrane transporter activity (GO:0015232), ATP hydrolysis activity (GO:0016887), ATPase-coupled transmembrane transporter activity (GO:0042626), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), ABC-type iron-sulfur cluster transporter activity (GO:0140481), nucleotide binding (GO:0000166), protein binding (GO:0005515), ABC-type transporter activity (GO:0140359)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
ABC-family protein mediated transport	1
Metabolism	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	2
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
metallo-sulfur cluster assembly	1
iron ion transport	1
monoatomic cation transmembrane transport	1
transport	1
cellular process	1
heme biosynthetic process	1
regulation of heme biosynthetic process	1
positive regulation of tetrapyrrole biosynthetic process	1
intercellular transport	1
iron-sulfur cluster transmembrane transport	1
iron-sulfur cluster assembly	1
positive regulation of cellular component organization	1
regulation of iron-sulfur cluster assembly	1
negative regulation of biosynthetic process	1
reactive oxygen species biosynthetic process	1
regulation of reactive oxygen species biosynthetic process	1
negative regulation of reactive oxygen species metabolic process	1
nitrogen compound transport	1
iron coordination entity transport	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
heme transport	1
transmembrane transporter activity	1
ribonucleoside triphosphate phosphatase activity	1
primary active transmembrane transporter activity	1
ATP hydrolysis activity	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
ABC-type transporter activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
ATPase-coupled transmembrane transporter activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1

Protein interactions and networks

STRING

1598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCB7	ALAS2	P22557	902
ABCB7	SLC25A37	Q9NYZ2	882
ABCB7	ACO1	P21399	869
ABCB7	FECH	P22830	862
ABCB7	GLRX5	Q86SX6	816
ABCB7	TMEM14C	Q9P0S9	806
ABCB7	SLC25A38	Q96DW6	776
ABCB7	NFS1	Q9Y697	771
ABCB7	FXN	Q16595	745
ABCB7	ISCU	Q9H1K1	744
ABCB7	PPOX	P50336	733
ABCB7	ISCA1	Q9BUE6	728
ABCB7	SLC25A28	Q96A46	726
ABCB7	LYRM4	Q9HD34	715
ABCB7	ISCA2	Q86U28	714

IntAct

66 interactions, top by confidence:

A	B	Type	Score
ABCB7	FECH	psi-mi:“MI:0914”(association)	0.710
ABCB7	FECH	psi-mi:“MI:0407”(direct interaction)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ABCB7	FECH	psi-mi:“MI:0915”(physical association)	0.710
FECH	ABCB7	psi-mi:“MI:0407”(direct interaction)	0.710
FECH	ABCB7	psi-mi:“MI:0915”(physical association)	0.710
ABCB7	ABCB7	psi-mi:“MI:0407”(direct interaction)	0.560
PCGF1	CBX4	psi-mi:“MI:0914”(association)	0.530
PDCD1	RTL8C	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
ABCB7	XAB2	psi-mi:“MI:0915”(physical association)	0.400
Kcnk1	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
FOXS1	DDX39A	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NUDT19	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NDUFS8	psi-mi:“MI:0914”(association)	0.350
COQ9	ACOT7	psi-mi:“MI:0914”(association)	0.350

BioGRID (174): ABCB7 (Affinity Capture-MS), ABCB7 (Affinity Capture-RNA), ABCB7 (Affinity Capture-MS), ABCB7 (Co-fractionation), ABCB7 (Co-fractionation), ABCB7 (Co-fractionation), ABCB7 (Co-fractionation), ABCB7 (Co-fractionation), ABCB7 (Co-fractionation), ABCB7 (Co-fractionation), EPRS (Co-fractionation), RPN1 (Co-fractionation), ABCB7 (Affinity Capture-MS), ABCB7 (Affinity Capture-MS), ABCB7 (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: A0A0D1BUH6, A0A0S6XH62, A0A179H0T5, A0R6H7, A0R6H8, A1USS5, B2GUP8, G7CBF6, H2LNR5, I1R9B3, I1RF50, I1S2J9, K0E4D9, O31707, O75027, O80725, P0AAG5, P0AAG6, P0AAG7, P0C086, P0C087, P0C529, P0CE69, P0DKX5, P0DKX6, P16532, P18767, P23702, P40416, P45081, P45861, P63392, P70864, P9WER4, P9WQJ8, P9WQJ9, Q00564, Q04473, Q0A4U4, Q0VQP5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	68
Likely pathogenic	8
Uncertain significance	132
Likely benign	95
Benign	55

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
11574	NM_001271696.3(ABCB7):c.1200T>G (p.Ile400Met)	Pathogenic
11575	NM_001271696.3(ABCB7):c.1297G>A (p.Glu433Lys)	Pathogenic
11576	NM_001271696.3(ABCB7):c.1231G>C (p.Val411Leu)	Pathogenic
126455	NM_001271696.3(ABCB7):c.624A>T (p.Glu208Asp)	Pathogenic
1341223	GRCh37/hg19 Xp22.33-q28(chrX:168546-155233731)x3	Pathogenic
144172	GRCh38/hg38 Xp22.33-q28(chrX:10679-156022826)x4	Pathogenic
144310	GRCh38/hg38 Xp22.33-q28(chrX:10701-155978689)x1	Pathogenic
144543	GRCh38/hg38 Xq11.1-28(chrX:62712230-155978888)x3	Pathogenic
145162	GRCh38/hg38 Xp22.33-q28(chrX:20297-155999253)x3	Pathogenic
145980	GRCh38/hg38 Xp11.22-q21.31(chrX:53985575-92203108)x1	Pathogenic
146240	GRCh38/hg38 Xp21.1-q28(chrX:36237706-156022206)x1	Pathogenic
146764	GRCh38/hg38 Xp22.33-q28(chrX:10001-156030895)x1	Pathogenic
146861	GRCh38/hg38 Xp22.33-q28(chrX:10701-156003229)x1	Pathogenic
147257	GRCh38/hg38 Xp22.33-q28(chrX:40904-155998166)x1	Pathogenic
148340	GRCh38/hg38 Xp11.23-q22.1(chrX:49100536-102174742)x1	Pathogenic
148821	GRCh38/hg38 Xp22.33-q22.3(chrX:10701-106113403)x1	Pathogenic
150510	GRCh38/hg38 Xp22.33-q21.31(chrX:10701-88318651)x1	Pathogenic
150589	GRCh38/hg38 Xq11.1-28(chrX:62712219-156003242)x3	Pathogenic
1526804	GRCh37/hg19 Xq11.1-21.1(chrX:61974855-79123671)	Pathogenic
153303	GRCh38/hg38 Xp11.22-q24(chrX:50289384-119297604)	Pathogenic
154251	GRCh38/hg38 Xq12-21.1(chrX:66445907-78172208)x3	Pathogenic
155064	GRCh38/hg38 Xp11.21-q13.3(chrX:56431359-76557419)x1	Pathogenic
155152	GRCh38/hg38 Xp22.33-q28(chrX:251880-156004066)x3	Pathogenic
155282	GRCh38/hg38 Xp11.22-q28(chrX:53144751-156003242)x1	Pathogenic
155357	GRCh38/hg38 Xq13.2-28(chrX:74684615-156004066)x1	Pathogenic
160983	GRCh38/hg38 Xp22.33-q28(chrX:10679-156013167)x1	Pathogenic
161088	GRCh38/hg38 Xp22.33-q28(chrX:26102-155996431)x1	Pathogenic
1707442	GRCh37/hg19 Xp22.2-q28(chrX:11522765-155233731)x1	Pathogenic
2506546	GRCh37/hg19 Xp22.33-q28(chrX:200855-155240074)	Pathogenic
253376	GRCh37/hg19 Xp22.33-q28(chrX:70297-155255839)x3	Pathogenic

SpliceAI

2442 predictions. Top by Δscore:

Variant	Effect	Δscore
X:75060217:TCTTA:T	donor_loss	1.0000
X:75060218:CTTAC:C	donor_loss	1.0000
X:75060219:TTACC:T	donor_loss	1.0000
X:75060220:TACCT:T	donor_loss	1.0000
X:75060221:A:AC	donor_gain	1.0000
X:75060222:C:CC	donor_gain	1.0000
X:75060222:C:T	donor_loss	1.0000
X:75060339:T:C	acceptor_gain	1.0000
X:75060339:T:TC	acceptor_gain	1.0000
X:75060342:G:C	acceptor_gain	1.0000
X:75060342:G:GC	acceptor_gain	1.0000
X:75060345:A:AC	acceptor_gain	1.0000
X:75060345:A:C	acceptor_gain	1.0000
X:75060347:A:AC	acceptor_gain	1.0000
X:75060347:A:C	acceptor_gain	1.0000
X:75060355:C:CT	acceptor_gain	1.0000
X:75060356:A:T	acceptor_gain	1.0000
X:75062323:CTTA:C	donor_loss	1.0000
X:75062324:TTACC:T	donor_loss	1.0000
X:75062325:TACC:T	donor_loss	1.0000
X:75062326:A:AC	donor_gain	1.0000
X:75062326:AC:A	donor_gain	1.0000
X:75062326:ACC:A	donor_loss	1.0000
X:75062327:C:CG	donor_gain	1.0000
X:75062327:CC:C	donor_gain	1.0000
X:75062327:CCT:C	donor_gain	1.0000
X:75062327:CCTCT:C	donor_gain	1.0000
X:75062429:CTC:C	acceptor_gain	1.0000
X:75062432:C:CC	acceptor_gain	1.0000
X:75065196:CA:C	acceptor_gain	1.0000

AlphaMissense

4891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:75062344:T:A	D640V	1.000
X:75062344:T:G	D640A	1.000
X:75065075:A:G	L609P	1.000
X:75065081:A:G	L607P	1.000
X:75065084:C:T	G606E	1.000
X:75065085:C:G	G606R	1.000
X:75065085:C:T	G606R	1.000
X:75073704:A:C	N339K	1.000
X:75073704:A:T	N339K	1.000
X:75073711:A:G	L337P	1.000
X:75073715:A:G	S336P	1.000
X:75073736:C:G	A329P	1.000
X:75075496:G:C	H241D	1.000
X:75060269:C:G	R666T	0.999
X:75060273:G:C	H665D	0.999
X:75062343:A:C	D640E	0.999
X:75062343:A:T	D640E	0.999
X:75062344:T:C	D640G	0.999
X:75062345:C:G	D640H	0.999
X:75062354:A:G	S637P	0.999
X:75062362:T:A	E634V	0.999
X:75062365:T:G	D633A	0.999
X:75062411:C:G	A618P	0.999
X:75062418:T:A	Q615H	0.999
X:75062418:T:G	Q615H	0.999
X:75062421:C:A	K614N	0.999
X:75062421:C:G	K614N	0.999
X:75062428:C:T	G612E	0.999
X:75062429:C:G	G612R	0.999
X:75062429:C:T	G612R	0.999

dbSNP variants (sampled 300 via entrez): RS1000001082 (X:75059241 T>C,G), RS1000023169 (X:75132504 A>C), RS1000038923 (X:75076415 C>T), RS1000073629 (X:75134267 C>T), RS1000079073 (X:75126278 C>A,T), RS1000131130 (X:75144143 C>T), RS1000182154 (X:75143692 A>G), RS1000185409 (X:75144272 C>T), RS1000188813 (X:75069999 C>T), RS1000203305 (X:75080120 G>A), RS1000317464 (X:75079751 T>G), RS1000326839 (X:75117304 A>G), RS1000373702 (X:75072861 T>C), RS1000391902 (X:75155733 A>C), RS1000438103 (X:75131948 G>C)

Disease associations

OMIM: gene MIM:300135 | disease phenotypes: MIM:301310

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked sideroblastic anemia with ataxia	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Moderate	XL

Mondo (5): X-linked sideroblastic anemia with ataxia (MONDO:0010524), epilepsy (MONDO:0005027), intellectual disability (MONDO:0001071), Klinefelter syndrome (MONDO:0006823), mitochondrial disease (MONDO:0044970)

Orphanet (3): X-linked sideroblastic anemia and spinocerebellar ataxia (Orphanet:2802), Mitochondrial disease (Orphanet:68380), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

64 total (30 of 64 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000486	Strabismus
HP:0000602	Ophthalmoplegia
HP:0000639	Nystagmus
HP:0000716	Depression
HP:0000717	Autism
HP:0000726	Dementia
HP:0000750	Delayed speech and language development
HP:0000980	Pallor
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001310	Dysmetria
HP:0001315	Reduced tendon reflexes
HP:0001321	Cerebellar hypoplasia
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001419	X-linked recessive inheritance
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001618	Dysphonia
HP:0001824	Weight loss
HP:0001903	Anemia
HP:0001924	Sideroblastic anemia
HP:0001992	Organic aciduria

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_1862	Metabolite levels	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010410	triacylglycerol 50:3 measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D007713	Klinefelter Syndrome	C12.050.351.875.253.795.500; C12.200.706.316.795.500; C12.800.316.795.500; C16.131.260.830.835.500; C16.131.939.316.795.500; C16.320.180.830.835.500; C19.391.119.795.500; C19.391.482.629
C536358	Anemia, sideroblastic spinocerebellar ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067020 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — ABCB subfamily

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.54	Kd	28.87	nM	CHEMBL5653589
7.54	ED50	28.87	nM	CHEMBL5653589
7.21	Kd	62.22	nM	CHEMBL3752910
7.21	ED50	62.22	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147767: Binding affinity to human ABCB7 incubated for 45 mins by Kinobead based pull down assay	kd	0.0289	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147767: Binding affinity to human ABCB7 incubated for 45 mins by Kinobead based pull down assay	kd	0.0622	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
beta-lapachone	increases expression	1
gallium nitrate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Capecitabine	decreases response to substance	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	increases expression	1
Cisplatin	affects response to substance	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Tunicamycin	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Fluorescein-5-isothiocyanate	affects binding	1
Cadmium Chloride	increases abundance, increases expression	1
Okadaic Acid	decreases expression	1
Vitamin K 3	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650809	Binding	Binding affinity to human ABCB7 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy