ABCB5

Summary

ABCB5 (ATP binding cassette subfamily B member 5, HGNC:46) is a protein-coding gene on chromosome 7p21.1, encoding ATP-binding cassette sub-family B member 5 (Q2M3G0). Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells.

ABCB5 belongs to the ATP-binding cassette (ABC) transporter superfamily of integral membrane proteins. These proteins participate in ATP-dependent transmembrane transport of structurally diverse molecules ranging from small ions, sugars, and peptides to more complex organic molecules (Chen et al., 2005 [PubMed 15760339]).

Source: NCBI Gene 340273 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 261 total — 16 pathogenic, 2 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001163941

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:46
Approved symbol	ABCB5
Name	ATP binding cassette subfamily B member 5
Location	7p21.1
Locus type	gene with protein product
Status	Approved
Aliases	EST422562, ABCB5beta, ABCB5alpha
Ensembl gene	ENSG00000004846
Ensembl biotype	protein_coding
OMIM	611785
Entrez	340273

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000258738, ENST00000404938, ENST00000406935, ENST00000441315, ENST00000443026, ENST00000477094

RefSeq mRNA: 4 — MANE Select: NM_001163941 NM_001163941, NM_001163942, NM_001163993, NM_178559

CCDS: CCDS5371, CCDS55090, CCDS55091, CCDS55092

Canonical transcript exons

ENST00000404938 — 28 exons

Exon	Start	End
ENSE00000672711	20658506	20658676
ENSE00000923947	20753360	20753506
ENSE00000976562	20704724	20704807
ENSE00000976563	20723016	20723219
ENSE00000976565	20728315	20728455
ENSE00000976567	20742877	20743074
ENSE00000976568	20745232	20745438
ENSE00001028962	20738983	20739139
ENSE00001321959	20698407	20698550
ENSE00001336606	20699825	20699929
ENSE00001336623	20681505	20681666
ENSE00001336668	20727040	20727140
ENSE00001336671	20700058	20700135
ENSE00001372750	20685696	20685836
ENSE00001556050	20615667	20615837
ENSE00001559952	20755427	20757008
ENSE00001624422	20632059	20632113
ENSE00001667035	20626557	20626611
ENSE00001692136	20645961	20646138
ENSE00001764023	20645756	20645880
ENSE00001769109	20628688	20628838
ENSE00001772496	20643184	20643375
ENSE00001786213	20643461	20643632
ENSE00002274500	20623265	20623338
ENSE00003546974	20650022	20650147
ENSE00003579057	20651420	20651623
ENSE00003585337	20647968	20648078
ENSE00003655164	20647535	20647648

Expression profiles

Bgee: expression breadth ubiquitous, 107 present calls, max score 88.14.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4743 / max 265.4442, expressed in 205 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77526	0.8892	145
77529	0.3301	102
77528	0.1194	54
77527	0.0742	31
77524	0.0299	2
77530	0.0268	11
77523	0.0047	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	88.14	gold quality
buccal mucosa cell	CL:0002336	83.65	silver quality
corpus epididymis	UBERON:0004359	79.82	gold quality
gall bladder	UBERON:0002110	70.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.18	gold quality
skin of hip	UBERON:0001554	66.61	gold quality
omental fat pad	UBERON:0010414	64.77	gold quality
peritoneum	UBERON:0002358	64.74	gold quality
tibia	UBERON:0000979	63.58	gold quality
adipose tissue of abdominal region	UBERON:0007808	63.45	gold quality
sperm	CL:0000019	62.54	gold quality
caput epididymis	UBERON:0004358	61.41	gold quality
secondary oocyte	CL:0000655	61.23	gold quality
subcutaneous adipose tissue	UBERON:0002190	61.18	gold quality
mucosa of stomach	UBERON:0001199	58.74	gold quality
pigmented layer of retina	UBERON:0001782	58.62	gold quality
adipose tissue	UBERON:0001013	57.84	gold quality
thoracic mammary gland	UBERON:0005200	57.40	gold quality
smooth muscle tissue	UBERON:0001135	57.36	gold quality
mammary gland	UBERON:0001911	57.11	gold quality
epithelium of nasopharynx	UBERON:0001951	56.31	gold quality
ventral tegmental area	UBERON:0002691	56.14	gold quality
nipple	UBERON:0002030	55.52	gold quality
cardia of stomach	UBERON:0001162	55.37	gold quality
ectocervix	UBERON:0012249	55.18	gold quality
trigeminal ganglion	UBERON:0001675	55.06	gold quality
inferior vagus X ganglion	UBERON:0005363	54.90	gold quality
rectum	UBERON:0001052	54.89	gold quality
colonic epithelium	UBERON:0000397	54.73	silver quality
subthalamic nucleus	UBERON:0001906	54.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	23.35
E-ANND-3	yes	6.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA

miRNA regulators (miRDB)

75 targeting ABCB5, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809

Literature-anchored findings (GeneRIF, showing 40)

• ABCB5 P-glycoprotein functions include: Regulation of progenitor cell fusion; Regulation of cell membrane potential; Rhodamine-123 transport. (PMID:12960149)
• expression of ABCB 5alpha/beta might possibly provide two novel molecular markers for differential diagnosis of melanomas and constitute potential molecular targets for therapy of melanomas (PMID:15760339)
• ABCB5 mediates chemoresistance in stem cell phenotype-expressing human malignant melanoma cells. (PMID:15899824)
• 6-mercaptopurine decreased iNOS expression and increased MRP5 mRNA levels. (PMID:17661346)
• ABCB5 expression identifies melanoma stem cells and correlates with clinical disease progression in melanoma patients. In vivo targeting of ABCB5+ melanoma stem cells inhibits tumor growth in human to mouse melanoma xenotransplantation models. (PMID:18202660)
• Results identify novel T-cell modulatory functions of ABCB5(+) melanoma subpopulations and suggest specific roles for these malignant melanoma initiating cells in the evasion of antitumor immunity and in cancer immunotherapeutic resistance. (PMID:20068175)
• Expression of GEP and ABCB5 in liver cancer stem cells is associated with chemoresistance and reduced survival times of patients with hepatocellular carcinoma. (PMID:20682318)
• Tenascin-C promotes melanoma progression by maintaining the ABCB5-positive side population. (PMID:20729912)
• Results demonstrate that VEGFR-1 expressed by ABCB5+ malignant melanoma initiating cells functions to induce tumor vasculogenic mimicry and associated production of the pro-proliferative melanoma mitogen laminin, thereby promoting tumor growth. (PMID:21212411)
• ABCB5 beta may have evolved to play a specific role in human pigment cells and/or melanoma cells where it is predominantly expressed. (PMID:21298007)
• ABCB5 mediates 5-FU resistance in cultured human colorectal cancer cells and affected tumor growth in xenografts. (PMID:21652540)
• ABCB5 may be responsible for both the progression and chemotherapeutic refractoriness of advanced acute leukemia. (PMID:22044138)
• the helicase HAGE is required for ABCB5+ MMIC-dependent tumor growth through promoting RAS protein expression (PMID:22393060)
• The gradual increase in the expression of ABCB5 from benign nevus to in situ to invasive melanoma suggests that it plays a role in melanomagenesis. (PMID:22555176)
• High ABCB5 expression was significantly associated with tumour progression and recurrence of the tumour. (PMID:22784549)
• Data show that CD133(+) and ABCB5(+) subpopulations are colocalized in melanomas in perivascular niches that contain CD144 (VE-cadherin)(+) melanoma cells forming vessel-like channels, a phenomenon termed vasculogenic mimicry (VM). (PMID:22865455)
• Genetically determined ABCB5 functionality correlates with pigmentation phenotype and melanoma risk. Three ABCB5 SNPs, i.e. rs10231520, rs17817117 and rs2301641 (encoding the non-synonymous amino acid change K115E), were associated with decreased clinical melanoma risk. Additionally, the rs2301641 SNP was associated with non-red compared to red human hair color. (PMID:23770371)
• Novel associations of the ABCB5 K115E polymorphism with human pigmentation phenotype and melanoma risk are observed. (PMID:23770371)
• Our results show that ABCB5 is preferentially expressed in the cytotrophoblast layer of placental villi. (PMID:24300535)
• Suggest that the helicase HAGE has a key role in the resistance of ABCB5+ malignant melanoma stem cells to IFNalpha treatment by promoting SOCS1 expression. (PMID:24525737)
• ABCB5 and MDR1 gene expression correlate with drug resistance in acute leukemia patients. (PMID:24804815)
• In melanoma-initiating cells, ABCB5 controls IL1beta secretion, which serves to maintain slow cycling, chemoresistant cells through an IL1beta/IL8/CXCR1 cytokine signaling circuit. (PMID:24934811)
• ATP-binding cassette, sub-family B, member 5 (ABCB5) marks limbal stem cells (LSCs) and is required for LSC maintenance, corneal development and repair (PMID:25030174)
• The resistance of CD133(+) melanoma subpopulation is attributed to the enhanced drug efflux mediated by ATP-binding cassette sub-family B member 5 (ABCB5), since the knockdown of ABCB5 was found to sensitize CD133(+) cells to CAPE. (PMID:25449786)
• ABCB5 alleles alter susceptibility to haloperidol-induced toxicity (HIT) in mouse and humans. (PMID:25647612)
• c-MYC confers resistance to 5-fluorouracil through regulating ABCB5 expression in human colon cancer cells. (PMID:25689483)
• ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1. (PMID:26321644)
• This is the first study showing the relationship between miR-340-5p and expression of ABCB5 in melanoma cells (PMID:26554847)
• Results suggest that ATP binding cassette subfamily B member 5 ABCB5/Abcb5 upregulates cellular glutathione levels to protect cells from various poisons. (PMID:26666373)
• ABCB5 has a role in chemoresistance in Merkel Cell Carcinoma (PMID:26827764)
• Findings demonstrated that the expression of ABCB5 was upregulated in ocular surface squamous neoplasia (OSSN) and that elevated expression of ABCB5 may be involved in the pathogenesis of OSSN. (PMID:26843453)
• Human limbal mesenchymal stem cells express ABCB5 and can grow on amniotic membrane. (PMID:26965478)
• No significant influence of the three newly identified ABCB5 polymorphisms. (PMID:26975227)
• Data indicate that the energy metabolism was virtually unaffected by ATP-binding cassette member B5 (ABCB5) expression. (PMID:27560924)
• The ABCB5 activates the NF-kappaB pathway by inhibiting p65 ubiquitination to enhance p65 protein stability. (PMID:28821433)
• the differential expression pattern of ABCC11 and ABCB5 genes may serve as outliers, potentially associated with incidence of multifocal/multicentric breast cancer (PMID:29552773)
• High ABCB5 expression is associated with tumor cell invasiveness in colorectal cancer. (PMID:29789423)
• upon culture in hepatocytic differentiation medium, ABCB5(+) skin-derived stem cells secreted immunomodulatory and anti-fibrotic factors as well as proteins, which may prompt hepatic morphogenesis besides others (PMID:29864400)
• These results confirm that, even though ABCB5 was overexpressed in SK-MEL-28 and A2058 melanoma cells that develop resistance to BRAF inhibitors, ABCB5 may not be a major targetable contributor to BRAF resistance. (PMID:29929490)
• Interaction analysis demonstrated that the following genotypes: MS4A14 DI+II, SLC2A DI+II and ABCB 5 CG+GG, were associated with a prothrombin time >/=12 sec and with Recurrent pregnancy loss (RPL) risk (PMID:29956771)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
mus_musculus	Abcb5	ENSMUSG00000072791
rattus_norvegicus	Abcb5	ENSRNOG00000006398
caenorhabditis_elegans		WBGENE00001817
caenorhabditis_elegans		WBGENE00001818
caenorhabditis_elegans		WBGENE00003995
caenorhabditis_elegans		WBGENE00003999
caenorhabditis_elegans		WBGENE00004000
caenorhabditis_elegans		WBGENE00004001
caenorhabditis_elegans		WBGENE00004002
caenorhabditis_elegans		WBGENE00004003
caenorhabditis_elegans		WBGENE00004006
caenorhabditis_elegans		WBGENE00004008

Paralogs (10): ABCB4 (ENSG00000005471), ABCB11 (ENSG00000073734), ABCB1 (ENSG00000085563), ABCB6 (ENSG00000115657), ABCB7 (ENSG00000131269), ABCB10 (ENSG00000135776), ABCB9 (ENSG00000150967), TAP1 (ENSG00000168394), ABCB8 (ENSG00000197150), TAP2 (ENSG00000204267)

Protein

Protein identifiers

ATP-binding cassette sub-family B member 5 — Q2M3G0 (reviewed: Q2M3G0)

Alternative names: ABCB5 P-gp, P-glycoprotein ABCB5

All UniProt accessions (2): Q2M3G0, H7C165

UniProt curated annotations — full annotation on UniProt →

Function. Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells. Specifically present in limbal stem cells, where it plays a key role in corneal development and repair.

Subcellular location. Cell membrane.

Tissue specificity. Expressed by CD133-expressing progenitor cells among epidermal melanocytes (at protein level). Widely expressed with specific expression in pigment cells. Highly expressed in several malignant tissues: highly expressed in clinical melanomas, with low expression in normal skin. In melanoma, marks malignant melanoma-initiating cells (MMIC), in which clinical virulence resides as a consequence of unlimited self-renewal capacity, resulting in inexorable tumor progression and metastasis. Also highly expressed in a number of leukemia cells. Expressed in basal limbal epithelium.

Miscellaneous. Acts as a marker of stem-like cells (CSC) in a number of malignancies. Associated with clinical drug resistance, tumor progression and disease recurrence in malignant melanoma and acute leukemias. Responsible for the resistance to doxorubicin of a subset of malignant melanomas. ABCB5-expressing cells selectively survive when exposed to dacarbazine drug, the reference treatment of metastatic melanoma, vemurafenib and other various chemotherapeutic drugs, suggesting that anti-melanoma chemotherapy participates in the chemoresistance acquisition by selecting tumor cell subpopulations expressing ABCB5. Present in melanoma-initiating cells that acts as an enhancer of tumor growth by promoting CSC maintenance and tumor growth by controlling IL-1beta (IL1B) secretion to maintain slow-cycling, chemoresistant cells through an IL-1beta (IL1B)/IL8/CXCR1 cytokine signaling circuit.

Similarity. Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q2M3G0-4	4	yes
Q2M3G0-2	2, ABCB5alpha
Q2M3G0-3	3
Q2M3G0-1	1, ABCB5beta

RefSeq proteins (4): NP_001157413, NP_001157414, NP_001157465, NP_848654 (=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

Enzyme classification (BRENDA):

• EC 7.6.2.2 — ABC-type xenobiotic transporter (BRENDA: 49 organisms, 716 substrates, 471 inhibitors, 280 Km, 31 kcat entries)

Substrate kinetics (BRENDA)

68 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0009–9	105
VERAPAMIL/IN	0.0006–0.0058	11
VINBLASTINE/IN	0.0002–0.1455	11
ESTRADIOL 17-BETA-D-GLUCURONIDE/IN	0.013–0.17	7
LEUKOTRIENE C4/IN	—	7
METHOTREXATE/IN	0.24–0.776	6
NICARDIPINE/IN	0.0004–0.0026	6
PROGESTERONE/IN	0.0038–0.0207	6
CYCLIC GUANOSINE MONOPHOSPHATE/IN	0.36–2	5
VERAPAMIL	0.0022–0.0115	5
COLCHICINE/IN	0.037–0.72	4
FOLIC ACID/IN	0.13–0.26	4
PACLITAXEL/IN	0.0007–0.0009	4
RHODAMINE 123/IN	0.0118–0.0354	4
DEXAMETHASONE	0.394–0.826	3

Catalyzed reactions (Rhea), 1 shown:

• daunorubicin(in) + ATP + H2O = daunorubicin(out) + ADP + phosphate + H(+) (RHEA:33147)

UniProt features (45 total): transmembrane region 11, glycosylation site 11, sequence variant 7, splice variant 5, domain 4, sequence conflict 3, binding site 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2M3G0-F1	85.01	0.55

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): 421–428; 1050–1057

Glycosylation sites (11): 17, 85, 91, 371, 390, 423, 789, 819, 910, 1104, 1188

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-382556	ABC-family protein mediated transport
R-HSA-382551	Transport of small molecules

MSigDB gene sets: 89 (showing top): KEGG_ABC_TRANSPORTERS, BRN2_01, GATA6_01, GOCC_APICAL_PLASMA_MEMBRANE, AACTTT_UNKNOWN, GOBP_SENSORY_ORGAN_DEVELOPMENT, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN, GOBP_TRANSMEMBRANE_TRANSPORT, YNGTTNNNATT_UNKNOWN, GOCC_APICAL_PART_OF_CELL, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_PLASMA_MEMBRANE_REGION, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_ATP_HYDROLYSIS_ACTIVITY

GO Biological Process (5): eye development (GO:0001654), cell differentiation (GO:0030154), regulation of membrane potential (GO:0042391), transmembrane transport (GO:0055085), xenobiotic transport (GO:0042908)

GO Molecular Function (7): ATP binding (GO:0005524), ABC-type xenobiotic transporter activity (GO:0008559), efflux transmembrane transporter activity (GO:0015562), ATP hydrolysis activity (GO:0016887), ATPase-coupled transmembrane transporter activity (GO:0042626), nucleotide binding (GO:0000166), ABC-type transporter activity (GO:0140359)

GO Cellular Component (3): plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
ATP-dependent activity	2
sensory organ development	1
visual system development	1
cellular developmental process	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
cellular process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
xenobiotic transmembrane transporter activity	1
ABC-type transporter activity	1
transmembrane transporter activity	1
ribonucleoside triphosphate phosphatase activity	1
primary active transmembrane transporter activity	1
ATP hydrolysis activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ATPase-coupled transmembrane transporter activity	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1824 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCB5	KCNJ11	Q14654	831
ABCB5	PROM1	O43490	786
ABCB5	ABCE1	P61221	623
ABCB5	ABCA1	O95477	590
ABCB5	NGFR	P08138	582
ABCB5	BRAF	P15056	581
ABCB5	AKT1	P31749	539
ABCB5	NR1I3	Q14994	536
ABCB5	XPR1	Q9UBH6	530
ABCB5	NR1H2	P55055	516
ABCB5	LRP1	Q07954	514
ABCB5	CYP7A1	P22680	512
ABCB5	PRAME	P78395	509
ABCB5	NR1I2	O75469	506
ABCB5	KDM5B	Q9UGL1	496

IntAct

11 interactions, top by confidence:

A	B	Type	Score
ABCB5	PPP1R15B	psi-mi:“MI:0915”(physical association)	0.400
ABCB5	RHBDD1	psi-mi:“MI:0915”(physical association)	0.400
ABCB5	PSMB9	psi-mi:“MI:0915”(physical association)	0.370
FBXW7	ABCB5	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	ABCB5	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (24): ABCB5 (Synthetic Lethality), PPP1R15B (Affinity Capture-MS), ABCB5 (Synthetic Lethality), EPHA2 (FRET), FGFR4 (FRET), CCND2 (FRET), CD44 (FRET), ERBB2 (FRET), RAF1 (FRET), STK11 (FRET), RHBDD1 (Affinity Capture-MS), RPL27 (Cross-Linking-MS (XL-MS)), ABCB5 (Cross-Linking-MS (XL-MS)), ABCB5 (Cross-Linking-MS (XL-MS)), ABCB5 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A059JJ46, A0A1U8QG99, B5X0E4, B8K1W2, F2PRR1, F2RP52, H6TB12, O70127, O95342, P06795, P08183, P16876, P16877, P21439, P21440, P21447, P21449, P23174, P34712, P34713, P43245, P91660, Q00449, Q00748, Q08201, Q0WML0, Q2M3G0, Q54JR2, Q6Q876, Q6YUU5, Q7FB56, Q8LPK2, Q9C7F2, Q9C7F8, Q9FHF1, Q9FNU2, Q9FWX8, Q9LHD1, Q9LHK4, Q9LJX0

Diamond homologs: A0A059JJ46, A0A059JK44, A0A095C325, A0A0D1BUH6, A0A1U8QG99, A0A1U9YI12, A0A2P1AAV1, A0A348AXX9, A1KF14, B2GUP8, B2KWH4, B5X0E4, B8K1W2, F2PRR1, F2Q5G0, F2RP52, F2RPA4, F2SQT8, F2T1C4, G5EG61, H6TB12, J9VF33, K3VYH8, O53645, O70127, O80725, O95342, P06795, P08183, P0CU83, P16875, P16876, P16877, P21439, P21440, P21447, P21448, P21449, P23174, P34712

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	2
Uncertain significance	201
Likely benign	17
Benign	4

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
144929	GRCh38/hg38 7p21.1-15.2(chr7:20210912-27849400)x1	Pathogenic
147357	GRCh38/hg38 7p22.3-15.2(chr7:54185-26827634)x3	Pathogenic
147684	GRCh38/hg38 7p21.1-15.3(chr7:19145712-22193713)x1	Pathogenic
1527335	GRCh37/hg19 7p21.3-15.3(chr7:9358316-20982082)	Pathogenic
154641	GRCh38/hg38 7p21.3-15.2(chr7:10610069-25760560)x1	Pathogenic
2685237	GRCh37/hg19 7p21.1-15.3(chr7:18603745-21437047)x1	Pathogenic
3062961	GRCh37/hg19 7p21.3-15.2(chr7:13107394-27514163)x1	Pathogenic
3391894	GRCh37/hg19 7p21.1-15.3(chr7:18195234-21496962)x1	Pathogenic
395204	GRCh37/hg19 7p21.3-14.2(chr7:11562624-36395416)x3	Pathogenic
442624	GRCh37/hg19 7p22.3-15.3(chr7:43360-23674928)x3	Pathogenic
442824	GRCh37/hg19 7p22.3-14.3(chr7:704573-29257946)x3	Pathogenic
4682688	GRCh37/hg19 7p21.3-15.3(chr7:12229502-21665553)x1	Pathogenic
4682692	GRCh37/hg19 7p21.1-15.3(chr7:18093509-25363633)x1	Pathogenic
4682698	GRCh37/hg19 7p22.3-14.3(chr7:158725-29918785)x3	Pathogenic
58535	GRCh38/hg38 7p21.1-15.3(chr7:18505390-21417733)x1	Pathogenic
59678	GRCh38/hg38 7p22.3-14.2(chr7:54185-37089712)x3	Pathogenic
1527336	GRCh37/hg19 7p21.3-14.2(chr7:10745750-35305167)	Likely pathogenic
4682686	GRCh37/hg19 7p21.2-15.2(chr7:16417575-27541028)x3	Likely pathogenic

SpliceAI

4566 predictions. Top by Δscore:

Variant	Effect	Δscore
7:20626607:AGATA:A	donor_gain	1.0000
7:20626608:GATA:G	donor_gain	1.0000
7:20626608:GATAG:G	donor_gain	1.0000
7:20626609:ATA:A	donor_gain	1.0000
7:20626609:ATAG:A	donor_loss	1.0000
7:20626610:TA:T	donor_gain	1.0000
7:20626611:AGT:A	donor_loss	1.0000
7:20626612:G:GG	donor_gain	1.0000
7:20626612:GTAA:G	donor_loss	1.0000
7:20628686:A:AG	acceptor_gain	1.0000
7:20628687:G:GG	acceptor_gain	1.0000
7:20628687:GTTCC:G	acceptor_gain	1.0000
7:20628834:CACAA:C	donor_gain	1.0000
7:20628836:CAA:C	donor_gain	1.0000
7:20628838:AGTG:A	donor_loss	1.0000
7:20628839:G:GG	donor_gain	1.0000
7:20628839:GTG:G	donor_loss	1.0000
7:20628840:TGAG:T	donor_loss	1.0000
7:20628841:GAGTA:G	donor_loss	1.0000
7:20632114:G:GG	donor_gain	1.0000
7:20643374:GA:G	donor_gain	1.0000
7:20643376:G:GG	donor_gain	1.0000
7:20643383:G:GT	donor_gain	1.0000
7:20643459:A:AG	acceptor_gain	1.0000
7:20643459:AGT:A	acceptor_gain	1.0000
7:20643460:G:GG	acceptor_gain	1.0000
7:20643460:GT:G	acceptor_gain	1.0000
7:20643460:GTG:G	acceptor_gain	1.0000
7:20643460:GTGAC:G	acceptor_gain	1.0000
7:20643629:TAGGG:T	donor_loss	1.0000

AlphaMissense

8241 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:20651469:G:C	R461P	0.994
7:20647556:A:C	S335R	0.985
7:20647558:C:A	S335R	0.985
7:20647558:C:G	S335R	0.985
7:20647559:A:C	S336R	0.984
7:20647561:T:A	S336R	0.984
7:20647561:T:G	S336R	0.984
7:20650123:G:C	R436S	0.980
7:20650123:G:T	R436S	0.980
7:20742916:T:C	F1022L	0.978
7:20742918:C:A	F1022L	0.978
7:20742918:C:G	F1022L	0.978
7:20699897:G:C	G743R	0.975
7:20643288:G:C	R140P	0.972
7:20643549:G:C	G199R	0.972
7:20647544:A:C	S331R	0.972
7:20647546:T:A	S331R	0.972
7:20647546:T:G	S331R	0.972
7:20743019:A:T	K1056I	0.971
7:20643538:G:A	G195D	0.970
7:20646065:G:A	G303E	0.970
7:20650122:G:C	R436T	0.970
7:20643270:G:C	R134P	0.969
7:20643537:G:C	G195R	0.969
7:20743037:T:C	L1062P	0.969
7:20698479:G:T	G695W	0.968
7:20704736:T:C	F784L	0.968
7:20704738:T:A	F784L	0.968
7:20704738:T:G	F784L	0.968
7:20643210:G:A	G114D	0.967

dbSNP variants (sampled 300 via entrez): RS1000011578 (7:20675309 G>A), RS1000035623 (7:20719839 C>T), RS1000072924 (7:20724454 C>A,T), RS1000078032 (7:20639214 A>C), RS1000082990 (7:20719396 T>C), RS1000092495 (7:20751122 C>G), RS1000096198 (7:20751593 A>G), RS1000118935 (7:20616591 A>C,G), RS1000131179 (7:20690317 T>C,G), RS1000154017 (7:20630948 A>G,T), RS1000167564 (7:20703413 A>G), RS1000196052 (7:20617702 C>T), RS1000211551 (7:20735407 T>C), RS1000240110 (7:20616411 C>A), RS1000249626 (7:20665388 C>A,T)

Disease associations

OMIM: gene MIM:611785 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST000635_9	Response to statin therapy	7.000000e-06
GCST001786_28	Dental caries	2.000000e-06
GCST001942_12	Prostate cancer	5.000000e-13
GCST002279_69	PR interval in Tripanosoma cruzi seropositivity	1.000000e-07
GCST004049_8	Cough in response to angiotensin-converting enzyme inhibitor drugs	4.000000e-06
GCST005038_113	Allergic disease (asthma, hay fever or eczema)	2.000000e-14
GCST005956_25	Waist-to-hip ratio adjusted for BMI	3.000000e-08
GCST005962_47	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7.000000e-07
GCST005975_14	Eosinophil count	3.000000e-18
GCST007797_54	Asthma onset (childhood vs adult)	7.000000e-08
GCST007798_81	Asthma	2.000000e-15
GCST007800_73	Asthma (childhood onset)	7.000000e-22
GCST007995_50	Asthma (childhood onset)	9.000000e-09
GCST009719_27	Allergic rhinitis	7.000000e-09
GCST009798_31	Asthma	2.000000e-13
GCST010042_83	Asthma	5.000000e-21
GCST010043_153	Asthma	7.000000e-24
GCST012226_706	Waist circumference adjusted for body mass index	4.000000e-08
GCST012490_125	Femur bone mineral density x serum urate levels interaction	2.000000e-08
GCST90013445_45	Type 1 diabetes	2.000000e-08
GCST90013445_55	Type 1 diabetes	2.000000e-08
GCST90014325_32	Asthma	7.000000e-11

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004842	eosinophil count
EFO:0004847	age at onset
EFO:0007789	BMI-adjusted waist circumference
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1772928 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs17143212	Toxicity	3	haloperidol	Psychotic Disorder

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17143212	ABCB5	3	1.75	1	haloperidol
rs10950831	ABCB5		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — ABCB subfamily

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects methylation, decreases expression, decreases methylation	3
Valproic Acid	decreases expression, increases expression, affects cotreatment	2
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, decreases methylation, increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	increases reaction, affects binding	1
abrine	decreases expression	1
AC 93253	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation, affects cotreatment, decreases methylation	1
Calcitriol	increases expression	1
Cisplatin	decreases response to substance, increases expression	1
Doxorubicin	decreases response to substance, increases secretion	1
Folic Acid	decreases expression	1
Hydralazine	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Methotrexate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Oxyquinoline	affects response to substance	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1775256	Binding	Modulation of P-gp in human K562 cells assessed as intracellular accumulation of daunorubicin at 45 uM after 30 mins by flow-cytometry	Synthesis and biological evaluation of 4-arylcoumarin analogues of combretastatins. Part 2. — J Med Chem

Cellosaurus cell lines

10 cell lines: 10 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7EF	Mel JuSo ABCB5 KO clone HO1	Cancer cell line	Female
CVCL_B7EG	Mel JuSo ABCB5 KO clone HO2	Cancer cell line	Female
CVCL_B7EH	Mel JuSo ABCB5 KO clone HO3	Cancer cell line	Female
CVCL_B7EI	Mel JuSo ABCB5 KO clone HO4	Cancer cell line	Female
CVCL_SA97	HAP1 ABCB5 (-) 1	Cancer cell line	Male
CVCL_SA98	HAP1 ABCB5 (-) 2	Cancer cell line	Male
CVCL_SA99	HAP1 ABCB5 (-) 3	Cancer cell line	Male
CVCL_SB00	HAP1 ABCB5 (-) 4	Cancer cell line	Male
CVCL_SB01	HAP1 ABCB5 (-) 5	Cancer cell line	Male
CVCL_SB02	HAP1 ABCB5 (-) 6	Cancer cell line	Male

Clinical trials (associated diseases)

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