HLA-B

Summary

HLA-B (major histocompatibility complex, class I, B, HGNC:4932) is a protein-coding gene on chromosome 6p21.33, encoding HLA class I histocompatibility antigen, B alpha chain (P01889). Antigen-presenting major histocompatibility complex class I (MHCI) molecule.

HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described.

Source: NCBI Gene 3106 — RefSeq curated summary.

At a glance

• GWAS associations: 304
• Clinical variants (ClinVar): 119 total — 1 pathogenic
• Phenotypes (HPO): 205
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 5 cancer types
• MANE Select transcript: NM_005514

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4932
Approved symbol	HLA-B
Name	major histocompatibility complex, class I, B
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000234745
Ensembl biotype	protein_coding
OMIM	142830
Entrez	3106

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 6 retained_intron, 1 nonsense_mediated_decay

ENST00000412585, ENST00000434333, ENST00000463574, ENST00000474381, ENST00000481849, ENST00000497377, ENST00000498007, ENST00000640094, ENST00000696558, ENST00000696559, ENST00000696560, ENST00000696561, ENST00000696562, ENST00000951754, ENST00000951755, ENST00000951756

RefSeq mRNA: 1 — MANE Select: NM_005514 NM_005514

CCDS: CCDS34394

Canonical transcript exons

ENST00000359635 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 813.6897 / max 20790.0143, expressed in 1767 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72672	771.5730	1763
72674	31.3518	1633
72663	2.2945	726
72665	1.9596	628
72667	1.7290	606
72671	1.3303	422
72669	1.1528	399
72670	0.9338	371
72673	0.8807	518
72666	0.4842	264

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.94	gold quality
spleen	UBERON:0002106	99.91	gold quality
granulocyte	CL:0000094	99.90	gold quality
upper lobe of left lung	UBERON:0008952	99.87	gold quality
vermiform appendix	UBERON:0001154	99.86	gold quality
leukocyte	CL:0000738	99.83	gold quality
bone marrow cell	CL:0002092	99.83	gold quality
bone marrow	UBERON:0002371	99.83	gold quality
monocyte	CL:0000576	99.82	gold quality
right lung	UBERON:0002167	99.82	gold quality
lymph node	UBERON:0000029	99.80	gold quality
colonic epithelium	UBERON:0000397	99.76	gold quality
gall bladder	UBERON:0002110	99.75	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.74	gold quality
small intestine	UBERON:0002108	99.72	gold quality
mucosa of transverse colon	UBERON:0004991	99.71	gold quality
stromal cell of endometrium	CL:0002255	99.70	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.69	gold quality
skin of abdomen	UBERON:0001416	99.67	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.67	gold quality
adipose tissue	UBERON:0001013	99.66	gold quality
duodenum	UBERON:0002114	99.66	gold quality
tonsil	UBERON:0002372	99.66	gold quality
zone of skin	UBERON:0000014	99.65	gold quality
rectum	UBERON:0001052	99.65	gold quality
transverse colon	UBERON:0001157	99.65	gold quality
thoracic mammary gland	UBERON:0005200	99.65	gold quality
skin of leg	UBERON:0001511	99.64	gold quality
omental fat pad	UBERON:0010414	99.64	gold quality
apex of heart	UBERON:0002098	99.62	gold quality

Single-cell (SCXA)

Detected in 47 experiment(s), a significant marker in 38.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	9405.90
E-MTAB-6308	yes	6757.76
E-MTAB-10287	yes	3757.04
E-CURD-79	yes	3592.95
E-MTAB-8142	yes	3453.93
E-MTAB-8911	yes	3418.12
E-MTAB-10137	yes	3145.09
E-MTAB-6653	yes	2925.28
E-MTAB-6505	yes	2812.53
E-CURD-97	yes	2764.08
E-GEOD-134144	yes	2515.13
E-HCAD-25	yes	2511.44
E-HCAD-1	yes	2368.44
E-CURD-84	yes	2088.53
E-MTAB-10885	yes	1786.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CIITA, CUX1, HIVEP2, IFNA2, IFNG, IRF8, MYC, MYCN, TP53

miRNA regulators (miRDB)

20 targeting HLA-B, 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-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-6800-3P	96.15	65.16	461
HSA-MIR-764	94.16	64.85	656
HSA-MIR-6822-5P	93.94	66.34	812
HSA-MIR-6750-5P	93.94	66.68	797

Literature-anchored findings (GeneRIF, showing 37)

• magnitude and specificity of influenza A virus-specific cytotoxic T-lymphocyte responses in humans is related to HLA-A and -B phenotype (PMID:11752149)
• association of TNF alleles with HLA-DR, -DQ and -B alleles in 216 healthy individuals from the north of England (PMID:11841486)
• Soluble HLA class I molecules induce natural killer cell apoptosis through the engagement of CD8. HLA-A2, -Cw4, and -Bw46 alleles, or HLA-G1 leads to NK cell apoptosis. (PMID:11861287)
• Disparate binding of chaperone proteins by HLA-A subtypes (PMID:11862383)
• MICA genetic polymorphism and linkage disequilibrium with HLA-B in 29 African-American families (PMID:11862403)
• T8 cells with HLA-B*5701 or 5703 show cross-reactive tetramer binding with common and rare variants of an HIV-1 p24 epitope. (PMID:11953462)
• identification of new allele, B*3805 (PMID:11972879)
• Identification of a new HLA-B*07 allele–HLA-B*0726. (PMID:11972884)
• Sequencing-based typing of HLA-B*51 alleles and the significant association of HLA-B*5101 and -B*5108 with Behcet’s disease in Greek patients. (PMID:12028538)
• Description of six new HLA-B alleles in the 5C CREG including a B*58 intron two sequence (PMID:12028545)
• Novel HLA-B alleles formed by an inter-locus recombination with HLA-C, HLA-B*0713 and B*6702. (PMID:12028546)
• Polymorphisms in HIV-1 reverse transcriptase were most evident at sites of least functional or structural constraint and frequently were associated with particular host HLA-A and HLA-B alleles (PMID:12029127)
• Distribution of HLA-B alleles in nasopharyngeal carcinoma patients and normal controls in Thailand. (PMID:12074714)
• Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS (PMID:12134147)
• isolation of a common peptide ligand bound to three HLA B44 alleles; preliminary crystallographic analysis of recombinant forms of each complex (PMID:12220628)
• subtle peptide conformational alterations may be responsible for the immunobiological differences between the HLA-B27 subtypes (PMID:12244049)
• HLA-B*27 is known to be associated with ankylosing spondylitis and several methods have been applied to determine its presence or absence. (PMID:12366780)
• A uniquely conformed peptide-containing beta 2m-free HLA-B2705 heavy chain has been isolated, a discovery that opens new avenues for further investigation of the role of HLA-B27 in spondyloarthropathies. (PMID:12370371)
• New HLA-B alleles identified and sequences extended in potential bone marrow donors: B*5804, B*4418, B*1558, and B*4805 (PMID:12392514)
• Conserved TCR beta chain usage in reactive arthritis; evidence for selection by a putative HLA-B27-associated autoantigen. (PMID:12472659)
• HLA-B allele associations with secondary dengue virus infections correlate with disease severity and the infecting viral serotype in ethnic Thais. (PMID:12472660)
• The cDNA matched partial genomic sequences of B*3924, an allele whose distribution appears to be restricted to Mediterranean and Arabian Caucasoids. A single amino acid change exclusive to B*3924 (threonine-98) distinguishes it from B*3903. (PMID:12558815)
• analyzed the HLA-B gene frequencies in 281 healthy individuals from four Mexican Amerindian populations (66 Mayos, 90 Mazatecans, 72 Nahuas and 53 Teenek) (PMID:12618907)
• Cloning and sequencing of full-length HLA-B genes (PMID:12622774)
• HLA-B phenotype modifies the course of Behcet’s disease in Moroccan patients (PMID:12622781)
• HLA-A, -B, and -DRB1 alleles in a total of 236 Taiwanese adults with Graves’ disease and 533 racially matched normal control subjects were examined (PMID:12694583)
• In Sardinia, 2 distinct haplotypes harbor the non-AS-associated HLA-B*2709 allele or the AS-associated B27 alleles. (PMID:12746911)
• results show that HLA*B2705 and HLA*B2702 are the subtypes most frequently associated with ankylosing spondylitis in a Mestizo population from Venezuela and suggest a possible protector role for HLA*B2708, which was found only in the healthy population (PMID:12826378)
• A computational method was used to predict the serologic specificity of HLA molecules encoded by HLA-B. (PMID:12859593)
• Two new HLA-B alleles are reported in a caucasoid male. (PMID:12859596)
• A Gambian TNF haplotype matches the European HLA-A1, B8, DR3 and Chinese HLA-A33, B58, DR3 haplotypes. (PMID:12859597)
• frequency of HLA-B51 in Iranian patients with Behcet’s disease (PMID:12918696)
• white B22 serogroup alleles (B*55 and *56) appear to predispose to unfavorable outcome of HIV infection as strongly as some or all B*35 and B*53 alleles (PMID:12964117)
• Results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. (PMID:12969506)
• HLA-B*3520 and B*1801 subtypes were more commonly observed among HIV individuals in Maharasthra, India compared with controls, which reached statistical significance (P<0.01) (PMID:14501803)
• HLA-B haplotypic variation was observed in population groups with ancestry of Africa South of the Sahara. (PMID:14551603)
• a new HLA-B allele (HLA-B*5808) detected in an Italian white volunteer bone marrow donor. (PMID:14617040)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-147g22.4	ENSDARG00000097275
danio_rerio	mhc1lia	ENSDARG00000097766
danio_rerio		ENSDARG00000115781

Paralogs (22): HFE (ENSG00000010704), FCGRT (ENSG00000104870), ULBP1 (ENSG00000111981), ULBP2 (ENSG00000131015), ULBP3 (ENSG00000131019), MR1 (ENSG00000153029), RAET1L (ENSG00000155918), CD1D (ENSG00000158473), CD1A (ENSG00000158477), CD1C (ENSG00000158481), CD1B (ENSG00000158485), CD1E (ENSG00000158488), AZGP1 (ENSG00000160862), RAET1E (ENSG00000164520), RAET1G (ENSG00000203722), MICB (ENSG00000204516), MICA (ENSG00000204520), HLA-C (ENSG00000204525), HLA-E (ENSG00000204592), HLA-G (ENSG00000204632), HLA-F (ENSG00000204642), HLA-A (ENSG00000206503)

Protein

Protein identifiers

HLA class I histocompatibility antigen, B alpha chain — P01889 (reviewed: P01889)

Alternative names: Human leukocyte antigen B

All UniProt accessions (4): P01889, A0A1W2PP29, A0A8Q3SIV3, E5FQ95

UniProt curated annotations — full annotation on UniProt →

Function. Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-B-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells. May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity. Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells. Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via constitutive proteasome and IFNG-induced immunoproteasome. Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9. Allele B07:02: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and mainly a Leu anchor residue at the C-terminus. Presents a long peptide (APRGPHGGAASGL) derived from the cancer-testis antigen CTAG1A/NY-ESO-1, eliciting a polyclonal CD8-positive T cell response against tumor cells. Presents viral epitopes derived from HIV-1 gag-pol (TPQDLNTML) and Nef (RPQVPLRPM). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (SPRWYFYYL). Displays self-peptides including a peptide derived from the signal sequence of HLA-DPB1 (APRTVALTA). Allele B08:01: Presents to CD8-positive T cells viral epitopes derived from EBV/HHV-4 EBNA3 (QAKWRLQTL), eliciting cytotoxic T cell response. Allele B13:02: Presents multiple HIV-1 epitopes derived from gag (RQANFLGKI, GQMREPRGSDI), nef (RQDILDLWI), gag-pol (RQYDQILIE, GQGQWTYQI) and rev (LQLPPLERL), all having in common a Gln residue at position 2 and mainly hydrophobic amino acids Leu, Ile or Val at the C-terminus. Associated with successful control of HIV-1 infection. Allele B18:01: Preferentially presents octameric and nonameric peptides sharing a common motif, namely a Glu at position 2 and Phe or Tyr anchor residues at the C-terminus. Presents an EBV/HHV-4 epitope derived from BZLF1 (SELEIKRY). May present to CD8-positive T cells an antigenic peptide derived from MAGEA3 (MEVDPIGHLY), triggering an anti-tumor immune response. May display a broad repertoire of self-peptides with a preference for peptides derived from RNA-binding proteins. Allele B27:05: Presents to CD8-positive T cells immunodominant viral epitopes derived from HCV POLG (ARMILMTHF), HIV-1 gag (KRWIILGLNK), IAV NP (SRYWAIRTR), SARS-CoV-2 N/nucleoprotein (QRNAPRITF), EBV/HHV-4 EBNA4 (HRCQAIRKK) and EBV/HHV-4 EBNA6 (RRIYDLIEL), conferring longterm protection against viral infection. Can present self-peptides derived from cytosolic and nuclear proteins. All peptides carry an Arg at position 2. The peptide-bound form interacts with NK cell inhibitory receptor KIR3DL1 and inhibits NK cell activation in a peptide-specific way, being particularly sensitive to the nature of the amino acid side chain at position 8 of the antigenic peptide. KIR3DL1 fails to recognize HLA-B27:05 in complex with B2M and EBV/HHV-4 EBNA6 (RRIYDLIEL) peptide, which can lead to increased activation of NK cells during infection. May present an altered repertoire of peptides in the absence of TAP1-TAP2 and TAPBPL. Allele B40:01: Presents immunodominant viral epitopes derived from EBV/HHV-4 LMP2 (IEDPPFNSL) and SARS-CoV-2 N/nucleoprotein (MEVTPSGTWL), triggering memory CD8-positive T cell response. Displays self-peptides sharing a signature motif, namely a Glu at position 2 and a Leu anchor residue at the C-terminus. Allele B41:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus. Allele B44:02: Presents immunodominant viral epitopes derived from EBV/HHV-4 EBNA4 (VEITPYKPTW) and EBNA6 (AEGGVGWRHW, EENLLDFVRF), triggering memory CD8-positive T cell response. Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Phe, Tyr or Trp anchor residues at the C-terminus. Allele B45:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus. Allele B46:01: Preferentially presents nonameric peptides sharing a signature motif, namely Ala and Leu at position 2 and Tyr, Phe, Leu, or Met anchor residues at the C-terminus. The peptide-bound form interacts with KIR2DL3 and inhibits NK cell cytotoxic response in a peptide-specific way. Allele B47:01: Displays self-peptides sharing a signature motif, namely an Asp at position 2 and Leu or Met anchor residues at the C-terminus. Allele B49:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ile or Val anchor residues at the C-terminus. Allele B50:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus. Allele B51:01: Presents an octameric HIV-1 epitope derived from gag-pol (TAFTIPSI) to the public TRAV17/TRBV7-3 TCR clonotype, strongly suppressing HIV-1 replication. Allele B54:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus. Allele B55:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus. Allele B56:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus. Allele B57:01: The peptide-bound form recognizes KIR3DL1 and inhibits NK cell cytotoxic response. Presents HIV gag peptides (immunodominant KAFSPEVIPMF and subdominant KALGPAATL epitopes) predominantly to CD8-positive T cell clones expressing a TRAV41-containing TCR, triggering HLA-B-restricted T cell responses. Allele B67:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Leu anchor residue at the C-terminus.

Subunit / interactions. Heterotrimer that consists of an alpha chain HLA-B, a beta chain B2M and a peptide (peptide-HLA-B-B2M). Early in biogenesis, HLA-B-B2M dimer interacts with the components of the peptide-loading complex composed of TAPBP, TAP1-TAP2, TAPBPL, PDIA3/ERP57 and CALR. Interacts with TAP1-TAP2 transporter via TAPBP; this interaction is obligatory for the loading of peptide epitopes delivered to the ER by TAP1-TAP2 transporter. Interacts with TAPBPL; TAPBPL binds peptide-free HLA-B-B2M complexes or those loaded with low affinity peptides, likely facilitating peptide exchange for higher affinity peptides. Only optimally assembled peptide-HLA-B-B2M trimer translocates to the surface of antigen-presenting cells, where it interacts with TCR and CD8 coreceptor on the surface of T cells. HLA-B (via polymorphic alpha-1 and alpha-2 domains) interacts with antigen-specific TCR (via CDR1, CDR2 and CDR3 domains). One HLA-B molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop); this interaction ensures peptide-HLA-B-B2M recognition by CD8-positive T cells only. Allele B57:01 interacts (via Bw4 motif) with KIR3DL1 (via Ig-like C2-type domain); this interaction may interfere with peptide binding. Allele B46:01 interacts with KIR2DL3. (Microbial infection) Interacts with HTLV-1 accessory protein p12I.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane.

Disease relevance. Stevens-Johnson syndrome (SJS) [MIM:608579] A rare blistering mucocutaneous disease that share clinical and histopathologic features with toxic epidermal necrolysis. Both disorders are characterized by high fever, malaise, and a rapidly developing blistering exanthema of macules and target-like lesions accompanied by mucosal involvement. Stevens-Johnson syndrome is a milder disease characterized by destruction and detachment of the skin epithelium and mucous membranes involving less than 10% of the body surface area. Ocular symptoms include ulcerative conjunctivitis, keratitis, iritis, uveitis and sometimes blindness. It can be caused by a severe adverse reaction to particular types of medication, although Mycoplasma infections may induce some cases. Disease susceptibility is associated with variants affecting the gene represented in this entry. Increased susceptibility to Stevens-Johnson syndrome is conferred by allele B15:02. Spondyloarthropathy 1 (SPDA1) [MIM:106300] A chronic rheumatic disease with multifactorial inheritance. It includes a spectrum of related disorders comprising ankylosing spondylitis, a subset of psoriatic arthritis, reactive arthritis (e.g. Reiter syndrome), arthritis associated with inflammatory bowel disease and undifferentiated spondyloarthropathy. These disorders may occur simultaneously or sequentially in the same patient, probably representing various phenotypic expressions of the same disease. Ankylosing spondylitis is the form of rheumatoid arthritis affecting the spine and is considered the prototype of seronegative spondyloarthropathies. It produces pain and stiffness as a result of inflammation of the sacroiliac, intervertebral, and costovertebral joints. Disease susceptibility is associated with variants affecting the gene represented in this entry. A restricted number of HLA-B27 subtypes can be associated with ankylosing spondylitis and other B27-related diseases, and an elevated frequency of the B27:02 allele in ankylosing spondylitis patients is identified. The allele B27:07 seems to have a protective role in some populations because it was found only in the healthy controls. There is evidence that HLA-B51 is associated with susceptibility to Behcet disease (BD). However, it is not certain whether HLA-B51 itself or a closely linked gene is responsible for susceptibility. The world distribution of HLA-B51 in healthy people corresponds to the global distribution of BD; in Southern hemisphere countries (Africa, South Pacific, etc.) and in some parts of Europe, the prevalence of HLA-B51 in healthy people is low or null, corresponding to a low prevalence of BD. The wide variation that exists in the relative risk of HLA-B51 would support other nongenetic risk factors. The presence of allele B57:01 is associated with increased susceptibility to abacavir hypersensitivity [MIM:142830] in HIV-1 patients. Allele group B08 is associated with increased susceptibility to rheumatoid arthritis, where affected individuals have antibodies to cyclic citrullinated peptide (anti-CCP-positive rheumatoid arthritis).

Domain organisation. The alpha-1 domain is a structural part of the peptide-binding cleft. Residues 101-107 determine Bw4/Bw6 motifs, which serologically distinguish HLA-B alleles. Each HLA-B allele possesses either the Bw4 or Bw6 motif. Only HLA-B alleles bearing the Bw4 epitope are recognized by NK cell inhibitory receptor KIR3DL1. The alpha-2 domain is a structural part of the peptide-binding cleft. Mediates the interaction with TAP1-TAP2 complex. The alpha-3 Ig-like domain mediates the interaction with CD8 coreceptor. The VL9 peptide/epitope (VMAPRT[V/L][L/V/I/F]L) derived from the signal sequence is loaded onto HLA-E and enables HLA-E expression at the plasma membrane. Distinct VL9 peptides presented by HLA-E variably affect its recognition by KLRD1-KLRC1 or KLRD1-KLRC2 receptors on NK cells. Most HLA-B allotypes contain VL9 peptides with low affinity for HLA-E. The VL9 peptide derived from HLA-B07, B08, B14, B38, B39, B42 and B*48 allotypes, displays high affinity for HLA-E yet fails to drive NK cell activation. It outcompetes other VL9 peptides derived from HLA-A and HLA-C for binding to HLA-E, lowering the threshold of NK cell activation.

Polymorphism. The most polymorphic of the mammalian genome. Polymorphic residues encode for alpha-1 and alpha-2 domains of the peptide-binding cleft, where they contribute to variations in peptide binding and TCR recognition among different alleles. The human population is estimated to have millions of HLA-B alleles. But only 17 common HLA-A alleles are considered core alleles, representing all functionally significant variation (polymorphism) in alpha-1 and alpha-2 domains. These are: B07:02; B08:01; B13:02; B15:01; B18:01; B27:05; B35:01; B37:01; B38:01; B40:01; B44:02; B45:01; B51:01; B54:01; B57:01 and B73:01. Among these, B07:02; B15:01; B18:01; B37:01; B51:01; B54:01; B57:01 and B73:01, were likely passed by introgression from archaic to modern humans. Functional alleles of more recent origin (non-core) were derived by recombination. The sequence shown is that of B07:02. The sequences of core alleles and common representative alleles of serologically distinct allele groups are described as variants of B07:02. Allelic variations of HLA-B signal peptide regulate HLA-E recognition by KLRD1-KLRC1 and KLRD1-KLRC2 receptors in viral infection and tumorigenesis by affecting its processing and by changing the affinity of HLA-E-VL9 complex for KLRD1-KLRC1 and KLRD1-KLRC2 receptors.

RefSeq proteins (1): NP_005505* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001039	MHC_I_a_a1/a2	Domain
IPR003006	Ig/MHC_CS	Conserved_site
IPR003597	Ig_C1-set	Domain
IPR007110	Ig-like_dom	Domain
IPR010579	MHC_I_a_C	Domain
IPR011161	MHC_I-like_Ag-recog	Domain
IPR011162	MHC_I/II-like_Ag-recog	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037055	MHC_I-like_Ag-recog_sf	Homologous_superfamily
IPR050208	MHC_class-I_related	Family

Pfam: PF00129, PF06623, PF07654

UniProt features (154 total): sequence variant 97, strand 22, helix 8, binding site 7, region of interest 6, turn 3, topological domain 2, disulfide bond 2, signal peptide 1, chain 1, short sequence motif 1, compositionally biased region 1, glycosylation site 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

237 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1K5N	X-RAY DIFFRACTION	1.09
4U1M	X-RAY DIFFRACTION	1.18
3CZF	X-RAY DIFFRACTION	1.2
6MT3	X-RAY DIFFRACTION	1.21
3LN4	X-RAY DIFFRACTION	1.3
3BWA	X-RAY DIFFRACTION	1.3
3SPV	X-RAY DIFFRACTION	1.3
6MT6	X-RAY DIFFRACTION	1.31
2BVP	X-RAY DIFFRACTION	1.35
6MTL	X-RAY DIFFRACTION	1.35
4U1J	X-RAY DIFFRACTION	1.38
6PYW	X-RAY DIFFRACTION	1.38
6P2C	X-RAY DIFFRACTION	1.4
2A83	X-RAY DIFFRACTION	1.4
4QRS	X-RAY DIFFRACTION	1.4
4QRT	X-RAY DIFFRACTION	1.4
5WMQ	X-RAY DIFFRACTION	1.4
4XXC	X-RAY DIFFRACTION	1.43
5IB2	X-RAY DIFFRACTION	1.44
6PYJ	X-RAY DIFFRACTION	1.44
6BXP	X-RAY DIFFRACTION	1.45
6PYV	X-RAY DIFFRACTION	1.45
1OGT	X-RAY DIFFRACTION	1.47
1XH3	X-RAY DIFFRACTION	1.48
6P2F	X-RAY DIFFRACTION	1.48
1ZHL	X-RAY DIFFRACTION	1.5
2HJL	X-RAY DIFFRACTION	1.5
4JQV	X-RAY DIFFRACTION	1.5
5IEH	X-RAY DIFFRACTION	1.5
6AT5	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01889-F1	89.23	0.81

Antibody-complex structures (SAbDab): 1 — 6UJ9

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 (7): 87; 108; 167; 170; 176; 183; 195

Disulfide bonds (2): 125–188, 227–283

Glycosylation sites (1): 110

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1236977	Endosomal/Vacuolar pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-2172127	DAP12 interactions
R-HSA-6798695	Neutrophil degranulation
R-HSA-877300	Interferon gamma signaling
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC

MSigDB gene sets: 930 (showing top): LEE_NEURAL_CREST_STEM_CELL_DN, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_DENDRITIC_CELL_DIFFERENTIATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, BENPORATH_ES_WITH_H3K27ME3, GOBP_TOLERANCE_INDUCTION, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOBP_REGULATION_OF_DENDRITIC_CELL_DIFFERENTIATION, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE

GO Biological Process (16): positive regulation of T cell mediated cytotoxicity (GO:0001916), adaptive immune response (GO:0002250), antigen processing and presentation of endogenous peptide antigen via MHC class Ib (GO:0002476), antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent (GO:0002486), regulation of T cell anergy (GO:0002667), defense response (GO:0006952), immune response (GO:0006955), detection of bacterium (GO:0016045), regulation of interleukin-12 production (GO:0032655), regulation of interleukin-6 production (GO:0032675), protection from natural killer cell mediated cytotoxicity (GO:0042270), innate immune response (GO:0045087), regulation of dendritic cell differentiation (GO:2001198), immune system process (GO:0002376), antigen processing and presentation of peptide antigen via MHC class I (GO:0002474), antigen processing and presentation (GO:0019882)

GO Molecular Function (5): signaling receptor binding (GO:0005102), peptide antigen binding (GO:0042605), TAP binding (GO:0046977), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (17): Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), ER to Golgi transport vesicle membrane (GO:0012507), membrane (GO:0016020), secretory granule membrane (GO:0030667), phagocytic vesicle membrane (GO:0030670), early endosome membrane (GO:0031901), MHC class I protein complex (GO:0042612), recycling endosome membrane (GO:0055038), extracellular exosome (GO:0070062), lumenal side of endoplasmic reticulum membrane (GO:0098553), endoplasmic reticulum membrane (GO:0005789)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Antigen processing-Cross presentation	2
Innate Immune System	2
Interferon Signaling	2
Adaptive Immune System	1
SARS-CoV-2-host interactions	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
immune response	2
immune system process	2
regulation of cytokine production	2
bounding membrane of organelle	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
endosome membrane	2
positive regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
positive regulation of T cell mediated immunity	1
antigen processing and presentation of peptide antigen via MHC class Ib	1
antigen processing and presentation of endogenous peptide antigen	1
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway	1
regulation of T cell tolerance induction	1
T cell anergy	1
regulation of lymphocyte anergy	1
response to stress	1
response to stimulus	1
response to bacterium	1
detection of other organism	1
interleukin-12 production	1
interleukin-6 production	1
negative regulation of natural killer cell mediated cytotoxicity	1
defense response to symbiont	1
dendritic cell differentiation	1
regulation of leukocyte differentiation	1
biological_process	1
antigen processing and presentation of peptide antigen	1
antigen binding	1
peptide binding	1
binding	1
Golgi apparatus	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1

Protein interactions and networks

STRING

2400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HLA-B	KIR3DL1	P43629	998
HLA-B	KIR3DL2	P43630	989
HLA-B	B2M	P01884	988
HLA-B	LILRB1	Q8NHL6	966
HLA-B	LILRB2	Q8N423	959
HLA-B	KIR2DL1	P43626	946
HLA-B	CD8A	P01732	909
HLA-B	CD4	P01730	875
HLA-B	C4A	P01028	870
HLA-B	HLA-C	P04222	869
HLA-B	KIR2DL3	P43628	860
HLA-B	HLA-DQA2	P01906	858
HLA-B	ERAP1	Q9NZ08	835
HLA-B	KLRD1	Q13241	830
HLA-B	HLA-A	P01891	823

IntAct

474 interactions, top by confidence:

A	B	Type	Score
HLA-C	HLA-B	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	PEBP1	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	EIF3I	psi-mi:“MI:0915”(physical association)	0.000
RANGAP1	HLA-B	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	HSPE1	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	PGD	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	CACYBP	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	DYNLRB1	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	TXN	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	PLS3	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	UQCRC2	psi-mi:“MI:0915”(physical association)	0.000
HLA-B		psi-mi:“MI:0915”(physical association)	0.000
HLA-B	CLPP	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	STRAP	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	MTPN	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	RNP24	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	TPP2	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	PPIB	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	ARF6	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	DCTPP1	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	OAT	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	ACTR1A	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	MCM3	psi-mi:“MI:0915”(physical association)	0.000
HLA-A	HLA-B	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	PSMB3	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	GANAB	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	ATP6V1A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (335): HLA-B (Affinity Capture-Western), HLA-B (Affinity Capture-Western), HLA-B (Affinity Capture-Western), TUBGCP2 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), HLA-C (Affinity Capture-MS), HLA-A (Affinity Capture-MS), HLA-E (Affinity Capture-MS), HLA-H (Affinity Capture-MS), INTS5 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), IPO13 (Affinity Capture-MS), ARFGEF1 (Affinity Capture-MS), ARFGEF2 (Affinity Capture-MS)

ESM2 similar proteins: P01889, P01893, P01894, P01897, P01899, P01900, P01901, P01902, P03991, P04223, P04439, P06140, P10321, P13747, P13748, P13749, P13750, P13751, P13752, P13753, P14426, P14427, P16209, P16210, P16211, P16212, P16215, P16391, P17693, P18466, P30375, P30376, P30377, P30378, P30379, P30380, P30381, P30382, P30383, P30385

Diamond homologs: C1ITJ8, O19477, O35799, P01888, P01889, P01893, P01894, P01895, P01896, P01897, P01898, P01899, P01900, P01901, P01902, P03991, P04223, P04439, P06126, P06140, P06339, P10321, P13747, P13748, P13749, P13750, P13751, P13752, P13753, P13765, P14426, P14427, P14428, P14429, P14430, P14431, P14432, P15464, P15978, P15979

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
IFNA2	“up-regulates quantity by expression”	HLA-B	“transcriptional regulation”
IFNG	“up-regulates quantity by expression”	HLA-B	“transcriptional regulation”
MYC	“down-regulates quantity by repression”	HLA-B	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 188 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Antigen processing: Ub, ATP-independent proteasomal degradation	7	25.1×	7e-08
Regulation of activated PAK-2p34 by proteasome mediated degradation	13	22.8×	9e-13
Regulation of ornithine decarboxylase (ODC)	13	22.2×	9e-13
Vpu mediated degradation of CD4	13	21.7×	9e-13
Autodegradation of the E3 ubiquitin ligase COP1	13	21.7×	9e-13
Ubiquitin-dependent degradation of Cyclin D	13	21.7×	9e-13
Cross-presentation of soluble exogenous antigens (endosomes)	13	20.8×	1e-12
Vif-mediated degradation of APOBEC3G	13	20.8×	1e-12

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	8	8.1×	2e-03
DNA replication	8	7.2×	4e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	17	4.8×	1e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 5 cancer types — CESC, DLBCLNOS, ESCA, HNSC, MLYM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	2
Likely benign	21
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2681311	NM_005514.8(HLA-B):c.722G>A (p.Trp241Ter)	Pathogenic

SpliceAI

1052 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31354476:CA:C	donor_loss	1.0000
6:31354477:ACCT:A	donor_loss	1.0000
6:31354478:C:A	donor_loss	1.0000
6:31354523:CTGC:C	acceptor_gain	1.0000
6:31354525:GCCT:G	acceptor_loss	1.0000
6:31354527:C:CC	acceptor_gain	1.0000
6:31354527:CTGG:C	acceptor_loss	1.0000
6:31354532:G:GC	acceptor_gain	1.0000
6:31354632:CA:C	donor_gain	1.0000
6:31355102:CCTAC:C	donor_loss	1.0000
6:31355104:TACCT:T	donor_loss	1.0000
6:31355105:A:T	donor_loss	1.0000
6:31355106:C:G	donor_loss	1.0000
6:31355116:T:TA	donor_gain	1.0000
6:31355219:CGGCT:C	acceptor_gain	1.0000
6:31355222:CT:C	acceptor_gain	1.0000
6:31355224:C:CC	acceptor_gain	1.0000
6:31356188:T:TA	donor_gain	1.0000
6:31356189:C:A	donor_gain	1.0000
6:31356686:ACCGG:A	donor_gain	1.0000
6:31356687:CCGGC:C	donor_gain	1.0000
6:31354293:CAGG:C	acceptor_gain	0.9900
6:31354295:GG:G	acceptor_gain	0.9900
6:31354297:C:CC	acceptor_gain	0.9900
6:31354477:A:AC	donor_gain	0.9900
6:31354478:C:CC	donor_gain	0.9900
6:31354524:TGC:T	acceptor_gain	0.9900
6:31354525:GC:G	acceptor_gain	0.9900
6:31354526:CC:C	acceptor_gain	0.9900
6:31354532:G:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001384765 (6:31358564 A>G), RS1001497166 (6:31354827 C>A), RS1002109462 (6:31359067 T>C), RS1002287490 (6:31353671 T>A,G), RS1002795639 (6:31354183 C>T), RS1003836378 (6:31353528 C>T), RS1004958963 (6:31354618 AC>A,ACC), RS1005106991 (6:31359039 C>A), RS1005296346 (6:31353547 CAGAAG>C), RS1005570809 (6:31358855 T>C), RS1005858482 (6:31358187 C>T), RS1006002378 (6:31354342 A>G), RS1006132641 (6:31358923 G>A), RS1006672162 (6:31357829 A>G), RS1007632750 (6:31355036 A>G)

Disease associations

OMIM: gene MIM:142830 | disease phenotypes: MIM:106300

GenCC curated gene-disease

Mondo (3): spondyloarthropathy, susceptibility to, 1 (MONDO:0007126), toxic epidermal necrolysis (MONDO:0019810), breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (2): Stevens-Johnson syndrome (Orphanet:36426), Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum (Orphanet:95455)

HPO phenotypes

205 total (30 of 205 shown, HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000031	Epididymitis
HP:0000083	Renal insufficiency
HP:0000099	Glomerulonephritis
HP:0000155	Oral ulcer
HP:0000206	Glossitis
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000421	Epistaxis
HP:0000488	Retinopathy
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000509	Conjunctivitis
HP:0000518	Cataract
HP:0000554	Uveitis
HP:0000572	Visual loss
HP:0000597	Ophthalmoparesis
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000621	Entropion
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000651	Diplopia
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000737	Irritability
HP:0000790	Hematuria
HP:0000795	Abnormality of the urethra
HP:0000822	Hypertension
HP:0000873	Diabetes insipidus

GWAS associations

304 associations (top):

Study	Trait	p-value
GCST000372_2	Height	5.000000e-08
GCST000415_4	Drug-induced liver injury (flucloxacillin)	9.000000e-33
GCST000424_3	Multiple sclerosis	1.000000e-17
GCST000549_23	HIV-1 control	1.000000e-11
GCST000549_41	HIV-1 control	5.000000e-35
GCST000553_1	CD4:CD8 lymphocyte ratio	2.000000e-28
GCST000656_9	HIV-1 viral setpoint	3.000000e-06
GCST000687_5	Nasopharyngeal carcinoma	3.000000e-33
GCST000692_1	Vitiligo	1.000000e-48
GCST000863_2	HIV-1 control	2.000000e-13
GCST000863_3	HIV-1 control	9.000000e-20
GCST000863_5	HIV-1 control	1.000000e-25
GCST001137_2	White blood cell count	1.000000e-11
GCST001149_2	Ankylosing spondylitis	1.000000e-200
GCST001200_3	Graves’ disease	2.000000e-65
GCST001337_17	Platelet count	9.000000e-10
GCST001341_16	Multiple sclerosis	1.000000e-11
GCST001474_6	Hypothyroidism	1.000000e-08
GCST001523_13	Visceral adipose tissue adjusted for BMI	2.000000e-06
GCST001812_2	Epstein-Barr virus immune response (EBNA-1)	2.000000e-10
GCST001863_10	Beta-2 microglubulin plasma levels	1.000000e-08
GCST001863_14	Beta-2 microglubulin plasma levels	2.000000e-10
GCST001863_15	Beta-2 microglubulin plasma levels	4.000000e-07
GCST001863_4	Beta-2 microglubulin plasma levels	2.000000e-20
GCST001863_9	Beta-2 microglubulin plasma levels	9.000000e-09
GCST001900_6	Cervical cancer	8.000000e-08
GCST001956_68	Height	4.000000e-12
GCST002084_12	Allergic sensitization	4.000000e-08
GCST002101_1	HIV-1 susceptibility	4.000000e-11
GCST002357_1	Rheumatoid arthritis (ACPA-negative)	9.000000e-09

EFO canonical traits (60, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0004839	CD4:CD8 lymphocyte ratio
EFO:0004587	lymphocyte count
EFO:0004309	platelet count
EFO:0004340	body mass index
EFO:0005197	beta-2 microglobulin measurement
EFO:0005298	allergic sensitization measurement
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0006956	intraocular pressure change measurement
EFO:0006319	HIV viral set point measurement
EFO:0007685	trichloroethylene-induced hypersensitivity
EFO:1001494	psoriasis vulgaris
EFO:0007838	response to anti-thyroid drug
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007985	platelet crit
EFO:0007989	monocyte percentage of leukocytes
EFO:0005090	basophil count
EFO:0004527	mean corpuscular hemoglobin
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008425	IgG galactosylation measurement
EFO:0008400	susceptibility to chickenpox measurement
EFO:0008402	susceptibility to cold sores measurement
EFO:0008401	susceptibility to shingles measurement
EFO:0008406	susceptibility to plantar warts measurement
EFO:0008407	susceptibility to Mycobacterium tuberculosis infection measurement
EFO:0008410	susceptibility to pneumonia measurement
EFO:0007924	tonsillectomy risk measurement
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066444 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

89 annotations.

Variant	Type	Level	Drugs	Phenotypes
HLA-B*07:02	Toxicity	3	sulfamethoxazole / trimethoprim	Respiratory Insufficiency
HLA-B*08:01	Toxicity	3	Antithyroid Preparations	Agranulocytosis
HLA-B08:01, HLA-B39:01	Toxicity	3	infliximab	Drug-induced liver injury
HLA-B*13:01	Toxicity	2A	dapsone	Drug Hypersensitivity;Drug Reaction with Eosinophilia and Systemic Symptoms;Leprosy;Maculopapular Exanthema;Severe Cutaneous Adverse Reactions;Stevens-Johnson Syndrome
HLA-B*13:01	Toxicity	3	trichloroethylene	Drug Hypersensitivity
HLA-B*13:01	Toxicity	3	sulfasalazine	Drug Reaction with Eosinophilia and Systemic Symptoms
HLA-B*13:01	Toxicity	3	phenytoin	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B13:01, HLA-B15:02, HLA-B*38:02	Toxicity	2A	sulfamethoxazole / trimethoprim	Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*13:02	Toxicity	3	oxcarbazepine	Maculopapular Exanthema
HLA-B*13:02	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:01	Toxicity	3	oxcarbazepine	Epilepsy
HLA-B*15:01	Efficacy	3	interferon beta-1a	Multiple Sclerosis
HLA-B*15:01	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:02	Toxicity	1A	oxcarbazepine	Stevens-Johnson Syndrome
HLA-B*15:02	Toxicity	1A	phenytoin	Drug Reaction with Eosinophilia and Systemic Symptoms;Severe Cutaneous Adverse Reactions;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:02	Toxicity	1A	lamotrigine	Epilepsy;Severe Cutaneous Adverse Reactions;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:02	Toxicity	2A	antiepileptics	Maculopapular Exanthema;Severe Cutaneous Adverse Reactions;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:02	Toxicity	3	dapsone	Severe Cutaneous Adverse Reactions;Stevens-Johnson Syndrome
HLA-B*15:02	Toxicity	4	oxcarbazepine	Maculopapular Exanthema
HLA-B15:02, HLA-B15:11	Toxicity	1A	carbamazepine	Drug Reaction with Eosinophilia and Systemic Symptoms;Maculopapular Exanthema;Severe Cutaneous Adverse Reactions;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:05	Toxicity	3	sulfasalazine	Drug Reaction with Eosinophilia and Systemic Symptoms
HLA-B*15:12	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:13	Toxicity	3	phenytoin	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:18	Toxicity	3	carbamazepine	Stevens-Johnson Syndrome
HLA-B15:18, HLA-B40:01	Toxicity	3	oxcarbazepine	Stevens-Johnson Syndrome
HLA-B*15:19	Toxicity	3	oxcarbazepine	Maculopapular Exanthema
HLA-B*15:21	Toxicity	3	carbamazepine	Drug Reaction with Eosinophilia and Systemic Symptoms;Severe Cutaneous Adverse Reactions;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:24	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:25	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:27	Toxicity	3	oxcarbazepine	Maculopapular Exanthema
HLA-B*15:27	Toxicity	3	clindamycin
HLA-B*15:27	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:32	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*15:35	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-B*18:01	Toxicity	3	amoxicillin;clavulanate
HLA-B*27:05	Toxicity	3	Antithyroid Preparations	Agranulocytosis
HLA-B*27:09	Toxicity	3	oxcarbazepine	Maculopapular Exanthema
HLA-B*35:01	Toxicity	3	nevirapine	Drug Hypersensitivity
HLA-B*35:02	Toxicity	3	minocycline	Drug-induced liver injury
HLA-B*35:05	Toxicity	3	nevirapine	Exanthema

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1071816	HLA-B	3	0.00	1	Antithyroid Preparations
rs9266271	HLA-B		0.00	0

PharmGKB dosing guidelines

18 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	abacavir	Annotation of CPIC Guideline for abacavir and HLA-B		yes
CPIC	allopurinol	Annotation of CPIC Guideline for allopurinol and HLA-B		yes
CPIC	carbamazepine	Annotation of CPIC Guideline for carbamazepine and HLA-A, HLA-B		yes
CPIC	fosphenytoin;phenytoin	Annotation of CPIC Guideline for fosphenytoin, phenytoin and CYP2C9, HLA-B	yes	yes
CPIC	oxcarbazepine	Annotation of CPIC Guideline for oxcarbazepine and HLA-B		yes
DPWG	abacavir	Annotation of DPWG Guideline for abacavir and HLA-B		yes
DPWG	allopurinol	Annotation of DPWG Guideline for allopurinol and HLA-B	yes	yes
DPWG	carbamazepine	Annotation of DPWG Guideline for carbamazepine and HLA-B		yes
DPWG	flucloxacillin	Annotation of DPWG Guideline for flucloxacillin and HLA-B		yes
DPWG	lamotrigine	Annotation of DPWG Guideline for lamotrigine and HLA-B		yes
DPWG	oxcarbazepine	Annotation of DPWG Guideline for oxcarbazepine and HLA-B		yes
DPWG	phenytoin	Annotation of DPWG Guideline for phenytoin and HLA-B		yes
DPWG	ribavirin	Annotation of DPWG Guideline for ribavirin and HLA-B
CPNDS	carbamazepine	Annotation of CPNDS Guideline for carbamazepine and HLA-A, HLA-B		yes
RNPGx	abacavir	Annotation of RNPGx Guideline for abacavir and HLA-B		yes
ACR	allopurinol	Annotation of ACR Guideline for allopurinol and HLA-B		yes
RNPGx	allopurinol	Annotation of RNPGx Guideline for allopurinol and HLA-B		yes
RNPGx	carbamazepine;oxcarbazepine	Annotation of RNPGx Guideline for carbamazepine, oxcarbazepine and HLA-A, HLA-B		yes

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.01	Kd	9.821	nM	CHEMBL3752910
8.01	ED50	9.821	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149871: Binding affinity to human HLA-B incubated for 45 mins by Kinobead based pull down assay	kd	0.0098	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	10
Carbamazepine	affects response to substance	7
sodium arsenite	decreases expression, increases abundance, increases expression	4
Arsenic Trioxide	decreases expression	4
Abacavir	increases response to substance, affects response to substance, increases expression, increases secretion	4
Penicillamine	affects response to substance	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
Tretinoin	increases expression	3
bisphenol A	affects expression, decreases expression	2
trichostatin A	increases expression	2
cobaltous chloride	increases expression	2
Lamotrigine	affects response to substance	2
Oxcarbazepine	affects response to substance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
peracetylated N-azidoacetylmannosamine	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
2,2,2-trichloroethanol	decreases reaction, affects cotreatment, decreases expression, affects localization, increases expression (+1 more)	1
ethyl-p-hydroxybenzoate	increases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, affects localization, decreases expression, decreases secretion, decreases reaction (+2 more)	1
nickel chloride	increases expression, affects cotreatment	1
ochratoxin A	increases acetylation, increases expression	1
aflatoxin G1	decreases 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
CHEMBL5652913	Binding	Binding affinity to human HLA-B 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

Cellosaurus cell lines

60 cell lines: 30 cancer cell line, 19 induced pluripotent stem cell, 7 transformed cell line, 4 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_6373	C1R-B7	Transformed cell line	Female
CVCL_6375	C1R-sB7	Transformed cell line	Female
CVCL_6488	J27-B7	Spontaneously immortalized cell line	Male
CVCL_A5AP	A904L-B39	Cancer cell line	Male
CVCL_B7RN	K-3501	Cancer cell line	Female
CVCL_B7RP	K-3502	Cancer cell line	Female
CVCL_B7RQ	K-3503	Cancer cell line	Female
CVCL_B7RR	K-3504	Cancer cell line	Female
CVCL_B7RS	K-3506	Cancer cell line	Female
CVCL_B7RT	K-3508	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01696500	PHASE3	COMPLETED	Phase III Clinical Trial of NPB-01 in Patients With Stevens-Johnson Syndrome/ Toxic Epidermal Necrolysis Unresponsive to Corticosteroids.
NCT06425224	PHASE3	RECRUITING	Effectiveness and Safety of TENS Therapy for Premature Ejaculation
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00372723	PHASE2	WITHDRAWN	Study of a Potential New Treatment for Patients With Toxic Epidermal Necrolysis (TEN)
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT02037347	PHASE1/PHASE2	TERMINATED	Study to Evaluate the Use of Palifermin to Treat Toxic Epidermal Necrolysis
NCT02319616	PHASE1/PHASE2	WITHDRAWN	Topical Clobetasol for the Treatment of Toxic Epidermal Necrolysis
NCT04711200	PHASE1/PHASE2	RECRUITING	LYell SYndrome MEsenchymal Stromal Cells Treatment
NCT05520086	PHASE1/PHASE2	UNKNOWN	Clinical Trial to Evaluate Safety and Efficacy of Cell Therapy in Patients With Cicatricial Conjuntivitis.
NCT07110662	PHASE1/PHASE2	NOT_YET_RECRUITING	New Therapeutic Target for Toxic Epidermal Necrolysis (TEN) Using Anti-CD38+ Monoclonal Antibodies.
NCT06119490	EARLY_PHASE1	RECRUITING	Evaluation of the Efficacy and Safety of Methylprednisolone Combined With the JAK Inhibitors in the Treatment of Toxic Epidermal Necrolysis
NCT02574988	Not specified	UNKNOWN	Severe Cutaneous Adverse Reactions in Thailand
NCT02795143	Not specified	WITHDRAWN	Evaluating the Effect of Isotretinoin in Regulatory T-cell Function in Adverse Cutaneous Drug Eruptions (ACDEs): A Pilot Study
NCT03548870	Not specified	TERMINATED	Transcutaneous Electrical Nerve Stimulation During Exercise in Patients With COPD
NCT03585946	Not specified	WITHDRAWN	Outcomes in Stevens Johnsons Syndrome and Toxic Epidermal Necrolysis
NCT03659227	Not specified	RECRUITING	Drug Reactions Sampling (COLLECTIONTOXIDERMIES)
NCT06474078	Not specified	COMPLETED	Study To Evaluate The Efficacy Of Tofacitinib In Patients With SJS/TEN
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery