HLA-C

Summary

HLA-C (major histocompatibility complex, class I, C, HGNC:4933) is a protein-coding gene on chromosome 6p21.33, encoding HLA class I histocompatibility antigen, C alpha chain (P10321). Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity. In precision oncology, HLA-C COPY-NEUTRAL LOSS OF HETEROZYGOSITY is associated with resistance to Therapeutic Tumor Infiltrating Lymphocytes in Colorectal Cancer (CIViC Level C). It is a selective cancer dependency (DepMap: 30.7% of cell lines).

HLA-C 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 endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, 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. About 6000 HLA-C alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.

Source: NCBI Gene 3107 — RefSeq curated summary.

At a glance

• GWAS associations: 247
• Clinical variants (ClinVar): 82 total
• Phenotypes (HPO): 6
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 30.7% of screened cell lines
• MANE Select transcript: NM_002117

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4933
Approved symbol	HLA-C
Name	major histocompatibility complex, class I, C
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204525
Ensembl biotype	protein_coding
OMIM	142840
Entrez	3107

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000376228, ENST00000376237, ENST00000383329, ENST00000415537, ENST00000466892, ENST00000470363, ENST00000484378, ENST00000487245, ENST00000495835, ENST00000956155, ENST00000956156

RefSeq mRNA: 1 — MANE Select: NM_002117 NM_002117

CCDS: CCDS34393

Canonical transcript exons

ENST00000376228 — 8 exons

Exon	Start	End
ENSE00003296924	31271599	31271868
ENSE00003485307	31269966	31270085
ENSE00003498981	31269493	31269525
ENSE00003557341	31270210	31270485
ENSE00003605599	31269338	31269385
ENSE00003639220	31268749	31269173
ENSE00003685062	31271073	31271348
ENSE00003922730	31271999	31272092

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 206.6041 / max 8822.3064, expressed in 1763 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72656	206.4371	1763
72652	0.1670	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.87	gold quality
right lung	UBERON:0002167	99.78	gold quality
spleen	UBERON:0002106	99.73	gold quality
granulocyte	CL:0000094	99.72	gold quality
right uterine tube	UBERON:0001302	99.63	gold quality
vermiform appendix	UBERON:0001154	99.60	gold quality
bone marrow	UBERON:0002371	99.59	gold quality
upper lobe of left lung	UBERON:0008952	99.56	gold quality
bone marrow cell	CL:0002092	99.54	gold quality
lymph node	UBERON:0000029	99.54	gold quality
metanephros cortex	UBERON:0010533	99.54	gold quality
leukocyte	CL:0000738	99.52	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.52	gold quality
monocyte	CL:0000576	99.49	gold quality
duodenum	UBERON:0002114	99.47	gold quality
mucosa of transverse colon	UBERON:0004991	99.47	gold quality
endocervix	UBERON:0000458	99.46	gold quality
left uterine tube	UBERON:0001303	99.45	gold quality
transverse colon	UBERON:0001157	99.43	gold quality
small intestine	UBERON:0002108	99.43	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.40	gold quality
body of uterus	UBERON:0009853	99.40	gold quality
stromal cell of endometrium	CL:0002255	99.38	gold quality
adipose tissue	UBERON:0001013	99.38	gold quality
apex of heart	UBERON:0002098	99.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.37	gold quality
ectocervix	UBERON:0012249	99.36	gold quality
omental fat pad	UBERON:0010414	99.35	gold quality
cortex of kidney	UBERON:0001225	99.34	gold quality
myometrium	UBERON:0001296	99.34	gold quality

Single-cell (SCXA)

Detected in 40 experiment(s), a significant marker in 34.

Experiment	Marker?	Max mean expression
E-MTAB-6308	yes	7076.50
E-CURD-126	yes	5043.53
E-CURD-55	yes	3845.47
E-GEOD-149689	yes	3389.99
E-CURD-79	yes	3019.10
E-MTAB-9435	yes	3015.51
E-HCAD-36	yes	2885.52
E-MTAB-9467	yes	2813.52
E-HCAD-1	yes	2095.22
E-HCAD-30	yes	1931.07
E-MTAB-6653	yes	1817.69
E-GEOD-134144	yes	1776.37
E-MTAB-7407	yes	1603.22
E-CURD-85	yes	1460.65
E-GEOD-135922	yes	1408.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CIITA, HIVEP2, MYC, MYCN

miRNA regulators (miRDB)

16 targeting HLA-C, 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-767-5P	99.95	70.85	993
HSA-MIR-4719	99.73	72.10	3329
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-11399	98.71	65.69	869
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-4660	97.79	67.44	1328
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
HSA-MIR-6889-5P	90.26	64.13	291
HSA-MIR-6767-5P	90.00	62.41	97

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 30.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• 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)
• This is the major genetic determinant for psoriasis. The HCR gene at this locus is the putative susceptibility gene for psoriasis. (PMID:11875053)
• identification of new allele, Cw*0408 (PMID:11972879)
• Sequence of two new HLA-Cw alleles: HLA-Cw*0313 and HLA-Cw*1208. (PMID:11972880)
• An association between young age of onset of psoriasis and HLA-Cw*0602 is confirmed in patients with psoriatic arthritis. (PMID:12011375)
• Elongation of the cytoplasmic domain, due to a point deletion at exon 7, results in an HLA-C null allele, Cw*0409 N (PMID:12028535)
• results indicate that the HLA-Cw*0409N allele may produce a putative long HLA-Cw4 heavy chain that is not expressed on the cell surface (PMID:12039411)
• Molecular diversity of the HLA-C gene identified in a caucasian population (PMID:12072195)
• Family-based analysis using a dense single-nucleotide polymorphism-based map defines genetic variation at PSORS1, the major psoriasis-susceptibility locus (PMID:12148091)
• Psoriasis is associated with a SNP haplotype of the corneodesmosin gene. A psoriasis susceptibility locus has been mapped to the HLA region in the proximity of the HLA-C locus. (PMID:12472658)
• the HLA-C locus may play a role in liver graft alloreactivity or allotolerance and, therefore, may be useful to avoid acute rejection and to achieve graft acceptance, resulting in a better final outcome in liver transplantation. (PMID:12619017)
• Cloning and sequencing of full-length HLA-C genes (PMID:12622774)
• Our results confirmed the published linkage with the PSORS1 locus, as well as the PSORS2 locus, which has not been previously shown in the Chinese population. (PMID:12709815)
• HLA-Cw*1507 association with HIV infection reported for the first time in Maharashtra, India (PMID:14501803)
• Based on the observations that HCR is detected in cancers of epithelial origin in Ki67-negative areas and that interferon-gamma downregulates its expression, it may have an antiproliferative function. (PMID:14675183)
• a relation between HLA-Cw7 and differentiated thyroid carcinoma (PMID:14716759)
• protective gene telomeric to the HLA-C locus in psoriasis vulgaris (PMID:15191522)
• results show that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of hepatitis C virus (HCV) infection (PMID:15297676)
• The data suggest that the microsatellite instability (MSI) and loss of heterozygosity (LOH) of HLA class I gene might participate in the carcinogenesis of cervical carcinoma. (PMID:15300630)
• A strong asociation between the HLA Cw*04 haplotype and persistent hepatitis C virus infection was observed (p = 0.006). (PMID:15301865)
• an endogenous retroviral dUTPase constitutes a candidate gene for the PSORS1 mutation. (PMID:15654959)
• PSORS1 is not a major inherited risk factor in the pathogenesis of late onset psoriasis (PMID:15654960)
• CTGGAC haplotype is a single-point score haplotypes telomeric to HLA-C and gives a 1 df, chi2 of 50.27 (p<0.0001). (PMID:15737195)
• we have identified a novel gene, PSORS1C3, and characterized it with regard to psoriasis (PMID:15848982)
• analysis of novel allele HLA-Cw*0208 (PMID:15896208)
• analysis of novel allele HLA-Cw*160102 (PMID:15896209)
• An examination of the association between HLA-C (Ala-73 and Asp-9) and susceptibility to psoriasis among Saudi patients. (PMID:15943912)
• new HLA class I alleles found in Caucasian population: A*3012, B*270505, B*3541 and Cw*0716 (PMID:15982258)
• analysis of novel allele HLA-Cw*1210 and confirmation of HLA-Cw*080102 (PMID:15982262)
• defined Cw alleles in 91 individuals from the Maratha community of Mumbai, Maharashtra, western India (PMID:16026588)
• Guangdong Han population in China has twelve HLA-A, 23 B, 11 Cw and 13 DRB1 alleles and a total of 9 HLA-A-B, 20 Cw-B, 7 A-Cw, and 8 A-DRB1, 9 B-DRB1, 10 Cw-DRB1 haplotypes. (PMID:16086295)
• HLA-Cw*010203 is a novel HLA-Cw*01 allele identified by sequence-based typing (PMID:16101836)
• preferential association of L31-reactive, beta2m-free H chains with calnexin in beta2m-defective cells, and with calreticulin and TAP in beta2m-expressing cells (PMID:16272320)
• HLA-Cw allele frequency distributions were consistent with the Hardy-Weinberg equilibrium in a group of indigenous Hans in Shenyang, China. (PMID:16331567)
• study of the HLA-C locus revealed that the analysis of the dimorphism at position 80 in the alpha1 helix may help to evaluate the risk and prognosis of melanoma in a Spanish population (PMID:16365741)
• Identification of two novel HLA-C alleles, HLA-Cw*1217 and HLA-Cw*030404 (PMID:16441500)
• Carrying a Cw*0801 HLA allele is a risk factor for SARS-CoV infection susceptibility [Cw*0801 HLA] (PMID:16455884)
• Intrathecal production and fluctuations in CSF and serum concentrations of sHLA-I were reciprocal in multiple sclerosis. (PMID:16459714)
• The HLA-Cw4 allele can act as a protector against the development of MG, as it occurs less frequently in the population with MG, and those with this allele develop smaller goiters with no intrathoracic component. (PMID:16490887)
• HLA-C mismatch is associated with inferior survival after myeloablative unrelated donor (URD) hematopoietic stem cell transplantation in hematologic cancers. (PMID:16532020)

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-E (ENSG00000204592), HLA-G (ENSG00000204632), HLA-F (ENSG00000204642), HLA-A (ENSG00000206503), HLA-B (ENSG00000234745)

Protein

Protein identifiers

HLA class I histocompatibility antigen, C alpha chain — P10321 (reviewed: P10321)

Alternative names: HLA-Cw, Human leukocyte antigen C

All UniProt accessions (5): A0A140T9E1, A2AEA2, P10321, F8W9Z8, Q6R739

UniProt curated annotations — full annotation on UniProt →

Function. Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity. In complex with B2M/beta 2 microglobulin displays a restricted repertoire of self and viral peptides and acts as a dominant ligand for inhibitory and activating killer immunoglobulin receptors (KIRs) expressed on NK cells. In an allogeneic setting, such as during pregnancy, mediates interaction of extravillous trophoblasts with KIR on uterine NK cells and regulate trophoblast invasion necessary for placentation and overall fetal growth. During viral infection, may present viral peptides with low affinity for KIRs, impeding KIR-mediated inhibition through peptide antagonism and favoring lysis of infected cells. Presents a restricted repertoire of viral peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-C-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected cells, particularly in chronic viral infection settings such as HIV-1 or CMV infection. 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 9 amino acids that arise from cytosolic proteolysis via proteasome. Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9. Preferentially displays peptides having a restricted repertoire of hydrophobic or aromatic amino acids (Phe, Ile, Leu, Met, Val and Tyr) at the C-terminal anchor. ALLELE C01:02: The peptide-bound form interacts with KIR2DL2 and KIR2DL3 inhibitory receptors on NK cells. The low affinity peptides compete with the high affinity peptides impeding KIR-mediated inhibition and favoring lysis of infected cells. Presents to CD8-positive T cells a CMV epitope derived from UL83/pp65 (RCPEMISVL), an immediate-early antigen necessary for initiating viral replication. ALLELE C04:01: Presents a conserved HIV-1 epitope derived from env (SFNCGGEFF) to memory CD8-positive T cells, eliciting very strong IFNG responses. Presents CMV epitope derived from UL83/pp65 (QYDPVAALF) to CD8-positive T cells, triggering T cell cytotoxic response. ALLELE C05:01: Presents HIV-1 epitope derived from rev (SAEPVPLQL) to CD8-positive T cells, triggering T cell cytotoxic response. ALLELE C06:02: In trophoblasts, interacts with KIR2DS2 on uterine NK cells and triggers NK cell activation, including secretion of cytokines such as GMCSF that enhances trophoblast migration. ALLELE C07:02: Plays an important role in the control of chronic CMV infection. Presents immunodominant CMV epitopes derived from IE1 (LSEFCRVL and CRVLCCYVL) and UL28 (FRCPRRFCF), both antigens synthesized during immediate-early period of viral replication. Elicits a strong anti-viral CD8-positive T cell immune response that increases markedly with age. ALLELE C08:01: Presents viral epitopes derived from CMV UL83 (VVCAHELVC) and IAV M1 (GILGFVFTL), triggering CD8-positive T cell cytotoxic response. ALLELE C12:02: Presents CMV epitope derived from UL83 (VAFTSHEHF) to CD8-positive T cells. ALLELE C15:02: Presents CMV epitope derived from UL83 CC (VVCAHELVC) to CD8-positive T cells, triggering T cell cytotoxic response.

Subunit / interactions. Heterotrimer that consists of an alpha chain HLA-C, a beta chain B2M and a peptide (peptide-HLA-C-B2M). Early in biogenesis, HLA-C-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 endoplasmic reticulum (ER) by TAP1-TAP2 transporter. Being very selective in the peptide binding, forms a stable interaction with TAP1-TAP2, often leading to the accumulation of free heavy chains in the ER. Only optimally assembled peptide-HLA-C-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-C (via polymorphic alpha-1 and alpha-2 domains) interacts with antigen-specific TCR (via CDR3 domains). One HLA-C molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop); this interaction ensures peptide-HLA-C-B2M recognition by CD8-positive T cells only. The peptide-HLA-C-B2M complex also interacts with KIRs. HLA-C type 1 (C1, with Asn104), including HLA-C02, C04, C05, C06 and C15, interact with KIR2DL1 and KIR2DS1, and HLA-C type 2 (C2, with Lys104), including HLA-C01, C03, C07 and C*08, interact with KIR2DL2 and KIR2DL3. (Microbial infection) Interacts with HTLV-1 p12I accessory protein.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitous. Highly expressed in fetal extravillous trophoblasts in the decidua basalis (at protein level).

Post-translational modifications. N-linked glycosylation at Asn-110 is required for efficient interaction with CANX and CALR chaperones and appropriate HLA-C-B2M folded conformers prior to peptide loading.

Disease relevance. Psoriasis 1 (PSORS1) [MIM:177900] A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. Disease susceptibility is associated with variants affecting the gene represented in this entry. Allele C*06:02 presents a melanocyte autoantigen ADAMTSL5 (VRSRRCLRL) to Valpha3S1/Vbeta13S1 TCR on CD8-positive T cells, and may trigger an autoimmune response against melanocytes.

Domain organisation. The alpha-1 domain is a structural part of the peptide-binding cleft. 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, setting NK cell activation threshold. Common HLA-C allotypes contain functional VL9 peptides (VMAPRTLIL and VMAPRTLLL). VL9 peptides (VMAPRTALL and VMAPRQALL) derived from HLA-C07, C17 and C*18 allotypes display low affinity for HLA-E and fail to drive NK cell activation.

Polymorphism. Displays lower polymorphism than HLA-A and HLA-B. 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-C alleles. But only 14 common HLA-C alleles are considered core alleles, representing all functionally significant variation (polymorphism) in alpha-1 and alpha-2 domains. These are: C01:02; C02:02; C03:02; C04:01; C05:01; C06:02; C07:01; C07:04; C08:01; C12:02; C14:02; C15:02; C16:01 and C17:01. Among these, C01:02; C02:02; C03:02; C08:01; C12:02; C14:02 and C15:02, 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 C07:02. The sequences of core alleles and common representative alleles of serologically distinct allele groups are described as variants of C*07:02. Allelic variations of HLA-C 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.

Miscellaneous. A transcript of allele C*16:01. This isoform lacks the transmembrane domain and is predicted to be a secreted protein.

Isoforms (2)

UniProt ID	Names	Canonical?
P10321-1	1	yes
P10321-2	2

RefSeq proteins (1): NP_002108* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001039	MHC_I_a_a1/a2	Domain
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 (127 total): sequence variant 75, strand 19, helix 8, region of interest 5, binding site 5, modified residue 2, disulfide bond 2, topological domain 2, splice variant 2, signal peptide 1, chain 1, turn 1, glycosylation site 1, transmembrane region 1, domain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
6JTO	X-RAY DIFFRACTION	1.7
5W6A	X-RAY DIFFRACTION	1.74
4NT6	X-RAY DIFFRACTION	1.84
5W67	X-RAY DIFFRACTION	2.3
5VGD	X-RAY DIFFRACTION	2.32
3BZF	X-RAY DIFFRACTION	2.5
6PAG	X-RAY DIFFRACTION	2.5
5VGE	X-RAY DIFFRACTION	2.6
1QQD	X-RAY DIFFRACTION	2.7
1IM9	X-RAY DIFFRACTION	2.8
5W69	X-RAY DIFFRACTION	2.8
1EFX	X-RAY DIFFRACTION	3
6PA1	X-RAY DIFFRACTION	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10321-F1	87.69	0.77

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): 87; 94; 101; 183; 195

Post-translational modifications (2): 357, 360

Disulfide bonds (2): 125–188, 227–283

Glycosylation sites (1): 110

Mutagenesis-validated functional residues (1):

Position	Phenotype
112	impairs n-linked glycosylation resulting in impaired interaction with canx and calr chaperones as well as tapbpl.

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: 364 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, BENPORATH_ES_WITH_H3K27ME3, 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, GOCC_SECRETORY_GRANULE, MODULE_151, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, MODULE_64, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2

GO Biological Process (11): 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), immune response (GO:0006955), innate immune response (GO:0045087), positive regulation of natural killer cell mediated cytotoxicity (GO:0045954), immune system process (GO:0002376), antigen processing and presentation of peptide antigen via MHC class I (GO:0002474), signal transduction (GO:0007165), antigen processing and presentation (GO:0019882)

GO Molecular Function (5): signaling receptor binding (GO:0005102), peptide antigen binding (GO:0042605), TAP binding (GO:0046977), receptor ligand activity (GO:0048018), 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
positive regulation of leukocyte mediated cytotoxicity	2
immune response	2
immune system process	2
protein binding	2
bounding membrane of organelle	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
endosome membrane	2
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
response to stimulus	1
defense response to symbiont	1
positive regulation of natural killer cell mediated immunity	1
natural killer cell mediated cytotoxicity	1
regulation of natural killer cell mediated cytotoxicity	1
biological_process	1
antigen processing and presentation of peptide antigen	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
antigen binding	1
peptide binding	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
binding	1
Golgi apparatus	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

335 interactions, top by confidence:

A	B	Type	Score
HLA-C	B2M	psi-mi:“MI:0915”(physical association)	0.880
KIR2DL1	HLA-C	psi-mi:“MI:0407”(direct interaction)	0.790
KIR2DL1	HLA-C	psi-mi:“MI:0915”(physical association)	0.790
LILRB2	HLA-C	psi-mi:“MI:0407”(direct interaction)	0.710
HLA-C	HLA-A	psi-mi:“MI:0914”(association)	0.670
KIR2DL3	HLA-C	psi-mi:“MI:0407”(direct interaction)	0.620
HLA-C	KIR2DL3	psi-mi:“MI:0407”(direct interaction)	0.620
KIR2DL2	HLA-C	psi-mi:“MI:0407”(direct interaction)	0.610
HLA-C	KIR2DL2	psi-mi:“MI:0915”(physical association)	0.610
KIR2DS1	HLA-C	psi-mi:“MI:0407”(direct interaction)	0.610

BioGRID (501): HLA-C (Affinity Capture-MS), HLA-C (Affinity Capture-MS), HLA-C (Affinity Capture-MS), HLA-C (Affinity Capture-MS), HLA-C (Affinity Capture-MS), HLA-C (Affinity Capture-MS), FAM213A (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), HLA-F (Affinity Capture-MS), HLA-A (Affinity Capture-MS), HLA-G (Affinity Capture-MS), HLA-E (Affinity Capture-MS), HLA-H (Affinity Capture-MS), PI4KA (Affinity Capture-MS), SCAP (Affinity Capture-MS)

ESM2 similar proteins: O35799, O62848, P01898, P01899, P06126, P06339, P10321, P11609, P11610, P13747, P13752, P13753, P14429, P14430, P15812, P15813, P15978, P16212, P16215, P17693, P23043, P29016, P29017, P30511, P30515, P30516, P30517, P60018, P70387, Q28565, Q29422, Q30201, Q3ZCH5, Q4ACW4, Q5YB65, Q63493, Q95IT1, Q95IT3, Q9GKZ0, Q9GL41

Diamond homologs: A0A0G2K7V7, O19477, O35799, P01896, P01899, P01900, P01901, P10321, P13752, P15979, P16391, P30377, P30379, P30380, P30381, P30386, P30388, P30511, P30516, P60018, P70387, Q29980, Q29983, Q30201, Q60I18, Q8HWE5, Q8HWE7, Q9GKZ0, Q9GL41, Q9GL42, Q9GL43, C1ITJ8, P01888, P01889, P01893, P01894, P01895, P01897, P01898, P01902

SIGNOR signaling

2 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 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 Presentation: Folding, assembly and peptide loading of class I MHC	5	21.6×	6e-04
AUF1 (hnRNP D0) binds and destabilizes mRNA	5	13.6×	5e-03
ER-Phagosome pathway	8	11.4×	3e-04
Proteasome assembly	5	11.2×	7e-03
Orc1 removal from chromatin	5	9.8×	8e-03
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	7	6.7×	7e-03
SARS-CoV-2 Infection	7	6.2×	8e-03
SARS-CoV Infections	9	5.5×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
immune response-regulating signaling pathway	8	34.4×	6e-08
protein folding	7	6.8×	6e-03
immune response	11	4.9×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — DLBCLNOS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

991 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31269975:T:TA	donor_gain	1.0000
6:31270208:ACC:A	donor_gain	1.0000
6:31270209:CCC:C	donor_gain	1.0000
6:31271068:GGTAC:G	donor_loss	1.0000
6:31271069:GTACC:G	donor_loss	1.0000
6:31271070:TACCT:T	donor_loss	1.0000
6:31271597:ACCGT:A	donor_gain	1.0000
6:31271598:CCGTC:C	donor_gain	1.0000
6:31269169:TCAGG:T	acceptor_gain	0.9900
6:31269170:CAGG:C	acceptor_gain	0.9900
6:31269170:CAGGC:C	acceptor_gain	0.9900
6:31269172:GGC:G	acceptor_loss	0.9900
6:31269174:C:CC	acceptor_gain	0.9900
6:31269174:C:T	acceptor_loss	0.9900
6:31269337:C:A	donor_loss	0.9900
6:31269382:CTGC:C	acceptor_gain	0.9900
6:31269386:C:CC	acceptor_gain	0.9900
6:31269387:T:C	acceptor_loss	0.9900
6:31269391:G:C	acceptor_gain	0.9900
6:31269391:G:GC	acceptor_gain	0.9900
6:31269491:A:AC	donor_gain	0.9900
6:31269492:C:CC	donor_gain	0.9900
6:31269492:CA:C	donor_gain	0.9900
6:31269492:CACG:C	donor_gain	0.9900
6:31269960:CCCTA:C	donor_loss	0.9900
6:31269961:CCTA:C	donor_loss	0.9900
6:31269962:CTACC:C	donor_loss	0.9900
6:31269963:TACCT:T	donor_loss	0.9900
6:31269964:A:AG	donor_loss	0.9900
6:31270081:TGGCT:T	acceptor_gain	0.9900

AlphaMissense

2355 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31270409:G:C	F232L	0.981
6:31270409:G:T	F232L	0.981
6:31270411:A:G	F232L	0.981
6:31270310:G:C	F265L	0.972
6:31270310:G:T	F265L	0.972
6:31270312:A:G	F265L	0.972
6:31271762:G:C	F60L	0.959
6:31271762:G:T	F60L	0.959
6:31271764:A:G	F60L	0.959
6:31270384:A:G	W241R	0.945
6:31270384:A:T	W241R	0.945
6:31270382:C:A	W241C	0.941
6:31270382:C:G	W241C	0.941
6:31270301:C:A	W268C	0.934
6:31270301:C:G	W268C	0.934
6:31271771:G:C	F57L	0.933
6:31271771:G:T	F57L	0.933
6:31271773:A:G	F57L	0.933
6:31271223:A:G	W157R	0.925
6:31271223:A:T	W157R	0.925
6:31271804:G:C	F46L	0.922
6:31271804:G:T	F46L	0.922
6:31271806:A:G	F46L	0.922
6:31271717:C:A	W75C	0.916
6:31271717:C:G	W75C	0.916
6:31271719:A:G	W75R	0.913
6:31271719:A:T	W75R	0.913
6:31271221:C:A	W157C	0.907
6:31271221:C:G	W157C	0.907
6:31270410:A:G	F232S	0.894

dbSNP variants (sampled 300 via entrez): RS1000145319 (6:31269294 C>A,T), RS1000365116 (6:31271887 T>A), RS1004076630 (6:31269018 G>C), RS1004207830 (6:31273389 T>C), RS1005904801 (6:31270100 G>A), RS1006550420 (6:31272658 T>C,G), RS1007496997 (6:31272240 G>A), RS1008251287 (6:31273444 C>T), RS1010446017 (6:31272342 C>T), RS1010711787 (6:31270652 T>C,G), RS1012688047 (6:31270813 G>A), RS1013600389 (6:31269233 G>A), RS1013600663 (6:31274088 C>A,T), RS1013859968 (6:31272764 C>G,T), RS1015409625 (6:31268761 C>A,G)

Disease associations

OMIM: gene MIM:142840 | disease phenotypes: MIM:177900

GenCC curated gene-disease

Mondo (1): psoriasis 1, susceptibility to (MONDO:0008334)

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0001369	Arthritis
HP:0001426	Non-Mendelian inheritance
HP:0001803	Nail pits
HP:0001806	Onycholysis
HP:0003765	Psoriasiform dermatitis
HP:0025088	Onychomadesis

GWAS associations

247 associations (top):

Study	Trait	p-value
GCST000165_2	Psoriasis	1.000000e-09
GCST000173_2	Psoriasis	2.000000e-26
GCST000173_3	Psoriasis	2.000000e-39
GCST000189_12	Protein quantitative trait loci	4.000000e-06
GCST000308_2	AIDS progression	6.000000e-08
GCST000322_1	Psoriasis	1.000000e-100
GCST000448_1	Follicular lymphoma	5.000000e-11
GCST000549_37	HIV-1 control	6.000000e-32
GCST000549_9	HIV-1 control	6.000000e-12
GCST000687_5	Nasopharyngeal carcinoma	3.000000e-33
GCST000692_1	Vitiligo	1.000000e-48
GCST000833_8	Psoriasis	4.000000e-214
GCST000835_2	Psoriatic arthritis	2.000000e-72
GCST000836_1	Psoriasis	4.000000e-32
GCST000863_6	HIV-1 control	3.000000e-35
GCST001137_2	White blood cell count	1.000000e-11
GCST001239_1	Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN)	2.000000e-08
GCST001401_4	Coronary heart disease	1.000000e-09
GCST001474_6	Hypothyroidism	1.000000e-08
GCST001679_6	Complement C3 and C4 levels	1.000000e-54
GCST001709_1	Atopic dermatitis	1.000000e-17
GCST001729_10	Crohn’s disease	5.000000e-28
GCST001737_23	Chronic obstructive pulmonary disease-related biomarkers	2.000000e-10
GCST001863_16	Beta-2 microglubulin plasma levels	8.000000e-08
GCST001863_5	Beta-2 microglubulin plasma levels	1.000000e-18
GCST001863_6	Beta-2 microglubulin plasma levels	1.000000e-06
GCST001863_8	Beta-2 microglubulin plasma levels	2.000000e-23
GCST001956_68	Height	4.000000e-12
GCST002083_20	Self-reported allergy	3.000000e-12
GCST002084_12	Allergic sensitization	4.000000e-08

EFO canonical traits (60, from GWAS)

EFO ID	Trait name
EFO:0004581	interleukin 18 measurement
EFO:0000180	HIV-1 infection
EFO:0004587	lymphocyte count
EFO:0004984	complement C4 measurement
EFO:0005081	surfactant protein D measurement
EFO:0005197	beta-2 microglobulin measurement
EFO:0005298	allergic sensitization measurement
EFO:0006319	HIV viral set point measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:1001494	psoriasis vulgaris
EFO:0007773	cutaneous psoriasis measurement
EFO:1001515	ovarian endometrioid carcinoma
EFO:1001516	ovarian serous carcinoma
EFO:0004458	C-reactive protein measurement
EFO:0004530	triglyceride measurement
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0007924	tonsillectomy risk measurement
EFO:0004318	smoking behavior
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0004509	hemoglobin measurement
EFO:0005090	basophil count
EFO:0007986	reticulocyte count
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0008380	perceived unattractiveness to mosquitos measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066967 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
HLA-C COPY-NEUTRAL LOSS OF HETEROZYGOSITY	Therapeutic Tumor Infiltrating Lymphocytes	Colorectal Cancer	Resistance	CIViC C	EID1899

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

PharmGKB clinical annotations

25 annotations.

Variant	Type	Level	Drugs	Phenotypes
HLA-C*01:02	Toxicity	2B	methazolamide	Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-C01:02, HLA-C02:02, HLA-C03:02, HLA-C04:01, HLA-C05:01, HLA-C06:02, HLA-C07:01, HLA-C08:01, HLA-C12:02, HLA-C14:02, HLA-C15:02, HLA-C16:01, HLA-C*17:01	Efficacy	3	peginterferon alfa-2b;ribavirin	Hepatitis C virus infection
HLA-C*03:02	Toxicity	2B	allopurinol	Severe Cutaneous Adverse Reactions;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-C*03:02	Toxicity	3	allopurinol	Exanthema
HLA-C*04:01	Toxicity	2B	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Exanthema;Hypersensitivity;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-C*04:03	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-C*04:06	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-C*04:07	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-C*05:01	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-C*05:09	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-C*06:02	Efficacy	3	ustekinumab	Psoriasis
HLA-C*06:02	Efficacy	3	methotrexate	Psoriasis
HLA-C06:02, HLA-C07:27, HLA-C*08:01	Toxicity	2B	sulfamethoxazole / trimethoprim	Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-C*07:02	Toxicity	3	sulfamethoxazole / trimethoprim	Respiratory Insufficiency
HLA-C*08:01	Toxicity	3	allopurinol	Drug Hypersensitivity;Stevens-Johnson Syndrome
HLA-C*08:01	Toxicity	3	carbamazepine	Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-C*08:01	Toxicity	3	phenytoin	Maculopapular Exanthema;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-C*12:03	Toxicity	3	infliximab	Drug-induced liver injury
HLA-C*14:03	Toxicity	3	ticlopidine	Toxic liver disease
HLA-C*14:03	Toxicity	3	acetaminophen
HLA-C*18:01	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
rs1049709	Toxicity	3	carboplatin;gemcitabine	Non-Small Cell Lung Carcinoma;Thrombocytopenia
rs12191877	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Psoriasis
rs9366772	Efficacy	3	allopurinol
rs9461684	Toxicity	3	nevirapine	HIV infectious disease

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9461684	HLA-C	3	3.25	1	nevirapine
rs1049709	HLA-C	3	2.50	1	carboplatin;gemcitabine

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
5.68	Kd	2073	nM	CHEMBL5653589
5.68	ED50	2073	nM	CHEMBL5653589
5.43	Kd	3749	nM	CHEMBL3752910
5.43	ED50	3749	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	2148516: Binding affinity to human HLA-C incubated for 45 mins by Kinobead based pull down assay	kd	2.0731	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148516: Binding affinity to human HLA-C incubated for 45 mins by Kinobead based pull down assay	kd	3.7494	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	7
sodium arsenite	affects binding, increases reaction, decreases expression, increases expression	3
Arsenic Trioxide	decreases expression, increases expression	3
Ozone	increases oxidation, increases abundance, increases expression, affects cotreatment	3
Tretinoin	increases expression	3
bisphenol A	affects expression	2
cobaltous chloride	increases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Vehicle Emissions	affects expression, increases reaction, affects cotreatment, increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Smoke	decreases expression, increases abundance	2
tert-Butylhydroperoxide	decreases expression	2
Particulate Matter	affects expression, increases reaction, decreases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
sulforaphane	decreases expression	1
beryllium sulfate	increases expression	1
ochratoxin A	increases acetylation, increases expression	1
bleomycetin	decreases expression	1
nivalenol	decreases expression	1
tamibarotene	increases expression	1
CD 437	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
CHEMBL5651558	Binding	Binding affinity to human HLA-C 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

5 cell lines: 2 induced pluripotent stem cell, 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C1FZ	585A1-C7 #3-1	Induced pluripotent stem cell	Male
CVCL_C1G0	585A1-C7 #3-3	Induced pluripotent stem cell	Male
CVCL_C7HQ	2A2 HLA-Cw3	Transformed cell line	Sex unspecified
CVCL_D3F0	SK-MEL-29.1.29	Cancer cell line	Male
CVCL_E0UD	Ubigene Hep G2 HLA-C KO	Cancer cell line	Male

Clinical trials (associated diseases)

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