KLRC2

Summary

KLRC2 (killer cell lectin like receptor C2, HGNC:6375) is a protein-coding gene on chromosome 12p13.2, encoding NKG2-C type II integral membrane protein (P26717). Immune activating receptor involved in self-nonself discrimination.

Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. NK cells preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation of NK cell function. The group, designated KLRC (NKG2) are expressed primarily in natural killer (NK) cells and encodes a family of transmembrane proteins characterized by a type II membrane orientation (extracellular C terminus) and the presence of a C-type lectin domain. The KLRC (NKG2) gene family is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed on NK cells. KLRC2 alternative splice variants have been described but their full-length nature has not been determined.

Source: NCBI Gene 3822 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_002260

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6375
Approved symbol	KLRC2
Name	killer cell lectin like receptor C2
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	NKG2-C, CD159c, NKG2C
Ensembl gene	ENSG00000205809
Ensembl biotype	protein_coding
OMIM	602891
Entrez	3822

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000381901, ENST00000381902, ENST00000535069, ENST00000536833, ENST00000537017

RefSeq mRNA: 1 — MANE Select: NM_002260 NM_002260

CCDS: CCDS31745

Canonical transcript exons

ENST00000381902 — 6 exons

Exon	Start	End
ENSE00001679551	10433791	10433942
ENSE00002290733	10430599	10431228
ENSE00003640794	10432106	10432206
ENSE00003654431	10434486	10434530
ENSE00003679837	10435312	10435410
ENSE00003914220	10435800	10436010

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 89.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1031 / max 15.0683, expressed in 38 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129525	0.1031	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	89.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.08	gold quality
amygdala	UBERON:0001876	77.97	gold quality
temporal lobe	UBERON:0001871	77.73	gold quality
hypothalamus	UBERON:0001898	75.75	gold quality
substantia nigra	UBERON:0002038	75.36	gold quality
Ammon’s horn	UBERON:0001954	74.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.99	gold quality
putamen	UBERON:0001874	72.37	gold quality
prefrontal cortex	UBERON:0000451	71.96	gold quality
anterior cingulate cortex	UBERON:0009835	71.93	gold quality
mucosa of transverse colon	UBERON:0004991	71.70	gold quality
nucleus accumbens	UBERON:0001882	71.45	gold quality
superior frontal gyrus	UBERON:0002661	71.22	gold quality
caudate nucleus	UBERON:0001873	69.92	gold quality
cerebral cortex	UBERON:0000956	69.18	gold quality
spleen	UBERON:0002106	69.07	gold quality
blood	UBERON:0000178	68.88	gold quality
frontal cortex	UBERON:0001870	68.87	gold quality
corpus callosum	UBERON:0002336	68.42	gold quality
right uterine tube	UBERON:0001302	67.84	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.70	gold quality
brain	UBERON:0000955	65.88	gold quality
endometrium	UBERON:0001295	65.49	gold quality
lower esophagus mucosa	UBERON:0035834	65.06	gold quality
primary visual cortex	UBERON:0002436	64.76	gold quality
right frontal lobe	UBERON:0002810	64.53	gold quality
Brodmann (1909) area 9	UBERON:0013540	62.90	gold quality
colonic epithelium	UBERON:0000397	61.70	gold quality
right lung	UBERON:0002167	60.60	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	739.26
E-CURD-95	yes	645.93
E-CURD-84	yes	262.83
E-CURD-77	yes	259.75
E-MTAB-6678	yes	30.19
E-HCAD-1	yes	28.99
E-CURD-122	yes	25.56
E-ANND-3	yes	12.14
E-MTAB-9067	yes	3.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting KLRC2, 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-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-1265	98.36	66.46	598
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-203B-5P	97.24	68.54	543
HSA-MIR-6718-5P	97.24	68.15	553

Literature-anchored findings (GeneRIF, showing 40)

• Common occurrence of NKG2-C gene deletion in the general population. (PMID:12618865)
• NKG2C is not essential for survival and reproduction, and is not associated with rheumatic diseases (PMID:14688071)
• strict gene regulatory mechanisms for CD94 and NKG2 gene expression on CD4+ cells (PMID:15550116)
• CD94/NKG2C may constitute an alternative T cell activation pathway capable of driving the expansion and triggering the effector functions of a cytotoxic T cell subset. (PMID:15940674)
• No significance was observed between the inhibitory (NKG2A) or activating (NKG2C and NKG2D) receptor genotypes and the presence of RF, ANA, or bony erosions in Rheumatoid arthritis. (PMID:18700876)
• KIR/HLA genotype and expression of NKG2C and NKG2D might play a significant role in regulating natural killer cell function and anti-cytomegalovirus immunity after kidney transplantation. (PMID:19032228)
• expression by Vdelta2+ T cells is lower in pregnant women (PMID:19395088)
• Although the percentages of both NKG2A- and NKG2C-positive NK cells were normal in preeclamptic women, the levels of NKG2A and NKG2C on NK cells were significantly up-regulated in these women (PMID:19694640)
• CD94/NKG2C might be involved in triggering cytotoxic lymphocytes in patients with Toxic epidermal necrolysis and Stevens-Johnson syndrome (PMID:20132973)
• NKG2A expression on gammadelta lymphoproliferative Disease of Large Granular Lymphocytes correlates with asymptomatic pathology, even in the presence of NKG2C coexpression. (PMID:20952657)
• Data indicate that the increased frequency of CD8(+) effector-memory T cells with activating NKR KIR2DS4, NKG2C and NKG2D, and cytotoxicity toward hematopoietic cell lines suggests involvement in bone marrow failure and clonal expansion in PNH. (PMID:21554925)
• The increased expression of NKG2C in HIV patients indicate that NKG2C is important in the defense against HIV infection and progression. (PMID:22074011)
• HCMV-infected NKG2C(+/+) children displayed higher absolute numbers of NKG2A(+) and total NK cells than NKG2C(+/-) individuals. (PMID:22965785)
• A significantly elevated proportion of ex vivo peripheral blood CD4 T cells, but not CD8 T cells or natural killer (NK) cells, from multiple sclerosis patients express NKG2C, which contributes to tissue injury. (PMID:23396942)
• NKG2Chi CD57hi natural killer cells are highly responsive to human cytomegalovirus-infected macrophages only in the presence of HCMV-specific antibodies, whereas they are functionally poor effectors of natural cytotoxicity. (PMID:23637420)
• NKG2Cnull does not seem to constitute a risk factor for HPV-induced cervical lesions. (PMID:23911737)
• coexpression of killer cell Ig-like receptor (KIR) and NKG2C on expanded NK cell subsets could be related to a functional contribution of KIR in cytomegalovirus infection (PMID:23918974)
• NKG2C zygosity influences CD94/NKG2C receptor function and the NK-cell compartment redistribution in response to human cytomegalovirus. (PMID:24030638)
• NKG2C receptor deletion and a functional polymorphism in its ligand HLA-E may play a role in psoriasis susceptibility (PMID:24079744)
• No difference in the prevalence of NKG2C deletion was observed. (PMID:24305414)
• NKG2C(hi)CD57+ NK cells respond specifically to acute infection with cytomegalovirus and not Epstein-Barr virus. (PMID:24740502)
• lack of expression of NKG2C may be associated with altered control of human cytomegalovirus infection in childhood (PMID:25150297)
• genetic polymorphism is not associated with nasopharyngeal carcinoma in China (PMID:25636564)
• Data suggest the proinflammatory potential of NKG2C(bright) NK cells. (PMID:25667418)
• HLA-E regulates NKG2C+ natural killer cell function through presentation of a restricted peptide repertoire (PMID:26382247)
• the data of this study extend the characterization of adaptive NK cell subsets that differentiate in response to human Cytomegalovirus, supporting a relationship between their distribution and NKG2C copy number (PMID:26994220)
• Assessment of NK cell repertoires in 60 NKG2C(-/-) donors revealed a broad range of NK cell populations displaying characteristic footprints of adaptive NK cells, including a terminally differentiated phenotype, functional reprogramming, and epigenetic remodeling of the interferon (IFN)-gamma promoter. (PMID:27117418)
• The new method offers the potential to use SNP arrays from genome wide association studies to study the frequency of KLRC2 deletion in other populations and its association with other diseases (PMID:27312142)
• a 16kb deletion encompassing the NKG2C gene is associated with lower carotid intimal media thickness values and higher humoral and T-cell responses to cytomegalovirus in renal transplant recipients (PMID:28987961)
• From all variants, only the NKG2Cwt/wt genotype was significantly associated with freedom from human cytomegalovirus viremia (P = .0002) and disease (P = .02), compared with the NKG2Cwt/del genotype. Thus, lung transplant recipients expressing the homozygous NKG2C wild type seem to have a selective advantage in human cytomegalovirus defense. (PMID:29220498)
• NKG2C copy number in the cord blood graft is an independent risk factor for Cytomegalovirus reactivation after double cor blood transplantation (PMID:30405633)
• the impact of both NKGC2 gene deletion and CCR5Delta32 gene variant on preeclampsia susceptibility, was examined. (PMID:30786156)
• Screening for the Biomarkers Associated with Myocardial Infarction by Bioinformatics Analysis. (PMID:31502863)
• expression of KLRC2 was significantly higher in brain tumor-initiating cells compared to normal brain controls (PMID:31556357)
• Phenotypic and Functional Analysis of Human NK Cell Subpopulations According to the Expression of FcepsilonRIgamma and NKG2C. (PMID:31867015)
• Adaptive NKG2C+ natural killer cells are related to exacerbations and nutritional abnormalities in COPD patients. (PMID:32131843)
• Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19. (PMID:33500568)
• Reduced expansion of CD94/NKG2C(+) NK cells in chronic lymphocytic leukemia and CLL-like monoclonal B-cell lymphocytosis is not related to increased human cytomegalovirus seronegativity or NKG2C deletions. (PMID:33615729)
• Surface NKG2C Identifies Differentiated alphabetaT-Cell Clones Expanded in Peripheral Blood. (PMID:33664730)
• Influence of NKG2C Genotypes on HIV Susceptibility and Viral Load Set Point. (PMID:34076484)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-193e13.5	ENSDARG00000052656
danio_rerio		ENSDARG00000074732
danio_rerio	si:dkey-26c10.5	ENSDARG00000088023
danio_rerio	si:ch211-170d8.8	ENSDARG00000090945
mus_musculus	Klri2	ENSMUSG00000043932
mus_musculus	Clec2m	ENSMUSG00000047720
mus_musculus	Klre1	ENSMUSG00000050241
mus_musculus	Klri1	ENSMUSG00000067610
mus_musculus	Klrh1	ENSMUSG00000071158
rattus_norvegicus	Klri1	ENSRNOG00000052803
rattus_norvegicus	Clec2m	ENSRNOG00000057254
rattus_norvegicus	Klri2	ENSRNOG00000057643
rattus_norvegicus	Klre1	ENSRNOG00000058714
rattus_norvegicus	Klrh1	ENSRNOG00000059182
drosophila_melanogaster	rgn	FBGN0261258
caenorhabditis_elegans		WBGENE00009156
caenorhabditis_elegans		WBGENE00013008

Paralogs (23): CLEC2D (ENSG00000069493), CD69 (ENSG00000110848), CLEC2B (ENSG00000110852), KLRB1 (ENSG00000111796), KLRD1 (ENSG00000134539), KLRC1 (ENSG00000134545), KLRG1 (ENSG00000139187), KLRF1 (ENSG00000150045), CLEC1A (ENSG00000150048), CLEC1B (ENSG00000165682), CLEC7A (ENSG00000172243), CLEC12A (ENSG00000172322), OLR1 (ENSG00000173391), KLRC4 (ENSG00000183542), CLEC2A (ENSG00000188393), KLRG2 (ENSG00000188883), CLEC9A (ENSG00000197992), KLRC3 (ENSG00000205810), KLRK1 (ENSG00000213809), CLEC2L (ENSG00000236279), CLEC12B (ENSG00000256660), KLRF2 (ENSG00000256797), CLEC5A (ENSG00000258227)

Protein

Protein identifiers

NKG2-C type II integral membrane protein — P26717 (reviewed: P26717)

Alternative names: CD159 antigen-like family member C, NK cell receptor C, NKG2-C-activating NK receptor

All UniProt accessions (5): F5H518, H0YFK4, H0YGY2, J3KPJ4, P26717

UniProt curated annotations — full annotation on UniProt →

Function. Immune activating receptor involved in self-nonself discrimination. In complex with KLRD1 on cytotoxic lymphocyte subsets, recognizes non-classical major histocompatibility (MHC) class Ib HLA-E loaded with signal sequence-derived peptides from non-classical MHC class Ib HLA-G molecules, likely playing a role in the generation and effector functions of adaptive natural killer (NK) cells and in maternal-fetal tolerance during pregnancy. Regulates the effector functions of terminally differentiated cytotoxic lymphocyte subsets, and in particular may play a role in adaptive NK cell response to viral infection. Upon HLA-E-peptide binding, transmits intracellular signals via the adapter protein TYROBP/DAP12, triggering the phosphorylation of proximal signaling molecules and cell activation.

Subunit / interactions. Heterodimer with KLRD1; disulfide-linked. KLRD1-KLRC2 receptor complex interacts with TYROBP homodimer; this interaction is necessary for the expression on the cell surface. KLRD1-KLRC2 receptor complex can bind with low affinity to HLA-E loaded with self-peptides derived from the signal sequence of classical MHC class Ia.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in NK cell subsets, in particular in adaptive CD57-positive NK cells (at protein level). Expressed in terminally differentiated cytotoxic gamma-delta T cells (at protein level). Expressed in alpha-beta T cells subsets (at protein level). KLRD1-KLRC1 and KLRD1-KLRC2 are differentially expressed within NK and T cell populations, with only minor subsets expressing both receptor complexes (at protein level).

Polymorphism. Two alleles are known. The sequence shown is that of allele NKG2-C*01.

RefSeq proteins (1): NP_002251* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR033992	NKR-like_CTLD	Domain
IPR050919	NKG2/CD94_NK_receptors	Family

Pfam: PF00059

UniProt features (19 total): disulfide bond 3, glycosylation site 3, topological domain 2, sequence variant 2, mutagenesis site 2, chain 1, sequence conflict 1, helix 1, transmembrane region 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2L35	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26717-F1	73.57	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (3): 117–128, 145–227, 206–219

Glycosylation sites (3): 100, 149, 178

Mutagenesis-validated functional residues (2):

Position	Phenotype
89	impairs the expression of klrd1-klrc2 on the cell surface.
165–168	increases the affinity for hla-e to a value similar to that observed for hla-e-klrd1-klrc1 complex.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2172127	DAP12 interactions
R-HSA-2424491	DAP12 signaling

MSigDB gene sets: 191 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INNATE_IMMUNE_SYSTEM, DORN_ADENOVIRUS_INFECTION_12HR_UP, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_DEGRANULATION, GOBP_REGULATION_OF_EXOCYTOSIS, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, STOSSI_RESPONSE_TO_ESTRADIOL, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_EXOCYTOSIS, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (12): stimulatory C-type lectin receptor signaling pathway (GO:0002223), natural killer cell mediated immunity (GO:0002228), adaptive immune response (GO:0002250), cellular defense response (GO:0006968), signal transduction (GO:0007165), regulation of natural killer cell activation (GO:0032814), positive regulation of natural killer cell degranulation (GO:0043323), positive regulation of natural killer cell mediated cytotoxicity (GO:0045954), immune system process (GO:0002376), immune response-regulating cell surface receptor signaling pathway (GO:0002768), regulation of natural killer cell mediated cytotoxicity (GO:0042269), innate immune response (GO:0045087)

GO Molecular Function (7): transmembrane signaling receptor activity (GO:0004888), MHC class I protein complex binding (GO:0023024), carbohydrate binding (GO:0030246), activating MHC class Ib receptor activity (GO:0062081), protein antigen binding (GO:1990405), protein binding (GO:0005515), MHC class Ib receptor activity (GO:0032394)

GO Cellular Component (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
DAP12 interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	2
natural killer cell mediated cytotoxicity	2
binding	2
innate immune response activating cell surface receptor signaling pathway	1
cellular response to lectin	1
lymphocyte mediated immunity	1
innate immune response	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
natural killer cell activation	1
regulation of lymphocyte activation	1
positive regulation of leukocyte degranulation	1
natural killer cell degranulation	1
regulation of natural killer cell degranulation	1
positive regulation of natural killer cell mediated cytotoxicity	1
positive regulation of leukocyte mediated cytotoxicity	1
positive regulation of natural killer cell mediated immunity	1
regulation of natural killer cell mediated cytotoxicity	1
biological_process	1
immune response-regulating signaling pathway	1
cell surface receptor signaling pathway	1
regulation of leukocyte mediated cytotoxicity	1
regulation of natural killer cell mediated immunity	1
defense response to symbiont	1
signaling receptor activity	1
MHC protein complex binding	1
MHC class Ib receptor activity	1
antigen binding	1
protein binding	1
transmembrane signaling receptor activity	1
MHC class Ib protein binding	1
immune receptor activity	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1

Protein interactions and networks

STRING

872 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLRC2	HLA-E	P13747	999
KLRC2	TYROBP	O43914	994
KLRC2	KLRD1	Q13241	986
KLRC2	NCR3	O14931	882
KLRC2	KIR2DL1	P43626	868
KLRC2	KLRB1	Q12918	864
KLRC2	CD226	Q15762	860
KLRC2	NCR1	O76036	813
KLRC2	B3GAT1	Q9P2W7	799
KLRC2	NCR2	O95944	791
KLRC2	KLRC3	Q07444	774
KLRC2	KIR2DL3	P43628	769
KLRC2	FCER1G	P30273	765
KLRC2	KIR3DL1	P43629	765
KLRC2	LILRB1	Q8NHL6	763

IntAct

7 interactions, top by confidence:

A	B	Type	Score
KLRC2	KLRD1	psi-mi:“MI:0407”(direct interaction)	0.610
KLRD1	HLA-E	psi-mi:“MI:0915”(physical association)	0.400
KLRC2	TYROBP	psi-mi:“MI:0915”(physical association)	0.400
KLRC2	FBP1	psi-mi:“MI:0915”(physical association)	0.370
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
KLRC2	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): KLRC2 (Affinity Capture-Western), NSUN3 (Affinity Capture-MS), SYNGR3 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), FZD2 (Affinity Capture-MS), GALNT13 (Affinity Capture-MS), PIGB (Affinity Capture-MS), SMIM11 (Affinity Capture-MS), FAM69A (Affinity Capture-MS), PXYLP1 (Affinity Capture-MS), KLRC2 (Affinity Capture-MS), TMEM39A (Affinity Capture-MS), LRP12 (Affinity Capture-MS), PIGG (Affinity Capture-MS)

ESM2 similar proteins: A4KWA5, A4KWA6, A4KWA8, B2KG20, D4AD02, O54709, O70215, P26717, P26718, P27471, P27811, P27814, P37217, P61252, Q07108, Q07444, Q0H8B9, Q149M0, Q504P2, Q5DT36, Q5DT37, Q5DT39, Q5M9I1, Q5RFR2, Q60652, Q60654, Q68D85, Q6QLQ4, Q6UXN8, Q80XD9, Q80ZC8, Q8C1T8, Q8MI05, Q8MJH1, Q8VBX4, Q8VI21, Q8WXI8, Q91V08, Q925N7, Q95MI4

Diamond homologs: A4KWA1, A4KWA5, A4KWA6, A4KWA8, O89335, P02706, P08290, P0C7M8, P0C7M9, P14371, P24721, P26715, P26717, P34927, P37217, Q07108, Q07444, Q0H8B9, Q0ZCA7, Q5M9I1, Q60660, Q6EIG7, Q6QLQ4, Q6UVW9, Q6UXN8, Q80XD9, Q8BWY2, Q8C1T8, Q8HY02, Q8HY10, Q8HY11, Q8HY12, Q8IUN9, Q8MIS5, Q8N1N0, Q8VI21, Q8WTT0, Q90WJ8, Q91V08, Q92478

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1004 predictions. Top by Δscore:

Variant	Effect	Δscore
12:10431132:A:AC	donor_gain	1.0000
12:10431133:C:CC	donor_gain	1.0000
12:10431133:CA:C	donor_gain	1.0000
12:10432104:A:AC	donor_gain	1.0000
12:10432105:C:CC	donor_gain	1.0000
12:10432108:A:AC	donor_gain	1.0000
12:10432109:T:C	donor_gain	1.0000
12:10432202:AATTT:A	acceptor_gain	1.0000
12:10432203:ATTT:A	acceptor_gain	1.0000
12:10432204:TTT:T	acceptor_gain	1.0000
12:10432205:TT:T	acceptor_gain	1.0000
12:10432207:C:CC	acceptor_gain	1.0000
12:10432207:C:T	acceptor_loss	1.0000
12:10432207:CTA:C	acceptor_loss	1.0000
12:10433891:CAA:C	acceptor_gain	1.0000
12:10434481:TGTA:T	donor_loss	1.0000
12:10434482:GTACC:G	donor_loss	1.0000
12:10434528:GGA:G	acceptor_gain	1.0000
12:10434531:C:CC	acceptor_gain	1.0000
12:10435310:A:AC	donor_gain	1.0000
12:10435311:C:CC	donor_gain	1.0000
12:10435794:TTTTA:T	donor_loss	1.0000
12:10435795:TTTA:T	donor_loss	1.0000
12:10435796:TTAC:T	donor_loss	1.0000
12:10435797:TACCT:T	donor_loss	1.0000
12:10435798:A:T	donor_loss	1.0000
12:10435799:C:CA	donor_loss	1.0000
12:10431133:CAATG:C	donor_gain	0.9900
12:10431227:TC:T	acceptor_gain	0.9900
12:10431228:CC:C	acceptor_gain	0.9900

AlphaMissense

1523 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:10433860:C:A	W138C	0.985
12:10433860:C:G	W138C	0.985
12:10433851:A:C	S141R	0.970
12:10433851:A:T	S141R	0.970
12:10433853:T:G	S141R	0.970
12:10432138:C:A	W184C	0.968
12:10432138:C:G	W184C	0.968
12:10433911:C:A	W121C	0.968
12:10433911:C:G	W121C	0.968
12:10432174:C:A	W172C	0.962
12:10432174:C:G	W172C	0.962
12:10433913:A:G	W121R	0.961
12:10433913:A:T	W121R	0.961
12:10431196:C:G	C206S	0.953
12:10431197:A:T	C206S	0.953
12:10431133:C:G	C227S	0.950
12:10431134:A:T	C227S	0.950
12:10432176:A:G	W172R	0.944
12:10432176:A:T	W172R	0.944
12:10432140:A:G	W184R	0.942
12:10432140:A:T	W184R	0.942
12:10432160:C:G	R177P	0.937
12:10433839:A:C	C145W	0.936
12:10433840:C:G	C145S	0.936
12:10433841:A:T	C145S	0.936
12:10431157:C:G	C219S	0.933
12:10431158:A:T	C219S	0.933
12:10431132:A:C	C227W	0.927
12:10433840:C:T	C145Y	0.921
12:10433841:A:G	C145R	0.919

dbSNP variants (sampled 300 via entrez): RS1000733034 (12:10434142 T>C), RS1002336991 (12:10430733 GT>G), RS1005212643 (12:10437162 G>A), RS1005738016 (12:10436189 T>A,C), RS1006808993 (12:10433907 T>C), RS1006881150 (12:10432960 T>C), RS1012021465 (12:10435501 A>G), RS1013693124 (12:10431102 G>A,C,T), RS1013781299 (12:10431632 G>A), RS1017474486 (12:10433063 G>A), RS1018480423 (12:10437168 T>C), RS1018513101 (12:10436213 G>A,C), RS1024656262 (12:10434347 CAT>C), RS1025173644 (12:10435510 G>A), RS1025743720 (12:10436085 T>A)

Disease associations

OMIM: gene MIM:602891 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004633_24	Neutrophil percentage of white cells	3.000000e-11
GCST008572_2	Composite immunoglobulin trait (IgA/IgG)	9.000000e-09
GCST90002388_422	Lymphocyte count	2.000000e-09
GCST90002393_410	Monocyte count	1.000000e-43
GCST90002394_363	Monocyte percentage of white cells	9.000000e-42
GCST90002399_331	Neutrophil percentage of white cells	1.000000e-19
GCST90002400_75	Plateletcrit	3.000000e-17
GCST90002403_217	Red blood cell count	9.000000e-18
GCST90011898_7	Alanine aminotransferase levels	2.000000e-12
GCST90011899_73	Aspartate aminotransferase levels	5.000000e-18
GCST90013405_141	Liver enzyme levels (alanine transaminase)	1.000000e-19

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004587	lymphocyte count
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0007985	platelet crit
EFO:0004305	erythrocyte count
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — CD molecules

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Raloxifene Hydrochloride	increases expression, decreases expression, affects expression, affects cotreatment, affects reaction	2
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	increases expression	1
Fulvestrant	increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Methotrexate	affects response to substance	1
Tamoxifen	affects cotreatment, increases expression	1
Dronabinol	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Fenretinide	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	affects expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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