KLRB1

Summary

KLRB1 (killer cell lectin like receptor B1, HGNC:6373) is a protein-coding gene on chromosome 12p13.31, encoding Killer cell lectin-like receptor subfamily B member 1 (Q12918). Plays an inhibitory role on natural killer (NK) cells cytotoxicity.

Natural killer (NK) cells are lymphocytes that mediate cytotoxicity and secrete cytokines after immune stimulation. Several genes of the C-type lectin superfamily, including the rodent NKRP1 family of glycoproteins, are expressed by NK cells and may be involved in the regulation of NK cell function. The KLRB1 protein contains an extracellular domain with several motifs characteristic of C-type lectins, a transmembrane domain, and a cytoplasmic domain. The KLRB1 protein is classified as a type II membrane protein because it has an external C terminus.

Source: NCBI Gene 3820 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_002258

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6373
Approved symbol	KLRB1
Name	killer cell lectin like receptor B1
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	CD161, NKR-P1, NKR-P1A, hNKR-P1A, CLEC5B
Ensembl gene	ENSG00000111796
Ensembl biotype	protein_coding
OMIM	602890
Entrez	3820

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000229402

RefSeq mRNA: 1 — MANE Select: NM_002258 NM_002258

CCDS: CCDS8601

Canonical transcript exons

ENST00000229402 — 6 exons

Exon	Start	End
ENSE00000718460	9598046	9598161
ENSE00000718465	9598499	9598653
ENSE00000718471	9599767	9599841
ENSE00000718477	9601501	9601599
ENSE00000821814	9607755	9607916
ENSE00001238849	9594551	9595421

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 98.07.

FANTOM5 (CAGE): breadth broad, TPM avg 9.5551 / max 1926.7707, expressed in 199 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129415	9.5551	199

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.07	gold quality
ileal mucosa	UBERON:0000331	89.91	gold quality
jejunal mucosa	UBERON:0000399	89.78	gold quality
blood	UBERON:0000178	88.77	gold quality
spleen	UBERON:0002106	87.07	gold quality
vermiform appendix	UBERON:0001154	87.02	gold quality
lymph node	UBERON:0000029	86.55	gold quality
caecum	UBERON:0001153	84.22	gold quality
amniotic fluid	UBERON:0000173	83.87	gold quality
bone marrow	UBERON:0002371	83.76	gold quality
colonic epithelium	UBERON:0000397	83.45	gold quality
gall bladder	UBERON:0002110	83.00	gold quality
epithelium of nasopharynx	UBERON:0001951	80.53	gold quality
nasopharynx	UBERON:0001728	80.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.21	gold quality
rectum	UBERON:0001052	80.11	gold quality
duodenum	UBERON:0002114	79.25	gold quality
bone marrow cell	CL:0002092	79.00	gold quality
leukocyte	CL:0000738	77.99	gold quality
palpebral conjunctiva	UBERON:0001812	77.50	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.14	gold quality
mucosa of sigmoid colon	UBERON:0004993	76.77	gold quality
small intestine	UBERON:0002108	76.52	gold quality
mononuclear cell	CL:0000842	76.12	gold quality
colonic mucosa	UBERON:0000317	75.80	gold quality
monocyte	CL:0000576	75.40	gold quality
superficial temporal artery	UBERON:0001614	75.05	gold quality
mucosa of transverse colon	UBERON:0004991	74.82	gold quality
pylorus	UBERON:0001166	74.14	silver quality
upper lobe of left lung	UBERON:0008952	73.53	gold quality

Single-cell (SCXA)

Detected in 42 experiment(s), a significant marker in 36.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	7145.73
E-MTAB-7407	yes	5835.94
E-MTAB-8142	yes	5707.86
E-CURD-46	yes	5232.13
E-HCAD-10	yes	3486.28
E-MTAB-9906	yes	3463.30
E-CURD-112	yes	3430.44
E-MTAB-8221	yes	3400.16
E-HCAD-32	yes	3111.65
E-MTAB-9467	yes	3083.94
E-HCAD-36	yes	3041.96
E-HCAD-4	yes	3018.11
E-MTAB-6701	yes	3010.28
E-CURD-88	yes	3005.64
E-HCAD-1	yes	2879.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RORC

Literature-anchored findings (GeneRIF, showing 40)

• Engagement of CD161 on NK cells with LLT1 expressed on target cells inhibited NK cell-mediated cytotoxicity and IFN-gamma secretion. LLT1/CD161 interaction in the presence of a TCR signal enhanced IFN-gamma production by T cells (PMID:16339512)
• LLT1 on target cells can inhibit NK cytotoxicity via interactions with CD161. LLT1 activates NFAT-GFP reporter cells expressing a CD3zeta-CD161 chimeric receptor; reciprocally, reporter cells with a CD3zeta-LLT1 chimeric receptor are stimulated by CD161 (PMID:16339513)
• define a novel signal transduction pathway for the CD161 (NKR-P1A) receptor and provide fresh insights into NK and NKT cell biology (PMID:16455998)
• NKRPIA binds to the alphaGal epitope of mouse laminin. Moreover, exposing NAcLac by removal of alphaGal resulted in an increase in binding. (PMID:16925668)
• The results of this work demonstrated that the transcription of the KLRB1 was suppressed in tumor tissues in 68% patients with nonsmall-lung-cancer (p < 0.0001) and 57% patients with esophageal squamous-cell carcinoma (p = 0.0003). (PMID:18159636)
• Expression of CD161 indicates a unique pattern of T cell differentiation that might help elucidate the mechanisms of hepatitis c virus immunity and pathogenesis. (PMID:18219672)
• Interactions between NKR-P1A on NK cells and LLT1 on target cells inhibit NK cell-mediated cytotoxicity and cytokine production (PMID:18453569)
• PILAR signaling through CD161 supports CD3 antibody-dependent and antigen-specific T-cell proliferation by increasing the expression of antiapoptotic Bcl-xL and induces secretion of T helper type 1 cytokines (PMID:18550855)
• all IL-17-producing cells originate from CD161(+) naive CD4(+) T cells of umbilical cord blood, as well as of the postnatal thymus (PMID:18663128)
• These data identify CD161(+) CD4 T cells as a resting Th17 pool that can be activated by IL-23 and mediate destructive tissue inflammation. (PMID:19273624)
• There is a significant positive correlation of CD161 expression with NK cytotoxicity. (PMID:19711124)
• CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. (PMID:20133607)
• Results reveal a functional relationship between CD161 expression and NK cell cytotoxicity as well as NK cell reactivity to glycans and mutated citrullinated vimentin, providing new insight into the pathogenesis of rheumatoid arthritis. (PMID:20359956)
• marker of IL-17-producing T-cell subsets (PMID:20486123)
• cytokines induce significant up-regulation of NKG2D expression while only IFN-alpha induced significant up-regulation of CD161 (PMID:20800424)
• Th17 cells from patients with head and neck squamous cell carcinoma downregulate the Th17 cell surface receptor CD161 in peripheral blood as well as in primary tumors and especially in metastatic lymph nodes. (PMID:21570678)
• Molecular basis for LLT1 protein recognition by human CD161 protein (NKRP1A/KLRB1). (PMID:21572041)
• our results indicate that KLRB1 gene expression is altered in multiple sclerosis (MS) and likely to be involved in the pathogenesis of the disease, whereas rs4763655 in KLRB1 seems to have a minimal role in MS susceptibility. (PMID:21610746)
• expression defines IL-25- and IL-33-responsive type 2 innate lymphoid cells (PMID:21909091)
• LLT1 and CD161 have roles in modulating immune responses to pathogens; and interferon-gamma contributes to modulate immune responses (PMID:21930700)
• CD161+CD4+ T lymphocytes, differentiated into Th1 cells and Th17 cells, are involved in the pathogenesis of giant cell arteritis and polymyalgia rheumatica. (PMID:22833233)
• Here we present a distinct population of Treg, defined by CD161 expression, as the major source of FoxP3+ Treg-derived proinflammatory cytokines. (PMID:23355538)
• The fraction of CD161high T cells is significantly higher in cerebrospinal fluid of patients with multiple sclerosis in relapse than those of controls. (PMID:23599932)
• CD161+ Th17/CD161+ Th1-cell imbalance may contribute to the development of rheumatoid arthritis. (PMID:24392804)
• Elevated expression of CD69 and CD161 on NK cells can be considered as immunological risk markers in RSA and IVF failure. (PMID:24975965)
• CD39 and CD161 modulate human Th17 responses in CD through alterations in purinergic nucleotide-mediated responses and ASM catalytic bioactivity, respectively. (PMID:25172498)
• Expression of CD161 hence identifies a transcriptional and functional phenotype, shared across human T lymphocytes. (PMID:25437561)
• these results suggest that the CD8(+) subset of CD161(+) T cells may have regulatory effects and that they provide a basis for predicting the occurrence of aGVHD after allogeneic SCT. (PMID:25543092)
• percentage of alveolar CD3(+)CD161(+) T lymphocytes that produced IFN-gamma/IL-17 was significantly higher than those in the peripheral blood (PMID:25906076)
• We suggest modulation of human Th17 responsiveness by CD39 and CD161 and describe novel molecular mechanisms integrating elements of both extracellular nucleotide and sphingolipid homeostasis–{REVIEW} (PMID:26059452)
• CD161-expressing Th17 cells are enriched at sites of autoinflammation, are highly proinflammatory and resistant to Treg-mediated suppression suggesting their important pathogenic role in rheumatoid arthritis. (PMID:26062995)
• A novel population of highly functional, memory CD8+ T cells enriched within the gut expresses CD161. (PMID:26220166)
• The regulation of NK cell homeostasis and activation apparently differs between carriers of the CC and TT variant of CD161. (PMID:26309225)
• CD161 expression levels were reduced in some NK and T cell subpopulations of systemic lupus erythematosus (SLE) patients, suggesting possible important role of CD161 and CD161-expressing immune cells in the SLE pathogenesis. (PMID:26590595)
• Our results reveal that in combination with IGRAs, CD161-based indices provide a novel, fast diagnostic solution addressing the limitation of current tuberculosis diagnostics. (PMID:26643453)
• these data suggest that LLT1-CD161 interactions play a novel and important role in B cell maturation within the Germinal center in humans. (PMID:26829983)
• Blocking LLT1-NKRP1A interaction will make prostate cancer cells susceptible to killing by NK cells, suggesting a therapeutic option for treatment of prostate cancer. (PMID:27626681)
• A subset of virus-specific CD161(+) T cells selectively express the multidrug transporter MDR1 and are resistant to chemotherapy in acute myeloid leukemia. (PMID:27821506)
• Purified soluble NKR-P1 is homogeneous, deglycosylatable, crystallizable and monomeric in solution, as shown by size-exclusion chromatography, multi-angle light scattering and analytical ultracentrifugation. (PMID:28757467)
• The killer cell lectin-like receptor B1 (KLRB1) 503T>C polymorphism (rs1135816) and acute rejection after liver transplantation. (PMID:29111570)

Cross-species orthologs

16 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	Klrb1f	ENSMUSG00000030154
mus_musculus	Klrb1c	ENSMUSG00000030325
mus_musculus	Klrb1a	ENSMUSG00000030361
mus_musculus	Klrb1b	ENSMUSG00000079298
mus_musculus	Klrb1	ENSMUSG00000079299
rattus_norvegicus	Klrb1b	ENSRNOG00000007310
rattus_norvegicus	Klrb1c	ENSRNOG00000007811
rattus_norvegicus	Klrb1	ENSRNOG00000057410
rattus_norvegicus	Klrb1b	ENSRNOG00000071746
drosophila_melanogaster	rgn	FBGN0261258
caenorhabditis_elegans		WBGENE00009156
caenorhabditis_elegans		WBGENE00013008

Paralogs (23): CLEC2D (ENSG00000069493), CD69 (ENSG00000110848), CLEC2B (ENSG00000110852), 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), KLRC2 (ENSG00000205809), KLRC3 (ENSG00000205810), KLRK1 (ENSG00000213809), CLEC2L (ENSG00000236279), CLEC12B (ENSG00000256660), KLRF2 (ENSG00000256797), CLEC5A (ENSG00000258227)

Protein

Protein identifiers

Killer cell lectin-like receptor subfamily B member 1 — Q12918 (reviewed: Q12918)

Alternative names: C-type lectin domain family 5 member B, HNKR-P1a, Natural killer cell surface protein P1A

All UniProt accessions (1): Q12918

UniProt curated annotations — full annotation on UniProt →

Function. Plays an inhibitory role on natural killer (NK) cells cytotoxicity. Activation results in specific acid sphingomyelinase/SMPD1 stimulation with subsequent marked elevation of intracellular ceramide. Activation also leads to AKT1/PKB and RPS6KA1/RSK1 kinases stimulation as well as markedly enhanced T-cell proliferation induced by anti-CD3. Acts as a lectin that binds to the terminal carbohydrate Gal-alpha(1,3)Gal epitope as well as to the N-acetyllactosamine epitope. Also binds to CLEC2D/LLT1 as a ligand and inhibits NK cell-mediated cytotoxicity as well as interferon-gamma secretion in target cells.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with acid sphingomyelinase/SMPD1.

Subcellular location. Membrane.

Tissue specificity. Expressed in a subset of NK cells predominantly in intestinal epithelium and liver. Detected in peripheral blood T-cells and preferentially in adult T-cells with a memory antigenic phenotype.

Post-translational modifications. N-glycosylated. Contains sialic acid residues.

Induction. By IL12/interleukin-12 in NK cells.

RefSeq proteins (1): NP_002249* (*=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
IPR051527	KLR_subfamily_B	Family

Pfam: PF00059

UniProt features (21 total): strand 8, disulfide bond 3, topological domain 2, helix 2, chain 1, turn 1, transmembrane region 1, domain 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5MGR	X-RAY DIFFRACTION	1.8
5MGS	X-RAY DIFFRACTION	1.9
5MGT	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12918-F1	81.43	0.58

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): 94–105, 122–210, 189–202

Glycosylation sites (1): 157

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 180 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GNF2_ZAP70, GOLDRATH_ANTIGEN_RESPONSE, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_205, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY

GO Biological Process (2): cell surface receptor signaling pathway (GO:0007166), regulation of natural killer cell mediated cytotoxicity (GO:0042269)

GO Molecular Function (4): transmembrane signaling receptor activity (GO:0004888), carbohydrate binding (GO:0030246), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
signal transduction	1
regulation of leukocyte mediated cytotoxicity	1
regulation of natural killer cell mediated immunity	1
natural killer cell mediated cytotoxicity	1
signaling receptor activity	1
molecular transducer activity	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1704 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLRB1	CLEC2D	Q9UHP7	999
KLRB1	CD69	Q07108	905
KLRB1	SMPD1	P17405	898
KLRB1	CCR6	P51684	892
KLRB1	HLA-E	P13747	883
KLRB1	CCRL2	O00421	873
KLRB1	KLRC2	P26717	864
KLRB1	CD1D	P15813	846
KLRB1	DCLK3	Q9C098	828
KLRB1	IL7R	P16871	800
KLRB1	FCGR3A	P08637	799
KLRB1	CLEC2A	Q6UVW9	799
KLRB1	FCGR3B	O75015	798
KLRB1	CD8A	P01732	797
KLRB1	IFNG	P01579	794

IntAct

7 interactions, top by confidence:

A	B	Type	Score
KLRB1	CLEC2D	psi-mi:“MI:0407”(direct interaction)	0.440
CLEC2D	KLRB1	psi-mi:“MI:0407”(direct interaction)	0.440
KLRB1	HOXD12	psi-mi:“MI:0914”(association)	0.350
KLRB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
rpoB	KLRB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (55): HOXD12 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), GAS6 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), SLC7A3 (Affinity Capture-MS), SFXN3 (Affinity Capture-MS), SPNS1 (Affinity Capture-MS), ARFGEF2 (Affinity Capture-MS), ARFGEF1 (Affinity Capture-MS), MFSD3 (Affinity Capture-MS), MROH1 (Affinity Capture-MS), ND5 (Affinity Capture-MS), CDC45 (Affinity Capture-MS), ARL5B (Affinity Capture-MS), PEX3 (Affinity Capture-MS)

ESM2 similar proteins: A4KWA1, D3W0D1, D4AD02, O54709, O70215, O88713, P20937, P26715, P27471, P27811, P27812, P27814, Q07108, Q0ZUP0, Q0ZUP1, Q12918, Q149M0, Q2HXU8, Q2NL33, Q5NKN2, Q5NKN4, Q5QGZ9, Q60652, Q60654, Q63378, Q64335, Q67EQ0, Q6QLQ4, Q6UXN8, Q80XD9, Q80ZC8, Q8BRU4, Q8BWY2, Q8C1T8, Q8CJC7, Q8MI05, Q8NC01, Q8VD98, Q8VI21, Q95MI5

Diamond homologs: A4KWA1, A4KWA6, P20693, P20937, P21063, P24765, P27471, P27811, P27812, P27814, P79391, Q0ZUP0, Q0ZUP1, Q12918, Q49BZ4, Q5NKN2, Q5NKN4, Q60651, Q60654, Q61830, Q63378, Q67EQ1, Q8HY06, Q8HY10, Q8HY11, Q8HY12, Q8HYC0, Q8VD98, Q8WTT0, Q90WJ8, Q91ZW8, Q925N7, Q95LG1, Q99JB4, Q9GLF3, Q9GME8, Q9H2X3, Q9JKF4, Q9NY25, Q9QZ15

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

689 predictions. Top by Δscore:

Variant	Effect	Δscore
12:9598080:T:TA	donor_gain	1.0000
12:9598506:T:TA	donor_gain	1.0000
12:9598512:T:C	donor_gain	1.0000
12:9599842:C:CC	acceptor_gain	1.0000
12:9599849:A:C	acceptor_gain	1.0000
12:9607753:AC:A	donor_gain	1.0000
12:9607754:CC:C	donor_gain	1.0000
12:9598044:A:AC	donor_gain	0.9900
12:9598045:C:CC	donor_gain	0.9900
12:9598045:CT:C	donor_gain	0.9900
12:9598494:TTTAC:T	donor_loss	0.9900
12:9598495:TTA:T	donor_loss	0.9900
12:9598496:TA:T	donor_loss	0.9900
12:9598497:A:AC	donor_gain	0.9900
12:9598497:A:AG	donor_loss	0.9900
12:9598498:C:CC	donor_gain	0.9900
12:9598650:CTCT:C	acceptor_gain	0.9900
12:9598654:C:CC	acceptor_gain	0.9900
12:9598659:G:GC	acceptor_gain	0.9900
12:9599837:TGTCA:T	acceptor_gain	0.9900
12:9599840:CA:C	acceptor_gain	0.9900
12:9599845:G:GC	acceptor_gain	0.9900
12:9599849:A:AC	acceptor_gain	0.9900
12:9607750:CTTA:C	donor_loss	0.9900
12:9607751:TTA:T	donor_loss	0.9900
12:9607753:A:AC	donor_gain	0.9900
12:9607753:ACC:A	donor_gain	0.9900
12:9607753:ACCC:A	donor_gain	0.9900
12:9607754:C:CC	donor_gain	0.9900
12:9607754:CCC:C	donor_gain	0.9900

AlphaMissense

1459 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:9598568:C:A	W115C	0.991
12:9598568:C:G	W115C	0.991
12:9598075:C:A	W167C	0.984
12:9598075:C:G	W167C	0.984
12:9598081:C:A	W165C	0.981
12:9598081:C:G	W165C	0.981
12:9598559:A:C	S118R	0.980
12:9598559:A:T	S118R	0.980
12:9598561:T:G	S118R	0.980
12:9598077:A:G	W167R	0.978
12:9598077:A:T	W167R	0.978
12:9598120:A:C	F152L	0.973
12:9598120:A:T	F152L	0.973
12:9598122:A:G	F152L	0.973
12:9598548:C:G	C122S	0.973
12:9598549:A:T	C122S	0.973
12:9598619:C:A	W98C	0.973
12:9598619:C:G	W98C	0.973
12:9595323:C:G	C210S	0.971
12:9595324:A:T	C210S	0.971
12:9598534:A:G	S127P	0.970
12:9595320:T:G	Q211P	0.968
12:9595375:A:G	S193P	0.968
12:9598547:A:C	C122W	0.968
12:9595386:C:G	C189S	0.966
12:9595387:A:T	C189S	0.966
12:9598083:A:G	W165R	0.966
12:9598083:A:T	W165R	0.966
12:9598117:C:A	W153C	0.964
12:9598117:C:G	W153C	0.964

dbSNP variants (sampled 300 via entrez): RS1000173054 (12:9601146 A>C,G), RS1000207497 (12:9596111 A>G), RS1000305114 (12:9609239 G>C), RS1000414141 (12:9603714 A>G), RS1000509580 (12:9606079 C>G), RS1000730690 (12:9596583 G>A,C), RS1000964546 (12:9605969 T>G), RS1001255936 (12:9596807 G>A), RS1001476861 (12:9609611 G>A), RS1001626951 (12:9604001 C>T), RS1001759220 (12:9609905 T>C), RS1001800240 (12:9609064 C>A), RS1001868862 (12:9609659 A>C,G), RS1002365484 (12:9608312 T>G), RS1002395922 (12:9602666 T>C)

Disease associations

OMIM: gene MIM:602890 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_1377	Blood protein levels	2.000000e-16
GCST009700_8	Obesity (extreme)	7.000000e-06
GCST010396_70	Gut microbiota (bacterial taxa, hurdle binary method)	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
triazacyclononane	affects binding, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
Microplastics	decreases expression, increases abundance	1
Amphotericin B	increases expression	1
Aspirin	increases expression	1
Cadmium	decreases expression	1
Copper	affects binding, affects cotreatment	1
Estradiol	affects cotreatment, decreases expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	decreases expression	1
Polyethylene Terephthalates	increases abundance, decreases expression	1
Progesterone	affects cotreatment, decreases expression	1
Zinc	affects expression	1
Antirheumatic Agents	decreases expression	1
Coordination Complexes	affects binding	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8JD	Abcam HCT 116 KLRB1 KO	Cancer cell line	Male
CVCL_B9LN	Abcam A-549 KLRB1 KO	Cancer cell line	Male
CVCL_D2G0	Abcam MCF-7 KLRB1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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