KLRG1

Summary

KLRG1 (killer cell lectin like receptor G1, HGNC:6380) is a protein-coding gene on chromosome 12p13.31, encoding Killer cell lectin-like receptor subfamily G member 1 (Q96E93). Plays an inhibitory role on natural killer (NK) cells and T-cell functions upon binding to their non-MHC ligands.

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. The protein encoded by this gene belongs to the killer cell lectin-like receptor (KLR) family, which is a group of transmembrane proteins preferentially expressed in NK cells. Studies in mice suggested that the expression of this gene may be regulated by MHC class I molecules.

Source: NCBI Gene 10219 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 247 total
• Phenotypes (HPO): 12
• MANE Select transcript: NM_005810

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6380
Approved symbol	KLRG1
Name	killer cell lectin like receptor G1
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	MAFA, 2F1, MAFA-L, CLEC15A
Ensembl gene	ENSG00000139187
Ensembl biotype	protein_coding
OMIM	604874
Entrez	10219

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000266551, ENST00000356986, ENST00000538029, ENST00000539240, ENST00000541957, ENST00000543895, ENST00000544226

RefSeq mRNA: 5 — MANE Select: NM_005810 NM_001329099, NM_001329101, NM_001329102, NM_001329103, NM_005810

CCDS: CCDS8599, CCDS86277

Canonical transcript exons

ENST00000356986 — 5 exons

Exon	Start	End
ENSE00001431472	9009426	9010751
ENSE00002251276	8989546	8989717
ENSE00003618631	9008975	9009075
ENSE00003630746	8992206	8992310
ENSE00003683401	8995119	8995288

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 90.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4397 / max 1163.9005, expressed in 987 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124020	5.4740	248
124019	2.6360	889
124029	1.5268	187
124021	0.2224	56
124023	0.1615	45
124022	0.1342	39
124024	0.1107	35
124025	0.0517	32
124028	0.0492	32
124027	0.0464	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	90.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.95	gold quality
blood	UBERON:0000178	81.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.54	gold quality
colonic epithelium	UBERON:0000397	79.75	gold quality
lymph node	UBERON:0000029	76.98	gold quality
spleen	UBERON:0002106	76.52	gold quality
ileal mucosa	UBERON:0000331	76.02	gold quality
tibialis anterior	UBERON:0001385	74.69	silver quality
pancreatic ductal cell	CL:0002079	74.64	silver quality
ganglionic eminence	UBERON:0004023	73.66	gold quality
gall bladder	UBERON:0002110	73.45	gold quality
bone marrow cell	CL:0002092	73.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.04	gold quality
leukocyte	CL:0000738	72.83	gold quality
cortical plate	UBERON:0005343	72.69	gold quality
ventricular zone	UBERON:0003053	72.36	gold quality
bone marrow	UBERON:0002371	71.69	gold quality
omental fat pad	UBERON:0010414	71.68	gold quality
peritoneum	UBERON:0002358	71.60	gold quality
apex of heart	UBERON:0002098	71.39	gold quality
adipose tissue of abdominal region	UBERON:0007808	71.01	gold quality
mononuclear cell	CL:0000842	70.83	gold quality
right atrium auricular region	UBERON:0006631	70.62	gold quality
secondary oocyte	CL:0000655	70.57	silver quality
monocyte	CL:0000576	70.26	gold quality
muscle of leg	UBERON:0001383	69.72	gold quality
cerebellar hemisphere	UBERON:0002245	69.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	69.38	gold quality
gastrocnemius	UBERON:0001388	69.34	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	767.92
E-HCAD-32	yes	629.34
E-GEOD-70580	yes	457.12
E-HCAD-4	yes	79.27
E-HCAD-1	yes	52.98
E-CURD-122	yes	52.77
E-CURD-46	yes	11.19
E-ANND-3	yes	8.83
E-MTAB-9801	yes	4.87
E-MTAB-6379	no	1752.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TBX21, XBP1

miRNA regulators (miRDB)

56 targeting KLRG1, 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-188-3P	100.00	68.76	1240
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-92B-5P	99.36	63.29	110
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-4667-3P	99.26	65.45	1608

Literature-anchored findings (GeneRIF, showing 40)

• human effector and memory T cells expressing KLRG1 lack proliferative capacity (PMID:12393723)
• KLRG1 expression discriminated between cord blood T cells that differed in their post-thymic expansion rate (PMID:15368283)
• KLRG1 is expressed in the overwhelming majority of CD8-positive T cells specific for epitopes of cytomegalovirus or Epstein- Barr virus during the latent stage; a slightly lower KLRG1 expression level is observed in HIV-specific T8 cells. (PMID:15879103)
• virus-specific CD8+ T cells are mostly KLRG1+ in chronic viral infections (human immunodeficiency virus, cytomegalovirus, and Epstein-Barr virus) but not in resolved infection (influenza virus) (PMID:16140789)
• peripheral HCV-specific CD8+ T cells were CD127+ and KLRG1-; Intrahepatic virus-specific CD8+ T cells displayed significantly reduced levels of CD127 expression but similar levels of KLRG1 expression compared to the peripheral blood. (PMID:17079288)
• study demonstrates that E-cadherin represents a ligand for KLRG1 and that ligation of KLRG1 by E-cadherin inhibited effector cell functions of polyclonal NK cells (PMID:17617594)
• Certain aspects of the dysfunction seen in highly differentiated CD8+ T cells are maintained actively by KLRG1 signaling. KLRG1 blockade enhances Akt (ser(473)) phosphorylation & T-cell-receptor-induced proliferation of CD8+CD28-CD27- T cells. (PMID:19406987)
• E-cadherin may coengage KLRG1 and alpha(E)beta(7) and that KLRG1 overcomes its exceptionally weak affinity for cadherins through multipoint attachment to target cells, resulting in inhibitory signaling. (PMID:19604491)
• Expression of MafA analyzed in conditional knockout mice during embryonic development is the first specific marker of a subpopulation of “early c-ret” positive sensory neurons. (PMID:20213756)
• Results demonstrated a substantial reduction in both CD94- and KLRG1- expressing CD3(-)CD56(+) NK cells with increased age. (PMID:20394788)
• trastuzumab-mediated antibody-dependent cellular cytotoxicity was markedly enhanced by KLRG1-negative peripheral blood mononuclear cells (PMID:21387286)
• cytomegalovirus positive had lower proportions of NK-cells expressing inhibitory receptors (KLRG1 and CD158a) (PMID:21933704)
• The lower inhibitory capacity of mKLRG1 compared with hKLRG1 can thus be rationalized by a decreased proportion of dimeric entities, which can be pinpointed to a single amino acid. (PMID:22684915)
• More T cells were KLRG1+ in the synovial fluid of patients with spondylarthritis/rheumatoid arthritis than crystal arthritis or controls. Those T cells were more functionally active, and migrated towards the synovial fluid of SpA/RA patients. (PMID:23740233)
• These results indicate that KLRG1 negatively regulates natural killer cell numbers and functions via the Akt pathway, thus providing a novel marker and therapeutic target for hepatitis C virus infection. (PMID:23966413)
• Data indicate that increments of CD8 + effector memory T cells in human and mouse chronic lymphocytic leukemia (CLL)(Emu-TCL1 model) were due to an expansion of the inhibitory killer cell lectin-like receptor G1 (KLRG1) expressing cellular subset. (PMID:24022692)
• KLRG1 was overexpressed on CD4(+) T cells. (PMID:24337749)
• high levels of TfRs such as those found on activated lymphocytes were found to be associated with decreased KLRG1 inhibitory function, indicating that TfRs may sequester KLRG1 from interacting with cadherins. (PMID:24752778)
• This finding provides a rationale for the reciprocal expression of KLRG1 and CD103 in different CD8(+) T-cell subsets. (PMID:26014037)
• Demonstrate the presence of increased KLRG1-expressing T-cells in tuberculosis-treated individuals, and present KLRG1 as a marker of decreased human T-cell proliferation following BCG-vaccination. (PMID:26750180)
• The results suggest that a disease-associated SNP located within the 3’UTR of KLRG1 directly interferes with miR-584-5p binding, allowing for KLRG1 mRNA differential accumulation, which in turn may contribute to pathogenesis of pemphigus. (PMID:27424220)
• KLRG1 might contribute to the impaired antitumor immunity of memory T cells in tumor microenvironment (PMID:27557510)
• Killer Cell Lectin-like Receptor G1 Inhibits NK Cell Function through Activation of Adenosine 5’-Monophosphate-Activated Protein Kinase (PMID:27566818)
• high coexpression of PD-1, TIGIT, and KLRG-1 on MiHA-reactive CD8(+) T cells was associated with relapse after allo-SCT. Taken together, these findings indicate that MiHA-specific CD8(+) T cells of relapsed patients have a distinctive coinhibitory expression signature compared with patients who stay in remission. (PMID:29197680)
• This study delineated the profile of KLRG1+CD4+ T cells in patients with tuberculosis and suggests that M. tuberculosis infection drives CD4+ T cells to acquire increased effector function in a terminally differentiated state. (PMID:29373700)
• KLRG1+ natural killer cells exert a novel antifibrotic function in chronic hepatitis B. (PMID:30905683)
• Tuberculosis-associated immune reconstitution inflammatory syndrome is preceded by a high level of exhausted (KLRG1+PD-1+) CD8hi T cells. (PMID:31022273)
• The presence of KLRG1 was identified on pathogenic inclusion body myositis muscle invading T cells. (PMID:31326977)
• The findings provide new insights into the roles of KLRG1 and CD57 expression in human T cells, forming the basis for a refined model of CD8(+) T cell differentiation during Cytomegalovirus infection. (PMID:31554693)
• KLRG1 and CD103 Expressions Define Distinct Intestinal Tissue-Resident Memory CD8 T Cell Subsets Modulated in Crohn’s Disease. (PMID:32477365)
• An atlas of immune cell exhaustion in HIV-infected individuals revealed by single-cell transcriptomics. (PMID:32954948)
• Expression and Clinical Significance of KLRG1 and 2B4 on T Cells in the Peripheral Blood and Tumour of Patients with Cervical Cancer. (PMID:33401997)
• Development of Antihuman Killer Cell Lectin-Like Receptor Subfamily G Member 1 Monoclonal Antibodies for Flow Cytometry. (PMID:33900816)
• Functions and clinical significance of KLRG1 in the development of lung adenocarcinoma and immunotherapy. (PMID:34187403)
• Expression of KLRG1 and CD127 defines distinct CD8(+) subsets that differentially impact patient outcome in follicular lymphoma. (PMID:34226281)
• Increased expression of TIGIT and KLRG1 correlates with impaired CD56(bright) NK cell immunity in HPV16-related cervical intraepithelial neoplasia. (PMID:35413989)
• N-cadherin protects oral cancer cells from NK cell killing in the circulation by inducing NK cell functional exhaustion via the KLRG1 receptor. (PMID:36096526)
• KLRG1 is reduced on NK cells in SLE patients, inversely correlates with disease activity and is modulated by hydroxychloroquine in vitro. (PMID:36876466)
• KLRG1 expression on natural killer cells is associated with HIV persistence, and its targeting promotes the reduction of the viral reservoir. (PMID:37741278)
• Expression of HLA-DR and KLRG1 enhances the cytotoxic potential and cytokine secretion capacity of CD3[+] T cells in tuberculosis patients. (PMID:38652959)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Klrg1	ENSMUSG00000030114
rattus_norvegicus	Klrg1	ENSRNOG00000014918
caenorhabditis_elegans		WBGENE00009156

Paralogs (23): CLEC2D (ENSG00000069493), CD69 (ENSG00000110848), CLEC2B (ENSG00000110852), KLRB1 (ENSG00000111796), KLRD1 (ENSG00000134539), KLRC1 (ENSG00000134545), 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 G member 1 — Q96E93 (reviewed: Q96E93)

Alternative names: C-type lectin domain family 15 member A, ITIM-containing receptor MAFA-L, MAFA-like receptor, Mast cell function-associated antigen

All UniProt accessions (3): Q96E93, F5H207, F5H8E3

UniProt curated annotations — full annotation on UniProt →

Function. Plays an inhibitory role on natural killer (NK) cells and T-cell functions upon binding to their non-MHC ligands. May mediate missing self recognition by binding to a highly conserved site on classical cadherins, enabling it to monitor expression of E-cadherin/CDH1, N-cadherin/CDH2 and R-cadherin/CDH4 on target cells.

Subunit / interactions. Forms a monomer and homodimer; disulfide-linked. Interacts (via ITIM motif) with PTPN11 and INPP5D.

Subcellular location. Cell membrane.

Tissue specificity. Expressed specifically on natural killer (NK) cells and T-cells, mainly CD8 T-cells.

Domain organisation. Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. Upon phosphorylation of ITIM motif KLRG1 associates with the two phosphatases PTPN11 and INPP5D.

Induction. By pathogens and viruses infections.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96E93-1	1	yes
Q96E93-2	2

RefSeq proteins (5): NP_001316028, NP_001316030, NP_001316031, NP_001316032, NP_005801* (*=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
IPR042190	KLRG1	Family

Pfam: PF00059

UniProt features (27 total): strand 6, glycosylation site 4, disulfide bond 3, sequence conflict 3, topological domain 2, helix 2, chain 1, splice variant 1, sequence variant 1, transmembrane region 1, turn 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3FF7	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96E93-F1	81.91	0.66

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): 75–86, 103–184, 163–176

Glycosylation sites (4): 65, 97, 137, 150

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: 339 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_INSULIN_SECRETION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, MEF2_02, GOBP_CELL_CELL_SIGNALING, GOLDRATH_ANTIGEN_RESPONSE, NKX62_Q2, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SECRETION, GOBP_SIGNAL_RELEASE, AACTTT_UNKNOWN

GO Biological Process (5): inflammatory response (GO:0006954), cellular defense response (GO:0006968), cell surface receptor signaling pathway (GO:0007166), innate immune response (GO:0045087), immune system process (GO:0002376)

GO Molecular Function (3): carbohydrate binding (GO:0030246), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), 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
defense response	2
binding	2
signal transduction	1
immune response	1
defense response to symbiont	1
biological_process	1
molecular transducer activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1292 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLRG1	CDH1	P12830	992
KLRG1	CDH2	P19022	943
KLRG1	CDH17	Q12864	929
KLRG1	IL7R	P16871	852
KLRG1	ITGAE	P38570	821
KLRG1	CD27	P26842	812
KLRG1	CDH4	P55283	805
KLRG1	SELL	P14151	802
KLRG1	CD8A	P01732	788
KLRG1	ITGAM	P11215	785
KLRG1	EOMES	O95936	781
KLRG1	TBX21	Q9UL17	774
KLRG1	CD160	O95971	772
KLRG1	IFNG	P01579	763
KLRG1	PDCD1	Q15116	744

IntAct

30 interactions, top by confidence:

A	B	Type	Score
LEPROTL1	KLRG1	psi-mi:“MI:0915”(physical association)	0.670
KLRG1	LEPROTL1	psi-mi:“MI:0915”(physical association)	0.670
KLRG1	SYNE4	psi-mi:“MI:0915”(physical association)	0.560
SYNE4	KLRG1	psi-mi:“MI:0915”(physical association)	0.560
KLRG1	GPX8	psi-mi:“MI:0915”(physical association)	0.560
KLRC1	KLRG1	psi-mi:“MI:0915”(physical association)	0.560
GPR42	KLRG1	psi-mi:“MI:0915”(physical association)	0.560
ARL13B	KLRG1	psi-mi:“MI:0915”(physical association)	0.560
MRM1	KLRG1	psi-mi:“MI:0915”(physical association)	0.560
GPX8	KLRG1	psi-mi:“MI:0915”(physical association)	0.560
KLRG1	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
KLRG1	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
CDH1	KLRG1	psi-mi:“MI:0407”(direct interaction)	0.440
LEPROTL1	KLRG1	psi-mi:“MI:0915”(physical association)	0.000
KLRG1	KLRC1	psi-mi:“MI:0915”(physical association)	0.000
KLRG1	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
KLRG1	MRM1	psi-mi:“MI:0915”(physical association)	0.000
KLRG1	GPR42	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): SYNE4 (Two-hybrid), LEPROTL1 (Two-hybrid), KLRG1 (Two-hybrid), KLRG1 (Two-hybrid), KLRG1 (Two-hybrid), GPX8 (Two-hybrid), ARL13B (Two-hybrid), MRM1 (Two-hybrid)

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: A4D1S0, O88713, P0C7M8, P0C7M9, Q0ZCA7, Q3UM83, Q92478, Q96E93, O35778, O54707, O54709, O70156, O70215, P21063, P24765, P26715, P26717, Q0VCS6, Q13241, Q149M0, Q2HXU8, Q2NL33, Q38HS3, Q6EIG7, Q6UXN8, Q80ZC8, Q863H3, Q8BWY2, Q8CJC7, Q8MHY9, Q8MJH1, Q95MI5, Q9EQ09, Q9GLF5, Q9MZ41, Q9MZK6, Q9MZK9, Q9UHP7, Q9ULY5, P14370

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	189
Likely benign	26
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

733 predictions. Top by Δscore:

Variant	Effect	Δscore
12:8992309:GG:G	donor_gain	1.0000
12:8992310:GG:G	donor_gain	1.0000
12:8989718:G:GG	donor_gain	0.9900
12:8990211:GT:G	acceptor_gain	0.9900
12:8992201:TGCA:T	acceptor_gain	0.9900
12:8992202:GCA:G	acceptor_loss	0.9900
12:8992202:GCAG:G	acceptor_gain	0.9900
12:8992203:CAGC:C	acceptor_gain	0.9900
12:8992203:CAGCT:C	acceptor_loss	0.9900
12:8992204:A:AG	acceptor_gain	0.9900
12:8992205:G:GG	acceptor_gain	0.9900
12:8992205:G:T	acceptor_gain	0.9900
12:8992205:GCTT:G	acceptor_gain	0.9900
12:8992205:GCTTC:G	acceptor_gain	0.9900
12:8992311:G:C	donor_loss	0.9900
12:8992311:G:GG	donor_gain	0.9900
12:8992312:T:G	donor_loss	0.9900
12:9008961:A:AG	acceptor_gain	0.9900
12:9008962:A:G	acceptor_gain	0.9900
12:8990210:A:AG	acceptor_gain	0.9800
12:8990211:G:GG	acceptor_gain	0.9800
12:8992200:TTGCA:T	acceptor_gain	0.9800
12:8992204:A:AT	acceptor_gain	0.9800
12:8992205:GC:G	acceptor_gain	0.9800
12:8992313:AAGT:A	donor_loss	0.9800
12:8989716:AT:A	donor_gain	0.9700
12:8990341:GACAG:G	donor_gain	0.9700
12:8992205:GCT:G	acceptor_gain	0.9700
12:8992308:AGG:A	donor_gain	0.9700
12:8992309:GGG:G	donor_gain	0.9700

AlphaMissense

1239 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:8995219:G:C	W96C	0.989
12:8995219:G:T	W96C	0.989
12:9009046:G:C	W143C	0.987
12:9009046:G:T	W143C	0.987
12:8995226:A:C	S99R	0.984
12:8995228:T:A	S99R	0.984
12:8995228:T:G	S99R	0.984
12:9009040:G:C	W141C	0.982
12:9009040:G:T	W141C	0.982
12:8995168:G:C	W79C	0.978
12:8995168:G:T	W79C	0.978
12:9009013:G:C	W132C	0.975
12:9009013:G:T	W132C	0.975
12:9009038:T:A	W141R	0.975
12:9009038:T:C	W141R	0.975
12:8995240:C:G	C103W	0.967
12:9009044:T:A	W143R	0.962
12:9009044:T:C	W143R	0.962
12:8995238:T:A	C103S	0.960
12:8995239:G:C	C103S	0.960
12:9009458:G:A	G164D	0.959
12:8995217:T:A	W96R	0.957
12:8995217:T:C	W96R	0.957
12:8995239:G:A	C103Y	0.957
12:9009021:T:C	L135P	0.955
12:9009454:T:A	C163S	0.953
12:9009455:G:C	C163S	0.953
12:8995227:G:T	S99I	0.951
12:9009460:G:C	A165P	0.948
12:8995238:T:C	C103R	0.946

dbSNP variants (sampled 300 via entrez): RS1000037815 (12:9030224 T>C), RS1000045190 (12:9173936 C>A), RS1000046307 (12:9080657 A>G), RS1000068960 (12:8993241 A>G), RS1000078744 (12:9080338 G>A), RS1000090934 (12:9034274 T>G), RS1000114989 (12:8985344 A>G,T), RS1000128485 (12:8975630 C>T), RS1000129083 (12:9176739 T>A), RS1000149673 (12:9126607 T>G), RS1000161319 (12:9018837 C>T), RS1000174967 (12:9085195 C>T), RS1000187059 (12:9167587 G>A), RS1000194632 (12:9022956 C>G,T), RS1000212841 (12:9066247 T>C)

Disease associations

OMIM: gene MIM:604874 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000519	Developmental cataract
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0001087	Developmental glaucoma
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0005978	Type II diabetes mellitus
HP:0008194	Multiple pancreatic beta-cell adenomas
HP:0011462	Young adult onset
HP:0012197	Insulinoma
HP:0040270	Impaired glucose tolerance

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004062_1	Sjögren’s syndrome	6.000000e-07
GCST010002_207	Refractive error	1.000000e-40
GCST90000025_1020	Appendicular lean mass	5.000000e-23
GCST90014023_1	Type 1 diabetes	5.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs669	A2M, KLRG1	3	4.00	1	Enzymes

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	decreases reaction, decreases expression	2
GSK-J4	decreases expression	1
Esketamine	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression, affects cotreatment	1
trichostatin A	decreases reaction, affects expression	1
hydroxyhydroquinone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Nickel	affects expression, decreases reaction	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
beta-Naphthoflavone	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A3S6	SEES3-1V human KLRG1, clone1	Embryonic stem cell	Male
CVCL_A3S7	SEES3-1V human KLRG1, clone2	Embryonic stem cell	Male
CVCL_A3S8	SEES3-1V human KLRG1, clone3	Embryonic stem cell	Male
CVCL_C5D7	CHO/PA-hKLRG1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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