KLRG2

Summary

KLRG2 (killer cell lectin like receptor G2, HGNC:24778) is a protein-coding gene on chromosome 7q34, encoding Killer cell lectin-like receptor subfamily G member 2 (A4D1S0).

Predicted to enable carbohydrate binding activity. Predicted to be located in membrane.

Source: NCBI Gene 346689 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_198508

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24778
Approved symbol	KLRG2
Name	killer cell lectin like receptor G2
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	FLJ44186, CLEC15B
Ensembl gene	ENSG00000188883
Ensembl biotype	protein_coding
Entrez	346689

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000340940, ENST00000393039, ENST00000869133, ENST00000915763, ENST00000941714

RefSeq mRNA: 1 — MANE Select: NM_198508 NM_198508

CCDS: CCDS5854

Canonical transcript exons

ENST00000340940 — 5 exons

Exon	Start	End
ENSE00001365507	139482886	139483673
ENSE00001366605	139480146	139480247
ENSE00001384582	139479627	139479772
ENSE00001386821	139454111	139454214
ENSE00001869781	139452690	139453707

Expression profiles

Bgee: expression breadth broad, 69 present calls, max score 77.75.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0463 / max 123.2056, expressed in 312 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86495	0.6245	232
86496	0.4217	193

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.75	gold quality
sural nerve	UBERON:0015488	74.23	gold quality
tibial nerve	UBERON:0001323	71.41	gold quality
right lobe of thyroid gland	UBERON:0001119	71.40	gold quality
lower esophagus mucosa	UBERON:0035834	71.18	gold quality
left lobe of thyroid gland	UBERON:0001120	70.87	gold quality
thyroid gland	UBERON:0002046	70.27	gold quality
esophagus mucosa	UBERON:0002469	69.87	gold quality
metanephros cortex	UBERON:0010533	67.09	gold quality
skin of leg	UBERON:0001511	66.44	gold quality
zone of skin	UBERON:0000014	66.01	gold quality
skin of abdomen	UBERON:0001416	65.63	gold quality
saliva-secreting gland	UBERON:0001044	64.07	gold quality
minor salivary gland	UBERON:0001830	63.23	gold quality
placenta	UBERON:0001987	62.37	gold quality
upper lobe of left lung	UBERON:0008952	59.08	gold quality
adult mammalian kidney	UBERON:0000082	58.16	gold quality
lung	UBERON:0002048	56.60	gold quality
tonsil	UBERON:0002372	56.42	gold quality
right lung	UBERON:0002167	56.28	gold quality
kidney	UBERON:0002113	55.24	gold quality
vagina	UBERON:0000996	54.00	gold quality
esophagus	UBERON:0001043	51.87	gold quality
cortex of kidney	UBERON:0001225	48.08	gold quality
colonic epithelium	UBERON:0000397	45.41	gold quality
thoracic mammary gland	UBERON:0005200	44.63	gold quality
ectocervix	UBERON:0012249	44.62	gold quality
uterine cervix	UBERON:0000002	42.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	42.45	gold quality
bone marrow cell	CL:0002092	42.38	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting KLRG2, 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-4267	99.96	66.53	2368
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-631	97.05	66.93	602

Literature-anchored findings (GeneRIF, showing 1)

• Genetic variants in the gene KLRG2 may affect Gleason score at diagnosis and hence the aggressiveness of prostate cancer. (PMID:20945404)

Cross-species orthologs

9 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	Klrg2	ENSMUSG00000071537
rattus_norvegicus	Klrg2	ENSRNOG00000006814
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), 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 2 — A4D1S0 (reviewed: A4D1S0)

Alternative names: C-type lectin domain family 15 member B

All UniProt accessions (1): A4D1S0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
A4D1S0-1	1	yes
A4D1S0-2	2

RefSeq proteins (1): NP_940910* (*=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
IPR043318	KLRG2	Family

Pfam: PF00059

UniProt features (17 total): compositionally biased region 4, disulfide bond 2, splice variant 2, sequence variant 2, region of interest 2, chain 1, transmembrane region 1, sequence conflict 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A4D1S0-F1	59.08	0.15

Functional residue map

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

Post-translational modifications (1): 158

Disulfide bonds (2): 321–404, 383–396

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MYC_UP.V1_UP, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, STK33_DN, STK33_SKM_DN, RYBP_TARGET_GENES, ZNF592_TARGET_GENES, ZSCAN31_TARGET_GENES, GSE13306_RA_VS_UNTREATED_TCONV_DN, GSE8685_IL2_ACT_IL2_STARVED_VS_IL21_ACT_IL2_STARVED_CD4_TCELL_DN, GSE7596_AKT_TRANSD_VS_CTRL_CD4_TCONV_WITH_TGFB_DN, GSE7568_CTRL_VS_24H_TGFB_TREATED_MACROPHAGES_WITH_IL4_AND_DEXAMETHASONE_DN

GO Biological Process (0):

GO Molecular Function (1): carbohydrate binding (GO:0030246)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLRG2	UBN2	Q6ZU65	657
KLRG2	FCGRT	P55899	546
KLRG2	TNFRSF4	P43489	534
KLRG2	IL1RN	P18510	526
KLRG2	TNFRSF8	P28908	518
KLRG2	PRAMEF18	Q5VWM3	510
KLRG2	SPATA31A6	Q5VVP1	474
KLRG2	RWDD2B	P57060	463
KLRG2	C7orf33	Q8WU49	433
KLRG2	FCER1G	P30273	430
KLRG2	FMC1	Q96HJ9	419
KLRG2	C1orf105	O95561	417
KLRG2	IL2RA	P01589	410
KLRG2	PRADC1	Q9BSG0	400
KLRG2	CCDC160	A6NGH7	399

IntAct

50 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GLRX3	KLRG2	psi-mi:“MI:0914”(association)	0.640
KLRG2	GLRX3	psi-mi:“MI:0914”(association)	0.640
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
ST8SIA3	KLRG2	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
FAM189B	KLRG2	psi-mi:“MI:0914”(association)	0.350
PCDHA12	KLRG2	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
PCDHA8	TMEM223	psi-mi:“MI:0914”(association)	0.350
KRTCAP3	SLC22A23	psi-mi:“MI:0914”(association)	0.350
CLRN2	FAM234B	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
CD8B	KLRG2	psi-mi:“MI:0914”(association)	0.350
TMEM74	KLRG2	psi-mi:“MI:0914”(association)	0.350

BioGRID (158): KLRG2 (Affinity Capture-MS), KLRG2 (Affinity Capture-MS), FGFRL1 (Affinity Capture-MS), EPHB1 (Affinity Capture-MS), ZDHHC6 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), WNT11 (Affinity Capture-MS), GLRX3 (Affinity Capture-MS), F5 (Affinity Capture-MS), APBA2 (Affinity Capture-MS), KLRG2 (Affinity Capture-MS), STBD1 (Affinity Capture-MS), WNT5B (Affinity Capture-MS), UBA52 (Affinity Capture-MS), LRRC4B (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2Z4LIS9, A2VE02, A4D1S0, A5PKC7, A5PL33, A6H7B4, A6NEL2, A6QP24, A6QPM6, A8MTW9, A8MYA2, D3ZAQ5, D4AAA5, E7EW31, O75474, O75638, O89113, O94850, P0C7X2, P14652, P50617, P70339, Q2KIS6, Q3UN58, Q5JPB2, Q5VZ46, Q6GQX2, Q6NZ36, Q6ZSJ8, Q6ZW13, Q76NI1, Q7TNS8, Q80TS7, Q86UU5, Q8IWN7, Q8N6K4, Q8N944

Diamond homologs: A4D1S0, O88713, P0C7M8, P0C7M9, Q0ZCA7, Q3UM83, Q92478, Q96E93, P14370, Q07444, Q5KU26, Q64335, Q9PSM5, A4KWA6, A4KWA8, D3W0D1, P02706, P06734, P07307, P08290, P14151, P22897, P24721, P37217, Q07108, Q0ZUP0, Q49BZ4, Q5M9I1, Q63378, Q6UVW9, Q863H3, Q8C1T8, Q8MI05, Q8VBX4, Q8VI21, Q91V08, Q95235, Q95237, Q9D676, Q9NZS2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

725 predictions. Top by Δscore:

Variant	Effect	Δscore
7:139454110:CAG:C	donor_gain	1.0000
7:139480140:CCATA:C	donor_loss	1.0000
7:139480141:CATAC:C	donor_loss	1.0000
7:139480142:ATACC:A	donor_loss	1.0000
7:139480143:TAC:T	donor_loss	1.0000
7:139480144:AC:A	donor_loss	1.0000
7:139480243:TAGCC:T	acceptor_gain	1.0000
7:139480244:AGCC:A	acceptor_gain	1.0000
7:139480245:GCC:G	acceptor_gain	1.0000
7:139480246:CC:C	acceptor_gain	1.0000
7:139480246:CCC:C	acceptor_gain	1.0000
7:139480247:CC:C	acceptor_gain	1.0000
7:139480248:C:CC	acceptor_gain	1.0000
7:139480248:CT:C	acceptor_loss	1.0000
7:139480249:T:C	acceptor_loss	1.0000
7:139453706:GT:G	acceptor_gain	0.9900
7:139453706:GTCT:G	acceptor_loss	0.9900
7:139453707:TCTG:T	acceptor_loss	0.9900
7:139453708:C:CC	acceptor_gain	0.9900
7:139453708:CT:C	acceptor_loss	0.9900
7:139453709:T:C	acceptor_loss	0.9900
7:139454109:A:AC	donor_gain	0.9900
7:139454110:C:CC	donor_gain	0.9900
7:139480145:CCTG:C	donor_gain	0.9900
7:139480248:C:T	acceptor_gain	0.9900
7:139480254:C:CT	acceptor_gain	0.9900
7:139480255:G:T	acceptor_gain	0.9900
7:139480260:C:CT	acceptor_gain	0.9900
7:139482879:CACT:C	donor_loss	0.9900
7:139482880:ACTC:A	donor_loss	0.9900

AlphaMissense

2586 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:139479690:C:A	W314C	0.997
7:139479690:C:G	W314C	0.997
7:139479741:C:A	W297C	0.997
7:139479741:C:G	W297C	0.997
7:139454146:C:A	W358C	0.995
7:139454146:C:G	W358C	0.995
7:139454176:C:A	W348C	0.995
7:139454176:C:G	W348C	0.995
7:139479670:C:G	C321S	0.991
7:139479671:A:T	C321S	0.991
7:139479669:G:C	C321W	0.990
7:139479670:C:T	C321Y	0.990
7:139453606:C:G	C404S	0.986
7:139453607:A:T	C404S	0.986
7:139454140:C:A	W360C	0.986
7:139454140:C:G	W360C	0.986
7:139454148:A:G	W358R	0.986
7:139454148:A:T	W358R	0.986
7:139479681:G:C	S317R	0.986
7:139479681:G:T	S317R	0.986
7:139479683:T:G	S317R	0.986
7:139453611:C:A	W402C	0.983
7:139453611:C:G	W402C	0.983
7:139453605:A:C	C404W	0.982
7:139453606:C:T	C404Y	0.982
7:139454178:A:G	W348R	0.982
7:139454178:A:T	W348R	0.982
7:139479672:G:C	F320L	0.982
7:139479672:G:T	F320L	0.982
7:139479674:A:G	F320L	0.982

dbSNP variants (sampled 300 via entrez): RS1000006699 (7:139442696 A>C), RS1000022805 (7:139443022 C>T), RS1000089679 (7:139430775 G>A), RS1000117203 (7:139483100 C>A,G,T), RS1000137855 (7:139455340 G>T), RS1000151988 (7:139464272 G>A), RS1000185993 (7:139442992 G>T), RS1000187217 (7:139477256 A>C), RS1000199013 (7:139463755 G>A), RS1000200882 (7:139472404 T>C), RS1000239582 (7:139468526 T>C,G), RS1000375181 (7:139458611 T>C), RS1000425447 (7:139436675 C>A), RS1000597570 (7:139478685 G>A), RS1000654002 (7:139463570 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	decreases expression	2
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
3,4-dichloroaniline	decreases expression	1
butyraldehyde	increases expression	1
hydroquinone	decreases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diuron	decreases expression	1
Estradiol	decreases expression	1
Formaldehyde	decreases expression	1
Phthalic Acids	increases methylation	1
Sodium Dodecyl Sulfate	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin M1	decreases expression	1

Clinical trials (associated diseases)

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