NKG7

Summary

NKG7 (natural killer cell granule protein 7, HGNC:7830) is a protein-coding gene on chromosome 19q13.41, encoding Protein NKG7 (Q16617). Regulates cytotoxic granule exocytosis in effector lymphocytes, thus acting as a critical mediator of inflammation in a broad range of infectious and non-infectious diseases.

Involved in defense response to protozoan. Located in cytolytic granule membrane and plasma membrane.

Source: NCBI Gene 4818 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_005601

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7830
Approved symbol	NKG7
Name	natural killer cell granule protein 7
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	GIG1, GMP-17
Ensembl gene	ENSG00000105374
Ensembl biotype	protein_coding
OMIM	606008
Entrez	4818

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000221978, ENST00000593572, ENST00000595157, ENST00000595217, ENST00000600427, ENST00000861190

RefSeq mRNA: 2 — MANE Select: NM_005601 NM_001363693, NM_005601

CCDS: CCDS12830, CCDS86796

Canonical transcript exons

ENST00000221978 — 4 exons

Exon	Start	End
ENSE00000722337	51372161	51372307
ENSE00000722348	51371940	51372074
ENSE00001125194	51371620	51371835
ENSE00003182449	51372379	51372654

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 99.84.

FANTOM5 (CAGE): breadth broad, TPM avg 46.7668 / max 7007.0750, expressed in 411 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182396	44.4199	397
182395	1.9561	126
182397	0.2168	77
182394	0.1201	44
182393	0.0538	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	99.76	gold quality
blood	UBERON:0000178	98.02	gold quality
bone marrow	UBERON:0002371	96.35	gold quality
spleen	UBERON:0002106	96.27	gold quality
bone marrow cell	CL:0002092	95.95	gold quality
leukocyte	CL:0000738	92.83	gold quality
mononuclear cell	CL:0000842	92.17	gold quality
monocyte	CL:0000576	91.95	gold quality
trabecular bone tissue	UBERON:0002483	91.72	gold quality
lymph node	UBERON:0000029	89.76	gold quality
decidua	UBERON:0002450	89.22	gold quality
upper lobe of left lung	UBERON:0008952	88.89	gold quality
right lung	UBERON:0002167	88.70	gold quality
gall bladder	UBERON:0002110	88.64	gold quality
upper lobe of lung	UBERON:0008948	87.16	gold quality
right lobe of liver	UBERON:0001114	86.40	gold quality
apex of heart	UBERON:0002098	86.34	gold quality
vermiform appendix	UBERON:0001154	84.25	gold quality
periodontal ligament	UBERON:0008266	81.10	gold quality
mucosa of transverse colon	UBERON:0004991	81.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.90	gold quality
omental fat pad	UBERON:0010414	79.67	gold quality
lung	UBERON:0002048	79.62	gold quality
peritoneum	UBERON:0002358	79.56	gold quality
adipose tissue of abdominal region	UBERON:0007808	79.17	gold quality
right coronary artery	UBERON:0001625	77.89	gold quality
caecum	UBERON:0001153	77.63	gold quality
rectum	UBERON:0001052	77.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.66	gold quality

Single-cell (SCXA)

Detected in 56 experiment(s), a significant marker in 54.

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	10604.09
E-MTAB-6505	yes	10366.41
E-CURD-55	yes	10323.95
E-MTAB-9467	yes	9922.16
E-MTAB-6701	yes	9633.75
E-MTAB-6653	yes	9501.66
E-GEOD-149689	yes	8885.05
E-MTAB-8207	yes	8702.98
E-HCAD-4	yes	8421.31
E-MTAB-10553	yes	7976.29
E-GEOD-139324	yes	7894.23
E-CURD-120	yes	7544.96
E-CURD-84	yes	7356.80
E-HCAD-15	yes	7165.98
E-CURD-122	yes	7068.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting NKG7, 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-3185	99.99	68.12	1959
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-7112-5P	99.59	65.76	104
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-574-3P	92.35	64.27	41
HSA-MIR-6743-3P	80.87	61.31	50

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nkg7	ENSMUSG00000004612
rattus_norvegicus	Nkg7	ENSRNOG00000017749

Paralogs (10): LIM2 (ENSG00000105370), PMP22 (ENSG00000109099), GSG1 (ENSG00000111305), EMP1 (ENSG00000134531), EMP3 (ENSG00000142227), CLDND2 (ENSG00000160318), GSG1L (ENSG00000169181), TMEM202 (ENSG00000187806), EMP2 (ENSG00000213853), GSG1L2 (ENSG00000214978)

Protein

Protein identifiers

Protein NKG7 — Q16617 (reviewed: Q16617)

Alternative names: G-CSF-induced gene 1 protein, Granule membrane protein of 17 kDa, Natural killer cell protein 7, p15-TIA-1

All UniProt accessions (5): Q16617, A0A0B4J2A6, M0QXT6, M0R0D6, M0R3G3

UniProt curated annotations — full annotation on UniProt →

Function. Regulates cytotoxic granule exocytosis in effector lymphocytes, thus acting as a critical mediator of inflammation in a broad range of infectious and non-infectious diseases. Essential for cytotoxic degranulation of natural killer (NK) cells and CD8(+) T-cells and for the activation of CD4(+) T-cells following infection. Plays a critical role in CD8(+) T-cell and NK cell-mediated cytolysis of target cells and contributes to the cytolytic activity via the perforin/granzyme pathway by enhancing exocytosis of LAMP1-carrying lytic granules. Contributes to NK cell-mediated control of cancer metastasis.

Subcellular location. Cell membrane. Cytolytic granule membrane.

Tissue specificity. Expressed in activated T-cells, in kidney, liver, lung and pancreas. Not expressed in brain, heart, or skeletal muscle. Expressed at high levels in TCR gamma delta-expressing CTL clones, and in some TCR alpha beta-expressing CTL clones (both CD4+ and CD8+), but is not expressed in other TCR alpha beta-expressing CTL clones and in cell lines representing B-cells, monocytes, and myeloid cells.

Induction. By CSF3/G-CSF. Up-regulated in CD4(+) T-cells from peripheral blood mononuclear cells of patients with visceral leishmaniasis.

Similarity. Belongs to the PMP-22/EMP/MP20 family.

RefSeq proteins (2): NP_001350622, NP_005592* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR004032	PMP22_EMP_MP20	Family
IPR050579	PMP-22/EMP/MP20-like	Family

Pfam: PF00822

UniProt features (5 total): transmembrane region 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16617-F1	87.06	0.57

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 287 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_INFLAMMATORY_RESPONSE, GOCC_VACUOLAR_MEMBRANE, MODULE_45, MODULE_64, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GNF2_ZAP70, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, HOFMANN_MYELODYSPLASTIC_SYNDROM_RISK_DN, GOBP_EXOCYTOSIS, GOBP_CD4_POSITIVE_ALPHA_BETA_T_CELL_ACTIVATION

GO Biological Process (9): natural killer cell mediated cytotoxicity directed against tumor cell target (GO:0002420), inflammatory response (GO:0006954), killing of cells of another organism (GO:0031640), CD4-positive, alpha-beta T cell activation (GO:0035710), natural killer cell mediated cytotoxicity (GO:0042267), defense response to protozoan (GO:0042832), natural killer cell degranulation (GO:0043320), positive regulation of inflammatory response (GO:0050729), granzyme-mediated programmed cell death signaling pathway (GO:0140507)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), cytolytic granule (GO:0044194), cytolytic granule membrane (GO:0101004), lysosome (GO:0005764), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
natural killer cell mediated cytotoxicity	2
natural killer cell mediated immune response to tumor cell	1
defense response	1
cell killing	1
disruption of cell in another organism	1
alpha-beta T cell activation	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
response to protozoan	1
defense response to other organism	1
natural killer cell activation involved in immune response	1
leukocyte degranulation	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
signal transduction	1
programmed cell death	1
binding	1
membrane	1
cell periphery	1
lysosome	1
lysosomal membrane	1
cytolytic granule	1
lytic vacuole	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1590 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NKG7	GZMH	P20718	784
NKG7	GNLY	P09325	783
NKG7	GZMK	P49863	712
NKG7	GZMA	P12544	697
NKG7	CD3D	P04234	693
NKG7	LAG3	P18627	674
NKG7	CSF3	P09919	654
NKG7	MS4A1	P08984	634
NKG7	GZMB	P10144	632
NKG7	MS4A2	Q01362	622
NKG7	CD3E	P07766	598
NKG7	TIGIT	Q495A1	590
NKG7	CD79A	P11912	583
NKG7	FGFBP2	Q9BYJ0	583
NKG7	KLRD1	Q13241	581

IntAct

141 interactions, top by confidence:

A	B	Type	Score
NKG7	MSR1	psi-mi:“MI:0915”(physical association)	0.780
MSR1	NKG7	psi-mi:“MI:0915”(physical association)	0.780
NKG7	STX1A	psi-mi:“MI:0915”(physical association)	0.600
NKG7	CLEC4E	psi-mi:“MI:0915”(physical association)	0.600
NKG7	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	NKG7	psi-mi:“MI:0915”(physical association)	0.560
NKG7	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
NKG7	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
NKG7	RAMP1	psi-mi:“MI:0915”(physical association)	0.560
NKG7	MGST3	psi-mi:“MI:0915”(physical association)	0.560
NKG7	FFAR2	psi-mi:“MI:0915”(physical association)	0.560
NKG7	RNF24	psi-mi:“MI:0915”(physical association)	0.560
NKG7	BAMBI	psi-mi:“MI:0915”(physical association)	0.560
NKG7	ISLR2	psi-mi:“MI:0915”(physical association)	0.560
NKG7	TMEM130	psi-mi:“MI:0915”(physical association)	0.560
NKG7	ATP6AP2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (52): NKG7 (Two-hybrid), AGTRAP (Two-hybrid), NKG7 (Two-hybrid), NKG7 (Two-hybrid), NKG7 (Two-hybrid), NKG7 (Two-hybrid), NKG7 (Two-hybrid), NKG7 (Two-hybrid), NKG7 (Two-hybrid), NKG7 (Two-hybrid), NKG7 (Two-hybrid), STX1A (Two-hybrid), PEX12 (Two-hybrid), FAM210B (Two-hybrid), ERGIC3 (Two-hybrid)

ESM2 similar proteins: A6NDP7, A6NFC5, A8MUP6, B1AQL3, B2RZ87, C9JDP6, E9Q9H8, O75204, P0C5X8, Q02644, Q08DL4, Q0IIL2, Q16617, Q1HG44, Q2KIG8, Q2KJ11, Q2KJ98, Q3SZ72, Q3SZT1, Q3UUA0, Q3YBM2, Q497B3, Q53RY4, Q5R8D6, Q6AYL2, Q6ICI0, Q7YQI4, Q7Z7M1, Q7Z7N9, Q80WE5, Q8BGP5, Q8CIP5, Q8K177, Q8R1W2, Q8WXS4, Q95KI5, Q96B33, Q96DZ7, Q96HP8, Q96JT2

Diamond homologs: Q16617, Q2KJ11, Q99PA5

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	30
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

298 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51372070:GATGG:G	acceptor_gain	1.0000
19:51372072:TGG:T	acceptor_gain	1.0000
19:51372074:GCTGG:G	acceptor_loss	1.0000
19:51372075:C:CA	acceptor_loss	1.0000
19:51372075:C:CC	acceptor_gain	1.0000
19:51372076:T:A	acceptor_loss	1.0000
19:51371935:GTCAC:G	donor_loss	0.9900
19:51371936:TCACC:T	donor_loss	0.9900
19:51371937:CA:C	donor_loss	0.9900
19:51371939:C:CT	donor_loss	0.9900
19:51372071:ATGG:A	acceptor_gain	0.9900
19:51372073:GG:G	acceptor_gain	0.9900
19:51372082:C:CT	acceptor_gain	0.9900
19:51372083:A:T	acceptor_gain	0.9900
19:51372155:CCTTA:C	donor_loss	0.9900
19:51372160:C:G	donor_loss	0.9900
19:51371960:G:C	donor_gain	0.9800
19:51372373:CCTTA:C	donor_loss	0.9800
19:51372374:CTTA:C	donor_loss	0.9800
19:51372375:TTA:T	donor_loss	0.9800
19:51372376:TACC:T	donor_loss	0.9800
19:51372377:ACCTG:A	donor_loss	0.9800
19:51372378:C:CG	donor_loss	0.9800
19:51371939:CCT:C	donor_gain	0.9700
19:51372160:CCTG:C	donor_gain	0.9700
19:51372308:C:CC	acceptor_gain	0.9600
19:51371833:CAC:C	acceptor_gain	0.9500
19:51371836:C:CA	acceptor_loss	0.9500
19:51371837:T:A	acceptor_loss	0.9500
19:51372159:A:AC	donor_gain	0.9500

AlphaMissense

1048 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51371980:G:C	F133L	0.991
19:51371980:G:T	F133L	0.991
19:51371982:A:G	F133L	0.991
19:51371970:A:G	W137R	0.982
19:51371970:A:T	W137R	0.982
19:51372454:A:G	W28R	0.976
19:51372454:A:T	W28R	0.976
19:51371984:G:A	S132F	0.972
19:51371992:G:C	F129L	0.971
19:51371992:G:T	F129L	0.971
19:51371994:A:G	F129L	0.971
19:51372493:C:G	G15R	0.969
19:51371988:A:G	W131R	0.968
19:51371988:A:T	W131R	0.968
19:51372462:G:A	T25I	0.966
19:51372407:C:A	W43C	0.963
19:51372407:C:G	W43C	0.963
19:51371973:C:G	G136R	0.962
19:51372452:C:A	W28C	0.961
19:51372452:C:G	W28C	0.961
19:51371981:A:G	F133S	0.960
19:51371825:G:C	S150R	0.958
19:51371825:G:T	S150R	0.958
19:51371827:T:G	S150R	0.958
19:51372279:G:C	S62R	0.958
19:51372279:G:T	S62R	0.958
19:51372281:T:G	S62R	0.958
19:51371940:C:G	G147R	0.956
19:51371972:C:T	G136D	0.956
19:51372045:A:C	Y112D	0.953

dbSNP variants (sampled 300 via entrez): RS1001031573 (19:51372594 T>A,C), RS1002087622 (19:51373001 T>G), RS1003396070 (19:51373789 T>C), RS1003613465 (19:51373412 TA>T), RS1004315919 (19:51374626 C>T), RS1004703283 (19:51374249 C>T), RS1006384314 (19:51371568 C>G), RS1006705828 (19:51371197 A>G), RS1006835985 (19:51371684 G>A), RS1007429493 (19:51372782 C>G,T), RS1009171204 (19:51372678 A>G), RS1009937308 (19:51371203 T>C), RS1010920048 (19:51373794 C>A), RS1011974696 (19:51373457 G>GC), RS1012332333 (19:51373667 C>A)

Disease associations

OMIM: gene MIM:606008 | 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
GCST004629_48	Neutrophil count	7.000000e-09
GCST90002398_93	Neutrophil count	1.000000e-12
GCST90002399_443	Neutrophil percentage of white cells	8.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
Tretinoin	increases expression	2
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases expression, decreases reaction	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Aspirin	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	increases expression	1
Diazinon	decreases methylation	1
Diuron	decreases expression	1
Progesterone	increases expression	1
Tetradecanoylphorbol Acetate	affects cotreatment, decreases expression, decreases reaction	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	increases methylation	1
Valproic Acid	increases methylation	1
Ionomycin	decreases expression, decreases reaction, affects cotreatment	1
Antirheumatic Agents	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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