GNG8

Summary

GNG8 (G protein subunit gamma 8, HGNC:19664) is a protein-coding gene on chromosome 19q13.32, encoding Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 (Q9UK08). Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems.

Predicted to enable G-protein beta-subunit binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within cellular response to pheromone; nose development; and social behavior. Predicted to be located in plasma membrane. Predicted to be part of heterotrimeric G-protein complex.

Source: NCBI Gene 94235 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_033258

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19664
Approved symbol	GNG8
Name	G protein subunit gamma 8
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167414
Ensembl biotype	protein_coding
Entrez	94235

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000300873, ENST00000693335, ENST00000907311, ENST00000938467, ENST00000953504, ENST00000953505, ENST00000953506, ENST00000953507

RefSeq mRNA: 1 — MANE Select: NM_033258 NM_033258

CCDS: CCDS12687

Canonical transcript exons

ENST00000693335 — 3 exons

Exon	Start	End
ENSE00001112770	46634599	46634725
ENSE00003924448	46633953	46634204
ENSE00003937952	46636147	46636202

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 93.46.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0506 / max 88.9969, expressed in 330 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181660	0.8227	314
181657	0.1248	38
181656	0.1032	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	93.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.81	gold quality
hypothalamus	UBERON:0001898	92.52	gold quality
right atrium auricular region	UBERON:0006631	91.50	gold quality
popliteal artery	UBERON:0002250	90.92	gold quality
tibial artery	UBERON:0007610	90.90	gold quality
monocyte	CL:0000576	90.77	gold quality
cardiac atrium	UBERON:0002081	90.38	gold quality
aorta	UBERON:0000947	90.35	gold quality
ascending aorta	UBERON:0001496	90.30	gold quality
adenohypophysis	UBERON:0002196	90.20	gold quality
thoracic aorta	UBERON:0001515	90.03	gold quality
descending thoracic aorta	UBERON:0002345	88.43	gold quality
spinal cord	UBERON:0002240	88.23	gold quality
leukocyte	CL:0000738	88.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.81	gold quality
right coronary artery	UBERON:0001625	87.79	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.57	gold quality
amygdala	UBERON:0001876	87.20	gold quality
pituitary gland	UBERON:0000007	86.90	gold quality
putamen	UBERON:0001874	85.79	gold quality
anterior cingulate cortex	UBERON:0009835	85.38	gold quality
nucleus accumbens	UBERON:0001882	84.26	gold quality
right frontal lobe	UBERON:0002810	83.93	gold quality
cortical plate	UBERON:0005343	83.92	gold quality
left coronary artery	UBERON:0001626	83.77	gold quality
caudate nucleus	UBERON:0001873	83.21	gold quality
body of uterus	UBERON:0009853	82.32	gold quality
substantia nigra	UBERON:0002038	81.77	gold quality
coronary artery	UBERON:0001621	81.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.77

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gng8	ENSDARG00000042970
mus_musculus	Gng8	ENSMUSG00000063594
rattus_norvegicus	Gng8	ENSRNOG00000016701

Paralogs (11): GNG11 (ENSG00000127920), GNGT1 (ENSG00000127928), GNG5B (ENSG00000133136), GNG3 (ENSG00000162188), GNGT2 (ENSG00000167083), GNG4 (ENSG00000168243), GNG12 (ENSG00000172380), GNG5 (ENSG00000174021), GNG7 (ENSG00000176533), GNG2 (ENSG00000186469), GNG10 (ENSG00000242616)

Protein

Protein identifiers

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 — Q9UK08 (reviewed: Q9UK08)

Alternative names: Gamma-9

All UniProt accessions (1): Q9UK08

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.

Subunit / interactions. G proteins are composed of 3 units, alpha, beta and gamma.

Subcellular location. Cell membrane.

Similarity. Belongs to the G protein gamma family.

RefSeq proteins (1): NP_150283* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001770	G-protein_gamma	Family
IPR015898	G-protein_gamma-like_dom	Domain
IPR036284	GGL_sf	Homologous_superfamily

Pfam: PF00631

UniProt features (4 total): chain 1, propeptide 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UK08-F1	90.02	0.73

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 (2): 67, 67

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-1296041	Activation of G protein gated Potassium channels
R-HSA-163359	Glucagon signaling in metabolic regulation
R-HSA-202040	G-protein activation
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-392170	ADP signalling through P2Y purinoceptor 12
R-HSA-392451	G beta:gamma signalling through PI3Kgamma
R-HSA-392851	Prostacyclin signalling through prostacyclin receptor
R-HSA-400042	Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-4086398	Ca2+ pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-418217	G beta:gamma signalling through PLC beta
R-HSA-418555	G alpha (s) signalling events
R-HSA-418592	ADP signalling through P2Y purinoceptor 1
R-HSA-418594	G alpha (i) signalling events
R-HSA-418597	G alpha (z) signalling events
R-HSA-420092	Glucagon-type ligand receptors
R-HSA-428930	Thromboxane signalling through TP receptor
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-500657	Presynaptic function of Kainate receptors
R-HSA-6814122	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
R-HSA-8964315	G beta:gamma signalling through BTK
R-HSA-8964616	G beta:gamma signalling through CDC42
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9634597	GPER1 signaling
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-997272	Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits

MSigDB gene sets: 146 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, MYOGENIN_Q6, GOBP_BEHAVIOR, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, NKX25_02, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, GCANCTGNY_MYOD_Q6, AREB6_03, REACTOME_GLUCAGON_SIGNALING_IN_METABOLIC_REGULATION, CAGCTG_AP4_Q5, GOBP_NOSE_DEVELOPMENT

GO Biological Process (6): G protein-coupled receptor signaling pathway (GO:0007186), nervous system development (GO:0007399), social behavior (GO:0035176), nose development (GO:0043584), cellular response to pheromone (GO:0071444), signal transduction (GO:0007165)

GO Molecular Function (3): GTPase activity (GO:0003924), G-protein beta-subunit binding (GO:0031681), protein binding (GO:0005515)

GO Cellular Component (3): heterotrimeric G-protein complex (GO:0005834), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
GPCR downstream signalling	5
Signal amplification	3
Regulation of insulin secretion	2
G-protein beta:gamma signalling	2
G protein gated Potassium channels	1
Integration of energy metabolism	1
Opioid Signalling	1
Platelet homeostasis	1
Beta-catenin independent WNT signaling	1
Class B/2 (Secretin family receptors)	1
Aquaporin-mediated transport	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	1
signal transduction	1
system development	1
behavior	1
biological process involved in intraspecies interaction between organisms	1
sensory organ development	1
respiratory system development	1
response to pheromone	1
cellular response to chemical stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ribonucleoside triphosphate phosphatase activity	1
protein binding	1
binding	1
extrinsic component of cytoplasmic side of plasma membrane	1
plasma membrane protein complex	1
GTPase complex	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1176 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNG8	BRS3	P32247	510
GNG8	GNGT2	O14610	507
GNG8	GNG13	Q9P2W3	492
GNG8	RAET1E	Q8TD07	453
GNG8	OR10A6	Q8NH74	412
GNG8	OR9G4	Q8NGQ1	410
GNG8	GNAL	P38405	408
GNG8	OR2A5	Q96R48	408
GNG8	ERBB2	P04626	402
GNG8	GNB4	Q9HAV0	400
GNG8	OR6C1	Q96RD1	391
GNG8	GNB5	O14775	388
GNG8	CNGA2	Q16280	385
GNG8	OR56A4	Q8NGH8	381
GNG8	GTSF1L	Q9H1H1	378

IntAct

25 interactions, top by confidence:

A	B	Type	Score
GNG8	GNAI1	psi-mi:“MI:0914”(association)	0.640
GNG8	GNB5	psi-mi:“MI:0914”(association)	0.640
GNG8	GNB1	psi-mi:“MI:0914”(association)	0.530
GNG8	GNB2	psi-mi:“MI:0914”(association)	0.530
CXCR5	GNB3	psi-mi:“MI:0915”(physical association)	0.400
CXCR5	GNG8	psi-mi:“MI:0915”(physical association)	0.400
GNG8	GNB3	psi-mi:“MI:0914”(association)	0.350
GNG8	GNAS	psi-mi:“MI:0914”(association)	0.350
GNG8	Ntsr1	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (127): GNG8 (Affinity Capture-Western), HP (Affinity Capture-MS), MPO (Affinity Capture-MS), IGLC2 (Affinity Capture-MS), TF (Affinity Capture-MS), APOB (Affinity Capture-MS), GNAS (Affinity Capture-MS), GNAI2 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAQ (Affinity Capture-MS), LYZ (Affinity Capture-MS), FGG (Affinity Capture-MS), CFH (Affinity Capture-MS), CFB (Affinity Capture-MS), IGHA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A804HLA8, O14610, O60262, O97564, P02698, P30671, P38040, P43425, P50150, P50151, P50153, P50154, P54406, P59768, P61952, P61953, P61954, P63077, P63078, P63210, P63211, P63212, P63213, P63214, P63215, P63216, P63217, P63218, P63219, Q28024, Q4VT26, Q5E9F0, Q5R639, Q5R7U4, Q5RBQ0, Q5REH7, Q61012, Q61016, Q61017, Q6CPB4

Diamond homologs: A0A804HLA8, O60262, P30671, P38040, P43425, P50150, P50151, P50153, P59768, P63077, P63078, P63212, P63213, P63214, P63215, P63216, P63217, P63218, P63219, Q28024, Q4VT26, Q5R639, Q5R7U4, Q5RBQ0, Q5REH7, Q61016, Q80SZ7, Q9CXP8, Q9DAS9, Q9UBI6, Q9UK08, O14610, O97564, P02698, P50154, P54406, P61952, P61953, P61954, P63210

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

105 predictions. Top by Δscore:

Variant	Effect	Δscore
19:46634601:T:A	donor_gain	1.0000
19:46634621:T:TA	donor_gain	1.0000
19:46634593:CAGCA:C	donor_loss	0.9900
19:46634595:GCAC:G	donor_loss	0.9900
19:46634596:CA:C	donor_loss	0.9900
19:46634597:ACCTT:A	donor_loss	0.9900
19:46634202:CAC:C	acceptor_gain	0.9800
19:46634204:CCT:C	acceptor_loss	0.9800
19:46634205:C:CC	acceptor_gain	0.9800
19:46634599:CTT:C	donor_loss	0.9700
19:46634200:GACAC:G	acceptor_gain	0.9600
19:46634201:ACAC:A	acceptor_gain	0.9600
19:46634202:CACC:C	acceptor_gain	0.9600
19:46634203:AC:A	acceptor_gain	0.9600
19:46634204:CC:C	acceptor_gain	0.9600
19:46634614:GTTCA:G	donor_loss	0.9300
19:46634615:TTCAC:T	donor_loss	0.9300
19:46634616:TCACC:T	donor_loss	0.9300
19:46634617:CACCT:C	donor_loss	0.9300
19:46634618:ACCTC:A	donor_loss	0.9300
19:46634619:C:A	donor_loss	0.9300
19:46634620:C:T	donor_loss	0.9300
19:46634589:G:GT	donor_gain	0.9200
19:46634622:C:A	donor_gain	0.9200
19:46634621:T:A	donor_loss	0.9100
19:46634203:ACC:A	acceptor_gain	0.9000
19:46634204:CCTGC:C	acceptor_gain	0.9000
19:46634595:G:C	donor_gain	0.9000
19:46634201:ACACC:A	acceptor_gain	0.8900
19:46634202:CACCT:C	acceptor_gain	0.8700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000142200 (19:46639323 T>A,C), RS1000747480 (19:46638042 C>G,T), RS1000961931 (19:46636951 C>A,T), RS1001158588 (19:46638285 C>T), RS1001851255 (19:46635910 G>A), RS1001967445 (19:46635312 CGCAGAG>C,CGCAGAGGCAGAG), RS1001978633 (19:46636480 C>T), RS1002321886 (19:46637935 A>G), RS1002618590 (19:46634904 G>A), RS1003104094 (19:46638997 A>C,G), RS1003167850 (19:46641006 C>A,T), RS1005210002 (19:46640858 T>C), RS1005656172 (19:46634777 C>T), RS1005774 (19:46633905 C>A), RS1005774278 (19:46635850 T>C,G)

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

1 associations (top):

Study	Trait	p-value
GCST004132_48	Crohn’s disease	4.000000e-07

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
Valproic Acid	affects expression, increases expression, increases methylation	4
mercuric bromide	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Estradiol	affects expression	1
Tretinoin	decreases expression, affects cotreatment	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2XX	Abcam HEK293T GNG8 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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