GPRIN3

Summary

GPRIN3 (GPRIN family member 3, HGNC:27733) is a protein-coding gene on chromosome 4q22.1, encoding G protein-regulated inducer of neurite outgrowth 3 (Q6ZVF9). May be involved in neurite outgrowth.

Predicted to be involved in neuron projection development. Predicted to act upstream of or within several processes, including excitatory chemical synaptic transmission; neuronal action potential; and vitamin D receptor signaling pathway. Predicted to be active in plasma membrane.

Source: NCBI Gene 285513 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 143 total — 1 pathogenic
• MANE Select transcript: NM_198281

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27733
Approved symbol	GPRIN3
Name	GPRIN family member 3
Location	4q22.1
Locus type	gene with protein product
Status	Approved
Aliases	GRIN3, FLJ42625
Ensembl gene	ENSG00000185477
Ensembl biotype	protein_coding
OMIM	611241
Entrez	285513

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000333209, ENST00000609438, ENST00000715382, ENST00000901096, ENST00000901097, ENST00000901098, ENST00000947775

RefSeq mRNA: 1 — MANE Select: NM_198281 NM_198281

CCDS: CCDS34030

Canonical transcript exons

ENST00000609438 — 2 exons

Exon	Start	End
ENSE00001373476	89307615	89307800
ENSE00003705425	89236383	89250233

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 92.88.

FANTOM5 (CAGE): breadth broad, TPM avg 6.4160 / max 229.0238, expressed in 703 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53146	3.4067	495
53148	2.5111	576
53145	0.3521	194
53147	0.1003	44
53149	0.0459	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	92.88	silver quality
pancreatic ductal cell	CL:0002079	92.23	gold quality
jejunal mucosa	UBERON:0000399	91.23	gold quality
cortical plate	UBERON:0005343	84.70	gold quality
ileal mucosa	UBERON:0000331	83.46	gold quality
cerebellar vermis	UBERON:0004720	82.57	gold quality
superficial temporal artery	UBERON:0001614	81.73	gold quality
visceral pleura	UBERON:0002401	80.88	gold quality
cerebellum	UBERON:0002037	80.76	gold quality
cerebellar cortex	UBERON:0002129	80.59	gold quality
vermiform appendix	UBERON:0001154	80.44	gold quality
cerebellar hemisphere	UBERON:0002245	80.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.27	gold quality
duodenum	UBERON:0002114	79.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.88	gold quality
lymph node	UBERON:0000029	78.75	gold quality
rectum	UBERON:0001052	78.65	gold quality
colonic mucosa	UBERON:0000317	78.52	gold quality
endothelial cell	CL:0000115	78.15	gold quality
jejunum	UBERON:0002115	77.99	gold quality
colonic epithelium	UBERON:0000397	77.85	gold quality
germinal epithelium of ovary	UBERON:0001304	76.93	silver quality
bone marrow cell	CL:0002092	76.26	gold quality
islet of Langerhans	UBERON:0000006	76.14	gold quality
caecum	UBERON:0001153	75.63	gold quality
granulocyte	CL:0000094	75.32	gold quality
right lung	UBERON:0002167	75.00	gold quality
tonsil	UBERON:0002372	74.41	gold quality
leukocyte	CL:0000738	73.85	gold quality
lateral nuclear group of thalamus	UBERON:0002736	73.69	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	31.70
E-CURD-122	yes	18.62
E-ANND-3	yes	5.56
E-CURD-112	no	3.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

139 targeting GPRIN3, 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-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-548AE-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 2)

• Functional compensation could occur to counteract the loss of one allele in GRIN2C and GRIN3 family genes. (PMID:22833210)
• miR-6838-5p Affects Cell Growth, Migration, and Invasion by Targeting GPRIN3 via the Wnt/beta-Catenin Signaling Pathway in Gastric Cancer. (PMID:33254176)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gprin3b	ENSDARG00000075043
mus_musculus	Gprin3	ENSMUSG00000045441
rattus_norvegicus	Gprin3	ENSRNOG00000023657

Paralogs (1): GPRIN2 (ENSG00000204175)

Protein

Protein identifiers

G protein-regulated inducer of neurite outgrowth 3 — Q6ZVF9 (reviewed: Q6ZVF9)

All UniProt accessions (1): Q6ZVF9

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in neurite outgrowth.

RefSeq proteins (1): NP_938022* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026646	GPRIN2-like/GPRIN3	Family
IPR032745	GRIN_C	Domain

Pfam: PF15235

UniProt features (23 total): compositionally biased region 9, sequence variant 6, region of interest 4, modified residue 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZVF9-F1	47.41	0.03

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): 332, 365

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 180 (showing top): RNGTGGGC_UNKNOWN, FXR_IR1_Q6, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, WWTAAGGC_UNKNOWN, HNF3ALPHA_Q6, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_COCAINE, RORA1_01, GOBP_CELLULAR_RESPONSE_TO_LIPID, MENSE_HYPOXIA_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_NEUROGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_CELL_CELL_SIGNALING

GO Biological Process (7): locomotory behavior (GO:0007626), neuronal action potential (GO:0019228), neuron projection development (GO:0031175), response to cocaine (GO:0042220), cell morphogenesis involved in neuron differentiation (GO:0048667), vitamin D receptor signaling pathway (GO:0070561), excitatory chemical synaptic transmission (GO:0098976)

GO Molecular Function (0):

GO Cellular Component (2): plasma membrane (GO:0005886), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron development	2
behavior	1
action potential	1
transmission of nerve impulse	1
plasma membrane bounded cell projection organization	1
response to alkaloid	1
response to oxygen-containing compound	1
cell morphogenesis	1
neuron differentiation	1
hormone-mediated signaling pathway	1
cellular response to vitamin D	1
nuclear receptor-mediated signaling pathway	1
chemical synaptic transmission	1
excitatory postsynaptic potential	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPRIN3	GNAZ	P19086	648
GPRIN3	GRIN1	P35437	622
GPRIN3	GNAO1	P09471	597
GPRIN3	GPRIN2	O60269	570
GPRIN3	ZNF644	Q9H582	505
GPRIN3	TIGD2	Q4W5G0	474
GPRIN3	UBOX5	O94941	459
GPRIN3	SH3BGRL2	Q9UJC5	455
GPRIN3	CNKSR3	Q6P9H4	440
GPRIN3	CHCHD2	Q9Y6H1	417
GPRIN3	GPRIN1	Q7Z2K8	416
GPRIN3	SDCCAG8	Q86SQ7	404
GPRIN3	CCSER1	Q9C0I3	402
GPRIN3	GRIN2D	O15399	400
GPRIN3	GRIN2A	Q12879	398

IntAct

12 interactions, top by confidence:

A	B	Type	Score
KCNJ2	KCNJ18	psi-mi:“MI:2364”(proximity)	0.660
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
GPRIN3	NLN	psi-mi:“MI:0915”(physical association)	0.400
CTDSPL	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
PTPRA	EXOC3	psi-mi:“MI:2364”(proximity)	0.270
EGFR	FAM171A2	psi-mi:“MI:2364”(proximity)	0.270
EPHB2	ARHGAP32	psi-mi:“MI:2364”(proximity)	0.270
FGFR1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
FGFR2	APBB1	psi-mi:“MI:2364”(proximity)	0.270
FGFR4	SH3PXD2B	psi-mi:“MI:2364”(proximity)	0.270
NTRK2	ARHGAP32	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (57): GPRIN3 (Proximity Label-MS), GPRIN3 (Proximity Label-MS), GPRIN3 (Affinity Capture-RNA), GPRIN3 (Proximity Label-MS), GPRIN3 (Affinity Capture-MS), GPRIN3 (Proximity Label-MS), GPRIN3 (Proximity Label-MS), GPRIN3 (Proximity Label-MS), GPRIN3 (Proximity Label-MS), GPRIN3 (Proximity Label-MS), GPRIN3 (Positive Genetic), GPRIN3 (Proximity Label-MS), GPRIN3 (Proximity Label-MS), GPRIN3 (Proximity Label-MS), GPRIN3 (Proximity Label-MS)

ESM2 similar proteins: A0JNH1, E9Q394, E9Q3S4, F1M3G7, M0RD54, O02665, O94854, P0C6C0, P48754, Q00756, Q0VGT4, Q12802, Q16821, Q283Q6, Q29106, Q2M3C7, Q3KR64, Q3U0P1, Q3ULM6, Q3URK3, Q3UXL4, Q3V089, Q49AJ0, Q5DTT3, Q5HZI1, Q5R5G4, Q5ZK13, Q69ZZ9, Q6DIA7, Q6NSW3, Q6RJR6, Q6ZVF9, Q711Q0, Q7T005, Q7Z434, Q80U44, Q86TB3, Q86YC2, Q8BJM3, Q8BWS5

Diamond homologs: O60269, Q3UNH4, Q6ZVF9, Q7Z2K8, Q8BWS5, Q9PWA3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by Aberrant PI3K in Cancer	6	47.6×	3e-07
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	36.3×	7e-07
PIP3 activates AKT signaling	6	25.0×	4e-06
RAF/MAP kinase cascade	6	22.9×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein autophosphorylation	5	38.2×	3e-05
positive regulation of MAPK cascade	5	21.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	128
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2571213	GRCh37/hg19 4q22.1(chr4:90168931-90874569)x3	Pathogenic

SpliceAI

870 predictions. Top by Δscore:

Variant	Effect	Δscore
4:89250229:CCAGC:C	acceptor_gain	0.9900
4:89250230:CAGC:C	acceptor_gain	0.9900
4:89250230:CAGCC:C	acceptor_gain	0.9900
4:89252429:A:AC	donor_gain	0.9900
4:89252430:C:CC	donor_gain	0.9900
4:89252430:CTGG:C	donor_gain	0.9900
4:89307609:TCCTA:T	donor_loss	0.9900
4:89307610:CCTA:C	donor_loss	0.9900
4:89307611:CTA:C	donor_loss	0.9900
4:89307612:TAC:T	donor_loss	0.9900
4:89307613:A:AT	donor_loss	0.9900
4:89307614:C:CG	donor_loss	0.9900
4:89250234:C:CC	acceptor_gain	0.9800
4:89250234:C:CG	acceptor_loss	0.9800
4:89250886:A:AC	donor_gain	0.9800
4:89250887:C:CC	donor_gain	0.9800
4:89250887:CGAAT:C	donor_gain	0.9800
4:89252465:T:A	donor_gain	0.9800
4:89307614:CCTG:C	donor_gain	0.9800
4:89247775:C:CA	donor_gain	0.9700
4:89250232:GC:G	acceptor_gain	0.9700
4:89250233:CC:C	acceptor_gain	0.9700
4:89255653:A:C	donor_gain	0.9700
4:89250231:AGC:A	acceptor_gain	0.9600
4:89250705:A:AC	donor_gain	0.9600
4:89250706:C:CC	donor_gain	0.9600
4:89307673:C:A	donor_gain	0.9600
4:89250683:A:AC	donor_gain	0.9500
4:89250683:AAT:A	donor_gain	0.9500
4:89307651:G:GA	donor_gain	0.9500

AlphaMissense

5065 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:89248032:C:A	W693C	0.999
4:89248032:C:G	W693C	0.999
4:89248034:A:G	W693R	0.999
4:89248034:A:T	W693R	0.999
4:89247973:A:G	L713S	0.998
4:89247985:A:G	I709T	0.998
4:89247985:A:T	I709N	0.998
4:89248051:T:A	D687V	0.998
4:89248051:T:G	D687A	0.998
4:89248053:C:A	W686C	0.998
4:89248053:C:G	W686C	0.998
4:89248055:A:G	W686R	0.998
4:89248055:A:T	W686R	0.998
4:89247985:A:C	I709S	0.997
4:89248052:C:G	D687H	0.997
4:89248039:A:G	M691T	0.995
4:89248050:A:C	D687E	0.995
4:89248050:A:T	D687E	0.995
4:89248060:A:T	V684D	0.995
4:89247976:T:G	H712P	0.994
4:89248033:C:G	W693S	0.994
4:89248042:C:A	G690V	0.994
4:89248054:C:G	W686S	0.994
4:89249103:G:C	S336R	0.994
4:89249103:G:T	S336R	0.994
4:89249105:T:G	S336R	0.994
4:89247964:T:G	Q716P	0.992
4:89247977:G:C	H712D	0.992
4:89248043:C:G	G690R	0.992
4:89248043:C:T	G690R	0.992

dbSNP variants (sampled 300 via entrez): RS1000042991 (4:89292056 G>C), RS1000056484 (4:89258452 T>A), RS1000107055 (4:89258181 T>C), RS1000118380 (4:89258020 T>A), RS1000207766 (4:89305228 G>A,C), RS1000266189 (4:89263693 C>T), RS1000312236 (4:89252450 A>G), RS1000400445 (4:89299240 T>C), RS10004253 (4:89293741 T>C), RS1000437444 (4:89280303 A>G), RS1000452676 (4:89239926 T>G), RS1000489777 (4:89279993 A>C), RS1000504986 (4:89262822 G>A), RS1000509169 (4:89304031 A>G), RS1000540485 (4:89303768 T>C)

Disease associations

OMIM: gene MIM:611241 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST003478_2	Hair greying	9.000000e-06
GCST003800_1	Response to bupropion in depression	3.000000e-08
GCST003922_2	Parkinson’s disease	1.000000e-32
GCST003984_20	Parkinson’s disease	1.000000e-56
GCST005956_59	Waist-to-hip ratio adjusted for BMI	5.000000e-08
GCST005957_14	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-06
GCST005962_35	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-08
GCST008270_2	Post-traumatic stress disorder symptoms in trauma-exposed soldiers	8.000000e-07
GCST010484_5	Stent thrombosis in response to clopidogrel treatment	7.000000e-06
GCST90002388_348	Lymphocyte count	6.000000e-19

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0008483	response to trauma exposure
EFO:0008535	post-traumatic stress disorder symptom measurement
EFO:0006919	cardiovascular event measurement
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Aflatoxin B1	decreases methylation, increases expression	3
Nickel	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Hydrogen Peroxide	increases expression	1
Lead	affects expression	1
Lipopolysaccharides	increases expression, affects cotreatment, decreases expression, affects response to substance	1
N-Nitrosopyrrolidine	increases expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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