GPRIN1

Summary

GPRIN1 (G protein regulated inducer of neurite outgrowth 1, HGNC:24835) is a protein-coding gene on chromosome 5q35.2, encoding G protein-regulated inducer of neurite outgrowth 1 (Q7Z2K8). May be involved in neurite outgrowth.

Predicted to enable phosphoprotein binding activity. Predicted to be involved in neuron projection development. Predicted to be located in growth cone. Predicted to be active in plasma membrane.

Source: NCBI Gene 114787 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 168 total
• Phenotypes (HPO): 134
• Druggable target: yes
• MANE Select transcript: NM_052899

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24835
Approved symbol	GPRIN1
Name	G protein regulated inducer of neurite outgrowth 1
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Aliases	GRIN1, KIAA1893
Ensembl gene	ENSG00000169258
Ensembl biotype	protein_coding
OMIM	611239
Entrez	114787

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000303991, ENST00000926001, ENST00000926002

RefSeq mRNA: 1 — MANE Select: NM_052899 NM_052899

CCDS: CCDS4405

Canonical transcript exons

ENST00000303991 — 2 exons

Exon	Start	End
ENSE00001159289	176595802	176599877
ENSE00001221130	176609999	176610156

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 96.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.0963 / max 176.3124, expressed in 1092 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65036	2.6502	1046
65035	0.4461	200

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.66	gold quality
ganglionic eminence	UBERON:0004023	91.76	gold quality
embryo	UBERON:0000922	91.75	gold quality
right frontal lobe	UBERON:0002810	85.18	gold quality
cerebellar hemisphere	UBERON:0002245	84.53	gold quality
cerebellar cortex	UBERON:0002129	84.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.32	gold quality
anterior cingulate cortex	UBERON:0009835	83.90	gold quality
cerebellum	UBERON:0002037	83.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.77	gold quality
amygdala	UBERON:0001876	82.24	gold quality
prefrontal cortex	UBERON:0000451	81.83	gold quality
neocortex	UBERON:0001950	81.73	gold quality
frontal cortex	UBERON:0001870	81.31	gold quality
frontal lobe	UBERON:0016525	81.31	gold quality
cerebral cortex	UBERON:0000956	80.48	gold quality
islet of Langerhans	UBERON:0000006	79.46	gold quality
hypothalamus	UBERON:0001898	79.13	gold quality
kidney epithelium	UBERON:0004819	78.78	gold quality
temporal lobe	UBERON:0001871	78.28	gold quality
ventricular zone	UBERON:0003053	77.87	gold quality
brain	UBERON:0000955	76.63	gold quality
Ammon’s horn	UBERON:0001954	76.49	gold quality
forebrain	UBERON:0001890	76.28	gold quality
superior frontal gyrus	UBERON:0002661	74.66	gold quality
entorhinal cortex	UBERON:0002728	73.54	gold quality
primary visual cortex	UBERON:0002436	73.48	gold quality
pituitary gland	UBERON:0000007	73.32	gold quality
nucleus accumbens	UBERON:0001882	73.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting GPRIN1, 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-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6827-5P	98.46	64.88	1256

Literature-anchored findings (GeneRIF, showing 1)

• A novel lncRNA-miRNA-mRNA competing endogenous RNA regulatory network in lung adenocarcinoma and kidney renal papillary cell carcinoma. (PMID:34453499)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gprin1	ENSMUSG00000069227
rattus_norvegicus	Gprin1	ENSRNOG00000017974

Protein

Protein identifiers

G protein-regulated inducer of neurite outgrowth 1 — Q7Z2K8 (reviewed: Q7Z2K8)

All UniProt accessions (1): Q7Z2K8

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in neurite outgrowth.

Subunit / interactions. Interacts with activated forms of GNAI1, GNAO1 and GNAZ.

Subcellular location. Cell membrane. Cell projection. Growth cone.

Tissue specificity. Widely expressed in the central nervous system, with highest levels in spinal cord.

Post-translational modifications. Palmitoylation on Cys-999 and/or Cys-1000 is required for membrane targeting.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z2K8-1	1	yes
Q7Z2K8-2	2

RefSeq proteins (1): NP_443131* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF15235

UniProt features (42 total): compositionally biased region 15, modified residue 13, sequence variant 4, region of interest 3, lipid moiety-binding region 2, splice variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z2K8-F1	44.02	0.02

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 (15): 60, 64, 75, 237, 436, 452, 615, 737, 799, 877, 895, 914, 993, 999, 1000

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9022699	MECP2 regulates neuronal receptors and channels

MSigDB gene sets: 623 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, MODULE_274, GOBP_BEHAVIOR, GOMF_GLUTAMATE_GATED_RECEPTOR_ACTIVITY, GOBP_RESPONSE_TO_ACID_CHEMICAL, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS

GO Biological Process (1): neuron projection development (GO:0031175)

GO Molecular Function (2): phosphoprotein binding (GO:0051219), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), growth cone (GO:0030426), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transcriptional Regulation by MECP2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
neuron development	1
plasma membrane bounded cell projection organization	1
protein binding	1
binding	1
membrane	1
cell periphery	1
site of polarized growth	1
distal axon	1

Protein interactions and networks

STRING

820 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPRIN1	GNAZ	P19086	769
GPRIN1	GNAO1	P09471	619
GPRIN1	GAMT	Q14353	566
GPRIN1	CDHR2	Q9BYE9	566
GPRIN1	FXYD1	O00168	546
GPRIN1	TUBA1B	P04687	541
GPRIN1	RBFOX1	Q9NWB1	537
GPRIN1	PEG10	Q86TG7	503
GPRIN1	TPGS1	Q6ZTW0	487
GPRIN1	SPMIP2	Q96LM5	482
GPRIN1	MECP2	P51608	474
GPRIN1	RNFT2	Q96EX2	430
GPRIN1	SUCLG1	P53597	426
GPRIN1	RAPGEFL1	Q9UHV5	426
GPRIN1	TUBA1B	P04687	423

IntAct

63 interactions, top by confidence:

A	B	Type	Score
RELL2	OXSR1	psi-mi:“MI:0914”(association)	0.830
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
STAMBPL1	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
Chrna7	GPRIN1	psi-mi:“MI:0915”(physical association)	0.540
Chrna7	GPRIN1	psi-mi:“MI:0403”(colocalization)	0.540
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
TMEM185A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
SDF4	GTPBP6	psi-mi:“MI:0914”(association)	0.530
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
HNRNPD	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
YEATS4	ING3	psi-mi:“MI:0914”(association)	0.350
ZNF281	KIF21B	psi-mi:“MI:0914”(association)	0.350
S1PR1	POTEF	psi-mi:“MI:0914”(association)	0.350
CYP2S1	MPP2	psi-mi:“MI:0914”(association)	0.350
VTN	HAT1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
AXL	PIK3R2	psi-mi:“MI:0914”(association)	0.350

BioGRID (111): GPRIN1 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS), GPRIN1 (Proximity Label-MS), GPRIN1 (Proximity Label-MS), GPRIN1 (Proximity Label-MS), GPRIN1 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YXV3, A0A172M4N0, A2VE23, A5PL33, C7EMF5, E7EW31, F1NSM7, I3L273, O15027, O48582, O55189, O55196, O97939, P0C671, P0DV77, P14138, Q14D33, Q1XI13, Q28989, Q3B7M4, Q4R729, Q5R7U0, Q5SWP3, Q62840, Q63003, Q6E0U4, Q6H236, Q6NUN9, Q6UXA7, Q7Z2K8, Q86UU5, Q8BM15, Q8K4E0, Q8K4L6, Q8N1P7, Q8N3D4, Q96D09, Q96JG9, Q9BGL9, Q9D7G9

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

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MECP2	“up-regulates quantity by expression”	GPRIN1	“post transcriptional regulation”
GPRIN1	up-regulates	Neurite_outgrowth

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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	5	15.1×	3e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	11.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	154
Likely benign	12
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4359 predictions. Top by Δscore:

Variant	Effect	Δscore
5:176609993:GCTTA:G	donor_loss	1.0000
5:176609994:CTTA:C	donor_loss	1.0000
5:176609995:TTACC:T	donor_loss	1.0000
5:176609996:TA:T	donor_loss	1.0000
5:176609997:A:AC	donor_gain	1.0000
5:176609997:A:T	donor_loss	1.0000
5:176609998:C:CC	donor_gain	1.0000
5:176609998:CCAGG:C	donor_gain	1.0000
9:137142008:CACA:C	acceptor_loss	1.0000
9:137142010:CA:C	acceptor_loss	1.0000
9:137142144:CAAGG:C	donor_loss	1.0000
9:137142146:AGG:A	donor_loss	1.0000
9:137142147:GGT:G	donor_loss	1.0000
9:137142148:G:C	donor_loss	1.0000
9:137142148:G:GG	donor_gain	1.0000
9:137142149:T:A	donor_loss	1.0000
9:137145725:GA:G	acceptor_gain	1.0000
9:137145887:GGAGC:G	donor_gain	1.0000
9:137145888:GAGCG:G	donor_gain	1.0000
9:137145890:GC:G	donor_gain	1.0000
9:137145900:AAG:A	donor_loss	1.0000
9:137145901:AG:A	donor_loss	1.0000
9:137145902:GG:G	donor_loss	1.0000
9:137145903:GTGAG:G	donor_loss	1.0000
9:137145904:T:A	donor_loss	1.0000
9:137148124:T:G	acceptor_gain	1.0000
9:137149007:A:AG	acceptor_gain	1.0000
9:137149008:G:GG	acceptor_gain	1.0000
9:137149008:GGCA:G	acceptor_gain	1.0000
9:137157014:G:GT	donor_gain	1.0000

AlphaMissense

6374 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:176597010:A:G	L942P	1.000
5:176597022:A:G	I938T	1.000
5:176597022:A:T	I938N	1.000
5:176597069:C:A	W922C	1.000
5:176597069:C:G	W922C	1.000
5:176597071:A:G	W922R	1.000
5:176597071:A:T	W922R	1.000
5:176597090:C:A	W915C	1.000
5:176597090:C:G	W915C	1.000
5:176597092:A:G	W915R	1.000
5:176597092:A:T	W915R	1.000
5:176597001:T:G	Q945P	0.999
5:176597010:A:T	L942Q	0.999
5:176597018:C:A	Q939H	0.999
5:176597018:C:G	Q939H	0.999
5:176597022:A:C	I938S	0.999
5:176597076:A:G	M920T	0.999
5:176597088:T:A	D916V	0.999
5:176597088:T:G	D916A	0.999
5:176597089:C:G	D916H	0.999
5:176597012:A:C	H941Q	0.998
5:176597012:A:T	H941Q	0.998
5:176597014:G:C	H941D	0.998
5:176597019:T:G	Q939P	0.998
5:176597026:C:G	A937P	0.998
5:176597032:C:G	G935R	0.998
5:176597034:A:T	L934Q	0.998
5:176597070:C:G	W922S	0.998
5:176597080:C:G	G919R	0.998
5:176597091:C:G	W915S	0.998

dbSNP variants (sampled 300 via entrez): RS1000175303 (5:176606299 C>T), RS1000191224 (5:176603564 G>C,T), RS1000586514 (5:176596461 A>G), RS1000729707 (5:176608654 C>G), RS1000737234 (5:176600433 C>T), RS1000786103 (5:176595383 G>A), RS1001088684 (5:176595615 T>A,G), RS1001341455 (5:176601940 G>A,T), RS1001575059 (5:176601261 A>C), RS1001725265 (5:176607236 G>A), RS1001764352 (5:176609772 G>A,C), RS1001847930 (5:176604726 T>C,G), RS1001957883 (5:176611937 G>C), RS1002222889 (5:176611546 G>A,T), RS1002498491 (5:176608651 T>A)

Disease associations

OMIM: gene MIM:611239 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

134 total (30 of 134 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000070	Ureterocele
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000340	Sloping forehead
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000708	Atypical behavior
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000748	Inappropriate laughter
HP:0000752	Hyperactivity
HP:0000817	Reduced eye contact
HP:0000826	Precocious puberty
HP:0000954	Single transverse palmar crease
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001272	Cerebellar atrophy
HP:0001302	Pachygyria

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5266 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, increases expression	2
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Endosulfan	decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression, increases expression, increases methylation	2
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
methyleugenol	increases expression	1
lead acetate	increases expression	1
methylparaben	increases expression	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
cupric chloride	increases expression	1
coumarin	affects phosphorylation	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluoro-n-nonanoic acid	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Folic Acid	decreases expression	1
N-Nitrosopyrrolidine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL977004	Binding	Inhibition of GRIN1	Chemical fragments as foundations for understanding target space and activity prediction. — J Med Chem

Clinical trials (associated diseases)

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