GPRIN2

Summary

GPRIN2 (G protein regulated inducer of neurite outgrowth 2, HGNC:23730) is a protein-coding gene on chromosome 10q11.22, encoding G protein-regulated inducer of neurite outgrowth 2 (O60269). May be involved in neurite outgrowth.

Predicted to be involved in neuron projection development. Predicted to be active in plasma membrane.

Source: NCBI Gene 9721 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_001385282

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23730
Approved symbol	GPRIN2
Name	G protein regulated inducer of neurite outgrowth 2
Location	10q11.22
Locus type	gene with protein product
Status	Approved
Aliases	MGC15171
Ensembl gene	ENSG00000204175
Ensembl biotype	protein_coding
OMIM	611240
Entrez	9721

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 42 protein_coding

ENST00000374314, ENST00000374317, ENST00000889306, ENST00000889307, ENST00000889308, ENST00000889309, ENST00000889310, ENST00000889311, ENST00000889312, ENST00000889313, ENST00000889314, ENST00000889315, ENST00000889316, ENST00000889317, ENST00000889318, ENST00000889319, ENST00000889320, ENST00000889321, ENST00000912560, ENST00000912561, ENST00000912562, ENST00000912563, ENST00000912564, ENST00000912565, ENST00000912566, ENST00000912567, ENST00000912568, ENST00000912569, ENST00000912570, ENST00000943943, ENST00000943944, ENST00000943945, ENST00000943946, ENST00000943947, ENST00000943948, ENST00000943949, ENST00000943950, ENST00000943951, ENST00000943952, ENST00000943953, ENST00000943954, ENST00000943955

RefSeq mRNA: 28 — MANE Select: NM_001385282 NM_001385275, NM_001385276, NM_001385277, NM_001385278, NM_001385279, NM_001385280, NM_001385281, NM_001385282, NM_001385283, NM_001385287, NM_001385289, NM_001385291, NM_001385293, NM_001385294, NM_001385295, NM_001385296, NM_001385297, NM_001385298, NM_001385299, NM_001385300, NM_001385301, NM_001394739, NM_001394740, NM_001394741, NM_001394742, NM_001394743, NM_001394744, NM_014696

CCDS: CCDS73101

Canonical transcript exons

ENST00000374314 — 3 exons

Exon	Start	End
ENSE00001463126	46554585	46554695
ENSE00003923399	46541736	46550742
ENSE00003926298	46556498	46556658

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 81.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3708 / max 28.5729, expressed in 132 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109277	0.3708	132

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper lobe of left lung	UBERON:0008952	81.58	gold quality
skin of leg	UBERON:0001511	81.56	gold quality
skin of abdomen	UBERON:0001416	81.02	gold quality
right lung	UBERON:0002167	78.90	gold quality
mucosa of transverse colon	UBERON:0004991	78.33	gold quality
upper lobe of lung	UBERON:0008948	78.23	gold quality
cortical plate	UBERON:0005343	78.15	gold quality
zone of skin	UBERON:0000014	77.94	gold quality
transverse colon	UBERON:0001157	72.32	gold quality
rectum	UBERON:0001052	72.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.02	gold quality
body of pancreas	UBERON:0001150	71.75	gold quality
hypothalamus	UBERON:0001898	70.96	gold quality
lower esophagus mucosa	UBERON:0035834	70.91	gold quality
cerebellar cortex	UBERON:0002129	70.78	gold quality
cerebellar hemisphere	UBERON:0002245	70.72	gold quality
small intestine	UBERON:0002108	70.49	gold quality
esophagus mucosa	UBERON:0002469	70.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	70.02	gold quality
body of stomach	UBERON:0001161	69.82	gold quality
cerebellum	UBERON:0002037	68.88	gold quality
lung	UBERON:0002048	68.70	gold quality
adenohypophysis	UBERON:0002196	68.38	gold quality
left lobe of thyroid gland	UBERON:0001120	67.92	gold quality
right lobe of thyroid gland	UBERON:0001119	67.58	gold quality
pituitary gland	UBERON:0000007	67.25	gold quality
metanephros cortex	UBERON:0010533	67.25	gold quality
stomach	UBERON:0000945	67.07	gold quality
thyroid gland	UBERON:0002046	66.94	gold quality
upper leg skin	UBERON:0004262	66.77	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting GPRIN2, 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-153-5P	99.89	73.86	6317
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-129-1-3P	98.86	68.41	779
HSA-MIR-129-2-3P	98.86	68.41	779
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-938	97.41	68.28	656
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-3940-3P	84.90	61.31	32

Literature-anchored findings (GeneRIF, showing 1)

• Four of these 16 variants were rare damaging mutations including novel mutations in KCNJ12/KCNJ18, and GPRIN2 genes. This WES study in Iranian patients with ESCC, provides insight into the identification of novel germline mutations in familial ESCC. Our data suggest an association between specific mutations and increased risk of ESCC (PMID:29405996)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gprin2	ENSMUSG00000071531
rattus_norvegicus	Gprin2	ENSRNOG00000077378

Paralogs (1): GPRIN3 (ENSG00000185477)

Protein

Protein identifiers

G protein-regulated inducer of neurite outgrowth 2 — O60269 (reviewed: O60269)

All UniProt accessions (1): O60269

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in neurite outgrowth.

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

Tissue specificity. Expressed specifically in the cerebellum.

RefSeq proteins (28): NP_001372204, NP_001372205, NP_001372206, NP_001372207, NP_001372208, NP_001372209, NP_001372210, NP_001372211, NP_001372212, NP_001372216, NP_001372218, NP_001372220, NP_001372222, NP_001372223, NP_001372224, NP_001372225, NP_001372226, NP_001372227, NP_001372228, NP_001372229, NP_001372230, NP_001381668, NP_001381669, NP_001381670, NP_001381671, NP_001381672, NP_001381673, NP_055511 (=MANE)

Domains & families (InterPro)

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

Pfam: PF15235

UniProt features (20 total): sequence variant 14, region of interest 2, compositionally biased region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60269-F1	51.18	0.04

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 60 (showing top): GOBP_NEUROGENESIS, MUELLER_PLURINET, MORF_PDPK1, GOBP_CELL_PROJECTION_ORGANIZATION, VANTVEER_BREAST_CANCER_ESR1_DN, MORF_MYST2, MORF_RBM8A, MODULE_13, WINNEPENNINCKX_MELANOMA_METASTASIS_DN, MORF_CNTN1, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MARTENS_TRETINOIN_RESPONSE_UP, MODULE_41, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, CBX5_TARGET_GENES

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

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

GO Cellular Component (1): plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron development	1
plasma membrane bounded cell projection organization	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

648 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPRIN2	HYDIN	Q4G0P3	914
GPRIN2	SRGAP2	O75044	858
GPRIN2	SRGAP3	O43295	850
GPRIN2	NBPF1	Q3BBV0	841
GPRIN2	DRD5	P21918	834
GPRIN2	UGT2B17	O75795	831
GPRIN2	NPEPPS	P55786	826
GPRIN2	GTF2I	P78347	780
GPRIN2	GNAZ	P19086	743
GPRIN2	GRIN1	P35437	676
GPRIN2	NPY4R2	P0DQD5	649
GPRIN2	GRIN2A	Q12879	582
GPRIN2	GNAO1	P09471	579
GPRIN2	GRIN2C	Q14957	578
GPRIN2	GRIN2B	Q13224	571

IntAct

14 interactions, top by confidence:

A	B	Type	Score
SFN	GPRIN2	psi-mi:“MI:0915”(physical association)	0.570
GPRIN2	DYNLL2	psi-mi:“MI:0915”(physical association)	0.550
GPRIN2	HTR4	psi-mi:“MI:0915”(physical association)	0.510
Hoxa1	GPRIN2	psi-mi:“MI:0915”(physical association)	0.370
TRIP13	GPRIN2	psi-mi:“MI:0915”(physical association)	0.370
GPRIN2	SPRY2	psi-mi:“MI:0915”(physical association)	0.370
MDFI	GPRIN2	psi-mi:“MI:0915”(physical association)	0.370
YWHAE	GPRIN2	psi-mi:“MI:0915”(physical association)	0.370
PLSCR1	GPRIN2	psi-mi:“MI:0915”(physical association)	0.370
GPRIN2	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (33): BCAP31 (Two-hybrid), KRTAP4-7 (Two-hybrid), DYNLL2 (Two-hybrid), KRTAP12-1 (Two-hybrid), KRTAP10-3 (Two-hybrid), GPRIN2 (Two-hybrid), SPRY2 (Two-hybrid), GPRIN2 (Two-hybrid), GPRIN2 (Two-hybrid), GPRIN2 (Two-hybrid), KRTAP4-12 (Two-hybrid), DYNLL2 (Two-hybrid), GPRIN2 (Two-hybrid), GPRIN2 (Reconstituted Complex), GPRIN2 (Two-hybrid)

ESM2 similar proteins: A0A096LP49, A0A8V8TNH8, A0A8V8TPE2, A2VE02, A5D7I0, A6NDY2, A6NGG8, A6NIJ5, A6NNJ1, A8MXJ8, A8MYA2, B1ASB6, B2RW88, D6RGX4, O60269, P0C7V4, P0C7W8, P0C7W9, P0C7X0, P0DV75, P0DV76, Q2KIS6, Q2NL68, Q3SY00, Q4R736, Q4V8B5, Q5RCQ2, Q5SZB4, Q5VZ46, Q5XIK6, Q658T7, Q66JV7, Q6NS69, Q6PAC4, Q6ZMY3, Q76N32, Q7TSA6, Q7Z591, Q80VW7, Q80X53

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

749 predictions. Top by Δscore:

Variant	Effect	Δscore
10:46550741:G:A	acceptor_loss	0.9900
10:46550741:G:GG	acceptor_gain	0.9900
10:46550741:GGC:G	acceptor_gain	0.9900
10:46550741:GGCA:G	acceptor_gain	0.9900
10:46550742:A:AG	acceptor_gain	0.9900
10:46550742:A:AT	acceptor_loss	0.9900
10:46550744:GCA:G	acceptor_loss	0.9900
10:46552084:G:GA	donor_gain	0.9900
10:46550745:T:A	acceptor_gain	0.9800
10:46550741:GG:G	acceptor_gain	0.9600
10:46550742:AG:A	acceptor_gain	0.9600
10:46552085:T:TA	donor_gain	0.9600
10:46554597:A:T	donor_gain	0.9200
10:46552104:G:GG	donor_gain	0.8900
10:46554582:G:GA	donor_loss	0.8900
10:46554583:GG:G	donor_loss	0.8900
10:46554584:AGGT:A	donor_loss	0.8900
10:46554585:AAG:A	donor_loss	0.8900
10:46554586:TAAG:T	donor_loss	0.8900
10:46554587:TTAAG:T	donor_loss	0.8900
10:46555497:GCCC:G	donor_gain	0.8800
10:46554007:G:GT	donor_gain	0.8700
10:46551536:G:T	acceptor_gain	0.8600
10:46551538:TAG:T	acceptor_gain	0.8600
10:46552006:GGT:G	acceptor_gain	0.8600
10:46552007:TGG:T	acceptor_gain	0.8600
10:46555375:GAG:G	donor_gain	0.8600
10:46552105:C:CG	donor_gain	0.8500
10:46553300:G:GA	donor_gain	0.8500
10:46554694:G:T	acceptor_gain	0.8500

AlphaMissense

2936 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:46549564:C:A	W391C	0.985
10:46549564:C:G	W391C	0.985
10:46549566:A:G	W391R	0.984
10:46549566:A:T	W391R	0.984
10:46549585:C:A	W384C	0.980
10:46549585:C:G	W384C	0.980
10:46549517:A:T	I407N	0.976
10:46549517:A:G	I407T	0.975
10:46549571:A:G	M389T	0.971
10:46549587:A:G	W384R	0.971
10:46549587:A:T	W384R	0.971
10:46549517:A:C	I407S	0.970
10:46549505:A:G	L411P	0.943
10:46549582:A:C	D385E	0.939
10:46549582:A:T	D385E	0.939
10:46549584:C:G	D385H	0.937
10:46549939:G:C	S266R	0.935
10:46549939:G:T	S266R	0.935
10:46549941:T:G	S266R	0.935
10:46549575:C:G	G388R	0.930
10:46549583:T:A	D385V	0.930
10:46549513:C:A	Q408H	0.929
10:46549513:C:G	Q408H	0.929
10:46549570:C:A	M389I	0.927
10:46549570:C:G	M389I	0.927
10:46549570:C:T	M389I	0.927
10:46549583:T:G	D385A	0.927
10:46549963:A:C	F258L	0.925
10:46549963:A:T	F258L	0.925
10:46549965:A:G	F258L	0.925

dbSNP variants (sampled 300 via entrez): RS1000155995 (10:46555124 T>G), RS1000330131 (10:46558899 G>A), RS1000565599 (10:46544846 A>G), RS1000957539 (10:46547764 C>T), RS1000976129 (10:46543665 T>C), RS1001052525 (10:46547903 G>C), RS1001294607 (10:46546874 C>A), RS1001379672 (10:46551031 G>A), RS1001389003 (10:46547026 A>G,T), RS1001597982 (10:46557931 T>C), RS1001745083 (10:46554433 T>C), RS1002023616 (10:46557257 C>T), RS1002081987 (10:46553186 C>G,T), RS1002091228 (10:46558061 C>G,T), RS1002155736 (10:46552980 G>A)

Disease associations

OMIM: gene MIM:611240 | 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

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
Estradiol	affects binding, increases expression, affects cotreatment, decreases expression	2
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
abrine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Methapyrilene	increases methylation	1
Rotenone	decreases expression	1
Selenium	decreases expression, affects cotreatment	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Vitamin E	decreases expression, affects cotreatment	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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