GRID2IP

Summary

GRID2IP (Grid2 interacting protein, HGNC:18464) is a protein-coding gene on chromosome 7p22.1, encoding Delphilin (A4D2P6). Postsynaptic scaffolding protein at the parallel fiber-Purkinje cell synapse, where it may serve to link GRID2 with actin cytoskeleton and various signaling molecules.

Glutamate receptor delta-2 (GRID2; MIM 602368) is predominantly expressed at parallel fiber-Purkinje cell postsynapses and plays crucial roles in synaptogenesis and synaptic plasticity. GRID2IP1 interacts with GRID2 and may control GRID2 signaling in Purkinje cells (Matsuda et al., 2006 [PubMed 16835239]).

Source: NCBI Gene 392862 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 278 total
• MANE Select transcript: NM_001145118

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18464
Approved symbol	GRID2IP
Name	Grid2 interacting protein
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000215045
Ensembl biotype	protein_coding
OMIM	610639
Entrez	392862

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000435185, ENST00000452113, ENST00000457091

RefSeq mRNA: 3 — MANE Select: NM_001145118 NM_001145118, NM_001388403, NM_001394781

CCDS: CCDS47537, CCDS94054

Canonical transcript exons

ENST00000457091 — 22 exons

Exon	Start	End
ENSE00001538640	6496778	6497845
ENSE00001538644	6498064	6498228
ENSE00001538652	6501781	6501899
ENSE00001538654	6501989	6502118
ENSE00001538657	6502786	6502872
ENSE00001538660	6503008	6503163
ENSE00001538662	6503491	6503687
ENSE00001538666	6504793	6504870
ENSE00001538669	6505820	6505907
ENSE00001538670	6507985	6508401
ENSE00001538674	6508958	6509313
ENSE00001538676	6510283	6510400
ENSE00001538679	6510609	6510706
ENSE00001538682	6510908	6511039
ENSE00001538685	6514375	6514529
ENSE00001538691	6520578	6520761
ENSE00001538698	6521429	6521523
ENSE00001538700	6521888	6521957
ENSE00001538702	6526224	6526309
ENSE00001538704	6526521	6526769
ENSE00001538707	6539718	6539872
ENSE00001538709	6551008	6551461

Expression profiles

Bgee: expression breadth ubiquitous, 112 present calls, max score 63.53.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4198 / max 53.9687, expressed in 158 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82657	0.2703	108
82658	0.1115	40
82656	0.0380	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	63.53	gold quality
cerebellum	UBERON:0002037	60.36	gold quality
cortical plate	UBERON:0005343	60.17	gold quality
cerebellar cortex	UBERON:0002129	60.10	gold quality
cerebellar hemisphere	UBERON:0002245	59.99	gold quality
lower esophagus mucosa	UBERON:0035834	58.87	gold quality
bone marrow cell	CL:0002092	58.10	gold quality
right adrenal gland	UBERON:0001233	57.86	gold quality
pituitary gland	UBERON:0000007	57.06	gold quality
right adrenal gland cortex	UBERON:0035827	56.99	gold quality
left adrenal gland	UBERON:0001234	56.82	gold quality
left adrenal gland cortex	UBERON:0035825	56.63	gold quality
adenohypophysis	UBERON:0002196	56.33	gold quality
adrenal gland	UBERON:0002369	55.69	gold quality
prefrontal cortex	UBERON:0000451	55.40	gold quality
esophagus mucosa	UBERON:0002469	54.71	gold quality
body of pancreas	UBERON:0001150	54.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	53.78	gold quality
adrenal tissue	UBERON:0018303	53.78	gold quality
colonic epithelium	UBERON:0000397	53.37	gold quality
primary visual cortex	UBERON:0002436	53.18	gold quality
duodenum	UBERON:0002114	53.10	gold quality
pancreas	UBERON:0001264	53.01	gold quality
saliva-secreting gland	UBERON:0001044	52.84	gold quality
bone marrow	UBERON:0002371	52.73	gold quality
skin of abdomen	UBERON:0001416	52.57	gold quality
minor salivary gland	UBERON:0001830	52.57	gold quality
putamen	UBERON:0001874	52.47	gold quality
right uterine tube	UBERON:0001302	52.31	gold quality
frontal cortex	UBERON:0001870	52.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting GRID2IP, 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-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-3151-3P	97.80	66.16	479
HSA-MIR-1913	97.07	66.20	1417

Literature-anchored findings (GeneRIF, showing 4)

• delphilin isoforms with differential palmitoylation and clustering capabilities may provide two separate intracellular and surface GluRdelta2 pools and may control GluRdelta2 signaling in Purkinje cells (PMID:16835239)
• Thus, phosphorylation of -2T and/or -1S of GluRdelta2 C-terminus by PKA may regulate the binding of GluRdelta2 to its scaffolding protein, Delphilin. (PMID:17027646)
• Delphilin is an actin nucleator that does not accelerate elongation. Delphilin exhibits a preference for actin isoforms, nucleating nonmuscle actin but not muscle actin. (PMID:29282276)
• Grid2 interacting protein is a potential biomarker related to immune infiltration in colorectal cancer. (PMID:37964339)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	grid2ipa	ENSDARG00000076103
danio_rerio	grid2ipb	ENSDARG00000095603
mus_musculus	Grid2ip	ENSMUSG00000010825
rattus_norvegicus	Grid2ip	ENSRNOG00000030927
caenorhabditis_elegans	fhod-1	WBGENE00016735
caenorhabditis_elegans		WBGENE00018976

Paralogs (18): DAAM1 (ENSG00000100592), FNBP4 (ENSG00000109920), DIAPH1 (ENSG00000131504), FHOD3 (ENSG00000134775), FHOD1 (ENSG00000135723), FHDC1 (ENSG00000137460), DIAPH3 (ENSG00000139734), DAAM2 (ENSG00000146122), DIAPH2 (ENSG00000147202), FMN2 (ENSG00000155816), FMNL2 (ENSG00000157827), FMNL3 (ENSG00000161791), FMNL1 (ENSG00000184922), FAM47A (ENSG00000185448), SHTN1 (ENSG00000187164), FAM47B (ENSG00000189132), FAM47C (ENSG00000198173), INF2 (ENSG00000203485)

Protein

Protein identifiers

Delphilin — A4D2P6 (reviewed: A4D2P6)

Alternative names: Glutamate receptor, ionotropic, delta 2-interacting protein 1

All UniProt accessions (3): A4D2P6, C9J5F6, C9JNS8

UniProt curated annotations — full annotation on UniProt →

Function. Postsynaptic scaffolding protein at the parallel fiber-Purkinje cell synapse, where it may serve to link GRID2 with actin cytoskeleton and various signaling molecules.

Subunit / interactions. Interacts with C-terminus of the glutamate receptor GRID2 via PDZ domain.

Subcellular location. Postsynaptic cell membrane.

RefSeq proteins (3): NP_001138590, NP_001375332, NP_001381710 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR015425	FH2_Formin	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR042201	FH2_Formin_sf	Homologous_superfamily
IPR051425	Formin_Homology	Family

Pfam: PF00595, PF02181

UniProt features (23 total): compositionally biased region 8, region of interest 6, modified residue 4, domain 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A4D2P6-F1	67.21	0.27

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 (4): 580, 621, 652, 655

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 48 (showing top): chr7p22, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_LONG_TERM_SYNAPTIC_DEPRESSION, GOBP_NEGATIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION, GOBP_SYNAPTIC_SIGNALING, GOBP_REGULATION_OF_CYTOSOLIC_CALCIUM_ION_CONCENTRATION, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOCC_EXCITATORY_SYNAPSE, GOCC_POSTSYNAPSE, GOBP_HOMEOSTATIC_PROCESS, GOCC_SYNAPSE, GOCC_POSTSYNAPTIC_MEMBRANE, GOBP_CHEMICAL_HOMEOSTASIS, GOCC_PLASMA_MEMBRANE_REGION

GO Biological Process (3): long-term synaptic depression (GO:0060292), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072), regulation of postsynaptic cytosolic calcium ion concentration (GO:0099566)

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

GO Cellular Component (8): postsynaptic membrane (GO:0045211), parallel fiber to Purkinje cell synapse (GO:0098688), postsynaptic density, intracellular component (GO:0099092), cerebellar granule cell to Purkinje cell synapse (GO:0150048), plasma membrane (GO:0005886), membrane (GO:0016020), synapse (GO:0045202), glutamatergic synapse (GO:0098978)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
postsynapse	2
regulation of synaptic plasticity	1
negative regulation of synaptic transmission	1
regulation of biological quality	1
regulation of cytosolic calcium ion concentration	1
binding	1
synaptic membrane	1
excitatory synapse	1
postsynaptic density	1
postsynaptic specialization, intracellular component	1
asymmetric, glutamatergic, excitatory synapse	1
membrane	1
cell periphery	1
cellular anatomical structure	1
cell junction	1
synapse	1

Protein interactions and networks

STRING

678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRID2IP	GRID2	O43424	978
GRID2IP	FNBP4	Q8N3X1	630
GRID2IP	FNBP1	Q96RU3	609
GRID2IP	KDELR2	P33947	583
GRID2IP	GRID1	Q9ULK0	559
GRID2IP	PFN3	P60673	551
GRID2IP	WBP4	O75554	547
GRID2IP	PFN4	Q8NHR9	538
GRID2IP	PRPF40A	O75400	529
GRID2IP	PFN1	P07737	525
GRID2IP	FMN2	Q9NZ56	523
GRID2IP	SRGAP2	O75044	516
GRID2IP	GRIK5	Q16478	488
GRID2IP	FHDC1	Q9C0D6	459
GRID2IP	CTTN	Q14247	406

IntAct

772 interactions, top by confidence:

A	B	Type	Score
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
GRID2IP	RPS6KA1	psi-mi:“MI:0407”(direct interaction)	0.610
PTEN	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.610
E6	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.610
GRID2IP	E6	psi-mi:“MI:0915”(physical association)	0.610
GRID2IP	PTEN	psi-mi:“MI:0915”(physical association)	0.610
GRID2IP	RPS6KA1	psi-mi:“MI:0915”(physical association)	0.610
RPS6KA1	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.610
BAIAP2L1	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
GRID2IP	E6	psi-mi:“MI:0407”(direct interaction)	0.440
Tax	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
NET1	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
GRID2IP	SLC22A3	psi-mi:“MI:0407”(direct interaction)	0.440
L2	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
OR8G1	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
GRID2IP	GNG4	psi-mi:“MI:0407”(direct interaction)	0.440
MCM7	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
CD46	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (9): GRID2IP (Protein-peptide), GRID2IP (Two-hybrid), GRID2IP (Reconstituted Complex), GRID2IP (Affinity Capture-Western), GRID2IP (Affinity Capture-MS), GRID2IP (Affinity Capture-MS), GRID2IP (Affinity Capture-MS), GRID2IP (Affinity Capture-MS), GRID2IP (Affinity Capture-RNA)

ESM2 similar proteins: A0A8I3NFE2, A0FI79, A1A5B6, A4D2P6, D7PF45, F1LXF1, O15357, O60346, O75808, P11274, P49796, P52734, P53349, P59672, P70268, P78524, P98174, Q0QWG9, Q13233, Q13905, Q16825, Q3MII6, Q50H33, Q5RDA9, Q62925, Q63433, Q6NS60, Q6P549, Q6PDJ6, Q6WVG3, Q7Z5H3, Q8BL80, Q8BUP8, Q8N2R8, Q8TF61, Q8VHK2, Q8WXD9, Q924W7, Q92625, Q96CX2

Diamond homologs: A0A1D5P556, A4D2P6, B0DOB5, O08808, O23373, O60610, O70566, Q6MWG9, Q80U19, Q86T65, Q8BPM0, Q9FJX6, Q9Y4D1, A0A8C0TYJ0, A5PKA5, A8MUH7, B7WN72, G5ECY0, O08774, O14745, O14924, O15085, O60879, P31007, P31016, P70175, P70441, P78352, P97879, Q09506, Q0D5P3, Q0QWG9, Q12959, Q13425, Q15599, Q15700, Q28619, Q28C55, Q3T0X8, Q3UHD6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GRID2IP	“up-regulates quantity”	GRID2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 158 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
Transcriptional and post-translational regulation of MITF-M expression and activity	7	11.8×	8e-04
Signaling by GPCR	12	4.5×	3e-03
GPCR downstream signalling	11	4.5×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	246
Likely benign	15
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3981 predictions. Top by Δscore:

Variant	Effect	Δscore
7:6501836:T:TA	donor_gain	1.0000
7:6501900:C:CC	acceptor_gain	1.0000
7:6501983:GCATA:G	donor_loss	1.0000
7:6501984:CATA:C	donor_loss	1.0000
7:6501986:TACCT:T	donor_loss	1.0000
7:6502116:CAG:C	acceptor_gain	1.0000
7:6502119:C:CC	acceptor_gain	1.0000
7:6502781:CTCA:C	donor_loss	1.0000
7:6502782:TCAC:T	donor_loss	1.0000
7:6502783:CACC:C	donor_loss	1.0000
7:6502784:A:AG	donor_loss	1.0000
7:6502785:CCT:C	donor_gain	1.0000
7:6502869:CAAA:C	acceptor_gain	1.0000
7:6502873:C:CC	acceptor_gain	1.0000
7:6503002:A:AC	donor_gain	1.0000
7:6503003:C:CC	donor_gain	1.0000
7:6503005:GACCT:G	donor_loss	1.0000
7:6503006:A:AC	donor_gain	1.0000
7:6503006:A:AT	donor_loss	1.0000
7:6503006:ACCT:A	donor_gain	1.0000
7:6503007:C:CC	donor_gain	1.0000
7:6503007:CCT:C	donor_gain	1.0000
7:6503007:CCTC:C	donor_gain	1.0000
7:6503009:T:TA	donor_gain	1.0000
7:6503502:A:AC	donor_gain	1.0000
7:6503503:C:CC	donor_gain	1.0000
7:6503685:TGG:T	acceptor_gain	1.0000
7:6504791:A:AC	donor_gain	1.0000
7:6504792:C:CC	donor_gain	1.0000
7:6504792:CAG:C	donor_gain	1.0000

AlphaMissense

7840 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:6503588:A:G	L937P	1.000
7:6503681:A:G	L906P	1.000
7:6503684:A:G	I905T	1.000
7:6503684:A:T	I905N	1.000
7:6504809:C:A	K898N	1.000
7:6504809:C:G	K898N	1.000
7:6507991:C:A	W846C	1.000
7:6507991:C:G	W846C	1.000
7:6507993:A:G	W846R	1.000
7:6507993:A:T	W846R	1.000
7:6508024:C:A	W835C	1.000
7:6508024:C:G	W835C	1.000
7:6508025:C:G	W835S	1.000
7:6508026:A:G	W835R	1.000
7:6508026:A:T	W835R	1.000
7:6508031:A:G	L833S	1.000
7:6521464:A:G	L350P	1.000
7:6521470:G:T	P348H	1.000
7:6521491:A:G	L341P	1.000
7:6521906:A:G	L324P	1.000
7:6521915:A:C	I321S	1.000
7:6521915:A:G	I321T	1.000
7:6521915:A:T	I321N	1.000
7:6526247:A:T	V299D	1.000
7:6526265:A:G	L293P	1.000
7:6526265:A:T	L293H	1.000
7:6526271:A:G	F291S	1.000
7:6501997:G:T	A1091D	0.999
7:6502069:A:G	L1067P	0.999
7:6502793:A:G	L1048P	0.999

dbSNP variants (sampled 300 via entrez): RS1000025927 (7:6547644 C>G), RS1000074170 (7:6528981 A>G), RS1000104534 (7:6508180 C>A,G,T), RS1000180692 (7:6550504 C>A,G), RS1000229441 (7:6510524 G>T), RS1000285418 (7:6545012 G>A), RS1000440460 (7:6540140 G>A), RS1000471580 (7:6518849 C>T), RS1000489832 (7:6540366 C>G,T), RS1000521206 (7:6509043 C>T), RS1000528563 (7:6525215 G>A), RS1000586368 (7:6520015 C>T), RS1000638289 (7:6548638 C>G,T), RS1000696711 (7:6545270 C>A,T), RS1000698054 (7:6509247 G>A,C)

Disease associations

OMIM: gene MIM:610639 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002629_2	Irritable bowel syndrome	5.000000e-06
GCST004131_9	Inflammatory bowel disease	4.000000e-08
GCST004133_37	Ulcerative colitis	2.000000e-06
GCST005951_155	Body mass index	1.000000e-08
GCST012489_19	Heel bone mineral density x serum urate levels interaction	6.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
bisphenol A	increases methylation	1
cypermethrin	decreases expression	1
benzo(e)pyrene	increases methylation	1
Fulvestrant	increases methylation	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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