GLIPR2

Summary

GLIPR2 (GLI pathogenesis related 2, HGNC:18007) is a protein-coding gene on chromosome 9p13.3, encoding Golgi-associated plant pathogenesis-related protein 1 (Q9H4G4).

Enables protein homodimerization activity. Involved in positive regulation of ERK1 and ERK2 cascade; positive regulation of epithelial cell migration; and positive regulation of epithelial to mesenchymal transition. Located in Golgi membrane. Biomarker of pancreatic ductal adenocarcinoma.

Source: NCBI Gene 152007 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_022343

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18007
Approved symbol	GLIPR2
Name	GLI pathogenesis related 2
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	GAPR-1
Ensembl gene	ENSG00000122694
Ensembl biotype	protein_coding
OMIM	607141
Entrez	152007

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000377959, ENST00000377960, ENST00000396613, ENST00000474050, ENST00000619700, ENST00000885959, ENST00000885960

RefSeq mRNA: 6 — MANE Select: NM_022343 NM_001287010, NM_001287011, NM_001287012, NM_001287013, NM_001287014, NM_022343

CCDS: CCDS6598, CCDS69595, CCDS75832, CCDS75833

Canonical transcript exons

ENST00000377960 — 5 exons

Exon	Start	End
ENSE00001844830	36136733	36136791
ENSE00003478827	36148547	36148650
ENSE00003603602	36150872	36150949
ENSE00003651987	36147786	36147894
ENSE00003845208	36162362	36163906

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 98.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.2095 / max 467.9053, expressed in 1705 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96660	31.6341	1691
96661	2.3506	1128
96659	0.2248	113

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.63	gold quality
leukocyte	CL:0000738	98.63	gold quality
granulocyte	CL:0000094	98.37	gold quality
blood	UBERON:0000178	97.71	gold quality
saphenous vein	UBERON:0007318	96.46	gold quality
smooth muscle tissue	UBERON:0001135	96.41	gold quality
nasal cavity epithelium	UBERON:0005384	96.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.69	gold quality
synovial joint	UBERON:0002217	95.41	gold quality
vermiform appendix	UBERON:0001154	95.20	gold quality
bone marrow	UBERON:0002371	95.16	gold quality
layer of synovial tissue	UBERON:0007616	95.10	gold quality
caecum	UBERON:0001153	94.98	gold quality
left uterine tube	UBERON:0001303	94.54	gold quality
myometrium	UBERON:0001296	94.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.18	gold quality
lower esophagus	UBERON:0013473	94.12	gold quality
body of uterus	UBERON:0009853	93.98	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.76	gold quality
bronchial epithelial cell	CL:0002328	93.72	gold quality
urethra	UBERON:0000057	93.68	gold quality
bronchus	UBERON:0002185	93.63	gold quality
trachea	UBERON:0003126	93.57	gold quality
mucosa of stomach	UBERON:0001199	93.44	gold quality
amniotic fluid	UBERON:0000173	92.88	gold quality
right lung	UBERON:0002167	92.81	gold quality
upper lobe of left lung	UBERON:0008952	92.79	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.78	gold quality
stromal cell of endometrium	CL:0002255	92.69	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	92.01
E-CURD-122	yes	66.92
E-MTAB-9067	yes	13.59
E-CURD-88	yes	11.27
E-MTAB-9388	yes	10.38
E-MTAB-8498	yes	10.09
E-CURD-112	yes	8.76
E-MTAB-8271	yes	7.20
E-MTAB-9801	yes	6.61
E-GEOD-124858	no	144.94
E-MTAB-7303	no	103.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting GLIPR2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378

Literature-anchored findings (GeneRIF, showing 8)

• the charge properties of the lipid bilayer can regulate GAPR-1 dynamics as a potential mechanism to modulate GAPR-1 function (PMID:22560898)
• GLIPR-2 overexpression in HK-2 cells can potentiate EMT-like processes in this cell type through the ERK1/2 signaling pathway (PMID:23516513)
• Hypoxia promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells via inducing GLIPR-2 expression. (PMID:24204846)
• This study identified a previously unrecognized role for GAPR-1 to control a unifying TLR4 signaling complex and to regulate type I Interferon signaling activation. (PMID:26678074)
• Here, sequence analyses, structural modeling, mutagenesis combined with pull-down assays, X-ray crystal structure determination and small-angle X-ray scattering were used to investigate the Beclin 1-GAPR-1 interaction. changes in the structure of the equatorial groove combined with the improved dimerization of pentad mutant GAPR-1 are likely to abrogate binding to Beclin 1. (PMID:28876241)
• GLIPR2 is a negative regulator of autophagy and the BECN1-ATG14-containing phosphatidylinositol 3-kinase complex. (PMID:33222586)
• Dynamic and Reversible Aggregation of the Human CAP Superfamily Member GAPR-1 in Protein Inclusions in Saccharomyces cerevisiae. (PMID:34298062)
• GAPR-1 Interferes with Condensate Formation of Beclin 1 in Saccharomyces cerevisiae. (PMID:36586462)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	glipr2l	ENSDARG00000016837
mus_musculus	Glipr2	ENSMUSG00000028480
rattus_norvegicus	Glipr2	ENSRNOG00000014838
drosophila_melanogaster	CG31482	FBGN0051482
caenorhabditis_elegans		WBGENE00008604

Paralogs (13): CRISP3 (ENSG00000096006), R3HDML (ENSG00000101074), CRISPLD2 (ENSG00000103196), CRISPLD1 (ENSG00000121005), CRISP2 (ENSG00000124490), CRISP1 (ENSG00000124812), PI15 (ENSG00000137558), GLIPR1 (ENSG00000139278), CLEC18B (ENSG00000140839), CLEC18A (ENSG00000157322), CLEC18C (ENSG00000157335), GLIPR1L1 (ENSG00000173401), GLIPR1L2 (ENSG00000180481)

Protein

Protein identifiers

Golgi-associated plant pathogenesis-related protein 1 — Q9H4G4 (reviewed: Q9H4G4)

Alternative names: Glioma pathogenesis-related protein 2

All UniProt accessions (4): A0A087WUM5, A0A088AWP7, Q9H4G4, Q5VZR0

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Homodimer. Interacts with CAV1.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Highest expression in lung and peripheral leukocytes, and minor expression in liver and kidney.

Similarity. Belongs to the CRISP family.

RefSeq proteins (6): NP_001273939, NP_001273940, NP_001273941, NP_001273942, NP_001273943, NP_071738* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001283	CRISP-related	Family
IPR014044	CAP_dom	Domain
IPR018244	Allrgn_V5/Tpx1_CS	Conserved_site
IPR034113	SCP_GAPR1-like	Domain
IPR035940	CAP_sf	Homologous_superfamily

Pfam: PF00188

UniProt features (22 total): helix 8, sequence conflict 3, strand 3, region of interest 2, initiator methionine 1, chain 1, domain 1, coiled-coil region 1, compositionally biased region 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5VHG	X-RAY DIFFRACTION	1.27
4AIW	X-RAY DIFFRACTION	1.5
1SMB	X-RAY DIFFRACTION	1.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4G4-F1	95.41	0.92

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 214 (showing top): AGGAAGC_MIR5163P, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, CEBPB_01, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, MODULE_205, GOBP_MESENCHYMAL_CELL_DIFFERENTIATION, FOSTER_TOLERANT_MACROPHAGE_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_TISSUE_MIGRATION, chr9p13, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (3): positive regulation of epithelial cell migration (GO:0010634), positive regulation of epithelial to mesenchymal transition (GO:0010718), positive regulation of ERK1 and ERK2 cascade (GO:0070374)

GO Molecular Function (1): protein homodimerization activity (GO:0042803)

GO Cellular Component (6): Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
epithelial cell migration	1
regulation of epithelial cell migration	1
positive regulation of cell migration	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
identical protein binding	1
protein dimerization activity	1
Golgi apparatus	1
bounding membrane of organelle	1
extracellular vesicle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLIPR2	BECN1	Q14457	857
GLIPR2	GLIPR1	P48060	574
GLIPR2	TMEM37	Q8WXS4	540
GLIPR2	CRISP1	P54107	527
GLIPR2	UVRAG	Q9P2Y5	521
GLIPR2	RUBCN	Q92622	499
GLIPR2	FAM90A7	A6NKC0	474
GLIPR2	TFEB	P19484	463
GLIPR2	SQSTM1	Q13501	446
GLIPR2	PRKN	O60260	396
GLIPR2	CRIP2	P52943	386
GLIPR2	SLC46A2	Q9BY10	381
GLIPR2	ZFYVE1	Q9HBF4	379
GLIPR2	PLAC8L1	A1L4L8	367
GLIPR2	EIF4E1B	A6NMX2	337

IntAct

14 interactions, top by confidence:

A	B	Type	Score
BECN1	GLIPR2	psi-mi:“MI:0915”(physical association)	0.400
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	E2F3	psi-mi:“MI:0914”(association)	0.350
VAMP5	ESYT2	psi-mi:“MI:0914”(association)	0.350
ZBTB18	DNASE1L1	psi-mi:“MI:0914”(association)	0.350
HASPIN	MYO1C	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): GLIPR2 (Two-hybrid), KRTAP10-3 (Two-hybrid), GLIPR2 (Affinity Capture-MS), GLIPR2 (Biochemical Activity), GLIPR2 (Affinity Capture-MS), GLIPR2 (Affinity Capture-MS), GLIPR2 (Affinity Capture-MS), GLIPR2 (Affinity Capture-MS), GLIPR2 (Affinity Capture-MS), GLIPR2 (Affinity Capture-MS), GLIPR2 (Affinity Capture-MS), GLIPR2 (Affinity Capture-MS), GLIPR2 (Affinity Capture-MS), GLIPR2 (Proximity Label-MS), GLIPR2 (Proximity Label-MS)

ESM2 similar proteins: A6MFK9, A8S6B6, B7FDI0, B7FDI1, F8J2D4, O19010, P04284, P07053, P08299, P09042, P0CB15, P0DMT4, P11670, P16563, P33154, P35792, P35793, P54108, P79845, P84808, Q00008, Q04108, Q05968, Q08697, Q2XXP4, Q2XXP5, Q2XXQ1, Q2XXQ5, Q2XXQ6, Q2XXQ7, Q3SB03, Q3SB04, Q3SB05, Q3SB06, Q3SB07, Q40374, Q41359, Q60477, Q7ZT99, Q7ZTA0

Diamond homologs: A2VEC9, B3EWY9, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXF5, D3YXG0, D3ZTD8, F1LW30, G5ECS8, O08721, O08722, O08747, O14514, O15072, O60241, O60242, O95185, O95428, O95450, P07053, P07996, P08299, P09042, P10643, P11670, P11680, P27918, P33154, P35440, P35441, P35442, P35446, P35447, P35448, P35792, P35793, P47032, P55314

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IRAK1	“up-regulates activity”	GLIPR2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1046 predictions. Top by Δscore:

Variant	Effect	Δscore
9:36136885:G:GT	donor_gain	1.0000
9:36136885:G:T	donor_gain	1.0000
9:36147775:A:AG	acceptor_gain	1.0000
9:36147895:G:GG	donor_gain	1.0000
9:36136787:GTCAG:G	donor_gain	0.9900
9:36136788:TCAGG:T	donor_loss	0.9900
9:36136789:CAGG:C	donor_loss	0.9900
9:36136790:AGGTG:A	donor_loss	0.9900
9:36136791:GGT:G	donor_loss	0.9900
9:36136792:GTGAG:G	donor_loss	0.9900
9:36136793:T:A	donor_loss	0.9900
9:36137805:GATGA:G	donor_gain	0.9900
9:36137806:A:G	donor_gain	0.9900
9:36147776:A:G	acceptor_gain	0.9900
9:36147782:CCA:C	acceptor_loss	0.9900
9:36147783:CAG:C	acceptor_loss	0.9900
9:36147784:A:AC	acceptor_loss	0.9900
9:36147784:A:AG	acceptor_gain	0.9900
9:36147785:G:GC	acceptor_gain	0.9900
9:36147785:GC:G	acceptor_gain	0.9900
9:36147785:GCTT:G	acceptor_gain	0.9900
9:36147785:GCTTC:G	acceptor_gain	0.9900
9:36147892:ACA:A	donor_gain	0.9900
9:36147892:ACAG:A	donor_loss	0.9900
9:36147895:G:A	donor_loss	0.9900
9:36147896:TGAGT:T	donor_loss	0.9900
9:36147898:AGT:A	donor_loss	0.9900
9:36147899:G:C	donor_loss	0.9900
9:36148457:G:T	donor_gain	0.9900
9:36136784:C:T	donor_gain	0.9800

AlphaMissense

1019 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:36150892:T:A	W83R	0.998
9:36150892:T:C	W83R	0.998
9:36162382:T:A	W109R	0.996
9:36162382:T:C	W109R	0.996
9:36162367:T:C	F104L	0.995
9:36162369:C:A	F104L	0.995
9:36162369:C:G	F104L	0.995
9:36147834:G:C	R21P	0.994
9:36150894:G:C	W83C	0.994
9:36150894:G:T	W83C	0.994
9:36148622:C:A	N66K	0.993
9:36148622:C:G	N66K	0.993
9:36162368:T:C	F104S	0.993
9:36162384:G:C	W109C	0.993
9:36162384:G:T	W109C	0.993
9:36150934:T:C	F97L	0.992
9:36150936:C:A	F97L	0.992
9:36150936:C:G	F97L	0.992
9:36162471:T:A	N138K	0.992
9:36162471:T:G	N138K	0.992
9:36150893:G:C	W83S	0.990
9:36162439:T:C	F128L	0.990
9:36162441:T:A	F128L	0.990
9:36162441:T:G	F128L	0.990
9:36162449:C:A	A131D	0.990
9:36150902:A:T	E86V	0.989
9:36148626:G:C	A68P	0.988
9:36150919:T:C	F92L	0.988
9:36150921:C:A	F92L	0.988
9:36150921:C:G	F92L	0.988

dbSNP variants (sampled 300 via entrez): RS1000286593 (9:36145248 A>C,G), RS1000293579 (9:36149341 C>T), RS1000324246 (9:36157060 G>A), RS1000409195 (9:36149620 C>T), RS1000624272 (9:36150620 A>G), RS1000629438 (9:36143353 ACCT>A), RS1000738354 (9:36150785 G>C), RS1000809735 (9:36139091 A>T), RS1001034748 (9:36144893 T>G), RS1001044107 (9:36139302 C>T), RS1001070185 (9:36145093 T>A,C), RS1001201923 (9:36149320 G>T), RS1001329072 (9:36155689 T>C), RS1001382457 (9:36156073 G>A,T), RS1001626169 (9:36155106 A>G)

Disease associations

OMIM: gene MIM:607141 | disease phenotypes: MIM:108120

GenCC curated gene-disease

Mondo (1): arthrogryposis, distal, type 1A (MONDO:0007157)

Orphanet (1): Distal arthrogryposis type 1 (Orphanet:1146)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002815_5	Bipolar disorder (inflammation and infection response interaction)	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007050	HSV1 seropositivity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, increases expression, increases methylation	5
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, decreases methylation	4
Valproic Acid	decreases expression, affects cotreatment, increases expression	4
bisphenol A	decreases expression, increases expression	2
sodium arsenite	increases abundance, decreases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression, increases expression	2
Acetaminophen	affects expression, increases expression	2
Nickel	increases expression	2
Smoke	decreases expression	2
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
calfactant	affects cotreatment, increases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	affects expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01144741	Not specified	TERMINATED	Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome
NCT05393375	Not specified	COMPLETED	Arthrogryposis Multiplex Congenita in Pediatric Age: Correlation Between MUScular MRI and Functional Evaluation
NCT05673265	Not specified	UNKNOWN	Pediatric and Adult Registry for Patients With ARThrogryposis
NCT06130592	Not specified	UNKNOWN	Technical Feasibility Study of Ultrasound Muscle Imaging in Antenatal Ultrasound
NCT07360574	Not specified	NOT_YET_RECRUITING	Piezo2-related Arthrogryposis & physiopathOLOgy 3