GIPC2

Summary

GIPC2 (GIPC PDZ domain containing family member 2, HGNC:18177) is a protein-coding gene on chromosome 1p31.1, encoding PDZ domain-containing protein GIPC2 (Q8TF65).

Enables identical protein binding activity. Located in extracellular exosome.

Source: NCBI Gene 54810 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_017655

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18177
Approved symbol	GIPC2
Name	GIPC PDZ domain containing family member 2
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20075, SEMCAP-2
Ensembl gene	ENSG00000137960
Ensembl biotype	protein_coding
OMIM	619089
Entrez	54810

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000370759, ENST00000476882, ENST00000911079, ENST00000911080, ENST00000911081, ENST00000911082, ENST00000911083, ENST00000936885

RefSeq mRNA: 2 — MANE Select: NM_017655 NM_001304725, NM_017655

CCDS: CCDS685

Canonical transcript exons

ENST00000370759 — 6 exons

Exon	Start	End
ENSE00001289777	78094952	78095132
ENSE00001300945	78119393	78119499
ENSE00001301792	78125881	78125962
ENSE00001453574	78135592	78138444
ENSE00001453577	78045966	78046334
ENSE00003676261	78080675	78080860

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 94.94.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9678 / max 151.4536, expressed in 608 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3656	0.6588	116
3655	0.6094	258
3643	0.5064	211
3642	0.1202	24
3657	0.0454	14
3654	0.0278	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	94.94	gold quality
duodenum	UBERON:0002114	93.37	gold quality
ileal mucosa	UBERON:0000331	92.28	gold quality
adrenal tissue	UBERON:0018303	92.20	gold quality
nephron tubule	UBERON:0001231	89.80	gold quality
mucosa of transverse colon	UBERON:0004991	88.54	gold quality
colonic mucosa	UBERON:0000317	87.86	gold quality
body of pancreas	UBERON:0001150	87.57	gold quality
left adrenal gland	UBERON:0001234	87.27	gold quality
right adrenal gland	UBERON:0001233	87.07	gold quality
adrenal gland	UBERON:0002369	86.96	gold quality
left adrenal gland cortex	UBERON:0035825	86.93	gold quality
right adrenal gland cortex	UBERON:0035827	86.64	gold quality
rectum	UBERON:0001052	86.62	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.60	gold quality
adrenal cortex	UBERON:0001235	86.24	gold quality
kidney epithelium	UBERON:0004819	86.17	gold quality
adult mammalian kidney	UBERON:0000082	85.68	gold quality
spleen	UBERON:0002106	83.62	gold quality
pancreas	UBERON:0001264	83.61	gold quality
kidney	UBERON:0002113	82.99	gold quality
metanephric glomerulus	UBERON:0004736	82.54	gold quality
oocyte	CL:0000023	82.13	gold quality
epithelial cell of pancreas	CL:0000083	81.57	silver quality
renal glomerulus	UBERON:0000074	81.30	gold quality
small intestine	UBERON:0002108	81.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.07	gold quality
right lobe of liver	UBERON:0001114	80.93	gold quality
germinal epithelium of ovary	UBERON:0001304	80.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-76312	yes	297.44
E-MTAB-5061	yes	18.27
E-ANND-3	yes	15.69
E-ENAD-27	yes	6.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

140 targeting GIPC2, 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-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165

Literature-anchored findings (GeneRIF, showing 3)

• Molecular cloning and characterization of human GIPC2, a novel gene homologous to human GIPC1 and Xenopus Kermit (PMID:11836570)
• GIPC2 is an endocrine-specific tumor suppressor gene for both sporadic and hereditary tumors of RET- and SDHB-, but not VHL-associated clusters of pheochromocytoma/paraganglioma. (PMID:33947839)
• GIPC2 interacts with Fzd7 to promote prostate cancer metastasis by activating WNT signaling. (PMID:35347223)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gipc2	ENSDARG00000009488
mus_musculus	Gipc2	ENSMUSG00000039131
rattus_norvegicus	Gipc2	ENSRNOG00000042152
drosophila_melanogaster	kermit	FBGN0010504
caenorhabditis_elegans		WBGENE00009681
caenorhabditis_elegans		WBGENE00016440

Paralogs (2): GIPC1 (ENSG00000123159), GIPC3 (ENSG00000179855)

Protein

Protein identifiers

PDZ domain-containing protein GIPC2 — Q8TF65 (reviewed: Q8TF65)

All UniProt accessions (2): A0A384P5H2, Q8TF65

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Probably interacts with SEMA5A.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed at highest levels in ascending colon and at moderate levels in adult kidney. Expressed at low levels in adult pancreas and at very low levels in adult liver. Expression is down-regulated in several primary tumors, such as kidney, colon and rectal tumors.

Similarity. Belongs to the GIPC family.

RefSeq proteins (2): NP_001291654, NP_060125* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR017379	GIPC1/2/3	Family
IPR036034	PDZ_sf	Homologous_superfamily
IPR055349	GH2_GIPC	Domain
IPR056814	GIPC1-3_GH1	Domain

Pfam: PF00595, PF25082, PF25083

UniProt features (14 total): strand 6, helix 2, sequence variant 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3GGE	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF65-F1	83.17	0.64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, TTTGTAG_MIR520D, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GERY_CEBP_TARGETS, HNF4_01, RASHI_RESPONSE_TO_IONIZING_RADIATION_5, BOQUEST_STEM_CELL_DN, ZHANG_GATA6_TARGETS_DN, HSF2_01, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CHEN_METABOLIC_SYNDROM_NETWORK, PR_Q2, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3

GO Biological Process (0):

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GIPC2	RGS19	P49795	647
GIPC2	FZD3	Q9NPG1	572
GIPC2	CRELD1	Q96HD1	461
GIPC2	MYCBP	Q99417	436
GIPC2	MUSK	O15146	433
GIPC2	NTRK1	P04629	418
GIPC2	PGR	P06401	416
GIPC2	ESR1	P03372	410
GIPC2	MIGA1	Q8NAN2	408
GIPC2	GADD45G	O95257	407
GIPC2	PTN	P21246	401
GIPC2	STC2	O76061	398
GIPC2	ZNF382	Q96SR6	396
GIPC2	EDNRB	P24530	379
GIPC2	WFDC2	Q14508	379

IntAct

413 interactions, top by confidence:

A	B	Type	Score
GIPC2	GIPC2	psi-mi:“MI:0915”(physical association)	0.700
GIPC2	SP100	psi-mi:“MI:0915”(physical association)	0.670
SP100	GIPC2	psi-mi:“MI:0915”(physical association)	0.670
E	GIPC2	psi-mi:“MI:0915”(physical association)	0.610
E	GIPC2	psi-mi:“MI:0407”(direct interaction)	0.610
ZBTB26	GIPC2	psi-mi:“MI:0915”(physical association)	0.560
GIPC2	ZBTB26	psi-mi:“MI:0915”(physical association)	0.560
SP100	GIPC2	psi-mi:“MI:0915”(physical association)	0.560
GIPC2	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
INADL	GIPC2	psi-mi:“MI:0915”(physical association)	0.560
IRF4	GIPC2	psi-mi:“MI:0915”(physical association)	0.560
GIPC2	PLEKHA2	psi-mi:“MI:0915”(physical association)	0.560
GIPC2	CTRC	psi-mi:“MI:0915”(physical association)	0.560
ZCCHC7	GIPC2	psi-mi:“MI:0915”(physical association)	0.560
UBE2I	GIPC2	psi-mi:“MI:0915”(physical association)	0.560
GIPC2	SH3BP4	psi-mi:“MI:0914”(association)	0.530
GIPC2	GIPC1	psi-mi:“MI:0914”(association)	0.480
PBK	GIPC2	psi-mi:“MI:0407”(direct interaction)	0.440
XKR7	GIPC2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC45A4	GIPC2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIN2B	GIPC2	psi-mi:“MI:0407”(direct interaction)	0.440
FAM110D	GIPC2	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	GIPC2	psi-mi:“MI:0407”(direct interaction)	0.440
GIPC2	ADAM17	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (39): GIPC2 (Two-hybrid), GIPC2 (Two-hybrid), ZBTB26 (Two-hybrid), SH3BP4 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), APPL1 (Affinity Capture-MS), SH3BP4 (Affinity Capture-MS), APPL1 (Affinity Capture-MS), GIPC2 (Affinity Capture-RNA), GIPC2 (Proximity Label-MS), GIPC2 (Proximity Label-MS), GIPC2 (Synthetic Lethality), GIPC2 (Affinity Capture-MS), GIPC2 (Two-hybrid), GIPC2 (Two-hybrid)

ESM2 similar proteins: A2XKU9, A3KMV5, A4FUZ6, A4IHJ3, A7RHL5, A7RWP6, A9NK39, B4YYA9, B5X8A5, O42130, O42131, O46374, P10871, P11498, P17248, P22314, P23489, P52873, Q02880, Q05920, Q1JQD4, Q29504, Q29RK2, Q2T9S3, Q3ZBN0, Q40073, Q498C5, Q498D9, Q558Y7, Q5U300, Q64399, Q64511, Q66KC4, Q6AVK1, Q6DI37, Q6P5L8, Q6PAY8, Q6TGV7, Q6V289, Q7X923

Diamond homologs: O14908, Q1JQD4, Q498D9, Q8R5M0, Q8TF64, Q8TF65, Q9Z0G0, Q9Z254, Q9Z2H7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 155 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
EPHB-mediated forward signaling	5	14.4×	3e-03
Neurexins and neuroligins	5	10.7×	8e-03
Cardiac conduction	7	8.3×	3e-03
Neurotransmitter receptors and postsynaptic signal transmission	7	7.6×	3e-03
Muscle contraction	8	6.7×	3e-03
Transmission across Chemical Synapses	8	6.6×	3e-03
Neuronal System	11	5.3×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
Wnt signaling pathway	10	7.3×	1e-03
negative regulation of canonical Wnt signaling pathway	8	6.9×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1751 predictions. Top by Δscore:

Variant	Effect	Δscore
1:78005317:GGAAG:G	donor_gain	1.0000
1:78005318:GAAGG:G	donor_gain	1.0000
1:78005319:AAGG:A	donor_loss	1.0000
1:78005321:GGT:G	donor_loss	1.0000
1:78080671:GCA:G	acceptor_loss	1.0000
1:78080673:A:AG	acceptor_gain	1.0000
1:78080673:A:C	acceptor_loss	1.0000
1:78080674:G:GA	acceptor_gain	1.0000
1:78080674:GA:G	acceptor_gain	1.0000
1:78080674:GAT:G	acceptor_gain	1.0000
1:78080674:GATC:G	acceptor_gain	1.0000
1:78080674:GATCT:G	acceptor_gain	1.0000
1:78080857:AAAGG:A	donor_loss	1.0000
1:78080858:AAGG:A	donor_loss	1.0000
1:78080859:AGGT:A	donor_loss	1.0000
1:78080860:GGTA:G	donor_loss	1.0000
1:78080861:G:GG	donor_gain	1.0000
1:78080861:GTA:G	donor_loss	1.0000
1:78080862:T:A	donor_loss	1.0000
1:78125873:T:TA	acceptor_gain	1.0000
1:78125877:A:AG	acceptor_gain	1.0000
1:78125878:A:G	acceptor_gain	1.0000
1:78125879:A:AG	acceptor_gain	1.0000
1:78125880:G:GG	acceptor_gain	1.0000
1:78125959:TTAGG:T	donor_loss	1.0000
1:78125960:TAGGT:T	donor_loss	1.0000
1:78125961:AGGT:A	donor_loss	1.0000
1:78125962:GGTAA:G	donor_loss	1.0000
1:78125963:GT:G	donor_loss	1.0000
1:78125964:T:TC	donor_loss	1.0000

AlphaMissense

2035 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:78080756:T:C	F108L	0.987
1:78080758:T:A	F108L	0.987
1:78080758:T:G	F108L	0.987
1:78135592:C:A	A266D	0.982
1:78046272:T:C	F60L	0.979
1:78046274:C:A	F60L	0.979
1:78046274:C:G	F60L	0.979
1:78080760:C:A	A109D	0.975
1:78080852:T:C	F140L	0.973
1:78080854:T:A	F140L	0.973
1:78080854:T:G	F140L	0.973
1:78135705:T:A	W304R	0.973
1:78135705:T:C	W304R	0.973
1:78080686:C:G	C84W	0.971
1:78080754:T:A	I107K	0.970
1:78080836:T:A	N134K	0.969
1:78080836:T:G	N134K	0.969
1:78095058:T:A	V178D	0.966
1:78080684:T:C	C84R	0.964
1:78080860:G:C	K142N	0.962
1:78080860:G:T	K142N	0.962
1:78046224:T:C	F44L	0.961
1:78046226:C:A	F44L	0.961
1:78046226:C:G	F44L	0.961
1:78095001:G:A	G159E	0.960
1:78080856:T:A	I141K	0.958
1:78080681:T:G	Y83D	0.955
1:78125962:G:C	A266P	0.954
1:78135703:T:A	V303D	0.954
1:78095001:G:T	G159V	0.953

dbSNP variants (sampled 300 via entrez): RS1000056492 (1:78094805 T>A), RS1000073774 (1:78048032 G>A), RS1000076258 (1:78105781 G>A), RS1000128860 (1:78061193 A>G), RS1000129652 (1:78105490 G>T), RS1000233105 (1:78084466 A>T), RS1000256907 (1:78066203 C>G), RS1000258514 (1:78077750 G>A), RS1000289526 (1:78066488 G>A,T), RS1000311227 (1:78091821 A>G), RS1000314884 (1:78113483 GC>G), RS1000323735 (1:78099585 C>A,T), RS1000337066 (1:78080380 A>G,T), RS1000403688 (1:78047681 C>T), RS1000425465 (1:78092096 G>A)

Disease associations

OMIM: gene MIM:619089 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST000817_198	Height	2.000000e-11
GCST002647_85	Height	4.000000e-16
GCST003123_3	Severe influenza A (H1N1) infection	4.000000e-08
GCST003262_362	Post bronchodilator FEV1	4.000000e-06
GCST004066_104	Hip circumference	7.000000e-08
GCST004066_63	Hip circumference	3.000000e-10
GCST004744_54	Lung adenocarcinoma	4.000000e-07
GCST004748_67	Lung cancer	3.000000e-08
GCST004749_60	Lung cancer in ever smokers	3.000000e-06
GCST005830_97	Hand grip strength	3.000000e-12
GCST008129_38	Body mass index	7.000000e-09
GCST008395_1	End-stage kidney disease	2.000000e-07
GCST010796_1758	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-11
GCST010796_1759	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-10
GCST010796_1760	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_1761	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-12
GCST90000050_5	Age at first birth	8.000000e-10
GCST90002386_368	High light scatter reticulocyte percentage of red cells	3.000000e-13
GCST90002391_61	Mean corpuscular hemoglobin concentration	1.000000e-16
GCST90002401_347	Platelet distribution width	5.000000e-10
GCST90002405_76	Reticulocyte count	5.000000e-11
GCST90002406_147	Reticulocyte fraction of red cells	4.000000e-13

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0004314	forced expiratory volume
EFO:0006941	grip strength measurement
EFO:0004340	body mass index
EFO:0004327	electrocardiography
EFO:0009101	age at first birth measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007984	platelet component distribution width
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	4
bisphenol A	affects expression, affects cotreatment, decreases methylation	2
Nickel	decreases expression	2
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
methyleugenol	decreases expression	1
arsenite	increases methylation	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	increases reaction, affects binding	1
licochalcone B	increases expression	1
bisphenol S	decreases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Azathioprine	decreases expression	1
Caffeine	affects phosphorylation	1
Estradiol	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Quercetin	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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