PCP2

Summary

PCP2 (Purkinje cell protein 2, HGNC:30209) is a protein-coding gene on chromosome 19p13.2, encoding Purkinje cell protein 2 homolog (Q8IVA1). May function as a cell-type specific modulator for G protein-mediated cell signaling.

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to act upstream of or within G protein-coupled opsin signaling pathway. Predicted to be located in neuronal cell body.

Source: NCBI Gene 126006 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 45 total — 1 pathogenic
• MANE Select transcript: NM_174895

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30209
Approved symbol	PCP2
Name	Purkinje cell protein 2
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC41903, GPSM4
Ensembl gene	ENSG00000174788
Ensembl biotype	protein_coding
OMIM	619344
Entrez	126006

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000311069, ENST00000598935

RefSeq mRNA: 2 — MANE Select: NM_174895 NM_001271830, NM_174895

CCDS: CCDS32893, CCDS62521

Canonical transcript exons

ENST00000311069 — 4 exons

Exon	Start	End
ENSE00001202217	7632716	7632830
ENSE00001202233	7632393	7632517
ENSE00001241372	7633407	7633719
ENSE00003065498	7631615	7631808

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 96.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7272 / max 352.0418, expressed in 22 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178854	0.3806	11
178856	0.1526	3
178855	0.1301	4
178857	0.0490	3
178853	0.0150	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.38	gold quality
right testis	UBERON:0004534	96.01	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.19	gold quality
testis	UBERON:0000473	92.96	gold quality
cerebellar cortex	UBERON:0002129	92.96	gold quality
cerebellar hemisphere	UBERON:0002245	92.87	gold quality
cerebellum	UBERON:0002037	92.53	gold quality
cerebellar vermis	UBERON:0004720	86.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.70	gold quality
right uterine tube	UBERON:0001302	81.78	gold quality
sperm	CL:0000019	80.77	silver quality
granulocyte	CL:0000094	80.70	gold quality
monocyte	CL:0000576	77.30	gold quality
leukocyte	CL:0000738	76.75	gold quality
metanephros cortex	UBERON:0010533	76.23	gold quality
right lobe of thyroid gland	UBERON:0001119	75.97	gold quality
lower esophagus mucosa	UBERON:0035834	75.78	gold quality
adult organism	UBERON:0007023	74.77	gold quality
left lobe of thyroid gland	UBERON:0001120	74.61	gold quality
saliva-secreting gland	UBERON:0001044	74.58	gold quality
body of pancreas	UBERON:0001150	74.49	gold quality
skin of abdomen	UBERON:0001416	74.37	gold quality
right lobe of liver	UBERON:0001114	74.32	gold quality
minor salivary gland	UBERON:0001830	74.22	gold quality
parotid gland	UBERON:0001831	73.79	gold quality
thyroid gland	UBERON:0002046	73.73	gold quality
inferior vagus X ganglion	UBERON:0005363	72.82	gold quality
skin of leg	UBERON:0001511	72.31	gold quality
adult mammalian kidney	UBERON:0000082	71.95	gold quality
cortex of kidney	UBERON:0001225	71.57	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	12484.03
E-GEOD-137537	yes	4072.95
E-MTAB-11121	yes	4030.61
E-GEOD-134144	yes	31.96
E-ANND-3	no	1.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN, NR2F1, POU1F1, RARA, RORA, RXRA, RXRB, THRA

Literature-anchored findings (GeneRIF, showing 2)

• The data demonstrate that PCP-2 is a comparatively weak GoLoco motif protein that exhibits highest affinity interactions and GDI activity toward Galphai1, Galphai2, and Galphai3 subunits. (PMID:16298104)
• characterization of the mouse 136 aa conserved isoform, Ret-PCP2 (PMID:18768681)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pcp2	ENSMUSG00000004630
rattus_norvegicus	Pcp2	ENSRNOG00000000993

Protein

Protein identifiers

Purkinje cell protein 2 homolog — Q8IVA1 (reviewed: Q8IVA1)

All UniProt accessions (1): Q8IVA1

UniProt curated annotations — full annotation on UniProt →

Function. May function as a cell-type specific modulator for G protein-mediated cell signaling.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IVA1-1	1	yes
Q8IVA1-2	2

RefSeq proteins (2): NP_001258759, NP_777555* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003109	GoLoco_motif	Conserved_site
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR042168	Pcp2	Family

Pfam: PF02188

UniProt features (9 total): domain 2, region of interest 2, compositionally biased region 2, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVA1-F1	70.65	0.17

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): 127

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 48 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_PHOTOTRANSDUCTION, GOBP_PHOTOTRANSDUCTION_VISIBLE_LIGHT, GOBP_RESPONSE_TO_RADIATION, GOBP_DETECTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_RADIATION, GOBP_RESPONSE_TO_LIGHT_STIMULUS, LEE_TARGETS_OF_PTCH1_AND_SUFU_DN, GOBP_CELLULAR_RESPONSE_TO_ABIOTIC_STIMULUS, LEIN_CEREBELLUM_MARKERS, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, chr19p13

GO Biological Process (1): G protein-coupled opsin signaling pathway (GO:0016056)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515), GTPase regulator activity (GO:0030695)

GO Cellular Component (0):

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	1
phototransduction	1
phototransduction, visible light	1
cellular response to light stimulus	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
GTPase activity	1
nucleoside-triphosphatase regulator activity	1

Protein interactions and networks

STRING

906 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCP2	RIC8A	Q9NPQ8	639
PCP2	RIC8B	Q9NVN3	581
PCP2	GPSM3	Q9Y4H4	570
PCP2	PET100	P0DJ07	542
PCP2	CBLN1	P02682	541
PCP2	GABRA6	Q16445	532
PCP2	RGS14	O43566	504
PCP2	RAP1GAP	P47736	477
PCP2	RGS12	O14924	474
PCP2	CABP5	Q9NP86	468
PCP2	CREG2	Q8IUH2	462
PCP2	GNAO1	P09471	457
PCP2	MCEMP1	Q8IX19	442
PCP2	CALB1	P05937	435
PCP2	ATXN1L	P0C7T5	434

IntAct

32 interactions, top by confidence:

A	B	Type	Score
PCP2	GNAI3	psi-mi:“MI:0915”(physical association)	0.680
GNAI3	PCP2	psi-mi:“MI:0915”(physical association)	0.680
SPANXN3	SUOX	psi-mi:“MI:0914”(association)	0.640
MEOX1	PCP2	psi-mi:“MI:0915”(physical association)	0.560
GNAI1	PCP2	psi-mi:“MI:0915”(physical association)	0.560
GNAI2	PCP2	psi-mi:“MI:0915”(physical association)	0.560
TMEM38A	DOK2	psi-mi:“MI:0914”(association)	0.530
CST9	ITGA4	psi-mi:“MI:0914”(association)	0.530
RNASE2	PCP2	psi-mi:“MI:0915”(physical association)	0.400
CENPM	DOK2	psi-mi:“MI:0914”(association)	0.350
HSD17B3	POTEI	psi-mi:“MI:0914”(association)	0.350
VPS28	DCAF6	psi-mi:“MI:0914”(association)	0.350
VPS28	PRPF6	psi-mi:“MI:0914”(association)	0.350
PCP2	MEOX1	psi-mi:“MI:0915”(physical association)	0.000
PCP2	GNAI3	psi-mi:“MI:0915”(physical association)	0.000
GNAI1	PCP2	psi-mi:“MI:0915”(physical association)	0.000
PCP2	GNAI2	psi-mi:“MI:0915”(physical association)	0.000
GNAI3	PCP2	psi-mi:“MI:0915”(physical association)	0.000
PCP2	GNAI1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): PCP2 (Affinity Capture-MS), GNAI3 (Affinity Capture-MS), PCP2 (Affinity Capture-MS), PCP2 (Affinity Capture-MS), PCP2 (Affinity Capture-MS), PCP2 (Affinity Capture-MS), PCP2 (Affinity Capture-MS), PCP2 (Affinity Capture-MS), GNAI3 (Affinity Capture-MS), PCP2 (Two-hybrid), PCP2 (Two-hybrid), PCP2 (Two-hybrid), PCP2 (Two-hybrid), PCP2 (Affinity Capture-MS), PCP2 (Affinity Capture-MS)

ESM2 similar proteins: A2AIP0, A2RRU4, A2RRW4, A4Q9F4, A6QM06, A6QNS9, A6QPC0, A8MTA8, E1BBQ2, F1LQY6, G3X6E2, H3BNL1, O70373, P29590, P50747, P55199, P97260, Q04841, Q12770, Q2TBR5, Q4QR77, Q5E9N3, Q5MNU5, Q5RDC3, Q69Z89, Q6GQT6, Q6J272, Q702N8, Q70EL4, Q7Z4S9, Q8BL74, Q8BUM9, Q8C419, Q8IVA1, Q8IW40, Q8N1F8, Q8N9H8, Q8WUA4, Q91ZP9, Q920N2

Diamond homologs: P12660, Q8IVA1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RORA	“up-regulates quantity by expression”	PCP2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	31
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3248484	NC_000019.9:g.(?7694720)(7712696_?)del	Pathogenic

SpliceAI

661 predictions. Top by Δscore:

Variant	Effect	Δscore
19:7632388:CCTA:C	donor_loss	1.0000
19:7632389:CTAC:C	donor_loss	1.0000
19:7632390:TA:T	donor_loss	1.0000
19:7632391:ACCTT:A	donor_loss	1.0000
19:7632392:CCTT:C	donor_loss	1.0000
19:7632514:CTCT:C	acceptor_gain	1.0000
19:7632516:CT:C	acceptor_gain	1.0000
19:7632518:C:CC	acceptor_gain	1.0000
19:7632538:T:C	acceptor_gain	1.0000
19:7632714:A:AC	donor_gain	1.0000
19:7632715:C:CC	donor_gain	1.0000
19:7632715:CGG:C	donor_gain	1.0000
19:7632715:CGGCT:C	donor_gain	1.0000
19:7632826:CCCGC:C	acceptor_gain	1.0000
19:7632827:CCGC:C	acceptor_gain	1.0000
19:7632827:CCGCC:C	acceptor_gain	1.0000
19:7632828:CGC:C	acceptor_gain	1.0000
19:7632828:CGCC:C	acceptor_gain	1.0000
19:7631807:TCCT:T	acceptor_loss	0.9900
19:7632391:A:AC	donor_gain	0.9900
19:7632392:C:CC	donor_gain	0.9900
19:7632516:CTCTG:C	acceptor_loss	0.9900
19:7632517:TC:T	acceptor_loss	0.9900
19:7632519:T:A	acceptor_loss	0.9900
19:7632537:C:CC	acceptor_gain	0.9900
19:7632538:T:TC	acceptor_gain	0.9900
19:7632714:ACGG:A	donor_gain	0.9900
19:7632715:CG:C	donor_gain	0.9900
19:7632715:CGGC:C	donor_gain	0.9900
19:7632829:GC:G	acceptor_gain	0.9900

AlphaMissense

895 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:7632440:G:T	R82S	0.986
19:7632439:C:G	R82P	0.984
19:7632441:T:A	Q81H	0.984
19:7632441:T:G	Q81H	0.984
19:7632796:A:G	L29P	0.984
19:7632455:G:T	R77S	0.983
19:7632454:C:G	R77P	0.978
19:7632793:A:G	L30P	0.976
19:7632451:A:G	M78T	0.974
19:7632805:A:G	F26S	0.973
19:7632412:A:G	F91S	0.968
19:7632475:A:G	L70P	0.964
19:7632475:A:T	L70Q	0.963
19:7632487:A:G	L66P	0.963
19:7632804:G:C	F26L	0.962
19:7632804:G:T	F26L	0.962
19:7632806:A:G	F26L	0.962
19:7632448:T:A	D79V	0.961
19:7632451:A:C	M78R	0.961
19:7632462:C:A	Q74H	0.960
19:7632462:C:G	Q74H	0.960
19:7632473:C:G	A71P	0.960
19:7632442:T:G	Q81P	0.959
19:7632449:C:G	D79H	0.958
19:7632451:A:T	M78K	0.957
19:7632475:A:C	L70R	0.957
19:7632411:G:C	F91L	0.953
19:7632411:G:T	F91L	0.953
19:7632413:A:G	F91L	0.953
19:7632455:G:C	R77G	0.952

dbSNP variants (sampled 300 via entrez): RS1000395037 (19:7637121 G>A), RS1000662251 (19:7637012 G>C), RS1000815194 (19:7637729 G>A), RS1000859301 (19:7637435 C>A,T), RS1001818407 (19:7638784 G>A), RS1001946530 (19:7638124 T>C), RS1002117633 (19:7633644 G>A), RS1002717016 (19:7634702 C>T), RS1002723883 (19:7635688 C>A), RS1002868048 (19:7631300 C>A,G,T), RS1003329572 (19:7631437 C>A,G,T), RS1003505006 (19:7631494 A>C,G), RS1003557616 (19:7631233 C>T), RS1004114131 (19:7635813 G>C), RS1006108737 (19:7637760 G>A,T)

Disease associations

OMIM: gene MIM:619344 | disease phenotypes: MIM:613101

GenCC curated gene-disease

Mondo (1): familial hemophagocytic lymphohistiocytosis 5 (MONDO:0013135)

Orphanet (1): Familial hemophagocytic lymphohistiocytosis (Orphanet:540)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005934_2	Neuropathic pain in head and neck cancer	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005762	neuropathic pain

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567752	Hemophagocytic Lymphohistiocytosis, Familial, 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
di-n-butylphosphoric acid	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Estradiol	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases expression, increases abundance	1

Clinical trials (associated diseases)

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