PIRT

Summary

PIRT (phosphoinositide interacting regulator of transient receptor potential channels, HGNC:37239) is a protein-coding gene on chromosome 17p12, encoding Phosphoinositide-interacting protein (P0C851). Regulatory subunit of TRPV1, a molecular sensor of noxious heat and capsaicin.

Predicted to enable phosphatidylinositol bisphosphate binding activity and transmembrane transporter binding activity. Predicted to be involved in regulation of sensory perception of pain. Predicted to act upstream of or within behavioral response to pain; positive regulation of cation channel activity; and response to heat. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 644139 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_001101387

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37239
Approved symbol	PIRT
Name	phosphoinositide interacting regulator of transient receptor potential channels
Location	17p12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000233670
Ensembl biotype	protein_coding
OMIM	612068
Entrez	644139

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000580256, ENST00000964337

RefSeq mRNA: 1 — MANE Select: NM_001101387 NM_001101387

CCDS: CCDS45614

Canonical transcript exons

ENST00000580256 — 2 exons

Exon	Start	End
ENSE00002280093	10837945	10838087
ENSE00002687436	10822470	10825783

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 95.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8333 / max 126.2826, expressed in 109 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164628	0.7118	105
164627	0.0831	35
164626	0.0383	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	95.59	gold quality
trigeminal ganglion	UBERON:0001675	85.85	gold quality
medial globus pallidus	UBERON:0002477	79.98	gold quality
hypothalamus	UBERON:0001898	79.12	gold quality
substantia nigra	UBERON:0002038	76.53	gold quality
globus pallidus	UBERON:0001875	75.88	gold quality
midbrain	UBERON:0001891	75.19	gold quality
spinal cord	UBERON:0002240	74.78	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	74.42	gold quality
medulla oblongata	UBERON:0001896	73.93	gold quality
superior vestibular nucleus	UBERON:0007227	72.35	gold quality
muscle layer of sigmoid colon	UBERON:0035805	70.83	gold quality
ventral tegmental area	UBERON:0002691	69.92	gold quality
lateral globus pallidus	UBERON:0002476	69.35	gold quality
rectum	UBERON:0001052	68.36	gold quality
amygdala	UBERON:0001876	65.63	gold quality
substantia nigra pars reticulata	UBERON:0001966	64.11	gold quality
substantia nigra pars compacta	UBERON:0001965	63.95	silver quality
inferior vagus X ganglion	UBERON:0005363	63.54	silver quality
Ammon’s horn	UBERON:0001954	63.48	gold quality
transverse colon	UBERON:0001157	63.14	gold quality
vermiform appendix	UBERON:0001154	62.74	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.72	gold quality
colon	UBERON:0001155	62.58	gold quality
pancreatic ductal cell	CL:0002079	62.42	silver quality
large intestine	UBERON:0000059	61.99	gold quality
corpus callosum	UBERON:0002336	61.43	gold quality
anterior cingulate cortex	UBERON:0009835	61.11	gold quality
cerebellar hemisphere	UBERON:0002245	60.85	gold quality
cerebellar cortex	UBERON:0002129	60.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

99 targeting PIRT, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-3180-5P	99.82	69.12	2422

Literature-anchored findings (GeneRIF, showing 2)

• These results have uncovered species-specific TRPM8 modulation by PIRT. They provide evidence for a direct interaction between PIRT and the TRPM8 S1-S4 domain with a 1:1 binding stoichiometry, suggesting that a functional tetrameric TRPM8 channel has four PIRT-binding sites. (PMID:29724821)
• Competitive Interactions between PIRT, the Cold Sensing Ion Channel TRPM8, and PIP2 Suggest a Mechanism for Regulation. (PMID:31575973)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pirt	ENSMUSG00000048070
rattus_norvegicus	Pirt	ENSRNOG00000063443

Paralogs (1): TMEM100 (ENSG00000166292)

Protein

Protein identifiers

Phosphoinositide-interacting protein — P0C851 (reviewed: P0C851)

All UniProt accessions (1): P0C851

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of TRPV1, a molecular sensor of noxious heat and capsaicin. Positively regulates TRPV1 channel activity via phosphatidylinositol 4,5-bisphosphate (PIP2). Binds various phosphoinositide, including phosphatidylinositol 4,5-bisphosphate (PIP2), but not phosphatidylinositol (PI).

Subunit / interactions. Interacts with TRPV1.

Subcellular location. Membrane.

RefSeq proteins (1): NP_001094857* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028068	PIRT	Family

Pfam: PF15099

UniProt features (3 total): transmembrane region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C851-F1	62.97	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): chr17p12, GOBP_BEHAVIOR, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_BEHAVIORAL_RESPONSE_TO_PAIN, GOBP_RESPONSE_TO_PAIN, GOBP_REGULATION_OF_SENSORY_PERCEPTION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_PROCESS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_REGULATION_OF_SYSTEM_PROCESS, GOBP_SENSORY_PERCEPTION, GOBP_RESPONSE_TO_HEAT, GOMF_PHOSPHATIDYLINOSITOL_PHOSPHATE_BINDING, GOMF_PHOSPHATIDYLINOSITOL_BINDING, GOMF_PHOSPHATIDYLINOSITOL_BISPHOSPHATE_BINDING

GO Biological Process (3): response to heat (GO:0009408), behavioral response to pain (GO:0048266), regulation of sensory perception of pain (GO:0051930)

GO Molecular Function (3): phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), transmembrane transporter binding (GO:0044325), phosphatidylinositol bisphosphate binding (GO:1902936)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anion binding	2
response to stress	1
response to temperature stimulus	1
behavior	1
response to pain	1
sensory perception of pain	1
regulation of sensory perception	1
phosphatidylinositol phosphate binding	1
protein binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

582 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIRT	TRPV1	Q8NER1	712
PIRT	WIPI1	Q5MNZ9	666
PIRT	STARD10	Q9Y365	628
PIRT	PIK3C3	Q8NEB9	611
PIRT	WIPI2	Q9Y4P8	608
PIRT	ATG14	Q6ZNE5	606
PIRT	ZFYVE1	Q9HBF4	541
PIRT	SQSTM1	Q13501	404
PIRT	PHF24	Q9UPV7	401
PIRT	ATG16L1	Q676U5	400
PIRT	ULK1	O75385	397
PIRT	RASD2	Q96D21	394
PIRT	RB1CC1	Q8TDY2	391
PIRT	ATG2A	Q2TAZ0	391
PIRT	ATG12	O94817	378

IntAct

0 interactions, top by confidence:

BioGRID (1): PIRT (Proximity Label-MS)

ESM2 similar proteins: D4A6L0, I3LMB3, O00168, O73698, O76095, O77049, O88823, O88824, O97797, P0C851, P54710, P56513, P59645, P59646, Q04645, Q04646, Q04679, Q04680, Q08CB3, Q14802, Q1RMB5, Q1XF11, Q3MHZ5, Q3SZX0, Q3UPR0, Q4R566, Q5RB29, Q5T848, Q61835, Q63113, Q66IQ1, Q6X9T8, Q70RD5, Q810F0, Q86XR5, Q8C419, Q8K467, Q8NEW7, Q8QZT4, Q8R143

Diamond homologs: P0C851, Q8BFY0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

272 predictions. Top by Δscore:

Variant	Effect	Δscore
17:10825791:C:CT	acceptor_gain	0.9900
17:10825792:A:T	acceptor_gain	0.9900
17:10837939:A:AC	donor_gain	0.9900
17:10837940:C:CC	donor_gain	0.9900
17:10837943:A:AC	donor_gain	0.9900
17:10837943:ACTGT:A	donor_gain	0.9900
17:10837944:C:CT	donor_gain	0.9900
17:10837944:CTGT:C	donor_gain	0.9900
17:10837944:CTGTC:C	donor_gain	0.9900
17:10837940:CTTA:C	donor_gain	0.9800
17:10837934:T:TA	donor_gain	0.9700
17:10837944:CT:C	donor_gain	0.9700
17:10825784:C:CC	acceptor_gain	0.9600
17:10825791:C:T	acceptor_gain	0.9600
17:10825674:A:T	acceptor_gain	0.9500
17:10837892:T:TA	donor_gain	0.9400
17:10837938:TAC:T	donor_loss	0.9400
17:10837939:ACT:A	donor_loss	0.9400
17:10837941:TTACT:T	donor_loss	0.9400
17:10837942:T:TC	donor_loss	0.9400
17:10837943:A:C	donor_loss	0.9400
17:10837937:TTAC:T	donor_loss	0.9300
17:10837944:CTG:C	donor_gain	0.9200
17:10825779:TTGTG:T	acceptor_gain	0.9100
17:10825780:TGTG:T	acceptor_gain	0.9100
17:10837930:T:A	donor_gain	0.9100
17:10837931:C:A	donor_gain	0.9100
17:10837947:T:A	donor_gain	0.9100
17:10825781:GTG:G	acceptor_gain	0.8900
17:10837834:G:A	donor_gain	0.8800

AlphaMissense

892 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:10825348:C:G	G100R	0.994
17:10825348:C:T	G100R	0.994
17:10825326:C:T	G107E	0.992
17:10825440:C:T	G69D	0.992
17:10825441:C:G	G69R	0.992
17:10825344:A:G	L101P	0.991
17:10825347:C:T	G100E	0.991
17:10825318:A:G	W110R	0.990
17:10825318:A:T	W110R	0.990
17:10825327:C:G	G107R	0.990
17:10825327:C:T	G107R	0.990
17:10825461:C:T	G62D	0.988
17:10825330:A:G	C106R	0.985
17:10825462:C:G	G62R	0.985
17:10825341:A:C	M102R	0.981
17:10825344:A:T	L101H	0.981
17:10825327:C:A	G107W	0.980
17:10825356:A:G	L97P	0.979
17:10825482:G:T	P55H	0.979
17:10825369:C:G	G93R	0.978
17:10825369:C:T	G93R	0.978
17:10825482:G:C	P55R	0.978
17:10825341:A:T	M102K	0.977
17:10825344:A:C	L101R	0.977
17:10825440:C:A	G69V	0.976
17:10825459:C:G	G63R	0.976
17:10825347:C:A	G100V	0.974
17:10825323:A:G	L108P	0.972
17:10825363:C:G	G95R	0.972
17:10825368:C:T	G93E	0.968

dbSNP variants (sampled 300 via entrez): RS1000230573 (17:10837312 G>A,T), RS1000520329 (17:10828118 T>C), RS1000552834 (17:10825740 A>G,T), RS1000699519 (17:10834374 T>C), RS1000824894 (17:10822600 T>C), RS1000923948 (17:10839989 C>G), RS1001059391 (17:10828388 T>C), RS1001137773 (17:10837166 G>A), RS1001598461 (17:10833116 G>A), RS1001679555 (17:10827757 G>A,T), RS1001712177 (17:10827361 A>G), RS1001815089 (17:10828025 G>A), RS1001833595 (17:10827004 G>A), RS1001866319 (17:10833738 G>A), RS1001903095 (17:10822032 C>T)

Disease associations

OMIM: gene MIM:612068 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005655_2	Seborrheic dermatitis	2.000000e-08
GCST007552_2	Colorectal cancer	8.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation	1
bisphenol S	affects cotreatment, increases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	decreases methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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