PIANP

Summary

PIANP (PILR alpha associated neural protein, HGNC:25338) is a protein-coding gene on chromosome 12p13.31, encoding PILR alpha-associated neural protein (Q8IYJ0). Acts as a ligand for PILRA in neural tissues, where it may be involved in immune regulation.

This gene encodes a ligand for the paired immunoglobin-like type 2 receptor alpha, and so may be involved in immune regulation. Alternate splicing results in multiple transcript variants encoding different proteins.

Source: NCBI Gene 196500 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_001244014

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25338
Approved symbol	PIANP
Name	PILR alpha associated neural protein
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp547D2210, PANP
Ensembl gene	ENSG00000139200
Ensembl biotype	protein_coding
OMIM	616065
Entrez	196500

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000320591, ENST00000534837, ENST00000536467, ENST00000540656, ENST00000542740, ENST00000545917, ENST00000908766, ENST00000908767, ENST00000922283, ENST00000922284, ENST00000972144

RefSeq mRNA: 3 — MANE Select: NM_001244014 NM_001244014, NM_001244015, NM_153685

CCDS: CCDS44818, CCDS58205

Canonical transcript exons

ENST00000534837 — 5 exons

Exon	Start	End
ENSE00000937038	6696443	6696524
ENSE00001222027	6697287	6697792
ENSE00001683450	6698045	6698104
ENSE00002278138	6693791	6695651
ENSE00003908726	6700614	6700815

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 96.21.

FANTOM5 (CAGE): breadth broad, TPM avg 6.8220 / max 408.1539, expressed in 759 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129176	3.2069	505
129177	1.3677	289
129174	0.9743	322
129170	0.3178	147
129173	0.2452	125
129172	0.2189	107
129165	0.1541	67
129171	0.1427	77
129175	0.0992	60
129166	0.0591	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
anterior cingulate cortex	UBERON:0009835	96.21	gold quality
nucleus accumbens	UBERON:0001882	95.96	gold quality
right frontal lobe	UBERON:0002810	95.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.64	gold quality
cerebellar hemisphere	UBERON:0002245	95.43	gold quality
cerebellar cortex	UBERON:0002129	95.29	gold quality
prefrontal cortex	UBERON:0000451	95.08	gold quality
putamen	UBERON:0001874	94.92	gold quality
caudate nucleus	UBERON:0001873	94.90	gold quality
amygdala	UBERON:0001876	94.82	gold quality
hypothalamus	UBERON:0001898	94.32	gold quality
cortical plate	UBERON:0005343	94.29	gold quality
cerebellum	UBERON:0002037	93.81	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.57	gold quality
neocortex	UBERON:0001950	93.27	gold quality
frontal cortex	UBERON:0001870	93.25	gold quality
cerebral cortex	UBERON:0000956	91.81	gold quality
forebrain	UBERON:0001890	90.60	gold quality
temporal lobe	UBERON:0001871	90.48	gold quality
brain	UBERON:0000955	90.37	gold quality
Ammon’s horn	UBERON:0001954	90.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.75	gold quality
superior frontal gyrus	UBERON:0002661	89.15	gold quality
ganglionic eminence	UBERON:0004023	88.87	gold quality
descending thoracic aorta	UBERON:0002345	88.80	gold quality
thoracic aorta	UBERON:0001515	88.22	gold quality
ascending aorta	UBERON:0001496	88.16	gold quality
postcentral gyrus	UBERON:0002581	88.05	gold quality
ventricular zone	UBERON:0003053	86.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting PIANP, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838

Literature-anchored findings (GeneRIF, showing 3)

• These results suggest that PANP is involved in immune regulation as a ligand of the PILRalpha. (PMID:21241660)
• Furin-like proprotein convertase-dependent processing precedes the plasma membrane localization of LEDA-1/PIANP that is required for functional receptor-ligand interactions in vitro and in vivo. (PMID:23558288)
• Functionally, Leda-1/Pianp increased the transepithelial electrical resistance generated by a polarized cell sheet. While Claudin 1 and 4 expression and activities of small GTPases were not affected, gamma-Secretase-mediated cleavage of E-Cadherin was attenuated by Leda-1/Pianp. (PMID:27216462)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pianp	ENSMUSG00000030329
rattus_norvegicus	Pianp	ENSRNOG00000017052

Protein

Protein identifiers

PILR alpha-associated neural protein — Q8IYJ0 (reviewed: Q8IYJ0)

Alternative names: PILR-associating neural protein, Paired immunoglobin-like type 2 receptor-associating neural protein

All UniProt accessions (4): Q8IYJ0, F5GZA6, F5H0N9, F5H191

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a ligand for PILRA in neural tissues, where it may be involved in immune regulation.

Subcellular location. Membrane.

Tissue specificity. Mainly expressed in adult brain and cerebellum. Weaker expression in fetal brain and virtually no expression in spleen, heart, kidney, liver and dorsal ganglion relative to brain.

Post-translational modifications. O-glycosylation at Thr-140 is essential for recognition by PILRA.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IYJ0-1	1	yes
Q8IYJ0-2	2

RefSeq proteins (3): NP_001230943, NP_001230944, NP_710152 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029198	AJAP1_PANP_C	Domain
IPR039628	PIANP	Family

Pfam: PF15298

UniProt features (13 total): sequence conflict 2, topological domain 2, region of interest 2, compositionally biased region 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYJ0-F1	54.82	0.03

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 140

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

MSigDB gene sets: 142 (showing top): GOBP_DENTATE_GYRUS_DEVELOPMENT, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_GLUTAMATE_SECRETION, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_COGNITION, GOBP_BEHAVIOR, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_ASSOCIATIVE_LEARNING, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_HIPPOCAMPUS_DEVELOPMENT, GOBP_LEARNING

GO Biological Process (10): response to stress (GO:0006950), gamma-aminobutyric acid signaling pathway (GO:0007214), visual learning (GO:0008542), gene expression (GO:0010467), glutamate secretion (GO:0014047), dentate gyrus development (GO:0021542), cerebellum development (GO:0021549), social behavior (GO:0035176), homeostasis of number of cells (GO:0048872), regulation of immune response (GO:0050776)

GO Molecular Function (2): protein domain specific binding (GO:0019904), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	2
cellular anatomical structure	2
response to stimulus	1
cell-cell signaling	1
GABA receptor activity	1
visual behavior	1
associative learning	1
macromolecule biosynthetic process	1
dicarboxylic acid transport	1
acidic amino acid transport	1
secretion by cell	1
nitrogen compound transport	1
hippocampus development	1
metencephalon development	1
behavior	1
biological process involved in intraspecies interaction between organisms	1
multicellular organismal-level homeostasis	1
regulation of immune system process	1
immune response	1
regulation of response to stimulus	1
protein binding	1
binding	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
synapse	1

Protein interactions and networks

STRING

600 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIANP	PILRA	Q9UKJ1	601
PIANP	AJAP1	Q9UKB5	550
PIANP	NPDC1	Q9NQX5	519
PIANP	NPPA	P01160	507
PIANP	SYT11	Q9BT88	454
PIANP	PLEKHM3	Q6ZWE6	433
PIANP	WDR89	Q96FK6	383
PIANP	PTPRJ	Q12913	380
PIANP	NSG1	P42857	376
PIANP	COLEC12	Q5KU26	371
PIANP	ITM2B	Q9Y287	369
PIANP	C16orf90	A8MZG2	348
PIANP	ASTN1	O14525	343
PIANP	SORCS1	Q8WY21	342
PIANP	APLP1	P51693	339

IntAct

15 interactions, top by confidence:

A	B	Type	Score
DEFB127	PIANP	psi-mi:“MI:0915”(physical association)	0.560
TMBIM6	PIANP	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	PIANP	psi-mi:“MI:0915”(physical association)	0.560
PIANP	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
PIANP	CMTM7	psi-mi:“MI:0915”(physical association)	0.560
PIANP	DEFB127	psi-mi:“MI:0915”(physical association)	0.560
PILRA	PIANP	psi-mi:“MI:0915”(physical association)	0.400
PIANP	TCAF2	psi-mi:“MI:0914”(association)	0.350
PIANP	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): GALNT4 (Affinity Capture-MS), ADCY9 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), PRUNE (Affinity Capture-MS), AKT3 (Affinity Capture-MS), LRRC16A (Affinity Capture-MS), PTPRD (Affinity Capture-MS), FAM115C (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), PTPRF (Affinity Capture-MS), GHITM (Affinity Capture-MS), PIANP (Two-hybrid), TMBIM6 (Two-hybrid), CMTM7 (Two-hybrid), UBQLN2 (Two-hybrid)

ESM2 similar proteins: A0A1B0GV85, A0A1L8HTT5, A2ALI5, A2BDC9, A4IFM1, A7YWL5, B0BN13, B5X1Q3, B5X216, B6ZI38, O35181, O60279, P07141, P09603, P0C7U0, P20934, P28906, P56975, Q0IIY7, Q1XFL1, Q28270, Q2T9L4, Q3UH99, Q3USH1, Q498S6, Q49A92, Q4V9H3, Q4W8E7, Q5JTD0, Q5U2P6, Q64314, Q68DK7, Q69ZB8, Q6P1B3, Q6PDM1, Q6ZSJ9, Q7TSX9, Q8C6Z1, Q8C8T7, Q8CAE9

Diamond homologs: Q5U2P6, Q6P1B3, Q8IYJ0, Q95K74

SIGNOR signaling

0 interactions.

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	38
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

939 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6696437:GCTTA:G	donor_loss	1.0000
12:6696438:CTTA:C	donor_loss	1.0000
12:6696441:A:C	donor_loss	1.0000
12:6696442:C:CA	donor_loss	1.0000
12:6695647:CCCAG:C	acceptor_gain	0.9900
12:6695648:CCAGC:C	acceptor_gain	0.9900
12:6695661:C:CT	acceptor_gain	0.9900
12:6695662:A:T	acceptor_gain	0.9900
12:6696441:A:AC	donor_gain	0.9900
12:6696442:C:CC	donor_gain	0.9900
12:6696525:C:CA	acceptor_loss	0.9900
12:6697282:CTCA:C	donor_loss	0.9900
12:6697283:TCA:T	donor_loss	0.9900
12:6697284:CA:C	donor_loss	0.9900
12:6697285:A:C	donor_loss	0.9900
12:6698100:CTTTA:C	acceptor_gain	0.9900
12:6698105:C:CC	acceptor_gain	0.9900
12:6700131:CGA:C	donor_loss	0.9900
12:6700132:GAC:G	donor_loss	0.9900
12:6700244:C:CA	donor_gain	0.9900
12:6700245:C:A	donor_gain	0.9900
12:6695648:CCAG:C	acceptor_gain	0.9800
12:6695649:CAG:C	acceptor_gain	0.9800
12:6695649:CAGC:C	acceptor_gain	0.9800
12:6695652:C:CC	acceptor_gain	0.9800
12:6698101:TTTA:T	acceptor_gain	0.9800
12:6700130:CCGA:C	donor_gain	0.9800
12:6695650:AG:A	acceptor_gain	0.9700
12:6695651:GCTG:G	acceptor_loss	0.9700
12:6695652:CTGGG:C	acceptor_loss	0.9700

AlphaMissense

1716 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6697486:C:A	W108C	1.000
12:6697486:C:G	W108C	1.000
12:6697498:C:A	W104C	1.000
12:6697498:C:G	W104C	1.000
12:6696467:G:T	A194D	0.999
12:6696479:A:T	I190N	0.999
12:6697488:A:G	W108R	0.999
12:6697488:A:T	W108R	0.999
12:6697500:A:G	W104R	0.999
12:6697500:A:T	W104R	0.999
12:6696476:A:T	V191D	0.998
12:6696491:A:T	I186N	0.998
12:6696503:A:T	V182D	0.998
12:6697485:C:A	G109C	0.998
12:6696445:G:C	F201L	0.997
12:6696445:G:T	F201L	0.997
12:6696447:A:G	F201L	0.997
12:6696488:G:T	S187Y	0.997
12:6696500:G:C	T183R	0.997
12:6696500:G:T	T183K	0.997
12:6697493:A:T	I106N	0.997
12:6696446:A:G	F201S	0.996
12:6696461:C:T	G196D	0.996
12:6696462:C:G	G196R	0.996
12:6696468:C:G	A194P	0.996
12:6697485:C:G	G109R	0.996
12:6696448:C:A	K200N	0.995
12:6696448:C:G	K200N	0.995
12:6696473:A:C	L192R	0.995
12:6696473:A:T	L192H	0.995

dbSNP variants (sampled 300 via entrez): RS1000914172 (12:6693759 G>A,C,T), RS1001249179 (12:6697715 G>A,C), RS1001634866 (12:6700313 G>A,C), RS1001956136 (12:6702100 C>A,T), RS1003485102 (12:6692371 C>G,T), RS1003577006 (12:6701697 C>T), RS1003804271 (12:6699176 G>A), RS1003931054 (12:6701957 T>A), RS1003967498 (12:6699689 C>G), RS1003991674 (12:6699483 G>A,C), RS1004859425 (12:6692975 C>T), RS1004907768 (12:6699783 A>G), RS1004961823 (12:6699478 G>A,C), RS1005090977 (12:6699945 A>C), RS1005149248 (12:6693050 T>C)

Disease associations

OMIM: gene MIM:616065 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance	2
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
pentanal	increases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Endosulfan	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Cadmium Chloride	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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