PTH2

Summary

PTH2 (parathyroid hormone 2, HGNC:30828) is a protein-coding gene on chromosome 19q13.33, encoding Tuberoinfundibular peptide of 39 residues (Q96A98). Plays a role as a potent and selective agonist of PTH2R resulting in adenyl cyclase activation and intracellular calcium levels elevation.

This gene encodes the precursor of a peptide hormone that shares sequence similarity with the parathyroid hormone. This gene is expressed in various regions of the brain where it plays a role in the release of pituitary hormones, anxiety and nociception. The encoded precursor protein is proteolytically processed to generate the biologically active neuropeptide.

Source: NCBI Gene 113091 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_178449

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30828
Approved symbol	PTH2
Name	parathyroid hormone 2
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	TIP39
Ensembl gene	ENSG00000142538
Ensembl biotype	protein_coding
OMIM	608386
Entrez	113091

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000270631, ENST00000923239

RefSeq mRNA: 1 — MANE Select: NM_178449 NM_178449

CCDS: CCDS12763

Canonical transcript exons

ENST00000270631 — 2 exons

Exon	Start	End
ENSE00000954800	49423212	49423441
ENSE00000954801	49422419	49422642

Expression profiles

Bgee: expression breadth broad, 50 present calls, max score 77.63.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	77.63	gold quality
nasal cavity epithelium	UBERON:0005384	77.43	gold quality
cardia of stomach	UBERON:0001162	77.16	gold quality
subthalamic nucleus	UBERON:0001906	77.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	77.02	gold quality
cerebellar vermis	UBERON:0004720	76.56	gold quality
body of tongue	UBERON:0011876	76.47	gold quality
thymus	UBERON:0002370	76.44	gold quality
dorsal plus ventral thalamus	UBERON:0001897	76.38	gold quality
superior surface of tongue	UBERON:0007371	76.36	gold quality
tongue	UBERON:0001723	76.30	gold quality
nipple	UBERON:0002030	76.30	gold quality
inferior vagus X ganglion	UBERON:0005363	76.24	gold quality
pharyngeal mucosa	UBERON:0000355	76.23	gold quality
ventral tegmental area	UBERON:0002691	76.22	gold quality
saphenous vein	UBERON:0007318	76.10	gold quality
substantia nigra pars reticulata	UBERON:0001966	76.06	gold quality
pericardium	UBERON:0002407	76.05	gold quality
lateral globus pallidus	UBERON:0002476	76.05	gold quality
trachea	UBERON:0003126	76.05	gold quality
lateral nuclear group of thalamus	UBERON:0002736	75.92	gold quality
pons	UBERON:0000988	75.86	gold quality
substantia nigra pars compacta	UBERON:0001965	75.76	gold quality
pylorus	UBERON:0001166	75.74	gold quality
medulla oblongata	UBERON:0001896	75.52	gold quality
superior vestibular nucleus	UBERON:0007227	75.37	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.22	gold quality
trigeminal ganglion	UBERON:0001675	75.03	gold quality
dorsal root ganglion	UBERON:0000044	74.99	gold quality
renal medulla	UBERON:0000362	74.98	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6108	no	891.19
E-ANND-3	no	0.29

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• The results demonstrate that TIP39 and the PTH2R are expressed in the brain of primates in locations that suggest involvement in regulation of fear, anxiety, reproductive behaviors, release of pituitary hormones, and nociception. (PMID:19401215)
• Bit1 promotes TGF-beta2 induced alpha-SMA expression and acts as an positive regulator of EMT. (PMID:27122244)
• modulator of endoplasmic reticulum calcium signalling (PMID:28094886)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pth2	ENSDARG00000022951
mus_musculus	Pth2	ENSMUSG00000038300
rattus_norvegicus	Pth2	ENSRNOG00000072882

Protein

Protein identifiers

Tuberoinfundibular peptide of 39 residues — Q96A98 (reviewed: Q96A98)

Alternative names: Parathyroid hormone 2

All UniProt accessions (1): Q96A98

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role as a potent and selective agonist of PTH2R resulting in adenyl cyclase activation and intracellular calcium levels elevation. Induces protein kinase C beta activation, recruitment of beta-arrestin and PTH2R internalization. May inhibit cell proliferation via its action on PTH2R activation. Neuropeptide which may also have a role in spermatogenesis. May activate nociceptors and nociceptive circuits.

Subunit / interactions. Ligand of high affinity for the PTH2 receptor (PTH2R).

Subcellular location. Secreted.

Tissue specificity. Highly expressed in fetal and adult brain, cerebellum and trachea. Weakly expressed in spinal cord, fetal liver, kidney and heart.

Similarity. Belongs to the parathyroid hormone family.

RefSeq proteins (1): NP_848544* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029396	TIP39	Family

Pfam: PF14980

UniProt features (4 total): signal peptide 1, propeptide 1, peptide 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7F16	ELECTRON MICROSCOPY	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96A98-F1	74.00	0.27

Antibody-complex structures (SAbDab): 1 — 7F16

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 42 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, BENPORATH_ES_WITH_H3K27ME3, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_NPC_HCP_WITH_H3K4ME3_AND_H3K27ME3, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GSE13522_WT_VS_IFNG_KO_SKING_T_CRUZI_Y_STRAIN_INF_UP, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_UP, CDC5L_TARGET_GENES, MEF2D_TARGET_GENES, PBXIP1_TARGET_GENES, RYBP_TARGET_GENES, ZNF512_TARGET_GENES

GO Biological Process (1): neuropeptide signaling pathway (GO:0007218)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR ligand binding	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

276 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTH2	PTH2R	P49190	987
PTH2	PTH1R	Q03431	781
PTH2	PTH	P01270	642
PTH2	PTHLH	P12272	542
PTH2	TCAIM	Q8N3R3	510
PTH2	TOR2A	Q5JU69	479
PTH2	PRLH	P81277	452
PTH2	SLC17A6	Q9P2U8	427
PTH2	ITGA8	P53708	396
PTH2	TAC4	Q86UU9	385
PTH2	MYRFL	Q96LU7	370
PTH2	UTS2B	Q765I0	363
PTH2	QRFP	P83859	362
PTH2	POLD1	P28340	353
PTH2	CRH	P06850	348

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PTH2	AMD1	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (2): AMD1 (Affinity Capture-MS), AMD1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA5, A0A1B0GVQ0, A0A286YF18, A0JNN8, A2VDX9, A5PK62, A6NGB7, A9CBA0, O09800, P04488, P06480, P06764, P07646, P0C171, P0DJK0, P0DJK1, P0DMQ5, P13291, P22389, P36342, P46695, P98162, Q08102, Q1RMT9, Q2HJ59, Q3TYP4, Q5BIR3, Q5EAA5, Q5JTB6, Q5NRQ0, Q6F5E0, Q6VUC0, Q6VUP9, Q703F0, Q765Z5, Q867A9, Q867D0, Q89448, Q8MJW9, Q8TEF2

Diamond homologs: P0C171, P0C172, Q8QGA2, Q91W27, Q96A98

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PTH2	up-regulates	PTH2R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

604 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49422558:G:C	F71L	0.984
19:49422558:G:T	F71L	0.984
19:49422560:A:G	F71L	0.984
19:49422559:A:C	F71C	0.982
19:49422513:C:A	W86C	0.975
19:49422513:C:G	W86C	0.975
19:49422559:A:G	F71S	0.973
19:49422526:T:A	E82V	0.960
19:49422524:G:T	R83S	0.957
19:49422492:C:A	K93N	0.947
19:49422492:C:G	K93N	0.947
19:49422503:A:C	Y90D	0.943
19:49422571:T:A	D67V	0.941
19:49422560:A:T	F71I	0.940
19:49422523:C:G	R83P	0.930
19:49422533:C:G	A80P	0.928
19:49422503:A:T	Y90N	0.926
19:49422507:G:C	N88K	0.925
19:49422507:G:T	N88K	0.925
19:49422568:T:A	D68V	0.924
19:49422553:T:A	E73V	0.918
19:49422508:T:A	N88I	0.917
19:49422515:A:G	W86R	0.916
19:49422515:A:T	W86R	0.916
19:49422572:C:G	D67H	0.910
19:49422490:A:G	L94P	0.907
19:49422527:C:T	E82K	0.903
19:49422569:C:G	D68H	0.899
19:49422572:C:A	D67Y	0.899
19:49422520:C:G	R84P	0.896

dbSNP variants (sampled 300 via entrez): RS1000815440 (19:49423092 G>A), RS1001251373 (19:49423603 A>C), RS1002024467 (19:49423638 G>A), RS1002919579 (19:49422673 G>T), RS1003177082 (19:49424633 T>C), RS1003798009 (19:49424440 G>A), RS1003848811 (19:49424584 C>G), RS1004854059 (19:49423566 G>T), RS1005194969 (19:49422607 G>A,T), RS1005858011 (19:49422430 G>A), RS1006806446 (19:49422772 T>G), RS1007306955 (19:49425110 G>A,C,T), RS1009279719 (19:49423042 C>A,G), RS1009827857 (19:49422888 A>G), RS1010086249 (19:49422702 C>T)

Disease associations

OMIM: gene MIM:608386 | 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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Triclosan	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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