PROKR2 (Prokineticin Receptor 2)
G protein-coupled receptor for prokineticins; implicated in Kallmann syndrome and GnRH neuronal migration
Gene Information Card
| Symbol | PROKR2 |
|---|---|
| Full Name | prokineticin receptor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 20p12.3 |
| NCBI Gene ID | 128674 ncbi.nlm.nih.gov/gene/128674 |
| Ensembl ID | ENSG00000101204 |
| UniProt ID | Q8NFJ6 |
| OMIM ID | 607123 |
| HGNC ID | 15836 |
| Aliases | GPR73L1, GPR73b, PKR2, dJ680N8.1 |
Description
PROKR2 encodes a G protein-coupled receptor that binds prokineticins (PROK1 and PROK2). It is essential for olfactory bulb morphogenesis and GnRH neuron migration. Loss-of-function mutations cause autosomal recessive or digenic forms of Kallmann syndrome (KS) and normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Kallmann syndrome 3 | Impaired PROKR2 signaling disrupts GnRH neuron migration and olfactory bulb development | OMIM #244200; multiple missense mutations (e.g., p.Arg85Cys, p.Trp178Ser) in KS families |
| Idiopathic hypogonadotropic hypogonadism (normosmic) | Partial loss of receptor function reduces GnRH secretion without anosmia | ClinVar; heterozygous or compound heterozygous variants |
| Central precocious puberty (rare association) | Gain-of-function variants may accelerate GnRH pulse generator | Limited case reports; functional studies show increased cAMP signaling |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 1.2 | Low |
| Testis | 0.8 | Low |
| Ovary | 0.5 | Not detected |
| Adrenal gland | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 0.9 | Endogenous expression |
| HEK293T | 0.0 | No endogenous expression; used for heterologous assays |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.254G>A (p.Arg85Cys) | Missense | ~5% in KS cohorts | Loss of function; impaired cell surface expression and signaling |
| c.533G>C (p.Trp178Ser) | Missense | ~3% in KS cohorts | Loss of function; defective ligand binding |
| c.337C>T (p.Arg113Trp) | Missense | Rare | Loss of function; reduced IP3 production |
| c.70G>A (p.Val24Met) | Missense | Rare | Likely benign; no functional effect |
Mutation functional classification
Loss of Function (LOF)
Most PROKR2 mutations (e.g., p.Arg85Cys, p.Trp178Ser) reduce receptor trafficking to the plasma membrane or impair Gq/11 signaling, leading to Kallmann syndrome.
Gain of Function (GOF)
Not well established; rare variants (e.g., p.Arg164Gln) show increased basal activity in vitro but clinical significance uncertain.
Dominant Negative (DN)
Not reported for PROKR2; mutations are typically recessive or digenic.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • prokineticin receptor activity |
| • Gq/11-coupled receptor activity | • plasma membrane |
| • integral component of membrane | • positive regulation of MAPK cascade |
| • cell migration | • olfactory bulb development |
| • GnRH neuron migration |
Pathways
• Prokineticin signaling pathway
• GPCR downstream signaling (Gq/11
• PLC
• IP3
• Ca2+)
• GnRH neuron migration and olfactory development
Protein Summary
PROKR2 is a 384-amino acid G protein-coupled receptor with seven transmembrane domains. It binds prokineticin 2 (PROK2) with high affinity, activating Gq/11 and downstream calcium mobilization. The receptor is critical for the migration of gonadotropin-releasing hormone (GnRH) neurons from the olfactory placode to the hypothalamus. Mutations cause hypogonadotropic hypogonadism with or without anosmia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PROKR2 Knockout HEK293 Cell Line | EDJ-KQ9195 | Human | 128674 | Details Get a Quote |
| PROKR2 Knockout HeLa Cell Line | EDJ-KQ58247 | Human | 128674 | Details Get a Quote |
| PROKR2 Knockout A-549 Cell Line | EDJ-KQ66735 | Human | 128674 | Details Get a Quote |
| PROKR2 Knockout HCT 116 Cell Line | EDJ-KQ75146 | Human | 128674 | Details Get a Quote |
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