PROKR2

prokineticin receptor 2, the group of Prokineticin receptors

Basic information

Region (hg38): 20:5299218-5316954

Previous symbols: [ "GPR73L1", "KAL3" ]

Links

ENSG00000101292 ∙ NCBI:128674 ∙ OMIM:607123 ∙ HGNC:15836 ∙ Uniprot:Q8NFJ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypogonadotropic hypogonadism 3 with or without anosmia (Definitive), mode of inheritance: AD
• hypogonadotropic hypogonadism 3 with or without anosmia (Strong), mode of inheritance: AD
• septooptic dysplasia (Supportive), mode of inheritance: AD
• Kallmann syndrome (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism 3 with or without anosmia (Strong), mode of inheritance: AD
• hypogonadotropic hypogonadism 3 with or without anosmia (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 3 with or without anosmia	AD/AR	Endocrine	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	Craniofacial; Endocrine; Neurologic	17054399; 20301509
Digenic inheritance (with KAL1) has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PROKR2 gene.

• Hypogonadotropic_hypogonadism_3_with_or_without_anosmia (116 variants)
• not_provided (113 variants)
• not_specified (34 variants)
• Inborn_genetic_diseases (30 variants)
• PROKR2-related_disorder (13 variants)
• Amenorrhea (3 variants)
• Male_infertility_with_azoospermia_or_oligozoospermia_due_to_single_gene_mutation (2 variants)
• Hypogonadotropic_hypogonadism (2 variants)
• Hypogonadotropic_hypogonadism_3_without_anosmia (2 variants)
• Hypogonadotropic_hypogonadism_2_with_or_without_anosmia (1 variants)
• Hypogonadotropic_hypogonadism_7_with_or_without_anosmia (1 variants)
• Infertility_disorder (1 variants)
• Male_infertility_with_spermatogenesis_disorder (1 variants)
• Hypogonadism_with_anosmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PROKR2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000144773.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	33	3	40
missense	1	12	126	12		151
nonsense		2	1			3
start loss						0
frameshift	2	3	1			6
splice donor/acceptor (+/-2bp)	1					1
Total	4	17	132	45	3

Highest pathogenic variant AF is 0.0011517754

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PROKR2	protein_coding	protein_coding	ENST00000546004	2	15062

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000244	0.306	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.119	238	233	1.02	0.0000158	2543
Missense in Polyphen		61	72.496	0.84142		766
Synonymous	-0.909	106	94.7	1.12	0.00000681	774
Loss of Function	0.250	9	9.85	0.914	4.33e-7	120

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000441	0.000441
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000220	0.000220
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for prokineticin 2. Exclusively coupled to the G(q) subclass of heteromeric G proteins. Activation leads to mobilization of calcium, stimulation of phosphoinositide turnover and activation of p44/p42 mitogen-activated protein kinase.
• Pathway: GPCRs, Other;Signaling by GPCR;Signal Transduction;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.504
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.54

Haploinsufficiency Scores

• pHI: 0.168
• hipred: N
• hipred_score: 0.296
• ghis: 0.417

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.156

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Prokr2
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;neuropeptide signaling pathway;circadian rhythm
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: G protein-coupled receptor activity;neuropeptide Y receptor activity