PRLR
prolactin receptor
Basic information
Region (hg38): 5:35048756-35230487
Links
Phenotypes
GenCC
Source:
- familial hyperprolactinemia (Supportive), mode of inheritance: AD
- familial hyperprolactinemia (Limited), mode of inheritance: Unknown
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hyperprolactinemia; Multiple fibroadenomas of the breast | AD | Endocrine | Women may require dopamine agonists after breastfeeding in order to treat galatorrhea | Endocrine; Oncologic | 18779591; 24195502; 30575453 |
| Knowledge of variants may be additionally helpful in consideration of women with breast masses |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRLR gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | |||||
| missense | 19 | 27 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 0 | |||||
| Total | 0 | 1 | 19 | 8 | 3 |
Variants in PRLR
This is a list of pathogenic ClinVar variants found in the PRLR region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-35049332-T-G | PRLR-related disorder | Likely benign (Aug 28, 2019) | ||
| 5-35065223-C-T | not specified | Uncertain significance (Nov 02, 2023) | ||
| 5-35065254-G-A | Benign (Dec 31, 2019) | |||
| 5-35065304-C-G | not specified | Uncertain significance (Jun 23, 2023) | ||
| 5-35065307-C-G | not specified | Likely benign (Feb 23, 2023) | ||
| 5-35065307-C-T | not specified | Likely benign (Apr 25, 2022) | ||
| 5-35065335-C-G | not specified | Uncertain significance (May 26, 2023) | ||
| 5-35065346-C-T | not specified | Likely benign (Jun 11, 2021) | ||
| 5-35065362-G-C | Likely benign (Jun 10, 2018) | |||
| 5-35065384-G-T | not specified | Uncertain significance (Aug 17, 2022) | ||
| 5-35065475-G-A | Familial hyperprolactinemia | Uncertain significance (Mar 22, 2022) | ||
| 5-35065504-T-G | not specified | Uncertain significance (Jan 01, 2024) | ||
| 5-35065548-C-T | PRLR-related disorder | Benign (Dec 31, 2019) | ||
| 5-35065622-C-T | not specified | Uncertain significance (Nov 18, 2022) | ||
| 5-35065663-T-C | not specified | Likely benign (Jan 18, 2023) | ||
| 5-35065759-T-C | not specified | Uncertain significance (Oct 02, 2023) | ||
| 5-35065762-A-G | not specified | Uncertain significance (Mar 08, 2024) | ||
| 5-35065803-A-G | PRLR-related disorder | Likely benign (Jun 07, 2019) | ||
| 5-35065955-T-G | not specified | Uncertain significance (Dec 03, 2021) | ||
| 5-35066018-A-G | not specified | Uncertain significance (Apr 11, 2023) | ||
| 5-35066074-G-A | not specified | Uncertain significance (Jun 21, 2021) | ||
| 5-35068220-A-C | Premature ovarian failure | Likely pathogenic (Mar 02, 2020) | ||
| 5-35068265-G-A | Familial hyperprolactinemia | Pathogenic (Jan 08, 2019) | ||
| 5-35068281-C-T | not specified | Uncertain significance (Aug 17, 2022) | ||
| 5-35068797-A-G | not specified | Uncertain significance (Mar 18, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRLR | protein_coding | protein_coding | ENST00000382002 | 8 | 181934 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.987 | 0.0127 | 125740 | 0 | 8 | 125748 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.681 | 295 | 330 | 0.894 | 0.0000162 | 4082 |
| Missense in Polyphen | 56 | 85.842 | 0.65236 | 1076 | ||
| Synonymous | 0.0271 | 129 | 129 | 0.997 | 0.00000710 | 1193 |
| Loss of Function | 4.22 | 3 | 26.4 | 0.114 | 0.00000120 | 335 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000881 | 0.0000881 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000353 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: This is a receptor for the anterior pituitary hormone prolactin (PRL). Acts as a prosurvival factor for spermatozoa by inhibiting sperm capacitation through suppression of SRC kinase activation and stimulation of AKT. Isoform 4 is unable to transduce prolactin signaling. Isoform 6 is unable to transduce prolactin signaling. {ECO:0000269|PubMed:12580759, ECO:0000269|PubMed:20032052}.;
- Disease
- DISEASE: Multiple fibroadenomas of the breast (MFAB) [MIM:615554]: A benign breast disease marked by lobuloalveolar growth with abnormally high proliferation of the epithelium, and characterized by the presence of more than 3 fibroadenomas in one breast. Fibroadenomas are adenomas containing fibrous tissue. {ECO:0000269|PubMed:18779591}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hyperprolactinemia (HPRL) [MIM:615555]: A disorder characterized by increased levels of prolactin in the blood not associated with gestation or the puerperium. HPRL may result in infertility, hypogonadism, and galactorrhea. {ECO:0000269|PubMed:24195502}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;Prolactin Signaling Pathway;Adipogenesis;Ovarian Infertility Genes;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Prolactin receptor signaling;Prolactin;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Immune System;ErbB4 signaling events;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation;Signaling events mediated by PTP1B
(Consensus)
Recessive Scores
- pRec
- 0.383
Intolerance Scores
- loftool
- 0.234
- rvis_EVS
- 0.02
- rvis_percentile_EVS
- 55.61
Haploinsufficiency Scores
- pHI
- 0.0760
- hipred
- N
- hipred_score
- 0.314
- ghis
- 0.465
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.984
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prlr
- Phenotype
- vision/eye phenotype; 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); limbs/digits/tail phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; neoplasm; 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); reproductive system phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- prlra
- Affected structure
- head
- Phenotype tag
- abnormal
- Phenotype quality
- decreased size
Gene ontology
- Biological process
- steroid biosynthetic process;cell surface receptor signaling pathway;activation of transmembrane receptor protein tyrosine kinase activity;embryo implantation;lactation;prolactin signaling pathway;T cell activation;activation of Janus kinase activity;negative regulation of apoptotic process;JAK-STAT cascade involved in growth hormone signaling pathway;positive regulation of cold-induced thermogenesis
- Cellular component
- extracellular region;plasma membrane;external side of plasma membrane;cell surface;integral component of membrane;endosome lumen;receptor complex
- Molecular function
- cytokine receptor activity;prolactin receptor activity;protein binding;peptide hormone binding;cytokine binding;protein homodimerization activity;ornithine decarboxylase activator activity;metal ion binding