PRLR

prolactin receptor

Basic information

Region (hg38): 5:35048755-35230487

Links

ENSG00000113494 ∙ NCBI:5618 ∙ OMIM:176761 ∙ HGNC:9446 ∙ Uniprot:P16471 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial hyperprolactinemia (Supportive), mode of inheritance: AD
• familial hyperprolactinemia (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the PRLR gene.

• Inborn genetic diseases (16 variants)
• not provided (5 variants)
• Familial hyperprolactinemia (1 variants)
• Premature ovarian failure (1 variants)

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					2	2
missense		1	15	4		20
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	15	4	2

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)
5-35068798-C-T			Uncertain significance (Sep 24, 2021)

GnomAD

Source: gnomAD

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: dbNSFP

• 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