GeneBe

PRLR

protein-coding

prolactin receptor

Gene summary

This gene encodes a receptor for the anterior pituitary hormone, prolactin, and belongs to the type I cytokine receptor family. Prolactin-dependent signaling occurs as the result of ligand-induced dimerization of the prolactin receptor. Several alternatively spliced transcript variants encoding different membrane-bound and soluble isoforms have been described for this gene, which may function to modulate the endocrine and autocrine effects of prolactin in normal tissue and cancer. [provided by RefSeq, Feb 2011]

MANE transcript

NM_000949.7

Inheritance

AD

ClinVar variants

P:4U:69B:17

Top phenotype

Hyperprolactinemia; Multiple fibroadenomas of the breast

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr5:35,048,756-35,230,487

External References & Databases

Ensembl (ENSG00000113494)NCBI Gene (5618)OMIM (176761)HGNC:9446GenCCUniProt (P16471)AlphaFoldClinVar (PRLR)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~181.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial hyperprolactinemiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014250

Submitter: Orphanet

familial hyperprolactinemiaLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014250

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Hyperprolactinemia; Multiple fibroadenomas of the breastAD

Manifestation: Endocrine; Oncologic

Intervention: Endocrine

Rationale: Women may require dopamine agonists after breastfeeding in order to treat galatorrhea

Comments: Knowledge of variants may be additionally helpful in consideration of women with breast masses

Refs: 18779591; 24195502; 30575453Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRLR variants in ClinVar

7 Conditions Cataloged
not specifiedTotal: 69
Familial hyperprolactinemiaTotal: 8
not providedTotal: 6
PRLR-related disorderTotal: 6
Multiple fibroadenoma of the breastTotal: 3
SchizophreniaTotal: 2
Premature ovarian failureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000949.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
5
clinvar
2
clinvar
 7
missense
2
clinvar
1
clinvar
67
clinvar
10
clinvar
 80
nonsense
1
clinvar
 1
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total316915290

Highest pathogenic variant AF is 0.000023559345

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000949.7RefSeqNP_000940.18MANE Select
ENST00000618457.5EnsemblENSP00000482954.18MANE Select
NM_001204314.2RefSeqNP_001191243.16Standard
NM_001204315.1RefSeqNP_001191244.19Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
prlraDanio rerio

Structure: head

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)

Biological Process

  • steroid biosynthetic process
  • cell surface receptor signaling pathway
  • activation of transmembrane receptor protein tyrosine kinase activity
  • embryo implantation
  • lactation

Molecular Function

  • cytokine receptor activity
  • prolactin receptor activity
  • protein binding
  • peptide hormone binding
  • cytokine binding

Cellular Component

  • extracellular region
  • plasma membrane
  • external side of plasma membrane
  • cell surface
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000382002
Coding exons
8
Length
181934
Individuals with no LoFs
125740
Homozygous LoFs
0
Heterozygous LoFs
8
Defined
125748
p
0.0000318
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.6812953300.8940.00001624082
Missense (PolyPhen)5685.8420.652361076
Synonymous0.02711291290.9970.000007101193
Loss of Function4.22326.40.1140.00000120335

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000880.000058rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000350.000035rare
South Asian0.0000330.000033rare
Other0.000160.00016rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.383

Intolerance Scores

LoFtool
0.234
RVIS EVS
0.02
RVIS percentile EVS
55.61

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.984

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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