PRL

Summary

PRL (prolactin, HGNC:9445) is a protein-coding gene on chromosome 6p22.3, encoding Prolactin (P01236). Prolactin acts primarily on the mammary gland by promoting lactation.

This gene encodes the anterior pituitary hormone prolactin. This secreted hormone is a growth regulator for many tissues, including cells of the immune system. It may also play a role in cell survival by suppressing apoptosis, and it is essential for lactation. Alternative splicing results in multiple transcript variants that encode the same protein.

Source: NCBI Gene 5617 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_000948

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9445
Approved symbol	PRL
Name	prolactin
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Aliases	pPRL
Ensembl gene	ENSG00000172179
Ensembl biotype	protein_coding
OMIM	176760
Entrez	5617

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000306482, ENST00000617911, ENST00000651245, ENST00000651757

RefSeq mRNA: 2 — MANE Select: NM_000948 NM_000948, NM_001163558

CCDS: CCDS4548

Canonical transcript exons

ENST00000306482 — 5 exons

Exon	Start	End
ENSE00001148390	22287246	22287593
ENSE00001174359	22290174	22290353
ENSE00001174368	22292538	22292645
ENSE00001174381	22294409	22294584
ENSE00003843148	22296955	22297036

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 99.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 189.9093 / max 145465.3922, expressed in 97 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72137	187.8668	19
72129	0.8360	13
72131	0.3265	3
72133	0.2082	14
72134	0.2023	24
72132	0.1192	3
72135	0.0999	30
72140	0.0930	15
72139	0.0859	19
72130	0.0525	3

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	99.96	gold quality
adenohypophysis	UBERON:0002196	99.84	gold quality
decidua	UBERON:0002450	99.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.52	gold quality
placenta	UBERON:0001987	79.41	gold quality
stromal cell of endometrium	CL:0002255	78.35	gold quality
lower esophagus mucosa	UBERON:0035834	76.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.11	gold quality
mucosa of stomach	UBERON:0001199	71.71	gold quality
secondary oocyte	CL:0000655	71.43	silver quality
body of uterus	UBERON:0009853	69.89	gold quality
mucosa of transverse colon	UBERON:0004991	69.12	gold quality
right coronary artery	UBERON:0001625	68.94	gold quality
tibialis anterior	UBERON:0001385	68.68	silver quality
omental fat pad	UBERON:0010414	68.21	gold quality
peritoneum	UBERON:0002358	68.14	gold quality
adipose tissue of abdominal region	UBERON:0007808	66.74	gold quality
right testis	UBERON:0004534	65.74	gold quality
descending thoracic aorta	UBERON:0002345	65.44	gold quality
left testis	UBERON:0004533	64.34	gold quality
myometrium	UBERON:0001296	64.24	gold quality
diaphragm	UBERON:0001103	63.01	gold quality
thymus	UBERON:0002370	62.95	silver quality
testis	UBERON:0000473	62.24	gold quality
embryo	UBERON:0000922	62.14	gold quality
right frontal lobe	UBERON:0002810	62.07	gold quality
hair follicle	UBERON:0002073	61.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	61.45	gold quality
ileal mucosa	UBERON:0000331	61.31	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	6804.08
E-HCAD-24	yes	3880.91
E-ANND-3	no	2.44

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
KRT14	Activation
KRT15	Activation
KRT19	Activation
KRT5	Activation

Upstream regulators (CollecTRI, top): AHR, ALX1, AP1, AR, BMAL1, CEBPA, CEBPB, CEBPD, CEBPG, CLOCK, CREB1, CREM, DDIT3, DNMT1, EGR3, ELK1, ELK3, ERF, ESR1, ESR2, ETS1, ETS2, ETV7, EZH2, FOXC1, FOXN1, FOXO1, GABPA, GLI3, HDAC9, HLTF, HOXA10, HOXA11, HOXB7, IKZF1, IRF1, JUN, JUNB, KAT5, KLF12

miRNA regulators (miRDB)

13 targeting PRL, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-4521	97.73	67.64	684
HSA-MIR-4327	97.21	67.71	676
HSA-MIR-490-5P	96.75	65.81	661
HSA-MIR-4330	95.44	66.39	993
HSA-MIR-659-5P	95.36	65.00	300
HSA-MIR-6816-3P	95.05	66.08	459

Literature-anchored findings (GeneRIF, showing 40)

• Prolactin expressed as a hexahistidine-tagged fusion protein is active in a rat Nb2 lymphoma cell proliferation bioassay and when purified can substitute for pituitary-derived prolactin. (PMID:11437600)
• review: the regulation of prolactin secretion, the clinical features and causes of hyperprolactinemia, and the use of dopamine agonists (PMID:11721691)
• Review: evidence demonstrating PRL synthesis by different subtypes of immune cells from humans, mice and rats, describe the regulation of PRL gene expression in human lymphocytes, and discuss the functions of PRL made by immune cells. (PMID:11721692)
• Review: Polymorphisms of the human prolactin gene–implications for production of lymphocyte prolactin and systemic lupus erythematosus (PMID:11721693)
• Review: proliferative actions of PRL and its survival promoting properties in immune cells (PMID:11721694)
• Review: Stimulation of interferon regulatory factor-1 by prolactin (PMID:11721695)
• Review: Effects of prolactin on hematopoiesis (PMID:11721696)
• Review: Effects of prolactin on signal transduction and gene expression: possible relevance for systemic lupus erythematosus. (PMID:11721698)
• Review: Effect of prolactin on the antigen presenting function of monocyte-derived dendritic cells (PMID:11721699)
• Review: evidence has accumulated to support the hypothesis that both mild and moderate elevations of serum prolactin participate in the clinical expression and pathogenesis of systemic lupus erythematosus (PMID:11721702)
• Review: Analysis of anti-prolactin autoantibodies in systemic lupus erythematosus (PMID:11721703)
• cyclin D1 may be a target gene for PRL in normal lobuloalveolar development, as well as in the development and/or progression of mammary cancer. (PMID:11923474)
• results presented are consistent with a role of the PRL-PRLR system in bone/cartilage formation/repair processes (PMID:11997178)
• a direct inhibition of PRL on tumour cell growth, while its reciprocal effect on apoptosis refers to an important regulatory role of PRL (PMID:12036601)
• study provides evidence that cortisol, prolactin and growth hormone respond to psychological stress in humans (PMID:12445833)
• transcriptional activity of prolactin promoter in GH3 cells co-transfected with menin was significantly decreased (PMID:12459032)
• expression and transcription in mammary cells (PMID:12485910)
• human ovarian follicular cells are an extrapituitary site of prolactin gene expression (PMID:12524085)
• To evaluate a possible role of prolactin genes in SLE & MS formed an association study of 19 PRL SNPs was done. No statistically significant difference in the prolactin receptor allele distribution was observed for any of the tested variations. (PMID:12559630)
• human T-lymphocytes are targets for PRL. (PMID:12668883)
• results demonstrate a direct effect of prolactin, via functional prolactin receptors, in reducing the lipoprotein lipase activity in human adipose tissue (PMID:12679477)
• serum leptin and prolactin levels does not seem to be related with angiogenic activity and metastasis in breast cancer patients. (PMID:12687277)
• backbone dynamics were investigated by analysis of 15N NMR relaxation phenomena and demonstrated a rigid four-helical bundle with relatively mobile interconnecting loops (PMID:12729745)
• K+ channel modulation by PRL, via the p59fyn pathway, is the primary ionic event in PRL signal transduction, triggering proliferation of androgen-sensitive prostate cancer cells. (PMID:14565846)
• The N-terminus of prolactin modulates its biological properties. (PMID:14580717)
• Prolactin may contribute significantly to early corpus luteum formation and survival by acting as a potent antiapoptotic factor for human granulosa cells (PMID:14645190)
• Human prolactin-G129R-induced breast cancer cell and/or mammary gland apoptosis which is mediated, at least in part, through the regulation of Bax and Bcl-2 gene expression. (PMID:14647416)
• differential changes in nocturnal prolactin secretion among HIV-infected men occurred while maintaining the normal coordinate feedback and/or feedforward control within the lactotropic axis (PMID:14984591)
• Endogenous prolactin induces estrogen receptor alpha and prolactin receptor expression and increases estrogen responsiveness in breast neoplasms. (PMID:15026085)
• the smad pathway and the tumor suppressor menin are key regulators of activin effects on PRL and Pit-1 expression, as well as on cell growth inhibition (PMID:15031321)
• PRL fragments are potentially physiological antiangiogenic inhibitors of tumor growth. (PMID:15192082)
• lack of endometrial PRL expression is involved in reproduction failure. (PMID:15218000)
• Data support an “induced-fit” model for prolactin receptor binding where binding of the first receptor to human prolactin induces a conformation change in the hormone creating the second receptor-binding site. (PMID:15504038)
• Prolactin and heregulin override DNA damage-induced growth arrest and promote PI-3 kinase-dependent proliferation in breast cancer cells (PMID:15645137)
• PRL takes part in the trigger of T-cell activation, and is produced and secreted by the same cells acting predominantly in autocrine form, collaborating in the expression of CD69 and CD154, and the secretion of IL-2 and INF-gamma. (PMID:15993365)
• solution structure and prolactin-prolactin receptor interaction (PMID:16045928)
• prolactin binding initiates limited proteasomal cleavage of its receptor, generating a cell-associated fragment containing the extracellular domain; findings described new potential mediator of prolactin action (PMID:16103113)
• Data suggest that the expression of Pit-1 in cells of the alpha SU-based gonadotropin cell lineage might also lead to the expression of growth hormone, prolactin, and thyroid-stimulating hormone beta subunit. (PMID:16133148)
• Review. The regulation of PRL gene expression in human lymphocytes & the functions of PRL made by the immune cells, including its involvement in autoimmunity, are reviewed. (PMID:16187706)
• cAMP induces PRL expression in T lymphocytes via cooperation of at least two different signaling pathways (PMID:16378242)

Cross-species orthologs

55 orthologs

Organism	Symbol	Gene ID
danio_rerio	prl	ENSDARG00000037946
mus_musculus	Prl4a1	ENSMUSG00000005891
mus_musculus	Prl7a1	ENSMUSG00000006488
mus_musculus	Prl8a9	ENSMUSG00000006490
mus_musculus	Prl5a1	ENSMUSG00000017064
mus_musculus	Prl3c1	ENSMUSG00000017922
mus_musculus	Prl8a2	ENSMUSG00000018259
mus_musculus	Prl8a1	ENSMUSG00000019756
mus_musculus	Prl	ENSMUSG00000021342
mus_musculus	Prl8a6	ENSMUSG00000021345
mus_musculus	Prl8a8	ENSMUSG00000021346
mus_musculus	Prl7b1	ENSMUSG00000021347
mus_musculus	Prl7d1	ENSMUSG00000021348
mus_musculus	Prl2a1	ENSMUSG00000022886
mus_musculus	Prl3a1	ENSMUSG00000038883
mus_musculus	Prl3b1	ENSMUSG00000038891
mus_musculus	Prl7a2	ENSMUSG00000046899
mus_musculus	Prl2c5	ENSMUSG00000055360
mus_musculus	Prl2c3	ENSMUSG00000056457
mus_musculus	Prl3d1	ENSMUSG00000057170
mus_musculus	Prl7c1	ENSMUSG00000060738
mus_musculus	Prl3d3	ENSMUSG00000062201
mus_musculus	Prl2c1	ENSMUSG00000062551
mus_musculus	Prl3d2	ENSMUSG00000062737
mus_musculus	Prl2b1	ENSMUSG00000069258
mus_musculus	Prl6a1	ENSMUSG00000069259
mus_musculus	Prl2c2	ENSMUSG00000079092
rattus_norvegicus	Prl5a1	ENSRNOG00000016307
rattus_norvegicus	Prl4a1	ENSRNOG00000016436
rattus_norvegicus	Prl2a1	ENSRNOG00000016463
rattus_norvegicus	Prl7d1	ENSRNOG00000016510
rattus_norvegicus	Prl7a3	ENSRNOG00000016616
rattus_norvegicus	Prl7b1	ENSRNOG00000016742
rattus_norvegicus	Prl3d4	ENSRNOG00000016792
rattus_norvegicus	Prl8a7	ENSRNOG00000016933
rattus_norvegicus	Prl2b1	ENSRNOG00000017007
rattus_norvegicus	Prl8a2	ENSRNOG00000017048
rattus_norvegicus	Prl6a1	ENSRNOG00000017089
rattus_norvegicus	Prl3a1	ENSRNOG00000017103
rattus_norvegicus	Prl3b1	ENSRNOG00000017185
rattus_norvegicus	Prl3c1	ENSRNOG00000017203
rattus_norvegicus	Prl	ENSRNOG00000017374
rattus_norvegicus	Prl8a9	ENSRNOG00000024843
rattus_norvegicus	Prl7a4	ENSRNOG00000029126
rattus_norvegicus	Prl2c1	ENSRNOG00000039058
rattus_norvegicus	Prl5a2	ENSRNOG00000039075
rattus_norvegicus	Prl8a5	ENSRNOG00000043237
rattus_norvegicus	Prl7c1	ENSRNOG00000047649
rattus_norvegicus	Prl7a1l-ps1	ENSRNOG00000069612
rattus_norvegicus	Rpl-1	ENSRNOG00000074382
rattus_norvegicus		ENSRNOG00000080461
rattus_norvegicus		ENSRNOG00000080988
rattus_norvegicus		ENSRNOG00000082513
rattus_norvegicus	Prl8a4	ENSRNOG00000089768
rattus_norvegicus		ENSRNOG00000091360

Paralogs (5): GH2 (ENSG00000136487), CSH1 (ENSG00000136488), CSHL1 (ENSG00000204414), CSH2 (ENSG00000213218), GH1 (ENSG00000259384)

Protein

Protein identifiers

Prolactin — P01236 (reviewed: P01236)

All UniProt accessions (5): P01236, A0A494C0Z0, A0A494C1P2, Q5I0G2, Q5THQ0

UniProt curated annotations — full annotation on UniProt →

Function. Prolactin acts primarily on the mammary gland by promoting lactation.

Subunit / interactions. Interacts with PRLR.

Subcellular location. Secreted.

Similarity. Belongs to the somatotropin/prolactin family.

RefSeq proteins (2): NP_000939, NP_001157030 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001400	Somatotropin/Prolactin	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily
IPR018116	Somatotropin_CS	Conserved_site

Pfam: PF00103

UniProt features (33 total): sequence conflict 8, helix 8, modified residue 5, disulfide bond 3, strand 3, turn 2, signal peptide 1, chain 1, mutagenesis site 1, glycosylation site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
3N06	X-RAY DIFFRACTION	2
3NCE	X-RAY DIFFRACTION	2
3MZG	X-RAY DIFFRACTION	2.1
3N0P	X-RAY DIFFRACTION	2.1
3NCB	X-RAY DIFFRACTION	2.1
3D48	X-RAY DIFFRACTION	2.5
3NCC	X-RAY DIFFRACTION	2.5
2Q98	X-RAY DIFFRACTION	2.7
3NCF	X-RAY DIFFRACTION	2.8
3NPZ	X-RAY DIFFRACTION	3.35
3EW3	X-RAY DIFFRACTION	3.8
1RW5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01236-F1	86.38	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 54, 62, 118, 163, 194

Disulfide bonds (3): 219–227, 32–39, 86–202

Glycosylation sites (1): 59

Mutagenesis-validated functional residues (1):

Position	Phenotype
157	inhibits signaling via prlr; mutant prl acts as a prlr antagonist.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1170546	Prolactin receptor signaling
R-HSA-977225	Amyloid fiber formation
R-HSA-982772	Growth hormone receptor signaling
R-HSA-9927426	Developmental Lineage of Mammary Gland Alveolar Cells

MSigDB gene sets: 187 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, LHX3_01, PID_REG_GR_PATHWAY, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, CHX10_01, AACWWCAANK_UNKNOWN, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (13): negative regulation of endothelial cell proliferation (GO:0001937), cell surface receptor signaling pathway (GO:0007166), female pregnancy (GO:0007565), lactation (GO:0007595), negative regulation of angiogenesis (GO:0016525), mammary gland development (GO:0030879), response to nutrient levels (GO:0031667), prolactin signaling pathway (GO:0038161), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), positive regulation of miRNA transcription (GO:1902895), positive regulation of lactation (GO:1903489), signal transduction (GO:0007165)

GO Molecular Function (4): prolactin receptor binding (GO:0005148), hormone activity (GO:0005179), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endosome lumen (GO:0031904), vesicle (GO:0031982)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cytokine Signaling in Immune system	2
Metabolism of proteins	1
Developmental Lineages of the Mammary Gland	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
signal transduction	1
multi-organism reproductive process	1
multi-multicellular organism process	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
gland development	1
response to stimulus	1
hormone-mediated signaling pathway	1
cytokine-mediated signaling pathway	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via JAK-STAT	1
positive regulation of receptor signaling pathway via STAT	1
positive regulation of DNA-templated transcription	1
miRNA transcription	1
regulation of miRNA transcription	1
positive regulation of miRNA metabolic process	1
lactation	1
positive regulation of secretion	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of lactation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine receptor binding	1
receptor ligand activity	1
binding	1
cation binding	1

Protein interactions and networks

STRING

2936 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRL	PRLR	P16471	999
PRL	POMC	P01189	959
PRL	TRH	P20396	951
PRL	INS	P01308	941
PRL	GHR	P10912	920
PRL	OXT	P01178	900
PRL	POU1F1	P28069	899
PRL	GNRH1	P01148	896
PRL	IGF1	P01343	889
PRL	GHRH	P01286	884
PRL	CSN2	P05814	881
PRL	IGF2	P01344	880
PRL	A6NFB4	A6NFB4	875
PRL	PROP1	O75360	869
PRL	JAK2	O60674	868

IntAct

12 interactions, top by confidence:

A	B	Type	Score
PRLR	PRL	psi-mi:“MI:0407”(direct interaction)	0.610
PRL	PRLR	psi-mi:“MI:0915”(physical association)	0.610
PRLR	PRL	psi-mi:“MI:0407”(direct interaction)	0.560
PRL	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
BMP1	PRL	psi-mi:“MI:0915”(physical association)	0.400
PRL	HLA-DQB2	psi-mi:“MI:0915”(physical association)	0.400
PRL	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): HLA-DQB2 (Affinity Capture-MS), HLA-DQB2 (Affinity Capture-MS), PRL (Two-hybrid), PPIB (Affinity Capture-Western), PPIB (Reconstituted Complex), PPIB (Two-hybrid), PRL (Two-hybrid), S100P (Reconstituted Complex), S100A6 (Reconstituted Complex)

ESM2 similar proteins: O62781, O62819, O73847, P01236, P01237, P01238, P01239, P01240, P01241, P01242, P06879, P09321, P09586, P0DML2, P0DML3, P10765, P11228, P12420, P14059, P14676, P17572, P18121, P22077, P22393, P29234, P33089, P33090, P33091, P33093, P37884, P43001, P46403, P55151, P55751, P55752, P55753, P55754, P58343, P58756, P58757

Diamond homologs: O35256, O35257, O54830, O62781, O62819, O93566, P01236, P01237, P01238, P01239, P01240, P04095, P04768, P04769, P05402, P06879, P09318, P09319, P09320, P09321, P09584, P09585, P09586, P09611, P10765, P12401, P12402, P12420, P14059, P14676, P16038, P17572, P18121, P18917, P19159, P20362, P21993, P22393, P24800, P29234

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PAK2	up-regulates	PRL	phosphorylation
PRL	“down-regulates activity”	LPL
PRL	“up-regulates quantity by expression”	KRT14	“transcriptional regulation”
PRL	“up-regulates quantity by expression”	KRT5	“transcriptional regulation”
PRL	“up-regulates quantity by expression”	KRT15	“transcriptional regulation”
PRL	“up-regulates quantity by expression”	KRT19	“transcriptional regulation”
HOXA11	“up-regulates quantity by expression”	PRL	“transcriptional regulation”
PRL	up-regulates	PRLR	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

36 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

490 predictions. Top by Δscore:

Variant	Effect	Δscore
6:22287590:GAACC:G	acceptor_loss	1.0000
6:22287595:T:C	acceptor_loss	1.0000
6:22290168:GCTCA:G	donor_loss	1.0000
6:22290169:CTCA:C	donor_loss	1.0000
6:22290170:TCA:T	donor_loss	1.0000
6:22290171:CACC:C	donor_loss	1.0000
6:22290172:ACCT:A	donor_loss	1.0000
6:22292533:CTCA:C	donor_loss	1.0000
6:22292534:TCA:T	donor_loss	1.0000
6:22292535:CAC:C	donor_loss	1.0000
6:22292536:A:AC	donor_gain	1.0000
6:22292536:A:C	donor_loss	1.0000
6:22292536:ACATT:A	donor_gain	1.0000
6:22292537:C:CA	donor_gain	1.0000
6:22292537:CA:C	donor_gain	1.0000
6:22292537:CATT:C	donor_gain	1.0000
6:22292537:CATTC:C	donor_gain	1.0000
6:22292641:TTATC:T	acceptor_gain	1.0000
6:22292643:ATC:A	acceptor_gain	1.0000
6:22292643:ATCCT:A	acceptor_loss	1.0000
6:22292644:TC:T	acceptor_gain	1.0000
6:22292645:CC:C	acceptor_gain	1.0000
6:22292645:CCT:C	acceptor_loss	1.0000
6:22292646:C:A	acceptor_loss	1.0000
6:22292646:C:CC	acceptor_gain	1.0000
6:22292647:T:A	acceptor_loss	1.0000
6:22292652:A:AC	acceptor_gain	1.0000
6:22287589:TGAAC:T	acceptor_gain	0.9900
6:22287594:C:CC	acceptor_gain	0.9900
6:22289610:C:CA	donor_gain	0.9900

AlphaMissense

1476 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:22287469:T:G	D206A	0.997
6:22290309:C:A	W119C	0.997
6:22290309:C:G	W119C	0.997
6:22287467:A:G	S207P	0.996
6:22287470:C:G	D206H	0.996
6:22290311:A:G	W119R	0.996
6:22290311:A:T	W119R	0.996
6:22292593:C:G	C86S	0.996
6:22292594:A:T	C86S	0.996
6:22287430:C:G	C219S	0.995
6:22287431:A:T	C219S	0.995
6:22287445:A:G	L214P	0.995
6:22287469:T:A	D206V	0.995
6:22287469:T:C	D206G	0.995
6:22287478:A:G	L203P	0.995
6:22287480:G:C	C202W	0.995
6:22287481:C:G	C202S	0.995
6:22287482:A:T	C202S	0.995
6:22290205:A:G	L154P	0.995
6:22287459:T:A	K209N	0.994
6:22287459:T:G	K209N	0.994
6:22287482:A:G	C202R	0.994
6:22292592:G:C	C86W	0.994
6:22292593:C:T	C86Y	0.994
6:22287431:A:G	C219R	0.993
6:22287475:C:G	R204P	0.993
6:22287481:C:T	C202Y	0.993
6:22292594:A:G	C86R	0.993
6:22287471:C:A	R205S	0.992
6:22287471:C:G	R205S	0.992

dbSNP variants (sampled 300 via entrez): RS1000159359 (6:22304149 A>G), RS1000232359 (6:22303593 A>C), RS1000405800 (6:22289400 A>G), RS1000768869 (6:22303259 A>G), RS1001425245 (6:22290886 G>A), RS1001663288 (6:22301818 G>C), RS1001852048 (6:22292680 T>A), RS1002003216 (6:22303640 A>G), RS1002127500 (6:22302230 G>A), RS1002324928 (6:22289678 T>C), RS1002609795 (6:22296498 A>G), RS1002875672 (6:22293305 G>T), RS1003027364 (6:22286770 G>A), RS1003077999 (6:22300131 G>A), RS1003203155 (6:22294942 A>T)

Disease associations

OMIM: gene MIM:176760 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000317_13	Obesity	3.000000e-07
GCST001086_7	Paget’s disease	4.000000e-06
GCST001784_13	Pulmonary function (smoking interaction)	2.000000e-07
GCST001784_35	Pulmonary function (smoking interaction)	2.000000e-07
GCST007692_56	Chronic obstructive pulmonary disease	1.000000e-09
GCST010002_49	Refractive error	6.000000e-38
GCST90011898_138	Alanine aminotransferase levels	2.000000e-11
GCST90011899_19	Aspartate aminotransferase levels	4.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

137 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Risperidone	decreases reaction, increases secretion, affects reaction, increases expression, affects cotreatment	30
Bromocriptine	decreases reaction, increases secretion, increases expression, decreases expression, decreases secretion	18
Haloperidol	affects expression, increases expression, increases secretion	14
Estradiol	decreases reaction, increases reaction, affects reaction, decreases abundance, increases abundance (+3 more)	12
Progesterone	increases secretion, increases expression, increases reaction, affects reaction, decreases abundance (+2 more)	12
Olanzapine	affects cotreatment, increases expression, increases secretion	11
Medroxyprogesterone Acetate	increases secretion, affects reaction, affects cotreatment, increases expression, increases reaction (+1 more)	11
Metoclopramide	decreases reaction, increases secretion, affects expression, increases expression	10
Sulpiride	decreases reaction, increases abundance, increases expression, increases secretion	9
8-Bromo Cyclic Adenosine Monophosphate	increases reaction, decreases reaction, increases expression, affects cotreatment, decreases expression (+2 more)	9
Cocaine	affects reaction, increases expression, affects secretion, decreases reaction, decreases expression (+2 more)	8
Testosterone	decreases reaction, increases abundance, affects abundance, decreases abundance, increases secretion (+2 more)	8
Aripiprazole	decreases reaction, increases expression, increases secretion, decreases expression	6
Amisulpride	increases secretion, increases expression	5
Cyclic AMP	increases reaction, decreases reaction, increases secretion, affects cotreatment, increases expression	5
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression, increases secretion	4
Clomipramine	decreases reaction, affects secretion, increases expression, increases secretion	4
Fenfluramine	affects reaction, increases expression	4
Verapamil	decreases reaction, increases secretion, increases reaction, increases expression	4
Cabergoline	decreases expression, decreases secretion	3
Clozapine	affects cotreatment, increases secretion, increases expression	3
Contraceptives, Oral	increases expression	3
Copper	affects binding, increases reaction, decreases expression, affects cotreatment, decreases reaction (+1 more)	3
Dexamethasone	affects cotreatment, increases expression	3
Bucladesine	affects cotreatment, increases reaction, increases secretion, increases expression, decreases reaction	3
Fluoxetine	increases expression, affects cotreatment	3
Methadone	affects secretion, increases expression, increases secretion	3
Raloxifene Hydrochloride	affects cotreatment, decreases expression, decreases reaction, increases reaction, increases secretion (+1 more)	3
dironyl	decreases expression	2
1-(3-chlorophenyl)piperazine	increases expression, decreases reaction	2

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_WS56	CHO-p658-hPRL	Transformed cell line	Female
CVCL_WS57	CHO-pEDdc-hPRL	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.