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PTHLH parathyroid hormone like hormone [ Homo sapiens (human) ]

Gene ID: 5744, updated on 3-Apr-2024

Summary

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Official Symbol
PTHLHprovided by HGNC
Official Full Name
parathyroid hormone like hormoneprovided by HGNC
Primary source
HGNC:HGNC:9607
See related
Ensembl:ENSG00000087494 MIM:168470; AllianceGenome:HGNC:9607
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HHM; PLP; BDE2; PTHR; PTHRP
Summary
The protein encoded by this gene is a member of the parathyroid hormone family. This hormone, via its receptor, PTHR1, regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. It is responsible for most cases of humoral hypercalcemia of malignancy, and mutations in this gene are associated with brachydactyly type E2 (BDE2). Alternatively spliced transcript variants have been found for this gene. There is also evidence for alternative translation initiation from non-AUG (CUG and GUG) start sites, downstream of the initiator AUG codon, resulting in nuclear forms of this hormone. [provided by RefSeq, Nov 2013]
Expression
Broad expression in esophagus (RPKM 1.7), endometrium (RPKM 1.5) and 19 other tissues See more
Orthologs
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Genomic context

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Location:
12p11.22
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (27958084..27972733, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (27829831..27844463, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (28111017..28125666, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_27159 Neighboring gene uncharacterized LOC105369709 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:27974511-27975710 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6152 Neighboring gene RN7SK pseudogene 15 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_27196 Neighboring gene MPRA-validated peak1633 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6153 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:28058285-28059082 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr12:28059083-28059881 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:28121815-28122325 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:28122326-28122835 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:28128050-28128738 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:28128739-28129427 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_27213 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_27218 Neighboring gene MPRA-validated peak1634 silencer Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:28175972-28177171 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:28180270-28180494 Neighboring gene uncharacterized LOC105369710 Neighboring gene uncharacterized LOC107984462 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:28283226-28284425 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_27297 Neighboring gene IFT57 pseudogene 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Involvement of parathyroid hormone-related peptide in the aggressive phenotype of colorectal cancer cells. Novoa Díaz MB, et al. World J Gastroenterol, 2021 Nov 7. PMID 34887626, Free PMC Article
  2. Involvement of the Parathyroid Hormone-Related Protein on Changes in the CYP3A Expression in Cancer Cachexia. Fujita I, et al. Mol Pharm, 2021 Dec 6. PMID 34734526
  3. Chondrodysplasia, enchondromas and a chest deformity causing severe pulmonary morbidity in a boy with a PTHLH duplication: A case report. Tacke CE, et al. Bone Rep, 2021 Jun. PMID 33981811, Free PMC Article
  4. High endogenous expression of parathyroid hormone-related protein (PTHrP) supports osteogenic differentiation in human dental follicle cells. Pieles O, et al. Histochem Cell Biol, 2020 Oct. PMID 32710187, Free PMC Article
  5. Mesenchymal Progenitor Regulation of Tooth Eruption: A View from PTHrP. Nagata M, et al. J Dent Res, 2020 Feb. PMID 31623502, Free PMC Article

See all (238) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. A novel heterozygous mutation in PTHLH causing autosomal dominant brachydactyly type E complicated with short stature.
    Title: A novel heterozygous mutation in PTHLH causing autosomal dominant brachydactyly type E complicated with short stature.
  2. Malignancy-related Hypercalcemia Caused by Metameric Cutaneous Metastasis of Parathyroid Hormone-related Protein-producing Bladder Carcinoma with Squamous Cell Differentiation: An Autopsy Case of Cobb Syndrome.
    Title: Malignancy-related Hypercalcemia Caused by Metameric Cutaneous Metastasis of Parathyroid Hormone-related Protein-producing Bladder Carcinoma with Squamous Cell Differentiation: An Autopsy Case of Cobb Syndrome.
  3. Role of Parathyroid Hormone and Parathyroid Hormone-Related Protein in Protein-Energy Malnutrition.
    Title: Role of Parathyroid Hormone and Parathyroid Hormone-Related Protein in Protein-Energy Malnutrition.
  4. Exosomal lncRNA HOTAIR promotes osteoclast differentiation by targeting TGF-beta/PTHrP/RANKL pathway.
    Title: Exosomal lncRNA HOTAIR promotes osteoclast differentiation by targeting TGF-β/PTHrP/RANKL pathway.
  5. Novel Pathogenetic Variants in PTHLH and TRPS1 Genes Causing Syndromic Brachydactyly.
    Title: Novel Pathogenetic Variants in PTHLH and TRPS1 Genes Causing Syndromic Brachydactyly.
  6. Involvement of the Parathyroid Hormone-Related Protein on Changes in the CYP3A Expression in Cancer Cachexia.
    Title: Involvement of the Parathyroid Hormone-Related Protein on Changes in the CYP3A Expression in Cancer Cachexia.
  7. Involvement of parathyroid hormone-related peptide in the aggressive phenotype of colorectal cancer cells.
    Title: Involvement of parathyroid hormone-related peptide in the aggressive phenotype of colorectal cancer cells.
  8. Role of SPARC in the epithelial-mesenchymal transition induced by PTHrP in human colon cancer cells.
    Title: Role of SPARC in the epithelial-mesenchymal transition induced by PTHrP in human colon cancer cells.
  9. Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase.
    Title: Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase.
  10. Role of the calcium-sensing receptor (CaSR) in cancer metastasis to bone: Identifying a potential therapeutic target.
    Title: Role of the calcium-sensing receptor (CaSR) in cancer metastasis to bone: Identifying a potential therapeutic target.
Submit: New GeneRIF Correction See all GeneRIFs (180)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Brachydactyly type E2
MedGen: C3150644 OMIM: 613382 GeneReviews: Not available
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Copy number response

Description
Copy number response
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2023-01-25)

ClinGen Genome Curation PagePubMed
Triplosensitivity

Little evidence for dosage pathogenicity (Last evaluated 2023-01-25)

ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
A genome-wide association study identifies susceptibility loci for ossification of the posterior longitudinal ligament of the spine.
EBI GWAS Catalog
Genetic variants associated with breast size also influence breast cancer risk.
EBI GWAS Catalog
Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.
EBI GWAS Catalog
Genome-wide association studies identify four ER negative-specific breast cancer risk loci.
EBI GWAS Catalog
Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer.
EBI GWAS Catalog
Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
EBI GWAS Catalog
Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC14611

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables hormone activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables peptide hormone receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables peptide hormone receptor binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within adenylate cyclase-activating G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in bone mineralization IEA
Inferred from Electronic Annotation
more info
  
involved_in cAMP metabolic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in cell-cell signaling TAS
Traceable Author Statement
more info
 PubMed 
involved_in epidermis development TAS
Traceable Author Statement
more info
 PubMed 
involved_in female pregnancy TAS
Traceable Author Statement
more info
 PubMed 
involved_in negative regulation of cell population proliferation TAS
Traceable Author Statement
more info
 PubMed 
acts_upstream_of_or_within negative regulation of chondrocyte development IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within negative regulation of chondrocyte differentiation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in osteoblast development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of cell population proliferation TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of chondrocyte differentiation IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within regulation of gene expression IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within skeletal system development IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi apparatus IDA
Inferred from Direct Assay
more info
  
located_in cytoplasm TAS
Traceable Author Statement
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in extracellular space TAS
Traceable Author Statement
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
parathyroid hormone-related protein
Names
PTH-rP
PTH-related protein
osteostatin
parathyroid hormone-like hormone preproprotein
parathyroid hormone-like related protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_023197.1 RefSeqGene

    Range
    4251..18900
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_002820.3 → NP_002811.1  parathyroid hormone-related protein isoform 2 preproprotein

    See identical proteins and their annotated locations for NP_002811.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 3' CDS and UTR, compared to variant 1. The resulting isoform (2) has a shorter C-terminus, as compared to isoform 1.
    Source sequence(s)
    AC008011, BC005961, BG680355, BI963162, J03802
    Consensus CDS
    CCDS8715.1
    UniProtKB/TrEMBL
    F5GZD9, Q53XY9
    Related
    ENSP00000201015.4, ENST00000201015.8
    Conserved Domains (1) summary
    pfam01279
    Location:35 → 117
    Parathyroid; Parathyroid hormone family

  2. NM_198964.2 → NP_945315.1  parathyroid hormone-related protein isoform 2 preproprotein

    See identical proteins and their annotated locations for NP_945315.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, and in the 3' CDS and UTR, compared to variant 1. The resulting isoform (2) has a shorter C-terminus, as compared to isoform 1.
    Source sequence(s)
    AC008011, BC005961, BG679319, BI963162, J03802
    Consensus CDS
    CCDS8715.1
    UniProtKB/TrEMBL
    F5GZD9, Q53XY9
    Related
    ENSP00000379209.3, ENST00000395868.7
    Conserved Domains (1) summary
    pfam01279
    Location:35 → 117
    Parathyroid; Parathyroid hormone family

  3. NM_198965.2 → NP_945316.1  parathyroid hormone-related protein isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_945316.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AC008011
    Consensus CDS
    CCDS44853.1
    UniProtKB/Swiss-Prot
    P12272, Q15251, Q6FH74
    UniProtKB/TrEMBL
    F5GZD9
    Related
    ENSP00000441765.1, ENST00000545234.6
    Conserved Domains (1) summary
    pfam01279
    Location:35 → 117
    Parathyroid; Parathyroid hormone family

  4. NM_198966.2 → NP_945317.1  parathyroid hormone-related protein isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_945317.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Both variants 1 and 4 encode the same isoform (1).
    Source sequence(s)
    AC008011, AI569027, AI591151, AI760061, BG676028, BG679319
    Consensus CDS
    CCDS44853.1
    UniProtKB/Swiss-Prot
    P12272, Q15251, Q6FH74
    UniProtKB/TrEMBL
    F5GZD9
    Conserved Domains (1) summary
    pfam01279
    Location:35 → 117
    Parathyroid; Parathyroid hormone family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    27958084..27972733 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017019675.2 → XP_016875164.1  parathyroid hormone-related protein isoform X1

    UniProtKB/Swiss-Prot
    P12272, Q15251, Q6FH74
    UniProtKB/TrEMBL
    F5GZD9
    Conserved Domains (1) summary
    pfam01279
    Location:35 → 117
    Parathyroid; Parathyroid hormone family

  2. XM_047429179.1 → XP_047285135.1  parathyroid hormone-related protein isoform X1

    UniProtKB/Swiss-Prot
    P12272, Q15251, Q6FH74

  3. XM_047429178.1 → XP_047285134.1  parathyroid hormone-related protein isoform X1

    UniProtKB/Swiss-Prot
    P12272, Q15251, Q6FH74
    Related
    ENSP00000379213.1, ENST00000395872.5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    27829831..27844463 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054372612.1 → XP_054228587.1  parathyroid hormone-related protein isoform X1

    UniProtKB/Swiss-Prot
    P12272, Q15251, Q6FH74

  2. XM_054372610.1 → XP_054228585.1  parathyroid hormone-related protein isoform X1

    UniProtKB/Swiss-Prot
    P12272, Q15251, Q6FH74

  3. XM_054372611.1 → XP_054228586.1  parathyroid hormone-related protein isoform X1

    UniProtKB/Swiss-Prot
    P12272, Q15251, Q6FH74
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P12272.1 GenPept UniProtKB/Swiss-Prot:P12272

Gene LinkOut

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