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

Summary

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: mouse all
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Genomic context

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_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
Novel Pathogenetic Variants in PTHLH and TRPS1 Genes Causing Syndromic Brachydactyly.
Title: Novel Pathogenetic Variants in PTHLH and TRPS1 Genes Causing Syndromic Brachydactyly.
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.
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.
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.
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.
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	Compare labs

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 EBI GWAS CatalogPubMed
Genetic variants associated with breast size also influence breast cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association studies identify four ER negative-specific breast cancer risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genotyping identifies 41 new loci associated with breast cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D12S1941 (e-PCR)
- UniSTS:47403

STS-J03802 (e-PCR)
- UniSTS:68403

GDB:217131 (e-PCR)
- UniSTS:156228

RH48084 (e-PCR)
- UniSTS:35144

G60028 (e-PCR)
- UniSTS:137294

D12S1337 (e-PCR), detects polymorphism
- UniSTS:149338

G63001 (e-PCR)
- UniSTS:140126

RH48408 (e-PCR)
- UniSTS:41571

PTHLH_2350 (e-PCR)
- UniSTS:280937

STS-AA035272 (e-PCR)
- UniSTS:83060

PMC123659P5 (e-PCR)
- UniSTS:270453

PMC153548P1 (e-PCR)
- UniSTS:271261

D12S2029 (e-PCR)
- UniSTS:14780

SHGC-17539 (e-PCR)
- UniSTS:82389

RH17692 (e-PCR)
- UniSTS:62430

PTHLH (e-PCR), detects polymorphism
- UniSTS:264164

STS-M24351 (e-PCR)
- UniSTS:23539

WI-9193 (e-PCR)
- UniSTS:80125

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

NG_023197.1 RefSeqGene

Range

4251..18900

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

27958084..27972733 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

P12272, Q15251, Q6FH74
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

NC_060936.1 Alternate T2T-CHM13v2.0

Range

27829831..27844463 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

P12272, Q15251, Q6FH74
XM_054372610.1 → XP_054228585.1 parathyroid hormone-related protein isoform X1

UniProtKB/Swiss-Prot

P12272, Q15251, Q6FH74
XM_054372611.1 → XP_054228586.1 parathyroid hormone-related protein isoform X1

UniProtKB/Swiss-Prot

P12272, Q15251, Q6FH74