PTHLH Gene (Protein Coding)

Parathyroid Hormone Like Hormone

GC12M027959
GIFtS:
45
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 brachyd... See more...

Aliases for PTHLH Gene

Aliases for PTHLH Gene

  • Parathyroid Hormone Like Hormone 2 3 5
  • Parathyroid Hormone-Like Hormone Preproprotein 2 3
  • Parathyroid Hormone-Related Protein 3 4
  • Osteostatin 2 3
  • PTH-RP 3 4
  • PTHRP 3 4
  • PLP 3 4
  • Parathyroid Hormone-Related Protein Preproprotein 2
  • Parathyroid Hormone-Like Related Protein 3
  • Parathyroid Hormone-Like Protein 4
  • PTH-Related Protein 3
  • PTHrP 4
  • BDE2 3
  • PTHR 3
  • HHM 3

External Ids for PTHLH Gene

Previous GeneCards Identifiers for PTHLH Gene

  • GC12M028487
  • GC12M028138
  • GC12M028011
  • GC12M028006
  • GC12M028002
  • GC12M027880
  • GC12M028111

Summaries for PTHLH Gene

Entrez Gene Summary for PTHLH Gene

  • 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]

GeneCards Summary for PTHLH Gene

PTHLH (Parathyroid Hormone Like Hormone) is a Protein Coding gene. Diseases associated with PTHLH include Brachydactyly, Type E2 and Brachydactyly, Type E1. Among its related pathways are Signaling by GPCR and Signaling events mediated by the Hedgehog family. Gene Ontology (GO) annotations related to this gene include hormone activity and peptide hormone receptor binding.

UniProtKB/Swiss-Prot Summary for PTHLH Gene

  • Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport. Regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Required for skeletal homeostasis. Promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. Upregulates BMPR1A expression in the mammary mesenchyme and this increases the sensitivity of these cells to BMPs and allows them to respond to BMP4 in a paracrine and/or autocrine fashion. BMP4 signaling in the mesenchyme, in turn, triggers epithelial outgrowth and augments MSX2 expression, which causes the mammary mesenchyme to inhibit hair follicle formation within the nipple sheath (By similarity). Promotes colon cancer cell migration and invasion in an integrin alpha-6/beta-1-dependent manner through activation of Rac1.
  • Osteostatin is a potent inhibitor of osteoclastic bone resorption.

Gene Wiki entry for PTHLH Gene

Additional gene information for PTHLH Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PTHLH Gene

Genomics for PTHLH Gene

GeneHancer (GH) Regulatory Elements for PTHLH Gene

Promoters and enhancers for PTHLH Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PTHLH on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PTHLH

Top Transcription factor binding sites by QIAGEN in the PTHLH gene promoter:
  • AP-1
  • deltaCREB

Genomic Locations for PTHLH Gene

Genomic Locations for PTHLH Gene
chr12:27,958,084-27,972,733
(GRCh38/hg38)
Size:
14,650 bases
Orientation:
Minus strand
chr12:28,111,017-28,125,638
(GRCh37/hg19)
Size:
14,622 bases
Orientation:
Minus strand

Genomic View for PTHLH Gene

Genes around PTHLH on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PTHLH Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PTHLH Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for PTHLH Gene

Proteins for PTHLH Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for PTHLH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P12272-PTHR_HUMAN
    Recommended name:
    Parathyroid hormone-related protein
    Protein Accession:
    P12272
    Secondary Accessions:
    • Q15251
    • Q6FH74

    Protein attributes for PTHLH Gene

    Size:
    177 amino acids
    Molecular mass:
    20194 Da
    Quaternary structure:
    • PTHrP interacts with PTH1R (via N-terminal extracellular domain).

    Three dimensional structures from OCA and Proteopedia for PTHLH Gene

    Alternative splice isoforms for PTHLH Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PTHLH Gene

Protein Expression for PTHLH Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for PTHLH Gene

  • There are 3 principal secretory forms, called PTHrP[1-36], PTHrP[38-94], and osteostatin (PTHrP[107-139]) arising from endoproteolytic cleavage of the initial translation product. Each of these secretory forms is believed to have one or more of its own receptors that mediates the normal paracrine, autocrine and endocrine actions.
  • Glycosylation at Thr108
  • Modification sites at PhosphoSitePlus

Other Protein References for PTHLH Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for PTHLH
  • Santa Cruz Biotechnology (SCBT) Antibodies for PTHLH

No data available for DME Specific Peptides for PTHLH Gene

Domains & Families for PTHLH Gene

Gene Families for PTHLH Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for PTHLH Gene

Blocks:
  • Parathyroid hormone
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for PTHLH Gene

GenScript: Design optimal peptide antigens:
  • Parathyroid hormone-like protein (PTHR_HUMAN)
  • PTHLH protein (Q15252_HUMAN)
  • cDNA, FLJ94023, Homo sapiens parathyroid hormone-like hormone (PTHLH), mRNA (Q53XY9_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P12272

UniProtKB/Swiss-Prot:

PTHR_HUMAN :
  • Belongs to the parathyroid hormone family.
Family:
  • Belongs to the parathyroid hormone family.
genes like me logo Genes that share domains with PTHLH: view

Function for PTHLH Gene

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Molecular function for PTHLH Gene

UniProtKB/Swiss-Prot Function:
Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport. Regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Required for skeletal homeostasis. Promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. Upregulates BMPR1A expression in the mammary mesenchyme and this increases the sensitivity of these cells to BMPs and allows them to respond to BMP4 in a paracrine and/or autocrine fashion. BMP4 signaling in the mesenchyme, in turn, triggers epithelial outgrowth and augments MSX2 expression, which causes the mammary mesenchyme to inhibit hair follicle formation within the nipple sheath (By similarity). Promotes colon cancer cell migration and invasion in an integrin alpha-6/beta-1-dependent manner through activation of Rac1.
UniProtKB/Swiss-Prot Function:
Osteostatin is a potent inhibitor of osteoclastic bone resorption.
GENATLAS Biochemistry:
parathyroid hormone-like hormone,expressed by pancreatic islet cells,putatively involved in the regulation of insulin secretion

LifeMap Function Summary for PTHLH Gene

During embryonic development, PTHLH as signaling molecule is secreted from the following cells
It affects the following cells:

Phenotypes From GWAS Catalog for PTHLH Gene

Gene Ontology (GO) - Molecular Function for PTHLH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005179 hormone activity TAS,IBA 21873635
GO:0005515 protein binding IPI 19674967
GO:0051428 peptide hormone receptor binding IDA,IBA 19674967
genes like me logo Genes that share ontologies with PTHLH: view
genes like me logo Genes that share phenotypes with PTHLH: view

Human Phenotype Ontology for PTHLH Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for PTHLH Gene

MGI Knock Outs for PTHLH:

Animal Model Products

CRISPR Products

miRNA for PTHLH Gene

miRTarBase miRNAs that target PTHLH

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PTHLH

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for PTHLH Gene

Localization for PTHLH Gene

Subcellular locations from UniProtKB/Swiss-Prot for PTHLH Gene

Cytoplasm. Nucleus. Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PTHLH gene
Compartment Confidence
extracellular 5
nucleus 5
cytosol 5
golgi apparatus 4
mitochondrion 3
plasma membrane 2
cytoskeleton 2
endoplasmic reticulum 2
peroxisome 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
  • Golgi apparatus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PTHLH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space TAS 8641188
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm TAS 10803599
genes like me logo Genes that share ontologies with PTHLH: view

Pathways & Interactions for PTHLH Gene

genes like me logo Genes that share pathways with PTHLH: view

Pathways by source for PTHLH Gene

1 GeneGo (Thomson Reuters) pathway for PTHLH Gene
  • Development_Hedgehog and PTH signaling pathways in bone and cartilage development

SIGNOR curated interactions for PTHLH Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for PTHLH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001501 skeletal system development IDA 9008714
GO:0002076 osteoblast development IBA 21873635
GO:0007165 signal transduction IEA --
GO:0007186 G protein-coupled receptor signaling pathway TAS --
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway IDA 9832460
genes like me logo Genes that share ontologies with PTHLH: view

Drugs & Compounds for PTHLH Gene

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  1. Drug

(68) Drugs for PTHLH Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Approved Nutra 7884

(47) Additional Compounds for PTHLH Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PTHLH: view

Transcripts for PTHLH Gene

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  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
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mRNA/cDNA for PTHLH Gene

4 REFSEQ mRNAs :
18 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PTHLH

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for PTHLH Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b · 4c · 4d ^ 5 ^ 6a · 6b · 6c · 6d ^ 7 ^ 8
SP1: - - -
SP2: - -
SP3: - -
SP4:

Relevant External Links for PTHLH Gene

GeneLoc Exon Structure for
PTHLH

Expression for PTHLH Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PTHLH Gene

mRNA expression in normal human tissues for PTHLH Gene
mRNA expression by BioGPS for PTHLH GenemRNA expression by GTEx for PTHLH Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for PTHLH Gene

This gene is overexpressed in Milk (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PTHLH Gene



Protein tissue co-expression partners for PTHLH Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PTHLH

SOURCE GeneReport for Unigene cluster for PTHLH Gene:

Hs.591159

mRNA Expression by UniProt/SwissProt for PTHLH Gene:

P12272-PTHR_HUMAN
Tissue specificity: Ubiquitous. Also expressed in the mammary gland.

Evidence on tissue expression from TISSUES for PTHLH Gene

  • Nervous system(4.4)
  • Liver(4.3)
  • Bone(3.2)
  • Lung(2.8)
  • Kidney(2.6)
  • Thyroid gland(2.4)
  • Blood(2.1)
  • Muscle(2)
  • Skin(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for PTHLH Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • skeleton
Regions:
Head and neck:
  • cheek
  • chin
  • face
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • skull
  • tooth
Thorax:
  • clavicle
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
genes like me logo Genes that share expression patterns with PTHLH: view

No data available for mRNA differential expression in normal tissues for PTHLH Gene

Orthologs for PTHLH Gene

This gene was present in the common ancestor of chordates.

Orthologs for PTHLH Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia PTHLH 31 30
  • 100 (n)
 OneToOne
dog
(Canis familiaris)
 Mammalia PTHLH 31 30
  • 90.77 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia PTHLH 31 30
  • 89.27 (n)
 OneToOne
mouse
(Mus musculus)
 Mammalia Pthlh 17 31 30
  • 83.43 (n)
rat
(Rattus norvegicus)
 Mammalia Pthlh 30
  • 83.33 (n)
oppossum
(Monodelphis domestica)
 Mammalia PTHLH 31
  • 79 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia PTHLH 31
  • 74 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves PTHRP 31
  • 74 (a)
 OneToOne
PTHLH 30
  • 72.19 (n)
lizard
(Anolis carolinensis)
 Reptilia PTHLH 31
  • 59 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia pthlh 30
  • 59.39 (n)
zebrafish
(Danio rerio)
 Actinopterygii pthlha 31 30
  • 57.89 (n)
 OneToMany
pthlhb 31 31
  • 30 (a)
 OneToMany
Species where no ortholog for PTHLH was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PTHLH Gene

ENSEMBL:
Gene Tree for PTHLH (if available)
TreeFam:
Gene Tree for PTHLH (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PTHLH: view image

Paralogs for PTHLH Gene

No data available for Paralogs for PTHLH Gene

Variants for PTHLH Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PTHLH Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
rs150566848 Uncertain Significance: not provided 27,969,488(-) G/A MISSENSE_VARIANT
rs1555124505 Likely Pathogenic: Inborn genetic diseases 27,963,346(-) A/G SPLICE_DONOR_VARIANT,STOP_LOST
rs267606985 Pathogenic: Brachydactyly type E2. Brachydactyly E2 (BDE2) [MIM:613382] 27,963,693(-) A/Gp.Leu60Pro MISSENSE_VARIANT
rs267606986 Pathogenic: Brachydactyly type E2. Brachydactyly E2 (BDE2) [MIM:613382] 27,963,741(-) A/Gp.Leu44Pro MISSENSE_VARIANT
rs267606987 Pathogenic: Brachydactyly type E2 27,958,559(-) T/C STOP_LOST

Additional dbSNP identifiers (rs#s) for PTHLH Gene

Structural Variations from Database of Genomic Variants (DGV) for PTHLH Gene

Variant ID Type Subtype PubMed ID
esv3628956 CNV loss 21293372
nsv1159991 CNV deletion 26073780
nsv557864 CNV gain 21841781
nsv557876 CNV gain 21841781

Variation tolerance for PTHLH Gene

Residual Variation Intolerance Score: 40.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.56; 12.07% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PTHLH Gene

Human Gene Mutation Database (HGMD)
PTHLH
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PTHLH

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PTHLH Gene

Disorders for PTHLH Gene

MalaCards: The human disease database

(84) MalaCards diseases for PTHLH Gene - From: LncRNADisease, UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
brachydactyly, type e2
  • bde2
brachydactyly, type e1
  • bde1
brachydactyly
dysgerminoma
ovarian small cell carcinoma
  • small cell carcinoma of the ovary
- elite association - COSMIC cancer census association via MalaCards
Search PTHLH in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

PTHR_HUMAN
  • Brachydactyly E2 (BDE2) [MIM:613382]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. Wide variability in the number of digits affected occurs from person to person, even in the same family. Some individuals are moderately short of stature. In brachydactyly type E2 variable combinations of metacarpals are involved, with shortening also of the first and third distal and the second and fifth middle phalanges. {ECO:0000269 PubMed:20170896}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for PTHLH

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with PTHLH: view

No data available for Genatlas for PTHLH Gene

Publications for PTHLH Gene

  1. Molecular dissection of the importin beta1-recognized nuclear targeting signal of parathyroid hormone-related protein. (PMID: 11401507) Lam MH … Jans DA (Biochemical and biophysical research communications 2001) 3 4 23 54
  2. Characterization of the human parathyroid hormone-like peptide gene. Functional and evolutionary aspects. (PMID: 2708388) Yasuda T … Goltzman D (The Journal of biological chemistry 1989) 2 3 4 54
  3. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41 54
  4. Deletion and point mutations of PTHLH cause brachydactyly type E. (PMID: 20170896) Klopocki E … Mundlos S (American journal of human genetics 2010) 3 4 54
  5. Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling. (PMID: 19240061) Trynka G … Wijmenga C (Gut 2009) 3 41 54

ExternalLinks

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