PTHLH
parathyroid hormone like hormone, the group of Receptor ligands|Neuropeptides
Basic information
Region (hg38): 12:27958084-27972733
Links
Phenotypes
GenCC
Source:
- brachydactyly type E2 (Strong), mode of inheritance: AD
- brachydactyly type E (Supportive), mode of inheritance: AD
- brachydactyly type E2 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Brachydactyly, type E2 | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Dental; Musculoskeletal | 20170896 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (92 variants)
- Inborn_genetic_diseases (19 variants)
- Brachydactyly_type_E2 (10 variants)
- PTHLH-related_disorder (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTHLH gene is commonly pathogenic or not. These statistics are base on transcript: NM_000198965.2. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 21 | 22 | |||
| missense | 3 | 63 | 1 | 67 | ||
| nonsense | 7 | 1 | 8 | |||
| start loss | 4 | 4 | ||||
| frameshift | 2 | 2 | 1 | 5 | ||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 3 | |||
| Total | 12 | 8 | 67 | 22 | 0 |
Highest pathogenic variant AF is 0.000006570993
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PTHLH | protein_coding | protein_coding | ENST00000395872 | 3 | 14622 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 125736 | 0 | 1 | 125737 | 0.00000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.15 | 74 | 108 | 0.687 | 0.00000660 | 1124 |
| Missense in Polyphen | 26 | 46.106 | 0.56392 | 482 | ||
| Synonymous | 1.39 | 33 | 44.9 | 0.735 | 0.00000273 | 361 |
| Loss of Function | 2.62 | 1 | 9.88 | 0.101 | 7.77e-7 | 86 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000879 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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. {ECO:0000250, ECO:0000269|PubMed:20637541}.;
- Disease
- DISEASE: 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.;
- Pathway
- Endoderm Differentiation;Vitamin D Receptor Pathway;Regulation of Apoptosis by Parathyroid Hormone-related Protein;Endochondral Ossification;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Class B/2 (Secretin family receptors);GPCR ligand binding;GPCR downstream signalling;Signaling events mediated by the Hedgehog family
(Consensus)
Recessive Scores
- pRec
- 0.489
Intolerance Scores
- loftool
- 0.239
- rvis_EVS
- 0.06
- rvis_percentile_EVS
- 58
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.804
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Zebrafish Information Network
- Gene name
- pthlhb
- Affected structure
- ceratohyal bone
- Phenotype tag
- abnormal
- Phenotype quality
- deformed
Gene ontology
- Biological process
- skeletal system development;osteoblast development;G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;cell-cell signaling;female pregnancy;positive regulation of cell population proliferation;negative regulation of cell population proliferation;epidermis development;regulation of gene expression;regulation of signaling receptor activity;bone mineralization;negative regulation of chondrocyte differentiation;cAMP metabolic process;negative regulation of chondrocyte development
- Cellular component
- extracellular region;extracellular space;nucleoplasm;cytoplasm;Golgi apparatus;cytosol
- Molecular function
- hormone activity;peptide hormone receptor binding