TMEM127

  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
TMEM127 (HGNC:26038) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
transmembrane protein 127
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
FLJ20507, FLJ22257
%HI
19.66(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.01(Read more about gnomAD pLI score)
LOEUF
1.15(Read more about gnomAD LOEUF score)
Cytoband
2q11.2
Genomic Coordinates
GRCh37/hg19: chr2:96914252-96931735 NCBI Ensembl UCSC
GRCh38/hg38: chr2:96248514-96265997 NCBI Ensembl UCSC
MANE Select Transcript
NM_017849.4 ENST00000258439.8 (Read more about MANE Select)
Function
Controls cell proliferation acting as a negative regulator of TOR signaling pathway mediated by mTORC1. May act as a tumor suppressor. {ECO:0000269|PubMed:20154675}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-10127
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Assoc. with Reduced Penetrance:
Yes
See PMID5
Last Evaluated:
07/13/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • hereditary pheochromocytoma-paraganglioma Monarch
HI Evidence:
  • PUBMED: 21156949
    Yao et al (2010) sequenced the TMEM127 gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without variants in other susceptibility genes from 8 independent worldwide referral centers. They identified 10 loss of function variants including small deletions, duplications, or nonsense or splice site substitutions that led to truncation or extension of the predicted TMEM127 product. There were reports of families with multiple affected individuals, but familial testing wasn't performed.
  • PUBMED: 20154675
    Qin et al (2010) reported 7 unrelated probands with pheochromocytoma; Six of which were truncating variants, consistent with a loss of function. The tumors examined showed loss of heterozygosity at the TMEM127 locus, suggesting a classic mechanism of the 2-hit model of tumor suppressor inactivation. Four of the probands had a family history of pheochromocytoma.
  • PUBMED: 28384794
    Bausch et al (2017) used the European-American-Asian Pheochromocytoma-Paraganglioma Registry, a population-based registry of unrelated patients presenting with symptomatic, histopathologically confirmed pheochromocytoma and paraganglioma. They excluded other known susceptibility genes. They found 6 LOF variants. There was evidence of family history and familial testing was performed.
  • PUBMED: 23551308
    Elston et al (2018) report a 33-year-old man who presented with an apparently sporadic adrenal pheochromocytoma with a novel TMEM127 germline variant (p.Gln139X). The variant was paternally inherited and the father was asymptomatic at 60 years old.
  • PUBMED: 25389632
    Toledo et al (2015) report on 47 individuals (six affected generations) with pheochromocytoma and a c.410-2A>C loss of function TMEM127 variant. The penetrance was calculated to be 3% by age 30 years, 24% by age 50 years and 32% by age 65 years.
HI Evidence Comments:
There are many reports of loss of function variants such as nonsense, framseshift and splice site mutations in the literature associated with familial pheochromocytoma, paraganglioma and renal cell carcinomas (with variable expressivity and reduced penetrance noted). Please note that as there are no reports of whole gene deletions a dominant negative effect can not therefore be completely ruled out.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000002.11) (NC_000002.12)