TMEM127 transmembrane protein 127 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TMEM127provided by HGNC
Official Full Name: transmembrane protein 127provided by HGNC
Primary source: HGNC:HGNC:26038
See related: Ensembl:ENSG00000135956 MIM:613403; AllianceGenome:HGNC:26038
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
Summary: This gene encodes a transmembrane protein with four predicted transmembrane domains. The protein is associated with a subpopulation of vesicular organelles corresponding to early endosomal structures, with the Golgi, and with lysosomes, and may participate in protein trafficking between these structures. Mutations in this gene and several other genes cause pheochromocytomas. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Aug 2022]
Expression: Ubiquitous expression in heart (RPKM 15.7), esophagus (RPKM 13.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q11.2

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (96248514..96265997, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (96755122..96772605, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (96914252..96931735, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TMEM127 suppresses tumor development by promoting RET ubiquitination, positioning, and degradation.
Title: TMEM127 suppresses tumor development by promoting RET ubiquitination, positioning, and degradation.
Genotype-Phenotype Features of Germline Variants of the TMEM127 Pheochromocytoma Susceptibility Gene: A 10-Year Update.
Title: Genotype-Phenotype Features of Germline Variants of the TMEM127 Pheochromocytoma Susceptibility Gene: A 10-Year Update.
The Tumour Suppressor TMEM127 Is a Nedd4-Family E3 Ligase Adaptor Required by Salmonella SteD to Ubiquitinate and Degrade MHC Class II Molecules.
Title: The Tumour Suppressor TMEM127 Is a Nedd4-Family E3 Ligase Adaptor Required by Salmonella SteD to Ubiquitinate and Degrade MHC Class II Molecules.
Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking.
Title: Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking.
n the present cases, the clinical picture does not seem to be very different from heterozygous TMEM127 mutation carriers, except for a relatively large tumor size and more pronounced plasma metanephrine concentration. It is unclear whether the mental retardation is causally related to homozygosity of the TMEM127 mutations.
Title: Homozygous TMEM127 mutations in 2 patients with bilateral pheochromocytomas.
We found that under nutrient-rich conditions TMEM127 expression reduces mTORC1 recruitment to Rags. In addition, TMEM127 interacts with LAMTOR in an amino acid-dependent manner and decreases the LAMTOR1-vATPase association, while TMEM127-vATPase binding requires intact lysosomal acidification but is amino acid independent
Title: The TMEM127 human tumor suppressor is a component of the mTORC1 lysosomal nutrient-sensing complex.
The SDHA, TMEM127, MAX, and SDHAF2 genes contribute to hereditary pheochromocytoma and paraganglioma.
Title: Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention.
Of which 4 SDHB and 2 TMEM127 mutations were novel.
Title: Novel SDHB and TMEM127 Mutations in Patients with Pheochromocytoma/Paraganglioma Syndrome.
Hereditary pheochromocytoma / paraganglioma associated with TMEM127 gene mutations has more aggressive course,bilateral adrenal involvement, higher recurrence rate, younger age at disease manifestations.
Title: [Hereditary pheochromocytoma-associated syndromes. Part 1].
We report the first case of an individual with both a pheochromocytoma and a multilocular clear cell renal cell carcinoma driven by a novel germline mutation in the TMEM127 gene, with a sibling and 2 sons with the same mutation.
Title: Familial pheochromocytoma and renal cell carcinoma syndrome: TMEM127 as a novel candidate gene for the association.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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
Pheochromocytoma MedGen: C0031511 OMIM: 171300 GeneReviews: Hereditary Paraganglioma-Pheochromocytoma Syndromes	not available

Copy number response

Description
Copy number response Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-07-13) ClinGen Genome Curation PagePubMed Triplosensitivity No evidence available (Last evaluated 2021-07-13) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of transmembrane protein 127 (TMEM127; FLJ20507) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

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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

SHGC-30679 (e-PCR)
- UniSTS:21283

D8S2279 (e-PCR)
- UniSTS:473907

MARC_3297-3298:991936980:1 (e-PCR)
- UniSTS:231008

RH68603 (e-PCR)
- UniSTS:57737

D2S1663E (e-PCR)
- UniSTS:52675

D2S2931 (e-PCR)
- UniSTS:33276

RH11591 (e-PCR)
- UniSTS:33277

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables small GTPase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in endosome organization	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of TOR signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of TOR signaling	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: transmembrane protein 127

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.