TMEM127

transmembrane protein 127

Basic information

Region (hg38): 2:96248500-96266047

Links

ENSG00000135956

∙ NCBI:55654 ∙ OMIM:613403 ∙ HGNC:26038 ∙ Uniprot:O75204 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

renal cell carcinoma (Moderate), mode of inheritance: AD
pheochromocytoma (Definitive), mode of inheritance: AD
pheochromocytoma (Strong), mode of inheritance: AD
pheochromocytoma (Definitive), mode of inheritance: AD
hereditary pheochromocytoma-paraganglioma (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pheochromocytoma	AD	Oncologic	Surveillance and awareness of cancer risk may allow early diagnosis and treatment of neoplasms, which may reduce morbidity and mortality	Oncologic	20154675; 22419703; 23666964
Although adults have been reported, surveillance in the pediatric period may nevertheless be warranted

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM127 gene.

Hereditary_pheochromocytoma-paraganglioma (705 variants)
Hereditary_cancer-predisposing_syndrome (657 variants)
Pheochromocytoma (122 variants)
not_provided (118 variants)
not_specified (18 variants)
TMEM127-related_disorder (11 variants)
Pheochromocytoma,_susceptibility_to (5 variants)
Ovarian_cancer (2 variants)
Uveal_melanoma (1 variants)
Multiple_mitochondrial_dysfunctions_syndrome_10 (1 variants)
Hereditary_cancer (1 variants)
Acute_myeloid_leukemia (1 variants)
Acute_promyelocytic_leukemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM127 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017849.4. 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	2 clinvar		3 clinvar	231 clinvar		236
missense		9 clinvar	525 clinvar	11 clinvar		545
nonsense	14 clinvar	12 clinvar	6 clinvar			32
start loss	5	2	2			9
frameshift	50 clinvar	16 clinvar	6 clinvar			72
splice donor/acceptor (+/-2bp)	5 clinvar	8 clinvar	2 clinvar			15
Total	76	47	544	242	0

Highest pathogenic variant AF is 0.0000163791

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM127	protein_coding	protein_coding	ENST00000258439	3	17479

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0129	0.869	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.448	123	138	0.893	0.00000808	1489
Missense in Polyphen		35	43.27	0.80887		495
Synonymous	-0.112	66	64.9	1.02	0.00000398	531
Loss of Function	1.29	4	7.92	0.505	3.41e-7	96

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: 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}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

loftool: 0.116
rvis_EVS: -0.05
rvis_percentile_EVS: 49.76

Haploinsufficiency Scores

pHI: 0.0827
hipred: Y
hipred_score: 0.501
ghis: 0.570

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.666

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Tmem127
Phenotype: limbs/digits/tail phenotype; skeleton phenotype; immune system phenotype; hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process: endosome organization;negative regulation of cell population proliferation;negative regulation of TOR signaling
Cellular component: cytoplasm;early endosome;plasma membrane;integral component of membrane
Molecular function: molecular_function;Rab GTPase binding