TMEM127

transmembrane protein 127

Basic information

Region (hg38): 2:96248513-96265997

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 (565 variants)
• Hereditary cancer-predisposing syndrome (416 variants)
• Pheochromocytoma (173 variants)
• not provided (74 variants)
• not specified (16 variants)
• Pheochromocytoma, susceptibility to (4 variants)
• Ovarian cancer (2 variants)
• Acute promyelocytic leukemia (1 variants)
• TMEM127-related condition (1 variants)
• Uveal melanoma (1 variants)
• Acute myeloid 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	169	1	175
missense		1	387	4		392
nonsense	10	3	4			17
start loss	3	2	1			6
frameshift	30	7	4			41
inframe indel			5			5
splice donor/acceptor (+/-2bp)	3	9	1			13
splice region			7	11		18
non coding			63	34	25	122
Total	46	22	470	207	26

Highest pathogenic variant AF is 0.0000197

Variants in TMEM127

This is a list of pathogenic ClinVar variants found in the TMEM127 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-96250224-C-G		Pheochromocytoma	Benign (Jan 13, 2018)
2-96250239-G-A		Pheochromocytoma	Benign (Jan 12, 2018)
2-96250240-G-C		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96250248-C-A		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96250412-C-T		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96250417-C-T		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96250460-C-G		Pheochromocytoma	Uncertain significance (Jan 12, 2018)
2-96250537-T-C		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96250599-T-C		Pheochromocytoma	Benign (Jan 12, 2018)
2-96250599-TAAC-T		Pheochromocytoma	Likely benign (Jun 14, 2016)
2-96250674-G-A		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96250759-A-G		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96250783-C-G		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96250842-G-C		Pheochromocytoma	Benign (Jan 13, 2018)
2-96250897-G-A		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96250919-TA-T		Pheochromocytoma	Likely benign (Jun 14, 2016)
2-96250933-T-C		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96250948-T-C		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96250963-A-C		Pheochromocytoma	Benign (Jan 13, 2018)
2-96251008-A-C		Pheochromocytoma	Uncertain significance (Jan 12, 2018)
2-96251048-T-G		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96251089-C-T		Pheochromocytoma	Uncertain significance (Jan 12, 2018)
2-96251091-G-C		Pheochromocytoma	Uncertain significance (Jun 14, 2016)
2-96251124-G-C		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
2-96251166-G-A		Pheochromocytoma	Uncertain significance (Jan 13, 2018)

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