TMEM127

Summary

TMEM127 (transmembrane protein 127, HGNC:26038) is a protein-coding gene on chromosome 2q11.2, encoding Transmembrane protein 127 (O75204). Controls cell proliferation acting as a negative regulator of TOR signaling pathway mediated by mTORC1. It is a selective cancer dependency (DepMap: 13.3% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 55654 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary pheochromocytoma-paraganglioma (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1,003 total — 54 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 51
• Cancer dependency (DepMap): dependent in 13.3% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_017849

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26038
Approved symbol	TMEM127
Name	transmembrane protein 127
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20507, FLJ22257
Ensembl gene	ENSG00000135956
Ensembl biotype	protein_coding
OMIM	613403
Entrez	55654

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 3 nonsense_mediated_decay

ENST00000258439, ENST00000432959, ENST00000435268, ENST00000713752, ENST00000713753, ENST00000713754, ENST00000713755, ENST00000713756, ENST00000910913, ENST00000910914, ENST00000910915, ENST00000939308, ENST00000939309, ENST00000963838, ENST00000963839

RefSeq mRNA: 4 — MANE Select: NM_017849 NM_001193304, NM_001407282, NM_001407283, NM_017849

CCDS: CCDS2018, CCDS92812

Canonical transcript exons

ENST00000258439 — 4 exons

Exon	Start	End
ENSE00000000280	96265869	96265997
ENSE00000921763	96265138	96265512
ENSE00001629346	96248514	96254115
ENSE00003610373	96254833	96254997

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 94.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.6220 / max 592.5172, expressed in 1815 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29730	35.6131	1814
29727	0.4762	198
29724	0.3239	157
29728	0.1072	48
29726	0.1016	52

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
leukocyte	CL:0000738	94.07	gold quality
monocyte	CL:0000576	94.06	gold quality
blood	UBERON:0000178	94.00	gold quality
mononuclear cell	CL:0000842	93.99	gold quality
heart left ventricle	UBERON:0002084	93.58	gold quality
cardiac ventricle	UBERON:0002082	93.42	gold quality
stromal cell of endometrium	CL:0002255	93.37	gold quality
buccal mucosa cell	CL:0002336	93.33	gold quality
apex of heart	UBERON:0002098	93.17	gold quality
endothelial cell	CL:0000115	93.03	gold quality
granulocyte	CL:0000094	92.75	gold quality
gall bladder	UBERON:0002110	92.63	gold quality
right atrium auricular region	UBERON:0006631	92.57	gold quality
lower esophagus mucosa	UBERON:0035834	92.53	gold quality
right coronary artery	UBERON:0001625	92.28	gold quality
heart	UBERON:0000948	92.00	gold quality
descending thoracic aorta	UBERON:0002345	91.51	gold quality
cardiac atrium	UBERON:0002081	91.32	gold quality
thoracic aorta	UBERON:0001515	91.31	gold quality
left adrenal gland	UBERON:0001234	91.30	gold quality
cortical plate	UBERON:0005343	91.28	gold quality
primary visual cortex	UBERON:0002436	91.23	gold quality
ascending aorta	UBERON:0001496	91.20	gold quality
lower esophagus	UBERON:0013473	91.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.14	gold quality
left adrenal gland cortex	UBERON:0035825	91.12	gold quality
periodontal ligament	UBERON:0008266	91.03	gold quality
aorta	UBERON:0000947	90.95	gold quality
right adrenal gland cortex	UBERON:0035827	90.90	gold quality
right adrenal gland	UBERON:0001233	90.88	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

218 targeting TMEM127, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6721-5P	99.93	68.92	2981

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 13.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 19)

• Germline mutations in TMEM127 confer susceptibility to pheochromocytoma and identify TMEM127 as a tumor suppressor gene. (PMID:20154675)
• Pathological and genomic data demonstrated that a TMEM127 gene mutation not previously described was causative of a new case of familial bilateral pheochromocytoma. (PMID:20923864)
• Germline mutations of FP/TMEM127 were associated with pheochromocytoma but not paraganglioma and occurred in an age group frequently excluded from genetic screening algorithms; mutations disrupt intracellular distribution of the FP/TMEM127 protein. (PMID:21156949)
• TMEM127 is a novel pheochromocytoma susceptibility gene.[review] (PMID:21447639)
• TMEM127 germline mutations confer risks of extraadrenal paraganglial tumors in addition to the documented adrenal pheochromocytoma. (PMID:21613359)
• TMEM127 protein localizes in lysosomes in HeLa cells (PMID:21752829)
• report shows that TMEM127 mutation plays a pathological role in pheochromocytoma in an Asian population. (PMID:22541004)
• A male patient with sporadic adrenal pheochromocytoma presents with a novel TMEM127 germline mutation, p. Gln139X. (PMID:23551308)
• Tumor multicentricity, nodular adrenomedullary hyperplasia, and the occurrence of symptoms more than a decade earlier than the age at diagnosis are novel findings in TMEM127-related pheochromocytoma. (PMID:25389632)
• 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. (PMID:25800244)
• Hereditary pheochromocytoma / paraganglioma associated with TMEM127 gene mutations has more aggressive course,bilateral adrenal involvement, higher recurrence rate, younger age at disease manifestations. (PMID:26591561)
• Of which 4 SDHB and 2 TMEM127 mutations were novel. (PMID:26960314)
• The SDHA, TMEM127, MAX, and SDHAF2 genes contribute to hereditary pheochromocytoma and paraganglioma. (PMID:28384794)
• 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. (PMID:29282712)
• 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 (PMID:29547888)
• The Tumour Suppressor TMEM127 Is a Nedd4-Family E3 Ligase Adaptor Required by Salmonella SteD to Ubiquitinate and Degrade MHC Class II Molecules. (PMID:32526160)
• Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking. (PMID:32575117)
• Genotype-Phenotype Features of Germline Variants of the TMEM127 Pheochromocytoma Susceptibility Gene: A 10-Year Update. (PMID:33051659)
• TMEM127 suppresses tumor development by promoting RET ubiquitination, positioning, and degradation. (PMID:37659079)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem127	ENSDARG00000030981
mus_musculus	Tmem127	ENSMUSG00000034850
rattus_norvegicus	Tmem127	ENSRNOG00000088819

Protein

Protein identifiers

Transmembrane protein 127 — O75204 (reviewed: O75204)

All UniProt accessions (5): A0AAQ5BGT7, A0AAQ5BGU6, O75204, A0AAQ5BGW9, C9J4H2

UniProt curated annotations — full annotation on UniProt →

Function. Controls cell proliferation acting as a negative regulator of TOR signaling pathway mediated by mTORC1. May act as a tumor suppressor.

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Widely expressed.

Disease relevance. Pheochromocytoma (PCC) [MIM:171300] A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Miscellaneous. Consistent with the observation that mTORC1 signaling regulates cell growth and size in many species, TMEM127 knockdown cells are larger and proliferate at higher rates compared to control cell lines. In contrast, cell proliferation is reduced in cells overexpressing TMEM127.

Similarity. Belongs to the TMEM127 family.

RefSeq proteins (4): NP_001180233, NP_001394211, NP_001394212, NP_060319* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033331	TMEM127	Family
IPR046795	TMEM127_TM	Domain

Pfam: PF20517

UniProt features (15 total): sequence variant 7, transmembrane region 3, modified residue 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75204-F1	77.38	0.37

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 1, 17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 314 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_ENDOSOME_ORGANIZATION, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_VESICLE_ORGANIZATION, GOMF_GTPASE_BINDING, GGGTGGRR_PAX4_03, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, CCANNAGRKGGC_UNKNOWN, CAGCAGG_MIR370, GNF2_ICAM3, GOBP_NEGATIVE_REGULATION_OF_TOR_SIGNALING, GNF2_S100A4, OCT1_06, GNF2_MYD88

GO Biological Process (4): endosome organization (GO:0007032), negative regulation of cell population proliferation (GO:0008285), regulation of TOR signaling (GO:0032006), negative regulation of TOR signaling (GO:0032007)

GO Molecular Function (1): small GTPase binding (GO:0031267)

GO Cellular Component (4): cytoplasm (GO:0005737), early endosome (GO:0005769), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
TOR signaling	2
cellular anatomical structure	2
endomembrane system organization	1
vesicle organization	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of intracellular signal transduction	1
regulation of TOR signaling	1
negative regulation of intracellular signal transduction	1
GTPase binding	1
intracellular anatomical structure	1
endosome	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

694 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM127	SDHD	O14521	960
TMEM127	SDHB	P21912	935
TMEM127	RET	P07949	903
TMEM127	SDHC	Q99643	903
TMEM127	F5H5T6	F5H5T6	891
TMEM127	SDHAF2	Q9NX18	886
TMEM127	NF1	P21359	882
TMEM127	KIF1B	O60333	866
TMEM127	SDHA	P31040	808
TMEM127	MAX	P25912	764
TMEM127	EGLN1	Q9GZT9	669
TMEM127	EPAS1	Q99814	666
TMEM127	CSDE1	O75534	659
TMEM127	MDH2	P40926	647
TMEM127	MEN1	O00255	594

IntAct

0 interactions, top by confidence:

BioGRID (15): TMEM127 (Affinity Capture-MS), TMEM127 (Affinity Capture-MS), TMEM127 (Affinity Capture-Western), TMEM127 (Affinity Capture-Western), TMEM127 (Affinity Capture-RNA), TMEM127 (Affinity Capture-RNA), TMEM127 (Affinity Capture-Western), RET (Affinity Capture-Western), TMEM127 (Affinity Capture-Western), NEDD4 (Affinity Capture-Western), GRB10 (Affinity Capture-Western), TMEM127 (Co-fractionation), TMEM127 (Co-fractionation), WWP2 (Affinity Capture-Western), TMEM127 (Affinity Capture-RNA)

ESM2 similar proteins: A4IIU3, A6NML5, D3YWQ9, O75204, P0DP42, P11836, P20490, P56749, Q01362, Q0IIL2, Q2KJ11, Q2YDM3, Q32KQ5, Q3T110, Q3YBM2, Q497B3, Q4G068, Q504G0, Q5EB63, Q5FWC3, Q5HYL7, Q5M962, Q5R8D6, Q5R9K1, Q5RCD5, Q5RFC1, Q6GV28, Q7T392, Q7TQI0, Q7YQI4, Q8BGP5, Q8BHH8, Q8C6V3, Q8K177, Q8NCR9, Q8VHW1, Q8WXS4, Q920C4, Q925D4, Q940P5

Diamond homologs: O75204, Q504G0, Q8BGP5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1003 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	54
Likely pathogenic	18
Uncertain significance	577
Likely benign	257
Benign	27

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065957	NM_017849.4(TMEM127):c.409+1G>C	Pathogenic
1067852	NM_017849.4(TMEM127):c.245-2A>G	Pathogenic
107	NM_017849.4(TMEM127):c.410-2A>C	Pathogenic
126974	NM_017849.4(TMEM127):c.76C>T (p.Gln26Ter)	Pathogenic
1377988	NM_017849.4(TMEM127):c.202dup (p.Val68fs)	Pathogenic
141471	NM_017849.4(TMEM127):c.248del (p.Phe83fs)	Pathogenic
1446027	NM_017849.4(TMEM127):c.291del (p.Ala98fs)	Pathogenic
1456579	NC_000002.11:g.(?96919546)(96920745_?)del	Pathogenic
1458727	NC_000002.11:g.(?96930866)(96931137_?)del	Pathogenic
1729830	NM_017849.4(TMEM127):c.328dup (p.Ala110fs)	Pathogenic
1749907	NM_017849.4(TMEM127):c.120dup (p.Ile41fs)	Pathogenic
1788399	NM_017849.4(TMEM127):c.224del (p.Val75fs)	Pathogenic
1789413	NM_017849.4(TMEM127):c.230del (p.Pro77fs)	Pathogenic
1794030	NM_017849.4(TMEM127):c.262C>T (p.Gln88Ter)	Pathogenic
1879480	NM_017849.4(TMEM127):c.278_288del (p.Leu93fs)	Pathogenic
2002970	NM_017849.4(TMEM127):c.347_348del (p.Phe116fs)	Pathogenic
2096030	NM_017849.4(TMEM127):c.379del (p.Arg127fs)	Pathogenic
2448387	NM_017849.4(TMEM127):c.147_159del (p.Glu50fs)	Pathogenic
2576554	NM_017849.4(TMEM127):c.410-1G>C	Pathogenic
2625511	NM_017849.4(TMEM127):c.182del (p.Cys61fs)	Pathogenic
2693569	NM_017849.4(TMEM127):c.327del (p.Ala110fs)	Pathogenic
2699377	NM_017849.4(TMEM127):c.438_442del (p.Phe146fs)	Pathogenic
2809154	NM_017849.4(TMEM127):c.332del (p.Phe111fs)	Pathogenic
2826900	NM_017849.4(TMEM127):c.193G>T (p.Glu65Ter)	Pathogenic
2833559	NM_017849.4(TMEM127):c.342_343insA (p.Val115fs)	Pathogenic
2839916	NM_017849.4(TMEM127):c.325_326del (p.Ser109fs)	Pathogenic
2993885	NM_017849.4(TMEM127):c.267_268del (p.Val90fs)	Pathogenic
3010801	NM_017849.4(TMEM127):c.483_487delinsGCATAAGT (p.His161_Lys163delinsGlnHisLysTer)	Pathogenic
3227066	NM_017849.4(TMEM127):c.190C>T (p.Gln64Ter)	Pathogenic
3227072	NM_017849.4(TMEM127):c.319del (p.Ser107fs)	Pathogenic

SpliceAI

594 predictions. Top by Δscore:

Variant	Effect	Δscore
2:96254116:C:CC	acceptor_gain	1.0000
2:96254117:T:C	acceptor_loss	1.0000
2:96254828:CTTAC:C	donor_loss	1.0000
2:96254831:A:AC	donor_gain	1.0000
2:96254831:AC:A	donor_gain	1.0000
2:96254832:C:CA	donor_loss	1.0000
2:96254832:C:CC	donor_gain	1.0000
2:96254832:CC:C	donor_gain	1.0000
2:96254997:TC:T	acceptor_loss	1.0000
2:96254998:C:CC	acceptor_gain	1.0000
2:96254998:C:CG	acceptor_loss	1.0000
2:96253881:T:TA	donor_gain	0.9900
2:96254111:CAGAA:C	acceptor_gain	0.9900
2:96254112:AGAA:A	acceptor_gain	0.9900
2:96254113:GAA:G	acceptor_gain	0.9900
2:96254114:AA:A	acceptor_gain	0.9900
2:96254124:C:CT	acceptor_gain	0.9900
2:96254125:A:T	acceptor_gain	0.9900
2:96254831:ACC:A	donor_gain	0.9900
2:96254832:CCC:C	donor_gain	0.9900
2:96254832:CCCG:C	donor_gain	0.9900
2:96254993:GAAAT:G	acceptor_gain	0.9900
2:96254994:AAAT:A	acceptor_gain	0.9900
2:96254995:AAT:A	acceptor_gain	0.9900
2:96254996:AT:A	acceptor_gain	0.9900
2:96255000:G:C	acceptor_gain	0.9900
2:96265132:CCTCA:C	donor_loss	0.9900
2:96265133:CTCA:C	donor_loss	0.9900
2:96265134:TCA:T	donor_loss	0.9900
2:96265135:CACCT:C	donor_loss	0.9900

AlphaMissense

1505 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:96253896:A:G	L210P	1.000
2:96253941:A:G	L195P	1.000
2:96253941:A:T	L195H	1.000
2:96253950:G:T	A192E	1.000
2:96253951:C:G	A192P	1.000
2:96253956:G:T	A190D	1.000
2:96253962:A:T	I188N	1.000
2:96253971:C:T	G185E	1.000
2:96253972:C:G	G185R	1.000
2:96253972:C:T	G185R	1.000
2:96253974:C:T	G184D	1.000
2:96253975:C:G	G184R	1.000
2:96253977:G:T	A183D	1.000
2:96253980:C:T	G182E	1.000
2:96253981:C:G	G182R	1.000
2:96253981:C:T	G182R	1.000
2:96253989:A:G	L179P	1.000
2:96253997:G:C	S176R	1.000
2:96253997:G:T	S176R	1.000
2:96253998:C:A	S176I	1.000
2:96253999:T:G	S176R	1.000
2:96254007:A:G	F173S	1.000
2:96254013:A:T	V171D	1.000
2:96254067:A:G	L153P	1.000
2:96254083:A:C	Y148D	1.000
2:96254091:C:T	G145D	1.000
2:96254092:C:G	G145R	1.000
2:96254103:G:T	A141D	1.000
2:96254105:A:C	C140W	1.000
2:96254107:A:G	C140R	1.000

dbSNP variants (sampled 300 via entrez): RS1000085330 (2:96248256 G>T), RS1000263825 (2:96254746 G>T), RS1000601296 (2:96259985 T>C), RS1000706979 (2:96253150 C>A,T), RS1001164235 (2:96266327 C>G,T), RS1001336155 (2:96265810 G>A,T), RS1001410609 (2:96249402 G>C), RS1001472443 (2:96260711 A>C), RS1001881882 (2:96254143 G>A), RS1002170440 (2:96249015 C>T), RS1002272966 (2:96260745 C>A,G), RS1002307524 (2:96249319 A>C), RS1002325843 (2:96266520 G>C,T), RS1002337090 (2:96266824 C>T), RS1002486573 (2:96260433 C>G)

Disease associations

OMIM: gene MIM:613403 | disease phenotypes: MIM:168000, MIM:171300, MIM:167000, MIM:620960, MIM:155720, MIM:601626

GenCC curated gene-disease

Disease	Classification	Inheritance
pheochromocytoma	Definitive	Autosomal dominant
renal cell carcinoma	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hereditary pheochromocytoma-paraganglioma	Definitive	AD

Mondo (9): hereditary neoplastic syndrome (MONDO:0015356), hereditary pheochromocytoma-paraganglioma (MONDO:0017366), pheochromocytoma (MONDO:0008233), ovarian cancer (MONDO:0008170), multiple mitochondrial dysfunctions syndrome 10 (MONDO:0975806), uveal melanoma (MONDO:0006486), acute myeloid leukemia (MONDO:0018874), TMEM127-related tumor predisposition (MONDO:0700345), renal cell carcinoma (MONDO:0005086)

Orphanet (5): Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary pheochromocytoma-paraganglioma (Orphanet:29072), Rare ovarian cancer (Orphanet:213500), Uveal melanoma (Orphanet:39044), Acute myeloid leukemia (Orphanet:519)

HPO phenotypes

51 total (30 of 51 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000093	Proteinuria
HP:0000096	Glomerular sclerosis
HP:0000405	Conductive hearing impairment
HP:0000519	Developmental cataract
HP:0000526	Aniridia
HP:0000740	Episodic paroxysmal anxiety
HP:0000790	Hematuria
HP:0000875	Episodic hypertension
HP:0000957	Cafe-au-lait spot
HP:0000975	Hyperhidrosis
HP:0000980	Pallor
HP:0001028	Hemangioma
HP:0001069	Episodic hyperhidrosis
HP:0001095	Hypertensive retinopathy
HP:0001293	Cranial nerve compression
HP:0001337	Tremor
HP:0001342	Cerebral hemorrhage
HP:0001605	Vocal cord paralysis
HP:0001618	Dysphonia
HP:0001635	Congestive heart failure
HP:0001649	Tachycardia
HP:0001824	Weight loss
HP:0001920	Renal artery stenosis
HP:0001962	Palpitations
HP:0002018	Nausea
HP:0002331	Recurrent paroxysmal headache
HP:0002574	Episodic abdominal pain
HP:0002640	Hypertension associated with pheochromocytoma
HP:0002664	Neoplasm

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009380_11	Type 2 diabetes (adjusted for BMI)	3.000000e-08

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002292	Carcinoma, Renal Cell	C04.557.470.200.025.390; C04.588.945.947.535.160; C12.050.351.937.820.535.160; C12.050.351.968.419.473.160; C12.200.758.820.750.160; C12.200.777.419.473.160; C12.900.820.535.160; C12.950.419.473.160; C12.950.983.535.160
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D010673	Pheochromocytoma	C04.557.465.625.650.700.725; C04.557.580.625.650.700.725

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Smoke	decreases expression	1
Sulindac	increases expression	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0R6	Ubigene HeLa TMEM127 KO	Cancer cell line	Female

Clinical trials (associated diseases)

328 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01379898	PHASE4	COMPLETED	Phenoxybenzamine Versus Doxazosin in PCC Patients
NCT01959711	PHASE4	COMPLETED	Randomized Clinical Trial of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Laparoscopic Adrenalectomy
NCT05702944	PHASE4	RECRUITING	The Effect and Safety of Omitting Preoperative Alpha-adrenergic Blockade for Normotensive Pheochromocytoma
NCT00414765	PHASE4	COMPLETED	Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
NCT00777504	PHASE4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT00930345	PHASE4	TERMINATED	Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma
NCT01206764	PHASE4	COMPLETED	A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.
NCT01266837	PHASE4	COMPLETED	Open Label, Single Arm Trial to Characterize Patients With Metastatic RCC Treated With Everolimus After Failure of the First VEGF-targeted Therapy (MARC-2)
NCT02056587	PHASE4	COMPLETED	Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
NCT02338570	PHASE4	TERMINATED	Outcome-related Factors in Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus (ORCHIDEE)
NCT02596035	PHASE4	COMPLETED	An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma
NCT02982954	PHASE4	COMPLETED	A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT07028125	PHASE4	RECRUITING	Digital Monitoring of Self-reported Symptoms by Patients Treated With Cabozantinib Plus Nivolumab for Advanced Clear-cell Renal Carcinoma
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00126412	PHASE3	COMPLETED	Meta-Iodobenzylguanidine (123I mIBG) Scintigraphy in Patients Being Evaluated for Phaeochromocytoma or Neuroblastoma
NCT01373736	PHASE3	UNKNOWN	123I-MIBG Scintigraphy in Patients Being Evaluated for Neuroendocrine Tumors
NCT03176693	PHASE3	COMPLETED	Preoperative Alpha Blockade for Pheochromocytoma
NCT00033904	PHASE3	COMPLETED	Survival Study Of Oncophage® vs. Observation In Patients With Kidney Cancer
NCT00126178	PHASE3	TERMINATED	Clinical Trial Studying a Personalized Cancer Vaccine in Patients With Non-metastatic Kidney Cancer
NCT00291369	PHASE3	COMPLETED	Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis
NCT00410124	PHASE3	COMPLETED	RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed After Treatment With Sorafenib and/or Sunitinib
NCT00474786	PHASE3	COMPLETED	Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib
NCT00478114	PHASE3	COMPLETED	Efficacy and Safety of Sorafenib in Advanced Renal Cell Carcinoma (RCC)
NCT00606632	PHASE3	COMPLETED	Pre-surgical Detection of Clear Cell Renal Cell Carcinoma (ccRCC) Using Radiolabeled G250-Antibody
NCT00606866	PHASE3	COMPLETED	MRI Study of BAY 43-9006 in Metastatic Renal Cell Carcinoma
NCT00631371	PHASE3	COMPLETED	Study Comparing Bevacizumab + Temsirolimus vs. Bevacizumab + Interferon-Alfa In Advanced Renal Cell Carcinoma Subjects
NCT00732914	PHASE3	COMPLETED	Sequential Study to Treat Renal Cell Carcinoma
NCT00869011	PHASE3	UNKNOWN	Exercise for Patients With Renal Cell Cancer Receiving Sunitinib
NCT00930033	PHASE3	COMPLETED	Clinical Trial to Assess the Importance of Nephrectomy
NCT01030783	PHASE3	COMPLETED	A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma
NCT01076010	PHASE3	COMPLETED	An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301).
NCT01198158	PHASE3	TERMINATED	Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
NCT01223027	PHASE3	COMPLETED	Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma
NCT01224288	PHASE3	ACTIVE_NOT_RECRUITING	Dynamic Contrast Enhancement Computed Tomography for Evaluating Tumor Perfusion in Patients With Metastatic Renal Cell Carcinoma Receiving Targeted Therapies: Renal Cell Carcinoma (RCC) Scramble
NCT01235962	PHASE3	COMPLETED	A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC)
NCT01265810	PHASE3	COMPLETED	Caphosol in Oral Mucositis Due to Targeted Therapy
NCT01265901	PHASE3	COMPLETED	IMA901 in Patients Receiving Sunitinib for Advanced/Metastatic Renal Cell Carcinoma