TMC5

Summary

TMC5 (transmembrane channel like 5, HGNC:22999) is a protein-coding gene on chromosome 16p12.3, encoding Transmembrane channel-like protein 5 (Q6UXY8). Probable component of an ion channel.

Predicted to enable mechanosensitive monoatomic ion channel activity. Predicted to be involved in monoatomic ion transmembrane transport. Located in extracellular exosome.

Source: NCBI Gene 79838 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 117 total
• MANE Select transcript: NM_001261841

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22999
Approved symbol	TMC5
Name	transmembrane channel like 5
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13593
Ensembl gene	ENSG00000103534
Ensembl biotype	protein_coding
OMIM	617197
Entrez	79838

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000219821, ENST00000381414, ENST00000396229, ENST00000541464, ENST00000542583, ENST00000561503, ENST00000563675, ENST00000564959, ENST00000567478, ENST00000572147, ENST00000574033, ENST00000856996, ENST00000856997, ENST00000856998, ENST00000856999, ENST00000857000, ENST00000857001, ENST00000949093, ENST00000949094

RefSeq mRNA: 5 — MANE Select: NM_001261841 NM_001105248, NM_001105249, NM_001261841, NM_001308161, NM_024780

CCDS: CCDS10577, CCDS42126, CCDS45431, CCDS76837

Canonical transcript exons

ENST00000542583 — 22 exons

Exon	Start	End
ENSE00001488591	19449542	19449631
ENSE00001488592	19444081	19444250
ENSE00001488593	19439960	19440826
ENSE00001488594	19430413	19430640
ENSE00001663599	19497920	19499113
ENSE00002241088	19417883	19418092
ENSE00003483594	19494262	19494366
ENSE00003484046	19481370	19481465
ENSE00003489739	19474125	19474276
ENSE00003497575	19463776	19464024
ENSE00003500117	19487193	19487326
ENSE00003500131	19466082	19466233
ENSE00003502659	19492150	19492228
ENSE00003540916	19460235	19460334
ENSE00003557904	19472088	19472243
ENSE00003589703	19486945	19487020
ENSE00003605434	19469681	19469825
ENSE00003638469	19463280	19463367
ENSE00003646802	19497121	19497163
ENSE00003651734	19479431	19479528
ENSE00003665906	19477440	19477518
ENSE00003685161	19490395	19490568

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 99.94.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7379 / max 312.1044, expressed in 254 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153010	0.5182	51
153007	0.3116	121
153006	0.2673	120
153003	0.2244	98
153012	0.1720	44
153014	0.1105	37
153013	0.0469	19
153004	0.0453	23
153005	0.0187	4
153011	0.0153	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.94	gold quality
nasal cavity epithelium	UBERON:0005384	99.66	gold quality
bronchial epithelial cell	CL:0002328	99.63	gold quality
bronchus	UBERON:0002185	99.56	gold quality
jejunal mucosa	UBERON:0000399	99.19	gold quality
pylorus	UBERON:0001166	99.00	gold quality
caput epididymis	UBERON:0004358	98.70	gold quality
cauda epididymis	UBERON:0004360	98.52	gold quality
corpus epididymis	UBERON:0004359	98.44	gold quality
trachea	UBERON:0003126	98.40	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.95	gold quality
cardia of stomach	UBERON:0001162	96.90	gold quality
epithelium of nasopharynx	UBERON:0001951	96.51	gold quality
nasopharynx	UBERON:0001728	96.49	gold quality
duodenum	UBERON:0002114	96.46	gold quality
epithelial cell of pancreas	CL:0000083	96.03	gold quality
nasal cavity mucosa	UBERON:0001826	95.89	gold quality
palpebral conjunctiva	UBERON:0001812	95.77	gold quality
ileal mucosa	UBERON:0000331	95.48	gold quality
oocyte	CL:0000023	95.16	gold quality
lower lobe of lung	UBERON:0008949	94.83	gold quality
visceral pleura	UBERON:0002401	93.71	gold quality
colonic mucosa	UBERON:0000317	93.53	gold quality
mucosa of transverse colon	UBERON:0004991	92.77	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.76	gold quality
gall bladder	UBERON:0002110	92.51	gold quality
secondary oocyte	CL:0000655	91.49	gold quality
rectum	UBERON:0001052	91.19	gold quality
upper lobe of lung	UBERON:0008948	88.98	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	1138.70
E-MTAB-8530	yes	989.33
E-CURD-114	yes	63.57
E-HCAD-1	yes	26.63
E-MTAB-8410	yes	23.13
E-GEOD-130148	yes	12.93
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting TMC5, 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-499A-5P	99.98	70.79	1323
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-657	99.48	66.02	848
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-6771-3P	98.20	66.53	971
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-5571-3P	97.80	66.07	640
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-204-3P	97.80	66.84	1656

Literature-anchored findings (GeneRIF, showing 1)

• This findings revealed that TMC5 promoted prostate cancer cell proliferation through cell cycle regulation and could be a powerful and hopeful target for prostate cancer treatment. (PMID:31356847)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmc5	ENSDARG00000013252
mus_musculus	Tmc5	ENSMUSG00000030650
rattus_norvegicus	Tmc5	ENSRNOG00000036760
caenorhabditis_elegans		WBGENE00015177
caenorhabditis_elegans		WBGENE00020490

Paralogs (7): TMC6 (ENSG00000141524), TMC2 (ENSG00000149488), TMC1 (ENSG00000165091), TMC4 (ENSG00000167608), TMC8 (ENSG00000167895), TMC7 (ENSG00000170537), TMC3 (ENSG00000188869)

Protein

Protein identifiers

Transmembrane channel-like protein 5 — Q6UXY8 (reviewed: Q6UXY8)

All UniProt accessions (5): Q6UXY8, F5GYU8, H3BN68, I3L0P3, I3L469

UniProt curated annotations — full annotation on UniProt →

Function. Probable component of an ion channel. Molecular function hasn’t been characterized yet.

Subcellular location. Membrane.

Similarity. Belongs to the TMC family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6UXY8-1	1	yes
Q6UXY8-2	2
Q6UXY8-3	3
Q6UXY8-4	4

RefSeq proteins (5): NP_001098718, NP_001098719, NP_001248770, NP_001295090, NP_079056 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012496	TMC_dom	Domain
IPR038900	TMC	Family

Pfam: PF07810

UniProt features (36 total): topological domain 11, transmembrane region 10, compositionally biased region 5, splice variant 4, sequence variant 2, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXY8-F1	63.70	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 107 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, BASAKI_YBX1_TARGETS_DN, MODULE_48, MODULE_95, GOBP_TRANSMEMBRANE_TRANSPORT, chr16p12, GOMF_GATED_CHANNEL_ACTIVITY, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, VECCHI_GASTRIC_CANCER_EARLY_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_TRANSPORTER_ACTIVITY, RICKMAN_HEAD_AND_NECK_CANCER_D, DOANE_BREAST_CANCER_ESR1_UP

GO Biological Process (1): monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (1): mechanosensitive monoatomic ion channel activity (GO:0008381)

GO Cellular Component (3): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic ion transport	1
transmembrane transport	1
monoatomic ion channel activity	1
gated channel activity	1
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMC5	KCNH8	Q96L42	494
TMC5	TMEM221	A6NGB7	472
TMC5	ADAMTS12	P58397	472
TMC5	CMC1	Q7Z7K0	455
TMC5	RNF175	Q8N4F7	435
TMC5	CCP110	O43303	434
TMC5	ANKUB1	A6NFN9	425
TMC5	LHFPL7	Q6ICI0	424
TMC5	GPR137C	Q8N3F9	420
TMC5	WSCD1	Q658N2	419
TMC5	LRRC71	Q8N4P6	387
TMC5	TMEM171	Q8WVE6	385
TMC5	TMEM132E	Q6IEE7	384
TMC5	OVOL3	O00110	375
TMC5	TRERF1	Q96PN7	370

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TMC5	CIB1	psi-mi:“MI:0915”(physical association)	0.400
NUMBL	TMC5	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (5): TMC5 (Affinity Capture-RNA), CIB1 (Affinity Capture-MS), TMC5 (Affinity Capture-MS), GAPDH (Cross-Linking-MS (XL-MS)), TMC5 (Two-hybrid)

ESM2 similar proteins: A0JPH4, A2AHL1, A8DZH4, D3ZWZ9, E7FFT2, F1QFU0, F1QZE9, P48763, P50482, P86044, Q28CV2, Q32NZ6, Q3TPR7, Q3ZAS0, Q4R7U0, Q4V8U5, Q5F3F5, Q5M7W4, Q5RH73, Q5YCC5, Q5ZKN3, Q68DH5, Q6GQE1, Q6P4P2, Q6UXY8, Q7L1W4, Q7Z2W7, Q7Z402, Q7ZYA0, Q810F5, Q8BH79, Q8C428, Q8C561, Q8CB19, Q8IZK6, Q8N3S3, Q8R455, Q8R4D5, Q8R4P4, Q8R4P5

Diamond homologs: A0A0U1QT59, E7FFT2, F1QFU0, F1QZE9, Q32NZ6, Q496Z4, Q4R7U0, Q5M7W4, Q6UXY8, Q7TN58, Q7TQ65, Q7Z402, Q7Z404, Q8C428, Q8IU68, Q8R4P4, Q8R4P5, Q8TDI7, Q8TDI8, D3KZG3, Q11069, Q5YCC7, Q7TQ69, Q7Z5M5, Q7TN60, Q7Z403

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2577 predictions. Top by Δscore:

Variant	Effect	Δscore
16:19460231:ATAG:A	acceptor_gain	1.0000
16:19460233:A:AG	acceptor_gain	1.0000
16:19460233:A:T	acceptor_loss	1.0000
16:19460234:G:GC	acceptor_loss	1.0000
16:19460234:G:GG	acceptor_gain	1.0000
16:19460234:GGACA:G	acceptor_gain	1.0000
16:19460331:TTAG:T	donor_loss	1.0000
16:19460336:T:G	donor_loss	1.0000
16:19463268:T:A	acceptor_gain	1.0000
16:19463278:A:T	acceptor_loss	1.0000
16:19463279:GGAA:G	acceptor_gain	1.0000
16:19463365:CGGG:C	donor_loss	1.0000
16:19463366:GG:G	donor_gain	1.0000
16:19463367:GG:G	donor_gain	1.0000
16:19463368:G:C	donor_loss	1.0000
16:19463368:G:GG	donor_gain	1.0000
16:19463369:TAA:T	donor_loss	1.0000
16:19464020:GGGTG:G	donor_gain	1.0000
16:19464021:GGTGG:G	donor_gain	1.0000
16:19466076:TTTCA:T	acceptor_loss	1.0000
16:19466077:TTCA:T	acceptor_loss	1.0000
16:19466080:A:G	acceptor_loss	1.0000
16:19466080:AG:A	acceptor_gain	1.0000
16:19466080:AGG:A	acceptor_gain	1.0000
16:19466081:GG:G	acceptor_gain	1.0000
16:19466081:GGG:G	acceptor_gain	1.0000
16:19466081:GGGT:G	acceptor_gain	1.0000
16:19466081:GGGTT:G	acceptor_gain	1.0000
16:19466229:TTCAG:T	donor_loss	1.0000
16:19466230:TCAG:T	donor_loss	1.0000

AlphaMissense

6660 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:19469757:T:A	W572R	0.994
16:19469757:T:C	W572R	0.994
16:19463863:T:C	F442L	0.993
16:19463865:T:A	F442L	0.993
16:19463865:T:G	F442L	0.993
16:19492218:A:C	Q939P	0.993
16:19481464:T:A	W788R	0.992
16:19481464:T:C	W788R	0.992
16:19494284:T:C	L950P	0.992
16:19481413:T:C	F771L	0.991
16:19481415:T:A	F771L	0.991
16:19481415:T:G	F771L	0.991
16:19492209:T:C	L936P	0.991
16:19494272:A:C	D946A	0.990
16:19494275:A:T	K947I	0.990
16:19494276:A:C	K947N	0.990
16:19494276:A:T	K947N	0.990
16:19469759:G:C	W572C	0.989
16:19469759:G:T	W572C	0.989
16:19494280:T:C	F949L	0.989
16:19494282:C:A	F949L	0.989
16:19494282:C:G	F949L	0.989
16:19463906:T:C	L456P	0.987
16:19494271:G:C	D946H	0.987
16:19463867:G:T	G443V	0.985
16:19463887:T:C	F450L	0.984
16:19463889:C:A	F450L	0.984
16:19463889:C:G	F450L	0.984
16:19469761:A:C	D573A	0.984
16:19469763:T:C	F574L	0.984

dbSNP variants (sampled 300 via entrez): RS1000076011 (16:19448653 T>G), RS1000150371 (16:19425349 T>C), RS1000164080 (16:19495521 T>C), RS1000211259 (16:19448475 C>T), RS1000220024 (16:19475515 C>A,T), RS1000295102 (16:19459706 C>T), RS1000309305 (16:19469214 C>T), RS1000312302 (16:19488161 C>T), RS1000321350 (16:19494918 G>A), RS1000324782 (16:19453831 G>T), RS1000325176 (16:19443048 C>T), RS1000355895 (16:19428360 G>T), RS1000380058 (16:19469995 C>G,T), RS1000416260 (16:19422949 A>T), RS1000497751 (16:19493916 T>C)

Disease associations

OMIM: gene MIM:617197 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002053_1	Sleep duration	8.000000e-07
GCST008141_4	HDL cholesterol	8.000000e-06
GCST010105_44	Nicotine dependence symptom count	8.000000e-07
GCST010397_114	Gut microbiota (bacterial taxa, rank normal transformation method)	4.000000e-07
GCST90000014_3	Parkinson’s disease motor subtype (tremor dominant vs postural instability/gait difficulty)	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009262	nicotine dependence symptom count
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	3
Tretinoin	increases expression	3
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
bisphenol A	increases methylation	1
potassium perchlorate	increases expression	1
trichostatin A	increases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases response to substance	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases expression	1
Copper	affects binding, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Selenium	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Theophylline	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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