TMC7

Summary

TMC7 (transmembrane channel like 7, HGNC:23000) is a protein-coding gene on chromosome 16p12.3, encoding Transmembrane channel-like protein 7 (Q7Z402). Acts as an inhibitory modulator of PIEZO2 mechanosensitive channel in dorsal root ganglion (DRG) neurons through physical interactions or interference with the interaction between PIEZO2 and the cytoskeleton.

Predicted to enable ion channel inhibitor activity and mechanosensitive monoatomic ion channel activity. Predicted to be involved in sensory perception of mechanical stimulus. Predicted to be located in plasma membrane. Predicted to be active in neuronal cell body.

Source: NCBI Gene 79905 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 140 total
• MANE Select transcript: NM_024847

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23000
Approved symbol	TMC7
Name	transmembrane channel like 7
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21240
Ensembl gene	ENSG00000170537
Ensembl biotype	protein_coding
OMIM	617198
Entrez	79905

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000304381, ENST00000421369, ENST00000561963, ENST00000568469, ENST00000569532, ENST00000877222, ENST00000877223, ENST00000931979, ENST00000931980

RefSeq mRNA: 6 — MANE Select: NM_024847 NM_001160364, NM_001300732, NM_001324263, NM_001324265, NM_001324268, NM_024847

CCDS: CCDS10573, CCDS53992, CCDS73837

Canonical transcript exons

ENST00000304381 — 16 exons

Exon	Start	End
ENSE00001154652	19037874	19038047
ENSE00001315472	19035676	19035823
ENSE00001600665	19059416	19059494
ENSE00001647895	19045341	19045438
ENSE00001700155	19047063	19047249
ENSE00001745381	19056542	19056697
ENSE00001746242	19061778	19063942
ENSE00001749993	19051686	19051816
ENSE00001791099	19044884	19045001
ENSE00001853380	18983934	18984130
ENSE00003502405	19023113	19023195
ENSE00003580190	19040289	19040446
ENSE00003583096	19016450	19016598
ENSE00003641828	19021629	19021796
ENSE00003647676	19009172	19009415
ENSE00003686166	19030224	19030369

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 82.61.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8336 / max 58.3769, expressed in 737 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152979	1.5657	674
152978	0.2679	142

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	82.61	gold quality
spinal cord	UBERON:0002240	80.76	gold quality
corpus callosum	UBERON:0002336	79.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.52	gold quality
cerebellar cortex	UBERON:0002129	76.75	gold quality
cerebellar hemisphere	UBERON:0002245	76.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.68	gold quality
rectum	UBERON:0001052	75.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.71	gold quality
cerebellum	UBERON:0002037	75.40	gold quality
left testis	UBERON:0004533	74.51	gold quality
substantia nigra	UBERON:0002038	74.35	gold quality
inferior vagus X ganglion	UBERON:0005363	73.64	gold quality
right testis	UBERON:0004534	73.58	gold quality
midbrain	UBERON:0001891	73.50	gold quality
putamen	UBERON:0001874	73.44	gold quality
prefrontal cortex	UBERON:0000451	73.29	gold quality
mucosa of transverse colon	UBERON:0004991	73.10	gold quality
testis	UBERON:0000473	72.68	gold quality
sural nerve	UBERON:0015488	72.31	gold quality
amygdala	UBERON:0001876	72.18	gold quality
caudate nucleus	UBERON:0001873	71.21	gold quality
Ammon’s horn	UBERON:0001954	70.87	gold quality
tibial nerve	UBERON:0001323	70.73	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.40	gold quality
right frontal lobe	UBERON:0002810	69.96	gold quality
frontal cortex	UBERON:0001870	69.53	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	69.24	gold quality
hypothalamus	UBERON:0001898	68.89	gold quality
medial globus pallidus	UBERON:0002477	68.67	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.72
E-CURD-11	no	57.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

118 targeting TMC7, 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-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4692	100.00	67.32	2066
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872

Literature-anchored findings (GeneRIF, showing 2)

• Identification of EMT-related alternative splicing event of TMC7 to promote invasion and migration of pancreatic cancer. (PMID:36713450)
• TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction. (PMID:38568807)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmc7	ENSMUSG00000042246
rattus_norvegicus	Tmc7	ENSRNOG00000016679
caenorhabditis_elegans		WBGENE00015177
caenorhabditis_elegans		WBGENE00020490

Paralogs (7): TMC5 (ENSG00000103534), TMC6 (ENSG00000141524), TMC2 (ENSG00000149488), TMC1 (ENSG00000165091), TMC4 (ENSG00000167608), TMC8 (ENSG00000167895), TMC3 (ENSG00000188869)

Protein

Protein identifiers

Transmembrane channel-like protein 7 — Q7Z402 (reviewed: Q7Z402)

All UniProt accessions (2): Q7Z402, H3BNW8

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an inhibitory modulator of PIEZO2 mechanosensitive channel in dorsal root ganglion (DRG) neurons through physical interactions or interference with the interaction between PIEZO2 and the cytoskeleton.

Subunit / interactions. Interacts with PIEZO2; the interaction inhibits PIEZO2-conducted mechanically activated currents.

Subcellular location. Membrane.

Similarity. Belongs to the TMC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z402-1	1	yes
Q7Z402-2	2

RefSeq proteins (6): NP_001153836, NP_001287661, NP_001311192, NP_001311194, NP_001311197, NP_079123* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012496	TMC_dom	Domain
IPR038900	TMC	Family

Pfam: PF07810

UniProt features (34 total): topological domain 10, transmembrane region 9, glycosylation site 5, sequence variant 4, region of interest 2, chain 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z402-F1	77.63	0.28

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 (1): 89

Glycosylation sites (5): 24, 84, 96, 259, 638

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 111 (showing top): GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, ATACCTC_MIR202, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_SENSORY_PERCEPTION, CUI_TCF21_TARGETS_2_DN, GOBP_TRANSMEMBRANE_TRANSPORT, chr16p12, GOCC_CELL_BODY, GOCC_SOMATODENDRITIC_COMPARTMENT, GOMF_GATED_CHANNEL_ACTIVITY, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, P53_02, GOMF_TRANSPORTER_ACTIVITY, OHGUCHI_LIVER_HNF4A_TARGETS_DN, PILON_KLF1_TARGETS_UP

GO Biological Process (3): sensory perception of mechanical stimulus (GO:0050954), response to mechanical stimulus (GO:0009612), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (2): ion channel inhibitor activity (GO:0008200), mechanosensitive monoatomic ion channel activity (GO:0008381)

GO Cellular Component (3): plasma membrane (GO:0005886), neuronal cell body (GO:0043025), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic ion channel activity	2
sensory perception	1
response to external stimulus	1
response to abiotic stimulus	1
monoatomic ion transport	1
transmembrane transport	1
channel inhibitor activity	1
transmembrane transporter binding	1
ion channel regulator activity	1
gated channel activity	1
membrane	1
cell periphery	1
somatodendritic compartment	1
cell body	1
cellular anatomical structure	1

Protein interactions and networks

STRING

434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMC7	LRRIQ3	A6PVS8	726
TMC7	FRMD3	A2A2Y4	612
TMC7	SAMD5	Q5TGI4	572
TMC7	STYK1	Q6J9G0	360
TMC7	PLEKHO2	Q8TD55	355
TMC7	FAM78B	Q5VT40	354
TMC7	METTL26	Q96S19	348
TMC7	SNX24	Q9Y343	346
TMC7	FSD1L	Q9BXM9	307
TMC7	TMEM45B	Q96B21	301
TMC7	HHIPL1	Q96JK4	300
TMC7	CARMIL3	Q8ND23	299
TMC7	ARFIP1	P53367	296
TMC7	SCARA3	Q6AZY7	290
TMC7	ZFP30	Q9Y2G7	286

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TMC7	HLCS	psi-mi:“MI:0914”(association)	0.530
TMC7	EEF1G	psi-mi:“MI:0915”(physical association)	0.400
TMC7	PSMD11	psi-mi:“MI:0914”(association)	0.350
	FAM171A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): HLCS (Affinity Capture-MS), ZFAND2B (Affinity Capture-MS), CIB1 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), TMC7 (Proximity Label-MS), TMC7 (Proximity Label-MS), TMC7 (Proximity Label-MS), TMC7 (Proximity Label-MS), TMC7 (Proximity Label-MS), TMC7 (Proximity Label-MS), TMC7 (Affinity Capture-MS), TMC7 (Affinity Capture-RNA), HLCS (Affinity Capture-MS), ZFAND2B (Affinity Capture-MS), CIB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A452G813, A0A8V0ZB02, A1L3G9, A2AWR3, A9LIW2, B6HTR9, D3ZNF5, F4I248, F4JCY2, O35379, O57428, O94886, O94911, P08983, Q059Y8, Q06538, Q09427, Q09428, Q09429, Q17JQ7, Q3KTM2, Q3TWI9, Q4R7U0, Q4V8U5, Q5GH22, Q5GH60, Q5GH68, Q5R826, Q5R9A7, Q5T3F8, Q5YCC5, Q6NP91, Q6PP77, Q6UR05, Q7Q5R7, Q7Z3F1, Q7Z402, Q8C428, Q8CBX0, Q8CG09

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, Q5YCC5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	111
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2544 predictions. Top by Δscore:

Variant	Effect	Δscore
16:18984127:CCAG:C	donor_loss	1.0000
16:18984128:CAGG:C	donor_loss	1.0000
16:18984129:AGGT:A	donor_loss	1.0000
16:18984130:GGTA:G	donor_loss	1.0000
16:18984131:GTAGG:G	donor_loss	1.0000
16:18984132:T:A	donor_loss	1.0000
16:19016444:A:AG	acceptor_gain	1.0000
16:19016444:AT:A	acceptor_gain	1.0000
16:19016445:T:G	acceptor_gain	1.0000
16:19016445:T:TA	acceptor_gain	1.0000
16:19016446:GCA:G	acceptor_loss	1.0000
16:19016447:CA:C	acceptor_loss	1.0000
16:19016448:A:AG	acceptor_gain	1.0000
16:19016448:A:AT	acceptor_loss	1.0000
16:19016448:AG:A	acceptor_gain	1.0000
16:19016448:AGG:A	acceptor_gain	1.0000
16:19016449:G:GA	acceptor_gain	1.0000
16:19016449:G:GC	acceptor_loss	1.0000
16:19016449:GG:G	acceptor_gain	1.0000
16:19016449:GGG:G	acceptor_gain	1.0000
16:19016449:GGGAC:G	acceptor_gain	1.0000
16:19016595:GAAG:G	donor_gain	1.0000
16:19016598:GGT:G	donor_loss	1.0000
16:19016599:G:GC	donor_loss	1.0000
16:19016600:T:A	donor_loss	1.0000
16:19021795:GG:G	donor_gain	1.0000
16:19021796:GG:G	donor_gain	1.0000
16:19021801:GT:G	donor_gain	1.0000
16:19023191:GCACT:G	donor_gain	1.0000
16:19023196:G:GG	donor_gain	1.0000

AlphaMissense

4783 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:19035755:T:A	W313R	1.000
16:19035755:T:C	W313R	1.000
16:19035757:G:C	W313C	0.999
16:19035757:G:T	W313C	0.999
16:19045346:G:C	W487C	0.999
16:19045346:G:T	W487C	0.999
16:19045359:G:T	G492W	0.999
16:19047121:T:C	F538L	0.999
16:19047123:T:A	F538L	0.999
16:19047123:T:G	F538L	0.999
16:19021634:T:C	F156L	0.998
16:19021636:T:A	F156L	0.998
16:19021636:T:G	F156L	0.998
16:19030347:A:C	S279R	0.998
16:19030349:C:A	S279R	0.998
16:19030349:C:G	S279R	0.998
16:19035819:T:C	L334P	0.998
16:19040335:T:C	L409P	0.998
16:19040446:G:T	R446M	0.998
16:19045343:C:G	C486W	0.998
16:19045360:G:A	G492E	0.998
16:19045378:T:C	L498P	0.998
16:19047122:T:C	F538S	0.998
16:19047122:T:G	F538C	0.998
16:19047178:G:A	G557R	0.998
16:19047178:G:C	G557R	0.998
16:19047179:G:A	G557E	0.998
16:19056696:T:C	C676R	0.998
16:19021638:G:T	G157V	0.997
16:19021658:T:C	F164L	0.997

dbSNP variants (sampled 300 via entrez): RS1000015347 (16:19020935 A>G), RS1000020848 (16:19017457 T>G), RS1000077161 (16:19026978 T>C,G), RS1000082894 (16:19053639 G>A,C), RS1000106821 (16:19013712 T>C), RS1000205928 (16:19054226 T>G), RS1000219506 (16:19057625 C>A,T), RS1000242694 (16:19047441 A>G), RS1000274600 (16:18987053 C>G,T), RS1000281242 (16:19026647 G>A), RS1000330992 (16:19008930 G>A,T), RS1000338140 (16:19051096 G>A,T), RS1000423919 (16:19001206 G>A), RS1000437602 (16:19041849 T>C), RS1000441258 (16:19019041 G>A,C)

Disease associations

OMIM: gene MIM:617198 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001520_14	Response to angiotensin II receptor blocker therapy	6.000000e-06
GCST004678_6	Psychosis proneness (hypomanic personality scale)	3.000000e-08
GCST007139_5	Shingles	6.000000e-09
GCST007741_14	Iris color (b* coordinate)	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008337	psychosis predisposition measurement
EFO:0009764	eye colour measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	4
Aflatoxin B1	affects expression, increases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
trichostatin A	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Azathioprine	increases expression	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Estradiol	affects cotreatment, increases expression	1
Lead	affects methylation	1
Lipopolysaccharides	affects cotreatment, decreases expression, affects response to substance, increases expression	1
Polychlorinated Biphenyls	affects expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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