TCHP

Summary

TCHP (trichoplein keratin filament binding, HGNC:28135) is a protein-coding gene on chromosome 12q24.11, encoding Trichoplein keratin filament-binding protein (Q9BT92). Tumor suppressor which has the ability to inhibit cell growth and be pro-apoptotic during cell stress.

Involved in apoptotic process; negative regulation of cell growth; and negative regulation of cilium assembly. Located in several cellular components, including apical cortex; cytoskeleton; and nuclear membrane.

Source: NCBI Gene 84260 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_001143852

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28135
Approved symbol	TCHP
Name	trichoplein keratin filament binding
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	MGC10854, TpMs
Ensembl gene	ENSG00000139437
Ensembl biotype	protein_coding
OMIM	612654
Entrez	84260

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000312777, ENST00000405876, ENST00000536408, ENST00000537218, ENST00000537880, ENST00000544838, ENST00000549524, ENST00000549550, ENST00000550780, ENST00000551627, ENST00000900219, ENST00000900220, ENST00000912830, ENST00000912831, ENST00000955360, ENST00000955361

RefSeq mRNA: 2 — MANE Select: NM_001143852 NM_001143852, NM_032300

CCDS: CCDS9137

Canonical transcript exons

ENST00000405876 — 13 exons

Exon	Start	End
ENSE00000938151	109904737	109904793
ENSE00000938152	109906572	109906640
ENSE00000938153	109907526	109907699
ENSE00000938154	109908586	109908698
ENSE00000938155	109908871	109908937
ENSE00001548957	109900274	109900426
ENSE00002408099	109916591	109918069
ENSE00003476563	109911063	109911235
ENSE00003494830	109903937	109904147
ENSE00003502487	109914442	109914627
ENSE00003543703	109903027	109903214
ENSE00003636281	109915403	109915546
ENSE00003691635	109912991	109913072

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 96.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.9002 / max 155.1186, expressed in 1785 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127956	12.6181	1784
127957	0.2821	112

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.38	gold quality
pancreatic ductal cell	CL:0002079	94.85	gold quality
sperm	CL:0000019	93.13	gold quality
ileal mucosa	UBERON:0000331	92.68	gold quality
lower esophagus mucosa	UBERON:0035834	92.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.13	gold quality
skin of leg	UBERON:0001511	91.04	gold quality
cerebellar hemisphere	UBERON:0002245	90.98	gold quality
skin of abdomen	UBERON:0001416	90.89	gold quality
cerebellar cortex	UBERON:0002129	90.75	gold quality
endothelial cell	CL:0000115	90.71	gold quality
tibialis anterior	UBERON:0001385	90.53	silver quality
apex of heart	UBERON:0002098	90.53	gold quality
zone of skin	UBERON:0000014	89.92	gold quality
cerebellum	UBERON:0002037	89.85	gold quality
esophagus mucosa	UBERON:0002469	89.80	gold quality
upper leg skin	UBERON:0004262	89.62	gold quality
monocyte	CL:0000576	89.17	gold quality
epithelial cell of pancreas	CL:0000083	88.99	gold quality
leukocyte	CL:0000738	88.86	gold quality
granulocyte	CL:0000094	88.74	gold quality
vagina	UBERON:0000996	88.65	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.63	gold quality
gingival epithelium	UBERON:0001949	88.28	gold quality
skin of hip	UBERON:0001554	88.18	gold quality
spleen	UBERON:0002106	88.09	gold quality
body of pancreas	UBERON:0001150	88.00	gold quality
esophagus	UBERON:0001043	87.80	gold quality
putamen	UBERON:0001874	87.36	gold quality
right uterine tube	UBERON:0001302	87.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting TCHP, 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-4425	100.00	67.59	1049
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-670-3P	99.03	68.88	2404

Literature-anchored findings (GeneRIF, showing 7)

• trichoplein is a keratin 8/18-binding protein that may be involved in the organization of the apical network of keratin filaments and desmosomes in simple epithelial cells (PMID:15731013)
• MITOSTATIN was found within a 3.2-kb transcript for an approximately 62 kDa mitochondrial protein with tumor suppressor activity. It inhibits cell growth, is proapoptotic and downregulates Hsp27. (PMID:18931701)
• Trichoplein/mitostatin is a new regulator of mitochondria-endoplasmic reticulum juxtaposition. (PMID:20930847)
• Trichoplein controls microtubule anchoring at the centrosome by binding to Odf2 and ninein. (PMID:21325031)
• These findings underscore the complexity of PGC-1alpha-mediated mitochondrial homeostasis and establish mitostatin as a key regulator of tumor cell mitophagy and angiostasis. (PMID:24403067)
• Ndel1 acts as a novel upstream regulator of the trichoplein-Aurora A pathway to inhibit primary cilia assembly. (PMID:26880200)
• Soluble matrix-derived cues being transduced downstream of receptor engagement converge upon a newly-discovered nexus of autophagic machinery consisting of Peg3 for endothelial cell autophagy and mitostatin for tumor cell mitophagy. (PMID:29080840)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Trichoplein keratin filament-binding protein — Q9BT92 (reviewed: Q9BT92)

Alternative names: Mitochondrial protein with oncostatic activity, Tumor suppressor protein

All UniProt accessions (2): F5GWH6, Q9BT92

UniProt curated annotations — full annotation on UniProt →

Function. Tumor suppressor which has the ability to inhibit cell growth and be pro-apoptotic during cell stress. Inhibits cell growth in bladder and prostate cancer cells by a down-regulation of HSPB1 by inhibiting its phosphorylation. May act as a ‘capping’ or ‘branching’ protein for keratin filaments in the cell periphery. May regulate K8/K18 filament and desmosome organization mainly at the apical or peripheral regions of simple epithelial cells. Is a negative regulator of ciliogenesis.

Subunit / interactions. Interacts specifically with keratin proteins including, KRT5, KRT6A, KRT8, KRT14, KRT16 and KRT18. Interacts with KCTD17.

Subcellular location. Cytoplasm. Cytoskeleton. Cell membrane. Mitochondrion. Cell junction. Desmosome. Microtubule organizing center. Centrosome.

Tissue specificity. Expressed at high levels in normal urothelial and breast epithelial cells. Also expressed in the smooth muscle and endothelial cells. Reduced expression seen in advanced bladder and breast carcinomas (at protein level). Ubiquitous. Expressed at highest levels in the heart, skeletal muscle, kidney, liver and testis.

Post-translational modifications. Ubiquitinated. Ubiquitination by the BCR(KCTD17) E3 ubiquitin ligase complex results in proteasomal degradation, and induces ciliogenesis.

Similarity. Belongs to the TCHP family.

RefSeq proteins (2): NP_001137324, NP_115676 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR043596	CFAP53/TCHP	Family
IPR043597	TPH_dom	Domain

Pfam: PF13868

UniProt features (19 total): region of interest 4, sequence variant 4, coiled-coil region 4, cross-link 2, mutagenesis site 2, chain 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BT92-F1	83.73	0.38

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): 50, 57

Mutagenesis-validated functional residues (2):

Position	Phenotype
50	decreased ubiquitination. negative effect on ubiquitination is higher when associated with r-57.
57	decreased ubiquitination. negative effect on ubiquitination is higher when associated with r-50.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME, GOBP_ORGANELLE_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_CILIUM_ASSEMBLY, GCM_CALM1, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_CELL_PROJECTION_ASSEMBLY

GO Biological Process (4): apoptotic process (GO:0006915), cell projection organization (GO:0030030), negative regulation of cell growth (GO:0030308), negative regulation of cilium assembly (GO:1902018)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (17): cytoplasm (GO:0005737), mitochondrion (GO:0005739), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), desmosome (GO:0030057), nuclear membrane (GO:0031965), ciliary basal body (GO:0036064), keratin filament (GO:0045095), apical cortex (GO:0045179), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), cytoskeleton (GO:0005856), membrane (GO:0016020), anchoring junction (GO:0070161), polymeric cytoskeletal fiber (GO:0099513)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	2
microtubule organizing center	2
sperm flagellum	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular component organization	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
cilium assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
negative regulation of organelle assembly	1
binding	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
centriole	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cell-cell junction	1
nucleus	1
nuclear envelope	1
organelle membrane	1
cilium	1
intermediate filament	1
cell cortex region	1
intracellular membraneless organelle	1
cell junction	1
cytoskeleton	1
supramolecular fiber	1

Protein interactions and networks

STRING

3296 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCHP	MDM2	Q00987	997
TCHP	AXIN1	O15169	989
TCHP	HIF1A	Q16665	983
TCHP	GSK3B	P49841	966
TCHP	TP53	P04637	946
TCHP	MDM4	O15151	863
TCHP	PTEN	P60484	853
TCHP	BCL2	P10415	851
TCHP	CDK4	P11802	840
TCHP	CTNNB1	P35222	834
TCHP	CDKN2A	P42771	828
TCHP	MFN2	O95140	815
TCHP	VHL	P40337	813
TCHP	AXIN2	Q9Y2T1	807
TCHP	DLG1	Q12959	762

IntAct

238 interactions, top by confidence:

A	B	Type	Score
TCHP	NME7	psi-mi:“MI:0915”(physical association)	0.900
NME7	TCHP	psi-mi:“MI:0915”(physical association)	0.900
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
CDR2	TCHP	psi-mi:“MI:0915”(physical association)	0.790
TCHP	CDR2	psi-mi:“MI:0915”(physical association)	0.790
CCDC172	TCHP	psi-mi:“MI:0915”(physical association)	0.780
MKRN3	TCHP	psi-mi:“MI:0915”(physical association)	0.780
TCHP	NAB2	psi-mi:“MI:0915”(physical association)	0.780
TCHP	NDOR1	psi-mi:“MI:0915”(physical association)	0.780
TCHP	MKRN3	psi-mi:“MI:0915”(physical association)	0.780
TCHP	CCDC172	psi-mi:“MI:0915”(physical association)	0.780
NDOR1	TCHP	psi-mi:“MI:0915”(physical association)	0.780
NAB2	TCHP	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (170): TCHP (Two-hybrid), TCHP (Two-hybrid), TCHP (Two-hybrid), TCHP (Two-hybrid), TCHP (Two-hybrid), TCHP (Two-hybrid), TCHP (Two-hybrid), LZTS2 (Two-hybrid), KRT40 (Two-hybrid), DYDC1 (Two-hybrid), MIPOL1 (Two-hybrid), CCDC172 (Two-hybrid), TCHP (Affinity Capture-MS), TCHP (Affinity Capture-MS), TCHP (Two-hybrid)

ESM2 similar proteins: A0A0R4IFG5, A0A480NP79, A0A974E306, A0AUT1, A0JLY1, A4IJ21, A5A6J4, A8I9E8, A8IRJ7, A8IUG5, E1BJL9, F1N7G5, M0R3K6, M1V4Y8, O95990, Q0VC09, Q0VFZ6, Q17QH9, Q1RM03, Q2KI00, Q2KIQ2, Q32LH1, Q3TGF2, Q3TVW5, Q4R698, Q4R7T8, Q4R8Y5, Q5NVP3, Q5RE49, Q5U4F3, Q5XIN9, Q61884, Q6AXN9, Q6AXQ8, Q6AYL4, Q6PBA8, Q6ZN84, Q78TU8, Q8BRC6, Q8N443

Diamond homologs: A0A974E306, A0AUT1, Q1RM03, Q3TVW5, Q5RE49, Q9BT92

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
KCTD17	“down-regulates quantity by destabilization”	TCHP	binding
“Cullin 3-RBX1-Skp1”	“down-regulates quantity by destabilization”	TCHP	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Loss of Nlp from mitotic centrosomes	12	38.1×	8e-15
Loss of proteins required for interphase microtubule organization from the centrosome	12	38.1×	8e-15
AURKA Activation by TPX2	12	36.5×	1e-14
Recruitment of mitotic centrosome proteins and complexes	13	35.4×	2e-15
Anchoring of the basal body to the plasma membrane	15	33.9×	2e-17
Regulation of PLK1 Activity at G2/M Transition	12	30.4×	9e-14
Recruitment of NuMA to mitotic centrosomes	13	30.3×	8e-15
Centrosome maturation	5	25.4×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	8	75.2×	3e-11
morphogenesis of an epithelium	8	35.3×	9e-09
intermediate filament organization	9	27.8×	7e-09
non-motile cilium assembly	7	26.1×	8e-07
epithelial cell differentiation	7	15.8×	2e-05
cilium assembly	12	11.3×	7e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5588 predictions. Top by Δscore:

Variant	Effect	Δscore
12:109900422:GAAAT:G	donor_gain	1.0000
12:109900425:ATGTG:A	donor_loss	1.0000
12:109900426:TGTG:T	donor_loss	1.0000
12:109900427:G:GG	donor_gain	1.0000
12:109900427:GTGA:G	donor_loss	1.0000
12:109903018:T:TA	acceptor_gain	1.0000
12:109903022:CTCA:C	acceptor_loss	1.0000
12:109903023:TCA:T	acceptor_loss	1.0000
12:109903025:A:AG	acceptor_gain	1.0000
12:109903025:AGAT:A	acceptor_gain	1.0000
12:109903025:AGATG:A	acceptor_gain	1.0000
12:109903026:G:GA	acceptor_gain	1.0000
12:109903026:GA:G	acceptor_gain	1.0000
12:109903026:GAT:G	acceptor_gain	1.0000
12:109903026:GATG:G	acceptor_gain	1.0000
12:109903026:GATGG:G	acceptor_gain	1.0000
12:109903152:G:GT	donor_gain	1.0000
12:109904086:A:T	donor_gain	1.0000
12:109904823:C:CG	donor_gain	1.0000
12:109904823:C:G	donor_gain	1.0000
12:109906641:GTGTG:G	donor_gain	1.0000
12:109907513:T:TA	acceptor_gain	1.0000
12:109907521:T:TA	acceptor_gain	1.0000
12:109907524:A:AG	acceptor_gain	1.0000
12:109907525:G:GA	acceptor_gain	1.0000
12:109907525:GC:G	acceptor_gain	1.0000
12:109907525:GCA:G	acceptor_gain	1.0000
12:109907525:GCAA:G	acceptor_gain	1.0000
12:109907691:G:GT	donor_gain	1.0000
12:109907698:AGG:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000079478 (12:109905135 A>G), RS1000259173 (12:109910979 A>G), RS1000347947 (12:109902125 T>A), RS1000525782 (12:109908987 A>G), RS1000555883 (12:109905425 T>A,C), RS1000606540 (12:109916891 T>C,G), RS1000649468 (12:109914976 C>T), RS1000717675 (12:109913654 T>C), RS1000792855 (12:109897370 T>C,G), RS1000810403 (12:109880688 C>T), RS1000845050 (12:109897724 A>G), RS1001019128 (12:109890699 C>G,T), RS1001089714 (12:109903661 C>T), RS1001092839 (12:109879129 G>A), RS1001408559 (12:109900223 A>C)

Disease associations

OMIM: gene MIM:612654 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001822_15	Metabolite levels (MHPG)	4.000000e-07
GCST004953_2	Disturbances of the gamma-frequency band of electroencephalography measures in schizophrenia	4.000000e-06
GCST007096_8	Pulse pressure	7.000000e-09
GCST007099_1	Systolic blood pressure	1.000000e-06
GCST008103_145	Bipolar disorder	3.000000e-06
GCST010476_18	Myocardial infarction	2.000000e-07
GCST90002402_146	Platelet count	1.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005133	MHPG measurement
EFO:0008388	gamma wave measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
arsenite	affects binding, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
jinfukang	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Methotrexate	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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