TTC36

Summary

TTC36 (tetratricopeptide repeat domain 36, HGNC:33708) is a protein-coding gene on chromosome 11q23.3, encoding Tetratricopeptide repeat protein 36 (A6NLP5).

The protein encoded by this gene has three tetratricopeptide repeats and is a chaperone for heat shock protein 70. The encoded protein may function as a tumor suppressor in hepatocellular carcinoma (HCC) since it promotes apoptosis but is downregulated in HCC.

Source: NCBI Gene 143941 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_001080441

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33708
Approved symbol	TTC36
Name	tetratricopeptide repeat domain 36
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	HBP21
Ensembl gene	ENSG00000172425
Ensembl biotype	protein_coding
OMIM	620701
Entrez	143941

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 nonsense_mediated_decay

ENST00000302783, ENST00000528570, ENST00000533501, ENST00000909208, ENST00000909209, ENST00000909210

RefSeq mRNA: 3 — MANE Select: NM_001080441 NM_001080441, NM_001346096, NM_001346097

CCDS: CCDS31687

Canonical transcript exons

ENST00000302783 — 3 exons

Exon	Start	End
ENSE00003495646	118528603	118528791
ENSE00003547151	118530654	118530993
ENSE00003891219	118527474	118527612

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 97.65.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8658 / max 185.2223, expressed in 319 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117008	0.5440	278
117006	0.2585	28
117007	0.0378	6
117005	0.0201	6
117004	0.0053	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.65	gold quality
liver	UBERON:0002107	96.53	gold quality
adult mammalian kidney	UBERON:0000082	79.64	gold quality
duodenum	UBERON:0002114	78.70	gold quality
kidney	UBERON:0002113	74.52	gold quality
cortex of kidney	UBERON:0001225	70.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	69.20	gold quality
thoracic mammary gland	UBERON:0005200	68.84	gold quality
small intestine	UBERON:0002108	68.59	gold quality
cortical plate	UBERON:0005343	66.83	gold quality
metanephros cortex	UBERON:0010533	66.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	66.23	gold quality
gastrocnemius	UBERON:0001388	66.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	66.06	gold quality
subcutaneous adipose tissue	UBERON:0002190	65.50	gold quality
muscle of leg	UBERON:0001383	65.46	gold quality
cerebellum	UBERON:0002037	65.28	gold quality
cerebellar cortex	UBERON:0002129	65.16	gold quality
cerebellar hemisphere	UBERON:0002245	65.15	gold quality
pituitary gland	UBERON:0000007	64.71	gold quality
adipose tissue	UBERON:0001013	64.55	gold quality
left adrenal gland	UBERON:0001234	64.35	gold quality
ganglionic eminence	UBERON:0004023	64.18	gold quality
right adrenal gland cortex	UBERON:0035827	63.99	gold quality
left adrenal gland cortex	UBERON:0035825	63.81	gold quality
apex of heart	UBERON:0002098	63.24	gold quality
right adrenal gland	UBERON:0001233	63.20	gold quality
omental fat pad	UBERON:0010414	62.96	gold quality
heart left ventricle	UBERON:0002084	62.88	gold quality
superior frontal gyrus	UBERON:0002661	62.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	486.23
E-ANND-3	yes	8.20

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• The newly discovered interaction between HBP21 and Hsp70 suggests that HBP21 may be involved in the inhibition of progression and metastasis of tumor cells. (PMID:18587674)
• As a chaperone of heat shock protein 70 (HSP70), HBP21 could inhibit interaction between HSP70 and Bax, increased Bax protein translocation from cytoplasm to mitochondria. (PMID:26246424)
• Heat Shock-Binding Protein 21 Regulates the Innate Immune Response to Viral Infection. (PMID:35254105)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttc36	ENSDARG00000011693
mus_musculus	Ttc36	ENSMUSG00000039438
rattus_norvegicus	Ttc36	ENSRNOG00000075307
drosophila_melanogaster	CG14105	FBGN0036359
caenorhabditis_elegans		WBGENE00009947

Protein

Protein identifiers

Tetratricopeptide repeat protein 36 — A6NLP5 (reviewed: A6NLP5)

Alternative names: HSP70-binding protein 21

All UniProt accessions (2): A6NLP5, E9PNF0

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the TTC36 family.

Isoforms (2)

UniProt ID	Names	Canonical?
A6NLP5-1	1	yes
A6NLP5-2	2

RefSeq proteins (3): NP_001073910, NP_001333025, NP_001333026 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR038906	TTC36	Family

Pfam: PF13424

UniProt features (6 total): repeat 3, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NLP5-F1	85.71	0.58

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_MEMORY, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_ASSOCIATIVE_LEARNING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS, GOBP_LEARNING

GO Biological Process (6): obsolete tyrosine metabolic process (GO:0006570), memory (GO:0007613), visual learning (GO:0008542), central nervous system neuron development (GO:0021954), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), negative regulation of protein polyubiquitination (GO:1902915)

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
learning or memory	1
visual behavior	1
associative learning	1
central nervous system neuron differentiation	1
neuron development	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
protein polyubiquitination	1
negative regulation of protein ubiquitination	1
regulation of protein polyubiquitination	1
binding	1

Protein interactions and networks

STRING

538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTC36	HSPA4	P34932	508
TTC36	STK33	Q9BYT3	472
TTC36	RNF138	Q8WVD3	446
TTC36	TMEM74B	Q9NUR3	433
TTC36	SRCIN1	Q9C0H9	422
TTC36	GCC2	Q8IWJ2	418
TTC36	TTC38	Q5R3I4	416
TTC36	FAH	P16930	415
TTC36	TMEM182	Q6ZP80	397
TTC36	PI4K2A	Q9BTU6	385
TTC36	TTC9C	Q8N5M4	367
TTC36	PELI1	Q96FA3	362
TTC36	SMIM24	O75264	343
TTC36	ZNF665	Q9H7R5	323
TTC36	SPDYC	Q5MJ68	322

IntAct

0 interactions, top by confidence:

BioGRID (3): TTC36 (Affinity Capture-MS), HPD (Affinity Capture-Western), TTC36 (Reconstituted Complex)

ESM2 similar proteins: A0A1D5PJB7, A1A4Q9, A5YM72, A6NLP5, D3KCC4, I3L5V6, O43292, P10938, Q00973, Q05B52, Q09200, Q10468, Q14623, Q148G5, Q16586, Q2V8X7, Q3SZV0, Q561R2, Q5E9M9, Q5M868, Q5ZL13, Q66H45, Q69ZF3, Q6P3D0, Q6P7A1, Q6P9Z4, Q6SZW1, Q6TEC1, Q6ZPS2, Q7TMC8, Q864R5, Q86TX2, Q8IXI1, Q8N0W3, Q8N3Y3, Q8N6R0, Q8NF37, Q8NI29, Q8TCD5, Q8VBW8

Diamond homologs: A6NLP5, A7RL75, A8E7I5, A8XHX1, Q20683, Q2M021, Q3SZV0, Q5EBF2, Q66H45, Q8VBW8, Q9VU70, Q57992, O16259, Q12118, Q5U2X2, O13797

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TTC36	“up-regulates quantity by stabilization”	HPD	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

389 predictions. Top by Δscore:

Variant	Effect	Δscore
11:118527585:G:GT	donor_gain	1.0000
11:118527597:G:GT	donor_gain	1.0000
11:118527609:GAAG:G	donor_gain	1.0000
11:118527609:GAAGG:G	donor_loss	1.0000
11:118527610:AAGG:A	donor_loss	1.0000
11:118527611:AGGT:A	donor_loss	1.0000
11:118527613:G:GC	donor_loss	1.0000
11:118527614:T:A	donor_loss	1.0000
11:118530643:C:A	acceptor_gain	1.0000
11:118527610:A:T	donor_gain	0.9900
11:118528560:C:G	acceptor_gain	0.9900
11:118528562:A:AG	acceptor_gain	0.9900
11:118528562:AACT:A	acceptor_gain	0.9900
11:118528565:T:A	acceptor_gain	0.9900
11:118528583:T:TA	acceptor_gain	0.9900
11:118528595:T:TA	acceptor_gain	0.9900
11:118528789:CAGGT:C	donor_loss	0.9900
11:118528790:AGGTA:A	donor_loss	0.9900
11:118528791:GG:G	donor_loss	0.9900
11:118528792:GTAA:G	donor_loss	0.9900
11:118528793:T:G	donor_loss	0.9900
11:118530652:A:AG	acceptor_gain	0.9900
11:118530653:G:GG	acceptor_gain	0.9900
11:118530653:GGC:G	acceptor_gain	0.9900
11:118528555:T:TA	acceptor_gain	0.9800
11:118528559:A:AG	acceptor_gain	0.9800
11:118528563:A:G	acceptor_gain	0.9800
11:118528570:ACCT:A	acceptor_gain	0.9800
11:118530648:CCGCA:C	acceptor_loss	0.9800
11:118530649:CGCA:C	acceptor_loss	0.9800

AlphaMissense

1210 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:118528656:G:T	G58W	0.981
11:118528668:G:C	A62P	0.981
11:118530735:G:A	G130E	0.979
11:118528656:G:A	G58R	0.977
11:118528656:G:C	G58R	0.977
11:118530806:A:C	S154R	0.977
11:118530808:C:A	S154R	0.977
11:118530808:C:G	S154R	0.977
11:118528693:C:A	A70D	0.976
11:118528758:G:C	A92P	0.974
11:118528756:G:C	R91P	0.973
11:118530719:A:C	S125R	0.973
11:118530721:C:A	S125R	0.973
11:118530721:C:G	S125R	0.973
11:118528759:C:A	A92D	0.972
11:118530858:G:A	C171Y	0.971
11:118530859:C:G	C171W	0.971
11:118530669:T:C	L108P	0.970
11:118530734:G:A	G130R	0.970
11:118530734:G:C	G130R	0.970
11:118528657:G:A	G58E	0.969
11:118528713:G:C	A77P	0.968
11:118530677:G:C	A111P	0.964
11:118528771:G:C	R96P	0.961
11:118528751:C:A	N89K	0.960
11:118528751:C:G	N89K	0.960
11:118530732:G:C	R129P	0.960
11:118530857:T:C	C171R	0.960
11:118528764:G:C	A94P	0.958
11:118530738:T:C	L131P	0.958

dbSNP variants (sampled 300 via entrez): RS1000988402 (11:118525894 G>T), RS1001040546 (11:118525628 A>G), RS1001304418 (11:118528663 T>C,G), RS1001440013 (11:118528401 A>G), RS1002451007 (11:118526528 T>C), RS1002955641 (11:118529377 A>C), RS1003809407 (11:118526541 T>G), RS1003839161 (11:118527108 T>C), RS1005058299 (11:118531387 G>A), RS1005484447 (11:118528453 C>T), RS1007011506 (11:118529263 T>C), RS1007065452 (11:118528996 G>A), RS1010077208 (11:118528331 C>A), RS1010460216 (11:118528008 T>C), RS1010721417 (11:118530630 C>A,T)

Disease associations

OMIM: gene MIM:620701 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
ferrous chloride	decreases expression	1
2-palmitoylglycerol	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	decreases expression, decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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