CCT8L2

Summary

CCT8L2 (chaperonin containing TCP1 subunit 8 like 2, HGNC:15553) is a protein-coding gene on chromosome 22q11.1, encoding T-complex protein 1 subunit theta-like 2 (Q96SF2). Possible molecular chaperone; assists the folding of proteins upon ATP hydrolysis.

Predicted to enable unfolded protein binding activity. Predicted to be involved in protein folding. Predicted to be located in cytoplasm. Predicted to be part of chaperonin-containing T-complex.

Source: NCBI Gene 150160 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 108 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_014406

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15553
Approved symbol	CCT8L2
Name	chaperonin containing TCP1 subunit 8 like 2
Location	22q11.1
Locus type	gene with protein product
Status	Approved
Aliases	CESK1
Ensembl gene	ENSG00000198445
Ensembl biotype	protein_coding
Entrez	150160

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000359963

RefSeq mRNA: 1 — MANE Select: NM_014406 NM_014406

CCDS: CCDS13738

Canonical transcript exons

ENST00000359963 — 1 exons

Exon	Start	End
ENSE00001806026	16590751	16592810

Expression profiles

Bgee: expression breadth broad, 14 present calls, max score 83.24.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.24	gold quality
right testis	UBERON:0004534	79.87	gold quality
left testis	UBERON:0004533	79.81	gold quality
testis	UBERON:0000473	76.93	gold quality
male germ cell	CL:0000015	55.43	gold quality
sperm	CL:0000019	55.04	gold quality
buccal mucosa cell	CL:0002336	52.71	gold quality
pancreatic ductal cell	CL:0002079	49.68	silver quality
epithelial cell of pancreas	CL:0000083	49.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
adult organism	UBERON:0007023	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
quadriceps femoris	UBERON:0001377	48.92	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.45	gold quality
thymus	UBERON:0002370	47.42	gold quality
kidney epithelium	UBERON:0004819	47.39	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting CCT8L2, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-339-5P	96.73	66.01	820
HSA-MIR-642B-5P	96.37	67.26	745
HSA-MIR-624-5P	96.00	68.88	728

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cct8l1	ENSMUSG00000038044
rattus_norvegicus	Cct8l2	ENSRNOG00000047114

Paralogs (13): PIKFYVE (ENSG00000115020), CCT4 (ENSG00000115484), TCP1 (ENSG00000120438), MKKS (ENSG00000125863), CCT6B (ENSG00000132141), CCT7 (ENSG00000135624), HSPD1 (ENSG00000144381), CCT6A (ENSG00000146731), CCT5 (ENSG00000150753), CCT8 (ENSG00000156261), CCT3 (ENSG00000163468), CCT2 (ENSG00000166226), BBS12 (ENSG00000181004)

Protein

Protein identifiers

T-complex protein 1 subunit theta-like 2 — Q96SF2 (reviewed: Q96SF2)

Alternative names: Chaperonin containing T-complex polypeptide 1 subunit 8-like 2

All UniProt accessions (1): Q96SF2

UniProt curated annotations — full annotation on UniProt →

Function. Possible molecular chaperone; assists the folding of proteins upon ATP hydrolysis.

Subcellular location. Cytoplasm.

Miscellaneous. Presence of two highly similar CCT8L genes (CCT8L1P and CCT8L2) in the genomes of human and chimp and of a single copy in other mammal genomes, including rhesus monkey, suggests that the duplication of this gene occurred in the ape lineage (Hominoidea) after its divergence from the old-world monkeys (Cercopithecidae). Expression of CCT8L2 is confirmed by many ESTs mostly identified from the testis.

Similarity. Belongs to the TCP-1 chaperonin family.

RefSeq proteins (1): NP_055221* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002423	Cpn60/GroEL/TCP-1	Family
IPR017998	TCP-1	Family
IPR027409	GroEL-like_apical_dom_sf	Homologous_superfamily
IPR027410	TCP-1-like_intermed_sf	Homologous_superfamily
IPR027413	GROEL-like_equatorial_sf	Homologous_superfamily

Pfam: PF00118

UniProt features (4 total): region of interest 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96SF2-F1	84.62	0.62

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 70 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_PROTEIN_MATURATION, GOBP_PROTEIN_FOLDING, GOBP_TRANSMEMBRANE_TRANSPORT, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, GOMF_UNFOLDED_PROTEIN_BINDING, GOMF_CALCIUM_ACTIVATED_POTASSIUM_CHANNEL_ACTIVITY, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_GATED_CHANNEL_ACTIVITY, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_ANION_CHANNEL_ACTIVITY, GOMF_MONOATOMIC_ANION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_POTASSIUM_CHANNEL_ACTIVITY

GO Biological Process (3): protein folding (GO:0006457), potassium ion transmembrane transport (GO:0071805), monoatomic anion transmembrane transport (GO:0098656)

GO Molecular Function (6): monoatomic anion channel activity (GO:0005253), ATP binding (GO:0005524), calcium-activated potassium channel activity (GO:0015269), obsolete unfolded protein binding (GO:0051082), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166)

GO Cellular Component (2): chaperonin-containing T-complex (GO:0005832), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
protein maturation	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic anion transport	1
monoatomic ion transmembrane transport	1
monoatomic ion channel activity	1
monoatomic anion transmembrane transporter activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
calcium-activated cation channel activity	1
potassium channel activity	1
protein folding chaperone	1
ATP-dependent activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
cytosol	1
protein folding chaperone complex	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1307 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCT8L2	LRRC74B	Q6ZQY2	571
CCT8L2	RIMBP3C	A6NJZ7	526
CCT8L2	GAB4	Q2WGN9	517
CCT8L2	BBS10	Q8TAM1	480
CCT8L2	C11orf87	Q6NUJ2	479
CCT8L2	OR5W2	Q8NH69	479
CCT8L2	Q6GMV1	Q6GMV1	448
CCT8L2	POTEH	Q6S545	425
CCT8L2	XKR3	Q5GH77	396
CCT8L2	LRRIQ1	Q96JM4	395
CCT8L2	C14orf132	Q9NPU4	391
CCT8L2	CCT3	P49368	385
CCT8L2	PI4KA	P42356	379
CCT8L2	LZTR1	Q8N653	378
CCT8L2	SERPIND1	P05546	371
CCT8L2	TMEM150B	A6NC51	371

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CCT8L2	ACSL4	psi-mi:“MI:0914”(association)	0.530
	CCT8L2	psi-mi:“MI:0915”(physical association)	0.400
CCT8L2	DVL2	psi-mi:“MI:0914”(association)	0.350

BioGRID (156): SATB2 (Affinity Capture-MS), MPP2 (Affinity Capture-MS), PLEKHG4 (Affinity Capture-MS), SPEN (Affinity Capture-MS), ANKS1A (Affinity Capture-MS), CAMK2D (Affinity Capture-MS), FBXO7 (Affinity Capture-MS), MAPRE2 (Affinity Capture-MS), IKBKB (Affinity Capture-MS), SKP2 (Affinity Capture-MS), DVL2 (Affinity Capture-MS), PEX6 (Affinity Capture-MS), CHUK (Affinity Capture-MS), TXNIP (Affinity Capture-MS), CIZ1 (Affinity Capture-MS)

ESM2 similar proteins: A0A193KX02, A0A5F8AH41, A1Y9I9, A4FUH1, A6NM43, A7YY46, B6CZ46, B6CZ56, B6CZ62, D3ZBP4, D3ZX08, E9QAM5, H9TB19, O43542, P10937, P11086, P40935, P41226, P55205, P86243, Q14CH7, Q2M296, Q32Q92, Q3URQ7, Q3V1F8, Q3ZBE0, Q53S58, Q5E9L5, Q5JTZ9, Q5JU69, Q5M936, Q5SS80, Q5XIL6, Q69ZP3, Q6AYR4, Q6NZB1, Q6ZSI9, Q80YU0, Q8N490, Q8R1J9

Diamond homologs: A0QKR2, A5FPR4, A6NM43, A8EY36, A8YTH8, A9NHL6, B2V8F1, B7H4Q7, B7IUT0, O68324, P42932, P50990, P60545, Q048Y3, Q1G937, Q29068, Q3AUZ9, Q3Z6L3, Q3ZCI9, Q4MPR6, Q4R5J0, Q5RAP1, Q6EE31, Q814B0, Q8R5T7, Q93G07, Q96SF2, Q9KJ23, A0A0K0XCY8, A8X6I9, O15891, O24730, O24731, O24732, O24734, O24735, O26320, O26885, O28045, O28821

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	96
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
59275	GRCh38/hg38 22q11.1-11.21(chr22:11121452-18167952)x3	Pathogenic
980799	GRCh37/hg19 22q11.1(chr22:16888899-17536145)x4	Likely pathogenic

SpliceAI

17 predictions. Top by Δscore:

Variant	Effect	Δscore
22:16591973:T:TA	donor_gain	0.3800
22:16591845:A:C	donor_gain	0.3100
22:16591516:G:A	donor_gain	0.2900
22:16591732:T:TA	donor_gain	0.2900
22:16591843:TAAC:T	donor_gain	0.2500
22:16591844:AACA:A	donor_gain	0.2500
22:16591843:TA:T	donor_gain	0.2400
22:16591844:AA:A	donor_gain	0.2400
22:16592213:T:TA	donor_gain	0.2400
22:16592258:G:GA	donor_gain	0.2400
22:16591607:A:AC	donor_gain	0.2300
22:16591601:G:C	donor_gain	0.2100
22:16592277:C:A	donor_gain	0.2100
22:16591807:A:T	acceptor_gain	0.2000
22:16591873:C:A	donor_gain	0.2000
22:16592145:AGG:A	donor_gain	0.2000
22:16592555:C:CT	acceptor_gain	0.2000

AlphaMissense

3575 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:16591051:T:A	K500N	0.968
22:16591051:T:G	K500N	0.968
22:16591228:A:C	F441L	0.962
22:16591228:A:T	F441L	0.962
22:16591230:A:G	F441L	0.962
22:16591068:C:G	D495H	0.954
22:16591462:A:C	F363L	0.946
22:16591462:A:T	F363L	0.946
22:16591464:A:G	F363L	0.946
22:16591987:G:C	C188W	0.945
22:16591463:A:G	F363S	0.941
22:16591512:A:G	C347R	0.941
22:16592196:C:G	A119P	0.941
22:16591052:T:A	K500I	0.940
22:16591502:A:T	V350D	0.940
22:16591067:T:A	D495V	0.938
22:16591010:A:G	L514P	0.936
22:16591670:A:T	V294E	0.936
22:16591067:T:G	D495A	0.935
22:16591807:A:C	F248L	0.933
22:16591807:A:T	F248L	0.933
22:16591809:A:G	F248L	0.933
22:16591741:A:C	F270L	0.932
22:16591741:A:T	F270L	0.932
22:16591743:A:G	F270L	0.932
22:16591957:G:C	F198L	0.932
22:16591957:G:T	F198L	0.932
22:16591959:A:G	F198L	0.932
22:16591185:C:G	A456P	0.931
22:16591430:G:A	T374I	0.931

dbSNP variants (sampled 300 via entrez): RS1000946370 (22:16593021 G>A), RS1002942513 (22:16590686 G>A), RS1003147181 (22:16590534 T>C), RS1003382916 (22:16594437 A>G), RS1005009023 (22:16593110 C>G), RS1005464556 (22:16593280 G>A), RS1008854177 (22:16593626 T>A), RS1008906636 (22:16593960 G>A,C,T), RS1011205870 (22:16590296 C>A,T), RS1011716895 (22:16590489 G>A), RS1012158297 (22:16594186 G>A,T), RS1013814502 (22:16593088 C>T), RS1014685973 (22:16594224 A>C), RS1015150585 (22:16594440 T>G), RS1016674568 (22:16591994 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002112_8	Celiac disease	5.000000e-06
GCST008758_86	Pre-treatment viral load in HIV-1 infection	4.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010125	viral load

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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