TTC22

Summary

TTC22 (tetratricopeptide repeat domain 22, HGNC:26067) is a protein-coding gene on chromosome 1p32.3, encoding Tetratricopeptide repeat protein 22 (Q5TAA0).

This gene encodes a protein with seven tetratricopeptide (TPR) repeats. Tetratricopeptide repeat containing motifs are found in a variety of proteins and may mediate protein-protein interactions and chaperone activity. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 55001 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 69 total
• MANE Select transcript: NM_001114108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26067
Approved symbol	TTC22
Name	tetratricopeptide repeat domain 22
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20619
Ensembl gene	ENSG00000006555
Ensembl biotype	protein_coding
Entrez	55001

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

ENST00000371274, ENST00000371276, ENST00000448308, ENST00000474654, ENST00000488771, ENST00000903394, ENST00000903395, ENST00000903396

RefSeq mRNA: 2 — MANE Select: NM_001114108 NM_001114108, NM_017904

CCDS: CCDS44152, CCDS598

Canonical transcript exons

ENST00000371276 — 7 exons

Exon	Start	End
ENSE00000772857	54786957	54787075
ENSE00000772859	54787711	54787826
ENSE00000772863	54788042	54788097
ENSE00001139717	54785983	54786144
ENSE00001454830	54800597	54801323
ENSE00001454832	54779712	54781779
ENSE00003512762	54782325	54782477

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 98.97.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0885 / max 45.8689, expressed in 286 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12477	0.8092	272
12476	0.1647	91
12474	0.0911	39
12475	0.0235	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	98.97	gold quality
gingival epithelium	UBERON:0001949	98.04	gold quality
gingiva	UBERON:0001828	97.48	gold quality
lower esophagus mucosa	UBERON:0035834	97.31	gold quality
oral cavity	UBERON:0000167	95.71	gold quality
pharyngeal mucosa	UBERON:0000355	95.68	gold quality
esophagus mucosa	UBERON:0002469	95.53	gold quality
palpebral conjunctiva	UBERON:0001812	93.77	gold quality
jejunal mucosa	UBERON:0000399	93.04	gold quality
epithelium of esophagus	UBERON:0001976	92.69	gold quality
colonic mucosa	UBERON:0000317	92.30	gold quality
buccal mucosa cell	CL:0002336	90.93	gold quality
upper leg skin	UBERON:0004262	90.92	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.81	gold quality
parotid gland	UBERON:0001831	90.21	gold quality
mammalian vulva	UBERON:0000997	89.29	gold quality
squamous epithelium	UBERON:0006914	88.68	gold quality
mucosa of transverse colon	UBERON:0004991	88.38	gold quality
vagina	UBERON:0000996	87.19	gold quality
bronchial epithelial cell	CL:0002328	86.42	gold quality
epithelium of nasopharynx	UBERON:0001951	86.32	gold quality
penis	UBERON:0000989	86.25	gold quality
skin of hip	UBERON:0001554	85.83	gold quality
skin of abdomen	UBERON:0001416	85.63	gold quality
skin of leg	UBERON:0001511	85.08	gold quality
zone of skin	UBERON:0000014	84.11	gold quality
amniotic fluid	UBERON:0000173	84.01	gold quality
body of tongue	UBERON:0011876	82.90	gold quality
duodenum	UBERON:0002114	82.88	gold quality
mouth mucosa	UBERON:0003729	82.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting TTC22, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-4752	98.71	68.04	833
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-376B-5P	98.46	66.40	606
HSA-MIR-376C-5P	98.46	66.64	589

Literature-anchored findings (GeneRIF, showing 2)

• Study results suggest that TTC22 variant 1 (TTC22V1) mRNA is a crucial miR663a target that directly promotes colon cancer cell migration/invasion. High TTC22V1 expression is a significant poor survival factor for patients with colon cancer. (PMID:30664167)
• Revealing PACMA 31 as a new chemical type TrxR inhibitor to promote cancer cell apoptosis. (PMID:35793738)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttc22	ENSDARG00000077836
mus_musculus	Ttc22	ENSMUSG00000034919
rattus_norvegicus	Ttc22	ENSRNOG00000007189

Protein

Protein identifiers

Tetratricopeptide repeat protein 22 — Q5TAA0 (reviewed: Q5TAA0)

All UniProt accessions (2): Q5TAA0, H0Y486

Isoforms (2)

UniProt ID	Names	Canonical?
Q5TAA0-1	1	yes
Q5TAA0-2	2

RefSeq proteins (2): NP_001107580, NP_060374 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR042342	TTC22	Family

Pfam: PF13181

UniProt features (13 total): repeat 7, sequence conflict 2, splice variant 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TAA0-F1	89.79	0.75

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): MORF_MT4, MODULE_95, MORF_CDC2L5, YAGI_AML_SURVIVAL, MODULE_7, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3_UNMETHYLATED, WAMUNYOKOLI_OVARIAN_CANCER_LMP_UP, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, MODULE_41, E47_02, MODULE_163, KRAS.600.LUNG.BREAST_UP.V1_UP, KRAS.LUNG_UP.V1_UP

GO Biological Process (0):

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
binding	1

Protein interactions and networks

STRING

332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTC22	KRTCAP3	Q53RY4	572
TTC22	ZNF490	Q9ULM2	475
TTC22	FAM228B	P0C875	450
TTC22	SPATS2L	Q9NUQ6	439
TTC22	KCTD18	Q6PI47	427
TTC22	TAL1	P17542	407
TTC22	PPP1R42	Q7Z4L9	396
TTC22	FRAT2	O75474	387
TTC22	TTC23	Q5W5X9	379
TTC22	C2CD2	Q9Y426	375
TTC22	MINDY4	Q4G0A6	368
TTC22	IER2	Q9BTL4	362
TTC22	RHBDL3	P58872	357
TTC22	FHOD3	Q2V2M9	349
TTC22	PLPPR2	Q96GM1	349

IntAct

0 interactions, top by confidence:

BioGRID (1): TTC22 (Affinity Capture-MS)

ESM2 similar proteins: A2BID5, A8MYJ7, D4A615, D4A6D7, O00562, O35095, O35954, O43299, O75153, O75800, O76024, O88480, O95248, O95996, P0CI65, P60330, Q0P5G1, Q14674, Q16JL4, Q2KHY7, Q2KJ97, Q3TYL0, Q3U829, Q5TAA0, Q5U2N3, Q5W5X9, Q69ZR2, Q6AXZ5, Q6DKK2, Q6NZL6, Q6ZNJ1, Q6ZPE2, Q6ZQA0, Q80TC6, Q8C159, Q8C7B8, Q8IYW2, Q8N8M0, Q8WZ19, Q96HA7

Diamond homologs: Q5TAA0, Q8C159

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1069 predictions. Top by Δscore:

Variant	Effect	Δscore
1:54786140:ATGGC:A	acceptor_gain	1.0000
1:54786141:TGGC:T	acceptor_gain	1.0000
1:54786142:GGC:G	acceptor_gain	1.0000
1:54786143:GC:G	acceptor_gain	1.0000
1:54786144:CC:C	acceptor_gain	1.0000
1:54786144:CCT:C	acceptor_loss	1.0000
1:54786145:C:CA	acceptor_loss	1.0000
1:54786145:C:CC	acceptor_gain	1.0000
1:54786149:G:GC	acceptor_gain	1.0000
1:54787822:CTAGC:C	acceptor_gain	1.0000
1:54787823:TAGC:T	acceptor_gain	1.0000
1:54787827:C:CC	acceptor_gain	1.0000
1:54787827:CTGTG:C	acceptor_loss	1.0000
1:54787834:C:CT	acceptor_gain	1.0000
1:54787835:G:T	acceptor_gain	1.0000
1:54800593:CTAC:C	donor_loss	1.0000
1:54800594:TAC:T	donor_loss	1.0000
1:54800595:A:AC	donor_gain	1.0000
1:54800595:ACC:A	donor_loss	1.0000
1:54800596:C:CC	donor_gain	1.0000
1:54800596:CCTG:C	donor_gain	1.0000
1:54785978:CCCA:C	donor_loss	0.9900
1:54785979:CCA:C	donor_loss	0.9900
1:54785980:CA:C	donor_loss	0.9900
1:54785982:CCTT:C	donor_loss	0.9900
1:54785983:C:G	donor_loss	0.9900
1:54786149:G:C	acceptor_gain	0.9900
1:54786160:G:GC	acceptor_gain	0.9900
1:54786953:GTAC:G	donor_loss	0.9900
1:54786954:TAC:T	donor_loss	0.9900

AlphaMissense

3667 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:54788073:A:G	W198R	0.989
1:54788073:A:T	W198R	0.989
1:54800849:A:C	N105K	0.984
1:54800849:A:T	N105K	0.984
1:54800861:A:C	N101K	0.981
1:54800861:A:T	N101K	0.981
1:54782392:G:T	A369D	0.980
1:54800704:C:G	G154R	0.978
1:54781637:C:T	G439D	0.977
1:54781638:C:G	G439R	0.977
1:54781710:C:G	A415P	0.977
1:54787026:G:C	F263L	0.977
1:54787026:G:T	F263L	0.977
1:54787028:A:G	F263L	0.977
1:54801068:G:C	N32K	0.977
1:54801068:G:T	N32K	0.977
1:54781632:A:G	C441R	0.975
1:54786144:C:G	A287P	0.975
1:54781764:C:G	G397R	0.973
1:54785988:C:G	A339P	0.973
1:54786010:G:C	N331K	0.972
1:54786010:G:T	N331K	0.972
1:54782380:A:G	L373P	0.971
1:54800703:C:T	G154D	0.970
1:54781637:C:A	G439V	0.969
1:54788058:C:G	A203P	0.967
1:54800867:G:C	N99K	0.965
1:54800867:G:T	N99K	0.965
1:54782462:A:C	Y346D	0.964
1:54785987:G:T	A339D	0.964

dbSNP variants (sampled 300 via entrez): RS1000136912 (1:54793083 C>A,T), RS1000479348 (1:54792660 C>T), RS1000569645 (1:54791474 C>T), RS1000625026 (1:54781829 G>A), RS1000800898 (1:54800418 G>A), RS1000830357 (1:54779444 G>T), RS1000997260 (1:54782069 T>A), RS1001033430 (1:54797572 C>T), RS1001039235 (1:54785613 A>G), RS1001072653 (1:54794390 A>G), RS1001402410 (1:54794702 C>T), RS1001482811 (1:54785894 C>A,G), RS1001640549 (1:54796392 T>G), RS1001765576 (1:54801707 G>C), RS1002026078 (1:54783033 G>C,T)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	decreases expression, increases methylation	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arbutin	decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Zinc	increases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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