TCAIM

Summary

TCAIM (T cell activation inhibitor, mitochondrial, HGNC:25241) is a protein-coding gene on chromosome 3p21.31, encoding T-cell activation inhibitor, mitochondrial (Q8N3R3). May regulate T-cell apoptosis.

Located in mitochondrion.

Source: NCBI Gene 285343 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_173826

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25241
Approved symbol	TCAIM
Name	T cell activation inhibitor, mitochondrial
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp313N0621, TOAG-1
Ensembl gene	ENSG00000179152
Ensembl biotype	protein_coding
OMIM	620787
Entrez	285343

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000342649, ENST00000383746, ENST00000396078, ENST00000412611, ENST00000417237, ENST00000417768, ENST00000431657, ENST00000444602, ENST00000462230, ENST00000462612, ENST00000469246, ENST00000494638, ENST00000876546, ENST00000876547, ENST00000876548, ENST00000876549, ENST00000876550, ENST00000876551

RefSeq mRNA: 6 — MANE Select: NM_173826 NM_001029839, NM_001029840, NM_001282913, NM_001282914, NM_001282915, NM_173826

CCDS: CCDS2712, CCDS43076

Canonical transcript exons

ENST00000342649 — 11 exons

Exon	Start	End
ENSE00001218452	44367456	44367708
ENSE00003461802	44407442	44409448
ENSE00003478752	44354739	44354811
ENSE00003516320	44401203	44401334
ENSE00003605374	44357741	44357876
ENSE00003621927	44400355	44400587
ENSE00003624005	44396400	44396497
ENSE00003667585	44361365	44361518
ENSE00003677167	44396743	44396834
ENSE00003691393	44392855	44392977
ENSE00003849468	44338766	44338834

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 91.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.2767 / max 107.6608, expressed in 1809 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36320	8.1577	1746
36323	8.0377	1730
36324	3.1431	1393
36321	0.7957	525
36322	0.1425	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	91.19	gold quality
liver	UBERON:0002107	90.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.30	gold quality
adrenal tissue	UBERON:0018303	89.05	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.67	gold quality
islet of Langerhans	UBERON:0000006	88.48	gold quality
ventricular zone	UBERON:0003053	88.36	gold quality
muscle of leg	UBERON:0001383	88.29	gold quality
gastrocnemius	UBERON:0001388	87.79	gold quality
ganglionic eminence	UBERON:0004023	87.79	gold quality
spinal cord	UBERON:0002240	87.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.40	gold quality
deltoid	UBERON:0001476	87.38	gold quality
secondary oocyte	CL:0000655	87.14	gold quality
tibialis anterior	UBERON:0001385	87.10	gold quality
esophagus squamous epithelium	UBERON:0006920	86.92	gold quality
metanephros cortex	UBERON:0010533	86.88	gold quality
smooth muscle tissue	UBERON:0001135	86.87	gold quality
calcaneal tendon	UBERON:0003701	86.86	gold quality
monocyte	CL:0000576	86.72	gold quality
oocyte	CL:0000023	86.71	gold quality
amniotic fluid	UBERON:0000173	86.49	gold quality
leukocyte	CL:0000738	86.46	gold quality
adult mammalian kidney	UBERON:0000082	86.33	gold quality
cortex of kidney	UBERON:0001225	86.28	gold quality
skeletal muscle tissue	UBERON:0001134	86.20	gold quality
biceps brachii	UBERON:0001507	86.08	gold quality
gall bladder	UBERON:0002110	85.85	gold quality
rectum	UBERON:0001052	85.76	gold quality
colonic epithelium	UBERON:0000397	85.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.79
E-MTAB-4850	no	93.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting TCAIM, 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-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
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-4775	99.98	75.00	6394
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-195-5P	99.90	72.81	2805

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcaim	ENSDARG00000079881
mus_musculus	Tcaim	ENSMUSG00000046603
rattus_norvegicus	Tcaim	ENSRNOG00000004085
drosophila_melanogaster	CG13295	FBGN0035674
drosophila_melanogaster	CG2854	FBGN0040391
caenorhabditis_elegans		WBGENE00016438

Protein

Protein identifiers

T-cell activation inhibitor, mitochondrial — Q8N3R3 (reviewed: Q8N3R3)

Alternative names: Tolerance associated gene-1 protein

All UniProt accessions (2): Q8N3R3, A0A0U1RQT4

UniProt curated annotations — full annotation on UniProt →

Function. May regulate T-cell apoptosis.

Subcellular location. Mitochondrion.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8N3R3-1	1	yes
Q8N3R3-2	2
Q8N3R3-3	3
Q8N3R3-4	4

RefSeq proteins (6): NP_001025010, NP_001025011, NP_001269842, NP_001269843, NP_001269844, NP_776187* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027986	TCAIM	Family
IPR027989	DUF4461	Domain
IPR028031	DUF4460	Domain

Pfam: PF14687, PF14688

UniProt features (29 total): helix 9, strand 9, splice variant 5, sequence conflict 2, chain 1, coiled-coil region 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8I0K	ELECTRON MICROSCOPY	2.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3R3-F1	79.77	0.47

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, HNF4_DR1_Q3, YAUCH_HEDGEHOG_SIGNALING_PARACRINE_UP, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, CHEMNITZ_RESPONSE_TO_PROSTAGLANDIN_E2_DN, CSR_EARLY_UP.V1_DN, BREDEMEYER_RAG_SIGNALING_VIA_ATM_NOT_VIA_NFKB_UP, chr3p21, CIITA_TARGET_GENES, F10_TARGET_GENES, HOXA7_TARGET_GENES, HOXB6_TARGET_GENES, ID2_TARGET_GENES, NFE2L1_TARGET_GENES, NFKBIA_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCAIM	PTH2	Q96A98	510
TCAIM	SMIM12	Q96EX1	459
TCAIM	CLEC2L	P0C7M8	438
TCAIM	BEND7	Q8N7W2	438
TCAIM	ITGA8	P53708	412
TCAIM	ZC3H8	Q8N5P1	409
TCAIM	LRRC40	Q9H9A6	407
TCAIM	SHISA4	Q96DD7	406
TCAIM	BTBD8	Q5XKL5	404
TCAIM	PAMR1	Q6UXH9	403
TCAIM	FAM177A1	Q8N128	402
TCAIM	MNMIP1	A4FU49	398
TCAIM	KRT36	O76013	386
TCAIM	MAN1A1	P33908	382
TCAIM	TIMM21	Q9BVV7	381

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TCAIM	KGD4	psi-mi:“MI:0914”(association)	0.350
TCAIM	cutA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): TCAIM (Proximity Label-MS), MRPS36 (Affinity Capture-MS), OGDHL (Affinity Capture-MS), OGDH (Affinity Capture-MS), TCAIM (Affinity Capture-MS), TCAIM (Affinity Capture-MS)

ESM2 similar proteins: A1A4J7, A2BID5, A2RRP1, A2RV06, B5DF07, E7FAW3, O00750, O15091, O35821, O70167, O70173, O75153, O75800, O76024, O88480, P0DKR2, P82650, Q08CY4, Q1LXZ7, Q28HN9, Q4R366, Q4R7V1, Q58CX2, Q5SW19, Q5TYW4, Q5U249, Q5XGL1, Q66JZ4, Q6AXZ5, Q6DRB1, Q6GPP1, Q7L8L6, Q7TPV4, Q811I0, Q86VS3, Q8BIR2, Q8C7B8, Q8CJF7, Q8IYW2, Q8JZY4

Diamond homologs: P0DKR2, Q66JZ4, Q8N3R3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1792 predictions. Top by Δscore:

Variant	Effect	Δscore
3:44358299:T:G	donor_gain	1.0000
3:44361364:GGAA:G	acceptor_gain	1.0000
3:44361519:G:GA	donor_loss	1.0000
3:44361519:G:GG	donor_gain	1.0000
3:44361520:TACG:T	donor_loss	1.0000
3:44367530:A:AG	acceptor_gain	1.0000
3:44367531:G:GG	acceptor_gain	1.0000
3:44367707:ACG:A	donor_loss	1.0000
3:44367709:G:T	donor_loss	1.0000
3:44367709:GTAT:G	donor_gain	1.0000
3:44367710:T:G	donor_loss	1.0000
3:44392850:TCTA:T	acceptor_loss	1.0000
3:44392852:TA:T	acceptor_loss	1.0000
3:44392853:A:AG	acceptor_gain	1.0000
3:44392853:AG:A	acceptor_loss	1.0000
3:44392854:G:GG	acceptor_gain	1.0000
3:44392854:GA:G	acceptor_gain	1.0000
3:44392854:GAT:G	acceptor_gain	1.0000
3:44392854:GATC:G	acceptor_gain	1.0000
3:44392976:AGG:A	donor_loss	1.0000
3:44392977:GGTAA:G	donor_loss	1.0000
3:44392978:G:GA	donor_loss	1.0000
3:44392979:T:A	donor_loss	1.0000
3:44396493:AAAAG:A	donor_loss	1.0000
3:44396494:AAAGG:A	donor_loss	1.0000
3:44396495:AAG:A	donor_loss	1.0000
3:44396496:AGG:A	donor_loss	1.0000
3:44396497:GG:G	donor_loss	1.0000
3:44396498:G:A	donor_loss	1.0000
3:44396499:T:A	donor_loss	1.0000

AlphaMissense

3311 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:44396401:T:A	W233R	0.997
3:44396401:T:C	W233R	0.997
3:44396826:T:A	W293R	0.997
3:44396826:T:C	W293R	0.997
3:44357841:C:G	H44D	0.995
3:44361458:T:C	F87L	0.995
3:44361459:T:C	F87S	0.995
3:44361460:T:A	F87L	0.995
3:44361460:T:G	F87L	0.995
3:44396446:A:C	S248R	0.995
3:44396448:T:A	S248R	0.995
3:44396448:T:G	S248R	0.995
3:44357853:T:C	F48L	0.994
3:44357855:T:A	F48L	0.994
3:44357855:T:G	F48L	0.994
3:44361380:T:C	S61P	0.994
3:44361384:T:C	L62P	0.994
3:44361393:T:C	L65S	0.994
3:44396441:T:C	L246P	0.994
3:44357827:T:C	F39S	0.993
3:44357839:T:A	V43E	0.993
3:44361373:T:A	N58K	0.993
3:44361373:T:G	N58K	0.993
3:44357818:T:C	L36S	0.992
3:44357843:T:A	H44Q	0.992
3:44357843:T:G	H44Q	0.992
3:44396828:G:C	W293C	0.991
3:44396828:G:T	W293C	0.991
3:44396413:T:A	W237R	0.990
3:44396413:T:C	W237R	0.990

dbSNP variants (sampled 300 via entrez): RS1000085646 (3:44356921 C>A), RS1000102677 (3:44351077 A>G), RS1000137924 (3:44356648 C>G), RS1000140133 (3:44377915 A>C), RS1000170770 (3:44356298 G>A), RS1000172725 (3:44338923 T>G), RS1000220857 (3:44338782 T>C,G), RS1000254671 (3:44401948 G>C), RS1000280920 (3:44378208 C>A), RS1000364825 (3:44409367 A>G), RS1000366325 (3:44364049 C>T), RS1000422052 (3:44371388 T>C), RS1000438523 (3:44409832 C>T), RS1000471343 (3:44340471 T>C,G), RS1000496480 (3:44388200 T>C,G)

Disease associations

OMIM: gene MIM:620787 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005839_8	Depression	5.000000e-08
GCST009600_32	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	4.000000e-08
GCST011494_83	Daytime nap	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	5
Acetaminophen	decreases expression	3
bisphenol A	increases expression	2
sodium arsenite	decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression, decreases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
trichostatin A	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression	1
pentanal	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
belinostat	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
(+)-JQ1 compound	increases expression	1
Zoledronic Acid	increases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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