TLCD3A

Summary

TLCD3A (TLC domain containing 3A, HGNC:29646) is a protein-coding gene on chromosome 17p13.3, encoding TLC domain-containing protein 3A (Q8TBR7).

The protein encoded by this gene is a membrane-associated protein that promotes lung carcinogenesis. The encoded protein may be involved in amino acid transport and glutathione metabolism since it can interact with a solute carrier family member (SLC3A2) and an isoform of gamma-glutamyltranspeptidase-like 3. An alternatively spliced variant encoding a protein that lacks a 32 aa internal segment showed the opposite effect, inhibiting lung cancer cell growth. Knockdown of this gene also inhibited lung carcinogenesis and tumor cell growth. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79850 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 61 total — 1 likely-pathogenic
• MANE Select transcript: NM_024792

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29646
Approved symbol	TLCD3A
Name	TLC domain containing 3A
Location	17p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22282, CT120
Ensembl gene	ENSG00000167695
Ensembl biotype	protein_coding
OMIM	611627
Entrez	79850

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000301324, ENST00000308278, ENST00000570699, ENST00000570892, ENST00000572018, ENST00000574327, ENST00000577008

RefSeq mRNA: 4 — MANE Select: NM_024792 NM_001318006, NM_001318007, NM_001318008, NM_024792

CCDS: CCDS10996, CCDS82031, CCDS82032

Canonical transcript exons

ENST00000308278 — 5 exons

Exon	Start	End
ENSE00001115745	733098	733181
ENSE00002640002	732596	732769
ENSE00002680345	741301	742968
ENSE00003573634	740505	740600
ENSE00003592809	737846	738047

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 95.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.0518 / max 126.8866, expressed in 1674 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158684	9.1796	1578
158683	3.7161	1473
158686	0.5291	343
158685	0.4087	213
158687	0.2183	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	95.26	gold quality
skin of leg	UBERON:0001511	94.25	gold quality
zone of skin	UBERON:0000014	93.94	gold quality
upper leg skin	UBERON:0004262	93.94	gold quality
tongue squamous epithelium	UBERON:0006919	93.04	silver quality
skin of hip	UBERON:0001554	91.47	gold quality
gingival epithelium	UBERON:0001949	91.03	gold quality
stromal cell of endometrium	CL:0002255	90.60	gold quality
gingiva	UBERON:0001828	90.03	gold quality
hair follicle	UBERON:0002073	89.14	silver quality
esophagus mucosa	UBERON:0002469	88.70	gold quality
ventricular zone	UBERON:0003053	88.50	gold quality
squamous epithelium	UBERON:0006914	87.43	gold quality
lower esophagus mucosa	UBERON:0035834	87.13	gold quality
esophagus squamous epithelium	UBERON:0006920	86.82	gold quality
epithelium of esophagus	UBERON:0001976	86.78	gold quality
cartilage tissue	UBERON:0002418	86.19	gold quality
islet of Langerhans	UBERON:0000006	86.06	gold quality
ganglionic eminence	UBERON:0004023	85.24	gold quality
body of stomach	UBERON:0001161	84.50	gold quality
vagina	UBERON:0000996	84.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.25	gold quality
gall bladder	UBERON:0002110	83.55	gold quality
esophagus	UBERON:0001043	83.12	gold quality
pancreatic ductal cell	CL:0002079	83.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.92	gold quality
stomach	UBERON:0000945	82.89	gold quality
cortical plate	UBERON:0005343	82.86	gold quality
mammalian vulva	UBERON:0000997	82.64	gold quality
mouth mucosa	UBERON:0003729	82.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.04
E-MTAB-7303	no	108.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZIC1

miRNA regulators (miRDB)

62 targeting TLCD3A, 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-513B-5P	99.99	69.96	2150
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-1827	99.63	68.57	3265

Literature-anchored findings (GeneRIF, showing 4)

• Molecular cloning and characterization of this novel membrane-associated gene involved in amino acid transport and glutathione metabolism (PMID:12270127)
• CT120B overexpression resulted in reduction of cell growth rate & inhibited tumorigenecity & anchorage-independent growth; findings suggest that the delayed G1/S phase transition might contribute to the inhibitory activities of CT120B on cell growth (PMID:16143812)
• The researchers found evidence that CT120 may be a key factor in tumor progression and that down-regulation of CT120 may be an effective treatment for lung neoplasms. (PMID:20024628)
• FAM57A (Family with Sequence Similarity 57 Member A) Is a Cell-Density-Regulated Protein and Promotes the Proliferation and Migration of Cervical Cancer Cells. (PMID:36291175)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tlcd3a	ENSDARG00000098860
mus_musculus	Tlcd3a	ENSMUSG00000069808
rattus_norvegicus	Tlcd3a	ENSRNOG00000007722
drosophila_melanogaster	CG17841	FBGN0028480

Paralogs (5): TLCD3B (ENSG00000149926), TLCD4 (ENSG00000152078), TLCD1 (ENSG00000160606), CLN8 (ENSG00000182372), TLCD2 (ENSG00000185561)

Protein

Protein identifiers

TLC domain-containing protein 3A — Q8TBR7 (reviewed: Q8TBR7)

Alternative names: Protein CT120, Protein FAM57A

All UniProt accessions (5): Q8TBR7, I3L0N4, I3L183, I3L336, I3L374

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with GGT7 isoform 3 and SLC3A2.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in pancreas. Detected at intermediate levels in heart, placenta and kidney, and at low levels in brain, liver and skeletal muscle. Not detected in normal lung.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TBR7-2	2, CT120A	yes
Q8TBR7-1	1, CT120B

RefSeq proteins (4): NP_001304935, NP_001304936, NP_001304937, NP_079068* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006634	TLC-dom	Domain
IPR050846	TLCD	Family

Pfam: PF03798

UniProt features (12 total): transmembrane region 7, sequence conflict 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBR7-F1	92.98	0.86

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 104 (showing top): HUMMERICH_BENIGN_SKIN_TUMOR_UP, GOBP_LIPID_HOMEOSTASIS, GTGCCTT_MIR506, BILD_E2F3_ONCOGENIC_SIGNATURE, DOUGLAS_BMI1_TARGETS_UP, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, NUYTTEN_NIPP1_TARGETS_DN, CASORELLI_ACUTE_PROMYELOCYTIC_LEUKEMIA_DN, GCACTTT_MIR175P_MIR20A_MIR106A_MIR106B_MIR20B_MIR519D, KARLSSON_TGFB1_TARGETS_DN, IVANOVSKA_MIR106B_TARGETS, KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3, KRIEG_HYPOXIA_NOT_VIA_KDM3A, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY

GO Biological Process (1): lipid homeostasis (GO:0055088)

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

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chemical homeostasis	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

749 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TLCD3A	GGT7	Q9UJ14	927
TLCD3A	SLC3A2	P08195	796
TLCD3A	VPS53	Q5VIR6	596
TLCD3A	GEMIN4	P57678	574
TLCD3A	MFSD12	Q6NUT3	493
TLCD3A	GGT1	P19440	468
TLCD3A	HOXB13	Q92826	463
TLCD3A	CTBP2	P56545	431
TLCD3A	ATP2B4	P23634	417
TLCD3A	STPG4	Q8N801	417
TLCD3A	RFX6	Q8HWS3	410
TLCD3A	TEX9	Q8N6V9	408
TLCD3A	PDLIM1	O00151	399
TLCD3A	SPEM2	Q0P670	398
TLCD3A	MREG	Q8N565	378

IntAct

16 interactions, top by confidence:

A	B	Type	Score
TUBA1C	TXNDC9	psi-mi:“MI:0914”(association)	0.730
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
PBXIP1	KCNN4	psi-mi:“MI:0914”(association)	0.530
GALNS	CLGN	psi-mi:“MI:0914”(association)	0.530
SGCA	TMEM131L	psi-mi:“MI:0914”(association)	0.350
TOR3A	CLGN	psi-mi:“MI:0914”(association)	0.350
TLCD3A	ADCY3	psi-mi:“MI:0914”(association)	0.350
ACTL6B	SLC25A16	psi-mi:“MI:0914”(association)	0.350
CLEC2D	ATP9A	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
PCDHGB4	AAMP	psi-mi:“MI:0914”(association)	0.350
SETD6	GFPT2	psi-mi:“MI:0914”(association)	0.350
TMED5	DGAT1	psi-mi:“MI:0914”(association)	0.350
TMEM95	NEMP1	psi-mi:“MI:0914”(association)	0.350
MAPK4	PSMA7	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): FAM57A (Affinity Capture-MS), FAM57A (Affinity Capture-MS), FAM57A (Affinity Capture-MS), SLC3A2 (Affinity Capture-Western), SLC3A2 (Two-hybrid), FAM57A (Affinity Capture-MS), SPECC1L (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), FAM57A (Affinity Capture-MS), SMPD4 (Affinity Capture-MS), RETSAT (Affinity Capture-MS), SYVN1 (Affinity Capture-MS), OXSR1 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), TYW1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4P6, A1A5B4, A5PK40, A6NDV4, A6NFX1, A6NGC4, A6QL84, A6QLK4, B1AWJ5, B6ID01, E1BY51, P58749, Q2TA01, Q2YDG0, Q32PG7, Q3T9M1, Q4R7X9, Q5HZE5, Q5JZQ7, Q5R6H1, Q5RBY7, Q60HE8, Q6AY05, Q6AYM9, Q6PHN7, Q6TCG5, Q6UX01, Q6UXD7, Q7RTT9, Q7Z403, Q80ZE4, Q8CE47, Q8R139, Q8TBR7, Q96FZ5, Q96HE8, Q96S97, Q9BSA9, Q9BZW5, Q9CQC4

Diamond homologs: Q5ND56, Q71RH2, Q7TNV1, Q8TBR7, Q6AYM9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	45
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
984984	GRCh37/hg19 17p13.3(chr17:1-1026797)x1	Likely pathogenic

SpliceAI

640 predictions. Top by Δscore:

Variant	Effect	Δscore
17:733179:CAGGT:C	donor_loss	1.0000
17:733180:AGGT:A	donor_loss	1.0000
17:733182:G:GC	donor_loss	1.0000
17:733183:T:G	donor_loss	1.0000
17:740488:C:CA	acceptor_gain	1.0000
17:740493:C:CA	acceptor_gain	1.0000
17:740504:GA:G	acceptor_gain	1.0000
17:741294:A:AG	acceptor_gain	1.0000
17:741298:CA:C	acceptor_loss	1.0000
17:741299:A:AG	acceptor_gain	1.0000
17:741299:AGC:A	acceptor_loss	1.0000
17:741300:G:GA	acceptor_gain	1.0000
17:741300:GCT:G	acceptor_gain	1.0000
17:741300:GCTA:G	acceptor_gain	1.0000
17:732765:ACCAG:A	donor_loss	0.9900
17:732766:CCAGG:C	donor_loss	0.9900
17:732767:CAG:C	donor_loss	0.9900
17:732768:AG:A	donor_loss	0.9900
17:732769:GG:G	donor_loss	0.9900
17:732770:G:C	donor_loss	0.9900
17:732771:T:G	donor_loss	0.9900
17:733096:AGGCT:A	acceptor_gain	0.9900
17:733097:GGCT:G	acceptor_gain	0.9900
17:733097:GGCTG:G	acceptor_gain	0.9900
17:733177:GGCAG:G	donor_gain	0.9900
17:733178:GCAG:G	donor_gain	0.9900
17:733178:GCAGG:G	donor_gain	0.9900
17:733179:C:T	donor_gain	0.9900
17:733182:G:GG	donor_gain	0.9900
17:737840:TTTCA:T	acceptor_loss	0.9900

AlphaMissense

1659 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:740562:A:C	S156R	0.998
17:740564:C:A	S156R	0.998
17:740564:C:G	S156R	0.998
17:741358:T:C	F188L	0.997
17:741360:C:A	F188L	0.997
17:741360:C:G	F188L	0.997
17:737899:A:T	D87V	0.996
17:737899:A:C	D87A	0.995
17:740538:G:C	G148R	0.993
17:741336:T:A	N180K	0.993
17:741336:T:G	N180K	0.993
17:738006:C:G	H123D	0.992
17:740539:G:A	G148D	0.992
17:740557:A:T	E154V	0.992
17:733139:G:A	G55E	0.991
17:732762:A:C	S39R	0.990
17:732764:C:A	S39R	0.990
17:732764:C:G	S39R	0.990
17:733138:G:T	G55W	0.990
17:737898:G:C	D87H	0.990
17:737899:A:G	D87G	0.990
17:741359:T:C	F188S	0.990
17:737900:C:A	D87E	0.989
17:737900:C:G	D87E	0.989
17:740527:A:T	D144V	0.989
17:740541:T:C	C149R	0.989
17:733127:C:A	A51D	0.988
17:740529:T:C	F145L	0.988
17:740531:C:A	F145L	0.988
17:740531:C:G	F145L	0.988

dbSNP variants (sampled 300 via entrez): RS1000483739 (17:741112 G>A,T), RS1000551116 (17:731339 G>A,C), RS1000767316 (17:740247 C>T), RS1000828676 (17:740180 C>T), RS1000879661 (17:739915 G>A), RS1001108643 (17:734630 G>A), RS1001177721 (17:736812 T>A,C,G), RS1001379972 (17:743091 G>A), RS1001458358 (17:734918 G>A), RS1001498675 (17:737366 G>C), RS1001724835 (17:731623 T>G), RS1001782904 (17:731706 G>A,C), RS1001831038 (17:742776 A>C), RS1001835610 (17:738849 G>A), RS1002061117 (17:733669 G>A,C)

Disease associations

OMIM: gene MIM:611627 | disease phenotypes: MIM:617667, MIM:618529

GenCC curated gene-disease

Mondo (2): Fraser syndrome 3 (MONDO:0054739), robinow syndrome, autosomal recessive 2 (MONDO:0032800)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001942_3	Prostate cancer	5.000000e-15
GCST011517_7	joint destruction in rheumatoid arthritis (rapid vs slow)	3.000000e-06
GCST011517_8	joint destruction in rheumatoid arthritis (rapid vs slow)	3.000000e-06
GCST90020026_70	Hip index	9.000000e-14
GCST90020026_71	Hip index	6.000000e-09
GCST90020028_1403	Hip circumference adjusted for BMI	3.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005413	joint damage measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	increases expression, decreases methylation	2
Aflatoxin B1	affects expression, increases expression	2
Particulate Matter	increases abundance, decreases expression	2
aristolochic acid I	decreases expression	1
2-amino-9H-pyrido(2,3-b)indole	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Calcitriol	decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Methyl Methanesulfonate	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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