TLCD1

Summary

TLCD1 (TLC domain containing 1, HGNC:25177) is a protein-coding gene on chromosome 17q11.2, encoding TLC domain-containing protein 1 (Q96CP7). Regulates the composition and fluidity of the plasma membrane. It is a selective cancer dependency (DepMap: 17.5% of cell lines).

Involved in several processes, including membrane assembly; phospholipid homeostasis; and regulation of membrane lipid distribution. Located in plasma membrane.

Source: NCBI Gene 116238 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 50 total
• Cancer dependency (DepMap): dependent in 17.5% of screened cell lines
• MANE Select transcript: NM_138463

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25177
Approved symbol	TLCD1
Name	TLC domain containing 1
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000160606
Ensembl biotype	protein_coding
OMIM	620966
Entrez	116238

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000292090, ENST00000394933, ENST00000580518, ENST00000581236

RefSeq mRNA: 2 — MANE Select: NM_138463 NM_001160407, NM_138463

CCDS: CCDS11242, CCDS54102

Canonical transcript exons

ENST00000292090 — 4 exons

Exon	Start	End
ENSE00001255690	28724348	28724893
ENSE00001312603	28725904	28726233
ENSE00002938591	28725304	28725386
ENSE00003583413	28725481	28725563

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 95.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.4091 / max 108.3331, expressed in 1400 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165069	4.7609	1366
165067	0.3977	227
165068	0.2157	90
165070	0.0347	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.20	gold quality
upper arm skin	UBERON:0004263	89.76	gold quality
mucosa of transverse colon	UBERON:0004991	87.42	gold quality
skin of leg	UBERON:0001511	84.77	gold quality
skin of abdomen	UBERON:0001416	84.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.63	gold quality
metanephros cortex	UBERON:0010533	83.53	gold quality
zone of skin	UBERON:0000014	83.39	gold quality
adult mammalian kidney	UBERON:0000082	82.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.46	gold quality
esophagus mucosa	UBERON:0002469	81.63	gold quality
islet of Langerhans	UBERON:0000006	81.31	gold quality
lower esophagus mucosa	UBERON:0035834	81.21	gold quality
upper leg skin	UBERON:0004262	81.19	gold quality
body of pancreas	UBERON:0001150	81.03	gold quality
minor salivary gland	UBERON:0001830	80.71	gold quality
right lobe of liver	UBERON:0001114	80.51	gold quality
nucleus accumbens	UBERON:0001882	80.36	gold quality
left testis	UBERON:0004533	80.34	gold quality
amygdala	UBERON:0001876	80.19	gold quality
pancreas	UBERON:0001264	79.89	gold quality
right testis	UBERON:0004534	79.70	gold quality
stromal cell of endometrium	CL:0002255	79.66	gold quality
kidney epithelium	UBERON:0004819	79.53	gold quality
anterior cingulate cortex	UBERON:0009835	79.52	gold quality
mouth mucosa	UBERON:0003729	79.46	gold quality
rectum	UBERON:0001052	79.02	gold quality
metanephros	UBERON:0000081	78.94	gold quality
testis	UBERON:0000473	78.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.34
E-MTAB-6142	no	36.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting TLCD1, 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-1305	99.91	71.43	3443
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-1468-5P	94.18	69.04	176

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• inhibition of FLD-1 or TLCD1/2 prevents lipotoxicity by allowing increased levels of membrane phospholipids that contain fluidizing long-chain polyunsaturated fatty acids. (PMID:30509349)
• TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis. (PMID:36241646)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tlcd1	ENSDARG00000002391
mus_musculus	Tlcd1	ENSMUSG00000019437
rattus_norvegicus	Tlcd1	ENSRNOG00000071015
caenorhabditis_elegans	fld-1	WBGENE00013407
caenorhabditis_elegans		WBGENE00019686
caenorhabditis_elegans	Y48G8AL.13	WBGENE00021691

Paralogs (5): TLCD3B (ENSG00000149926), TLCD4 (ENSG00000152078), TLCD3A (ENSG00000167695), CLN8 (ENSG00000182372), TLCD2 (ENSG00000185561)

Protein

Protein identifiers

TLC domain-containing protein 1 — Q96CP7 (reviewed: Q96CP7)

Alternative names: Calfacilitin

All UniProt accessions (3): Q96CP7, K7ELX5, K7ESD9

UniProt curated annotations — full annotation on UniProt →

Function. Regulates the composition and fluidity of the plasma membrane. Inhibits the incorporation of membrane-fluidizing phospholipids containing omega-3 long-chain polyunsaturated fatty acids (LCPUFA) and thereby promotes membrane rigidity. Does not appear to have any effect on LCPUFA synthesis.

Subcellular location. Cell membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96CP7-1	1	yes
Q96CP7-2	2

RefSeq proteins (2): NP_001153879, NP_612472* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006634	TLC-dom	Domain
IPR050846	TLCD	Family

Pfam: PF03798

UniProt features (15 total): topological domain 6, transmembrane region 4, signal peptide 1, chain 1, domain 1, splice variant 1, intramembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CP7-F1	90.06	0.80

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): GOBP_MEMBRANE_BIOGENESIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, chr17q11, GOBP_LIPID_HOMEOSTASIS, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_MEMBRANE_ORGANIZATION, HNF1_01, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, MARTENS_TRETINOIN_RESPONSE_DN, LU_EZH2_TARGETS_UP

GO Biological Process (4): plasma membrane organization (GO:0007009), phospholipid homeostasis (GO:0055091), membrane assembly (GO:0071709), regulation of membrane lipid distribution (GO:0097035)

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

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
membrane organization	3
endomembrane system organization	1
lipid homeostasis	1
cellular component assembly	1
membrane biogenesis	1
regulation of biological quality	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TLCD1	DHRS7B	Q6IAN0	561
TLCD1	MED15	Q96RN5	521
TLCD1	CEPT1	Q9Y6K0	503
TLCD1	POP1	Q99575	480
TLCD1	DHRS12	A0PJE2	470
TLCD1	MTRNR2L3	P0CJ70	445
TLCD1	TRAM1L1	Q8N609	435
TLCD1	OCEL1	Q9H607	431
TLCD1	EFCAB8	A8MWE9	428
TLCD1	A0A2U3TZT1	A0A2U3TZT1	419
TLCD1	ADIPOR2	Q86V24	409
TLCD1	THTPA	Q9BU02	405
TLCD1	BBLN	Q9BUW7	397
TLCD1	RIMBP2	O15034	392
TLCD1	YIPF3	Q9GZM5	385

IntAct

48 interactions, top by confidence:

A	B	Type	Score
CREB3L1	TLCD1	psi-mi:“MI:0915”(physical association)	0.560
SSMEM1	TLCD1	psi-mi:“MI:0915”(physical association)	0.560
EBP	TLCD1	psi-mi:“MI:0915”(physical association)	0.560
FXYD3	TLCD1	psi-mi:“MI:0915”(physical association)	0.560
CD40	TLCD1	psi-mi:“MI:0915”(physical association)	0.560
TLCD1	TMEM80	psi-mi:“MI:0915”(physical association)	0.560
TLCD1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
AQP6	TLCD1	psi-mi:“MI:0915”(physical association)	0.560
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
SLC6A15	GPR89A	psi-mi:“MI:0914”(association)	0.350
SH2D3C	TMEM14DP	psi-mi:“MI:0914”(association)	0.350
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
BSCL2	TMEM223	psi-mi:“MI:0914”(association)	0.350
CRELD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
ATP2A1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
ATP2A3	GPR89A	psi-mi:“MI:0914”(association)	0.350
ATP2A3	UBXN8	psi-mi:“MI:0914”(association)	0.350
SPPL2B	HAS3	psi-mi:“MI:0914”(association)	0.350
SLC1A1	SCD	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A14	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC6A15	EI24	psi-mi:“MI:0914”(association)	0.350
SLC7A1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TCTN3	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270
TCTN2	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (32): TLCD1 (Proximity Label-MS), TLCD1 (Proximity Label-MS), TLCD1 (Affinity Capture-MS), TLCD1 (Affinity Capture-MS), TLCD1 (Affinity Capture-MS), TLCD1 (Two-hybrid), TLCD1 (Two-hybrid), TLCD1 (Two-hybrid), TLCD1 (Two-hybrid), TLCD1 (Two-hybrid), TLCD1 (Two-hybrid), SSMEM1 (Two-hybrid), TMEM80 (Two-hybrid), TLCD1 (Affinity Capture-MS), TLCD1 (Affinity Capture-MS)

ESM2 similar proteins: A2AKM2, A4FUY9, A5D6V4, A7YY55, A8WGS4, Q01685, Q0P5C7, Q15629, Q3T124, Q4R8A8, Q4V8U5, Q5BJF2, Q5GH60, Q5GH61, Q5GH68, Q5HZE5, Q5ND56, Q5NVQ2, Q5R7Z3, Q5U2T1, Q5VWC8, Q5XI41, Q5ZM57, Q60457, Q6DED0, Q6GLX2, Q6GNB5, Q6P4N1, Q6PP77, Q6YWS8, Q7SY06, Q84QC0, Q86X19, Q8CGF5, Q8K0U3, Q8K2C9, Q8N609, Q8QZR0, Q8R000, Q8VZB2

Diamond homologs: A6NGC4, A8WGS4, F1NZP5, G5EF48, Q8VC26, Q96CP7, Q5U2T1, Q99JT6, Q6GLX2, Q6P4N1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of small molecules	7	8.4×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

281 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28724889:ATGGC:A	acceptor_gain	1.0000
17:28724890:TGGC:T	acceptor_gain	1.0000
17:28724891:GGC:G	acceptor_gain	1.0000
17:28724892:GC:G	acceptor_gain	1.0000
17:28724893:CC:C	acceptor_gain	1.0000
17:28724894:C:CA	acceptor_loss	1.0000
17:28724894:C:CC	acceptor_gain	1.0000
17:28724894:C:T	acceptor_gain	1.0000
17:28724895:T:A	acceptor_loss	1.0000
17:28725300:TTACC:T	donor_loss	1.0000
17:28725301:TA:T	donor_loss	1.0000
17:28725302:A:AC	donor_gain	1.0000
17:28725302:ACC:A	donor_loss	1.0000
17:28725303:C:A	donor_loss	1.0000
17:28725303:C:CC	donor_gain	1.0000
17:28725382:ATACC:A	acceptor_gain	1.0000
17:28725383:TACC:T	acceptor_gain	1.0000
17:28725383:TACCC:T	acceptor_loss	1.0000
17:28725384:ACC:A	acceptor_gain	1.0000
17:28725384:ACCC:A	acceptor_loss	1.0000
17:28725385:CC:C	acceptor_gain	1.0000
17:28725385:CCC:C	acceptor_gain	1.0000
17:28725386:CC:C	acceptor_gain	1.0000
17:28725387:C:CC	acceptor_gain	1.0000
17:28725387:C:T	acceptor_gain	1.0000
17:28725387:CTA:C	acceptor_loss	1.0000
17:28725390:G:C	acceptor_gain	1.0000
17:28725390:G:GC	acceptor_gain	1.0000
17:28725898:A:AC	donor_gain	0.9900
17:28725899:C:CC	donor_gain	0.9900

AlphaMissense

1606 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28724810:G:C	N148K	0.999
17:28724810:G:T	N148K	0.999
17:28724813:G:C	S147R	0.999
17:28724813:G:T	S147R	0.999
17:28724815:T:G	S147R	0.999
17:28724820:T:A	E145V	0.999
17:28725315:G:C	H117D	0.999
17:28725371:T:A	D98V	0.999
17:28725371:T:G	D98A	0.999
17:28724794:G:T	R154S	0.998
17:28724802:A:G	L151P	0.998
17:28725310:G:C	H118Q	0.998
17:28725310:G:T	H118Q	0.998
17:28725371:T:C	D98G	0.998
17:28725384:A:G	Y94H	0.998
17:28725922:C:T	G59E	0.998
17:28725923:C:G	G59R	0.998
17:28725923:C:T	G59R	0.998
17:28725934:G:A	S55F	0.998
17:28724707:G:T	R183S	0.997
17:28724814:C:A	S147I	0.997
17:28724820:T:G	E145A	0.997
17:28725312:G:C	H118D	0.997
17:28725313:A:C	H117Q	0.997
17:28725313:A:T	H117Q	0.997
17:28725315:G:T	H117N	0.997
17:28725324:A:G	Y114H	0.997
17:28725370:A:C	D98E	0.997
17:28725370:A:T	D98E	0.997
17:28725372:C:G	D98H	0.997

dbSNP variants (sampled 300 via entrez): RS1000340537 (17:28723984 C>A,G), RS1001389577 (17:28729145 G>A,T), RS1001630399 (17:28726155 G>A,C), RS1001666210 (17:28724805 A>G), RS1001876402 (17:28729320 G>A,C,T), RS1002898265 (17:28729533 T>A,C), RS1003710719 (17:28728036 C>T), RS1003835898 (17:28729911 T>C), RS1003938326 (17:28729578 A>G), RS1004844330 (17:28728626 G>T), RS1006299626 (17:28724997 T>C), RS1006319673 (17:28726918 G>A), RS1006682567 (17:28726562 C>G), RS1008186837 (17:28727079 G>A), RS1008523686 (17:28727036 C>A,G,T)

Disease associations

OMIM: gene MIM:620966 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
TL8-506	affects cotreatment, increases expression	1
sodium arsenite	increases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
corosolic acid	increases expression	1
monomethylarsonous acid	decreases expression	1
ICG 001	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
jinfukang	affects cotreatment, increases expression	1
trametinib	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Coumestrol	increases expression	1
Demecolcine	decreases expression	1
Mustard Gas	increases expression	1

Clinical trials (associated diseases)

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