TLCD4

Summary

TLCD4 (TLC domain containing 4, HGNC:26477) is a protein-coding gene on chromosome 1p21.3, encoding TLC domain-containing protein 4 (Q96MV1).

Predicted to be involved in lipid homeostasis. Predicted to be located in membrane. Predicted to be active in endoplasmic reticulum.

Source: NCBI Gene 148534 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_152487

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26477
Approved symbol	TLCD4
Name	TLC domain containing 4
Location	1p21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31842
Ensembl gene	ENSG00000152078
Ensembl biotype	protein_coding
Entrez	148534

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000370203, ENST00000455656, ENST00000456991, ENST00000463375, ENST00000882686, ENST00000882687, ENST00000882688, ENST00000882689, ENST00000882690, ENST00000882691, ENST00000882692, ENST00000882693, ENST00000882694, ENST00000882695, ENST00000882696, ENST00000941043

RefSeq mRNA: 2 — MANE Select: NM_152487 NM_001199679, NM_152487

CCDS: CCDS753

Canonical transcript exons

ENST00000370203 — 7 exons

Exon	Start	End
ENSE00001452059	95191550	95197607
ENSE00001452064	95117355	95117617
ENSE00003484007	95173816	95173889
ENSE00003486151	95151325	95151419
ENSE00003565921	95148702	95148791
ENSE00003583841	95150208	95150266
ENSE00003656095	95143891	95144056

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 96.53.

FANTOM5 (CAGE): breadth broad, TPM avg 4.7724 / max 242.8384, expressed in 910 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4122	4.4756	900
4123	0.2968	127

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	96.53	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.79	gold quality
pigmented layer of retina	UBERON:0001782	94.98	gold quality
liver	UBERON:0002107	94.27	gold quality
myocardium	UBERON:0002349	93.72	gold quality
right lobe of liver	UBERON:0001114	92.79	gold quality
upper leg skin	UBERON:0004262	91.57	gold quality
ileal mucosa	UBERON:0000331	90.42	gold quality
heart right ventricle	UBERON:0002080	90.41	gold quality
colonic epithelium	UBERON:0000397	90.19	gold quality
trabecular bone tissue	UBERON:0002483	89.56	gold quality
bone marrow	UBERON:0002371	86.74	gold quality
mammalian vulva	UBERON:0000997	86.38	gold quality
bone marrow cell	CL:0002092	86.30	gold quality
endothelial cell	CL:0000115	85.56	gold quality
epithelial cell of pancreas	CL:0000083	85.38	silver quality
colonic mucosa	UBERON:0000317	84.35	gold quality
rectum	UBERON:0001052	84.06	gold quality
cardiac atrium	UBERON:0002081	83.83	gold quality
deltoid	UBERON:0001476	83.55	gold quality
cardiac ventricle	UBERON:0002082	83.44	gold quality
heart	UBERON:0000948	83.40	gold quality
heart left ventricle	UBERON:0002084	83.34	gold quality
right atrium auricular region	UBERON:0006631	83.25	gold quality
biceps brachii	UBERON:0001507	83.07	gold quality
upper arm skin	UBERON:0004263	82.95	silver quality
adrenal tissue	UBERON:0018303	82.90	gold quality
vastus lateralis	UBERON:0001379	82.45	gold quality
muscle tissue	UBERON:0002385	82.38	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.34	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	57.19
E-MTAB-10042	yes	40.45
E-GEOD-135922	yes	16.19
E-MTAB-9388	yes	7.62
E-MTAB-9067	yes	5.80
E-HCAD-10	yes	3.88
E-GEOD-75367	no	697.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

293 targeting TLCD4, 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-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-10f21.4	ENSDARG00000057743
danio_rerio	tlcd4a	ENSDARG00000098451
mus_musculus	Tlcd4	ENSMUSG00000028132
rattus_norvegicus	Tlcd4	ENSRNOG00000025160

Paralogs (5): TLCD3B (ENSG00000149926), TLCD1 (ENSG00000160606), TLCD3A (ENSG00000167695), CLN8 (ENSG00000182372), TLCD2 (ENSG00000185561)

Protein

Protein identifiers

TLC domain-containing protein 4 — Q96MV1 (reviewed: Q96MV1)

Alternative names: Transmembrane protein 56

All UniProt accessions (3): Q96MV1, C9J6J2, C9JJM2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the TLCD4 family.

RefSeq proteins (2): NP_001186608, NP_689700* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006634	TLC-dom	Domain
IPR050846	TLCD	Family

Pfam: PF03798

UniProt features (9 total): transmembrane region 6, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MV1-F1	94.27	0.87

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 165

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 190 (showing top): RNGTGGGC_UNKNOWN, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_LIPID_HOMEOSTASIS, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, GUO_HEX_TARGETS_DN, HOOI_ST7_TARGETS_DN, LE_EGR2_TARGETS_DN, chr1p21, EVI1_04, SENESE_HDAC3_TARGETS_DN, GOBP_HOMEOSTATIC_PROCESS

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

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

GO Cellular Component (2): endoplasmic reticulum (GO:0005783), 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
cellular anatomical structure	1

Protein interactions and networks

STRING

912 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TLCD4	METTL8	Q9H825	647
TLCD4	HEXIM2	Q96MH2	562
TLCD4	MBOAT2	Q6ZWT7	496
TLCD4	SMIM3	Q9BZL3	493
TLCD4	GATA1	P15976	446
TLCD4	CCDC74A	Q96AQ1	437
TLCD4	NOCT	Q9UK39	426
TLCD4	DNAJC6	O75061	422
TLCD4	GFI1B	Q5VTD9	419
TLCD4	ITGA2B	P08514	415
TLCD4	LRRN4CL	Q8ND94	382
TLCD4	HEMGN	Q9BXL5	370
TLCD4	RWDD3	Q9Y3V2	369
TLCD4	NRIP2	Q9BQI9	363
TLCD4	RGS7BP	Q6MZT1	353

IntAct

256 interactions, top by confidence:

A	B	Type	Score
TMEM19	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
CHPT1	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
NKG7	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
REEP6	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
EMP1	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
BNIP3	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
EBP	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
TLCD4	CLEC7A	psi-mi:“MI:0915”(physical association)	0.560
TLCD4	MYG1	psi-mi:“MI:0915”(physical association)	0.560
CYP4F22	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
CMTM5	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
TLCD4	CCDC167	psi-mi:“MI:0915”(physical association)	0.560
TLCD4	UBE2J1	psi-mi:“MI:0915”(physical association)	0.560
TLCD4	SFXN1	psi-mi:“MI:0915”(physical association)	0.560
TLCD4	SERP1	psi-mi:“MI:0915”(physical association)	0.560
FA2H	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
CXCL16	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
COMT	TLCD4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (117): TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Affinity Capture-MS), TMEM56 (Two-hybrid), TMEM56 (Two-hybrid)

ESM2 similar proteins: A2AKM2, A2AWR3, A8MR93, A8WGS4, D4A612, F1NZP5, G5EF48, O13752, O70536, P47153, Q0P5C7, Q0VD42, Q1A3B0, Q1LXV8, Q32NI8, Q3TYE7, Q4R516, Q500W7, Q57X51, Q5M8U1, Q5ND56, Q5RFL5, Q5U2T1, Q5XIY2, Q60457, Q6GLX2, Q6GNB5, Q6P4N1, Q6PGS5, Q6YWS8, Q6ZRR5, Q84QC0, Q8BHI7, Q8CGF5, Q8GYK7, Q8IU89, Q8K2C9, Q8N609, Q8QZR0, Q96CP7

Diamond homologs: O13752, Q06107, Q5UQN8, Q96MV1, P47153, Q55BP8, Q6GLX2, Q6PGS5, Q8CGF5, Q5XIY2, Q6P4N1, Q8VC26

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1715 predictions. Top by Δscore:

Variant	Effect	Δscore
1:95138380:G:GT	donor_gain	1.0000
1:95138400:G:T	donor_gain	1.0000
1:95143885:TAACA:T	acceptor_loss	1.0000
1:95143886:AACAG:A	acceptor_loss	1.0000
1:95143887:ACAGG:A	acceptor_loss	1.0000
1:95143888:CAG:C	acceptor_loss	1.0000
1:95143888:CAGGT:C	acceptor_loss	1.0000
1:95143889:A:AT	acceptor_loss	1.0000
1:95143890:G:C	acceptor_loss	1.0000
1:95148701:GGGTA:G	acceptor_gain	1.0000
1:95150206:A:AG	acceptor_gain	1.0000
1:95150206:AG:A	acceptor_gain	1.0000
1:95150206:AGG:A	acceptor_gain	1.0000
1:95150207:G:GG	acceptor_gain	1.0000
1:95150207:GG:G	acceptor_gain	1.0000
1:95150207:GGG:G	acceptor_gain	1.0000
1:95150207:GGGGT:G	acceptor_gain	1.0000
1:95150264:CTGG:C	donor_loss	1.0000
1:95150267:G:T	donor_loss	1.0000
1:95150268:T:G	donor_loss	1.0000
1:95173802:T:G	acceptor_gain	1.0000
1:95173814:A:AG	acceptor_gain	1.0000
1:95173815:G:GG	acceptor_gain	1.0000
1:95173886:AGCGG:A	donor_loss	1.0000
1:95173887:GCG:G	donor_gain	1.0000
1:95173887:GCGGT:G	donor_loss	1.0000
1:95173888:CGG:C	donor_loss	1.0000
1:95173888:CGGT:C	donor_loss	1.0000
1:95173890:G:GA	donor_loss	1.0000
1:95173890:G:GG	donor_gain	1.0000

AlphaMissense

1740 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:95144046:T:A	W49R	0.997
1:95144046:T:C	W49R	0.997
1:95173870:A:C	S152R	0.996
1:95173872:C:A	S152R	0.996
1:95173872:C:G	S152R	0.996
1:95191626:T:C	F184L	0.994
1:95191628:C:A	F184L	0.994
1:95191628:C:G	F184L	0.994
1:95191766:T:A	N230K	0.993
1:95191766:T:G	N230K	0.993
1:95173884:T:A	N156K	0.991
1:95173884:T:G	N156K	0.991
1:95191773:T:A	W233R	0.991
1:95191773:T:C	W233R	0.991
1:95143944:A:C	S15R	0.990
1:95143946:C:A	S15R	0.990
1:95143946:C:G	S15R	0.990
1:95143980:A:C	S27R	0.990
1:95143982:T:A	S27R	0.990
1:95143982:T:G	S27R	0.990
1:95151381:C:G	H121D	0.990
1:95173850:G:C	R145P	0.990
1:95173868:C:T	S151F	0.989
1:95173889:G:C	R158P	0.989
1:95148702:G:C	R52S	0.988
1:95148702:G:T	R52S	0.988
1:95191639:G:C	R188P	0.988
1:95144048:G:C	W49C	0.986
1:95144048:G:T	W49C	0.986
1:95151325:A:C	D102A	0.986

dbSNP variants (sampled 300 via entrez): RS1000014289 (1:95153048 C>A,G), RS1000017455 (1:95136425 A>G), RS1000048224 (1:95136927 G>A,T), RS1000084500 (1:95101972 G>A,T), RS1000133360 (1:95193378 A>G), RS1000161443 (1:95125732 G>A), RS1000173242 (1:95114562 A>G), RS1000186695 (1:95173344 C>T), RS1000210456 (1:95143668 T>C,G), RS1000217721 (1:95173081 A>G), RS1000232835 (1:95150828 C>T), RS1000264032 (1:95151128 A>G), RS1000285317 (1:95150576 A>C), RS1000299256 (1:95173969 CAA>C), RS1000318959 (1:95131409 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

10 associations (top):

Study	Trait	p-value
GCST001838_4	Palmitic acid (16:0) levels	3.000000e-11
GCST001840_8	Stearic acid (18:0) levels	2.000000e-18
GCST002701_35	Verbal declarative memory	9.000000e-06
GCST008103_62	Bipolar disorder	6.000000e-07
GCST008103_84	Bipolar disorder	1.000000e-06
GCST009028_33	Adverse response to drug	5.000000e-07
GCST009391_1620	Metabolite levels	4.000000e-06
GCST011125_14	Caffeine consumption from coffee	9.000000e-11
GCST012091_10	Bipolar disorder (MTAG)	1.000000e-08
GCST90002401_350	Platelet distribution width	8.000000e-18

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0009658	adverse effect
EFO:0010379	phosphatidylcholine 36:1 measurement
EFO:0006781	coffee consumption measurement
EFO:0007984	platelet component distribution width

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	increases expression, decreases methylation	5
potassium chromate(VI)	affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Nickel	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression, increases expression	1
trichostatin A	increases expression	1
butyraldehyde	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	affects methylation	1
entinostat	increases expression	1
clothianidin	increases expression	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Toluene	decreases methylation, increases expression	1
Tretinoin	increases expression	1
Vanadates	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TT02	HAP1 TMEM56 (-) 1	Cancer cell line	Male
CVCL_TT03	HAP1 TMEM56 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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