TMCO4

Summary

TMCO4 (transmembrane and coiled-coil domains 4, HGNC:27393) is a protein-coding gene on chromosome 1p36.13, encoding Transmembrane and coiled-coil domain-containing protein 4 (Q5TGY1).

Predicted to be located in membrane.

Source: NCBI Gene 255104 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 145 total
• MANE Select transcript: NM_181719

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27393
Approved symbol	TMCO4
Name	transmembrane and coiled-coil domains 4
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686C23231
Ensembl gene	ENSG00000162542
Ensembl biotype	protein_coding
Entrez	255104

Gene structure

Transcript identifiers

Ensembl transcripts: 70 — 64 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000294543, ENST00000375127, ENST00000462171, ENST00000488449, ENST00000489135, ENST00000489814, ENST00000494342, ENST00000496528, ENST00000866952, ENST00000866953, ENST00000866954, ENST00000866955, ENST00000866956, ENST00000866957, ENST00000866958, ENST00000866959, ENST00000866960, ENST00000866961, ENST00000866962, ENST00000866963, ENST00000866964, ENST00000866965, ENST00000866966, ENST00000866967, ENST00000866968, ENST00000866969, ENST00000866970, ENST00000866971, ENST00000866972, ENST00000866973, ENST00000866974, ENST00000866975, ENST00000866976, ENST00000866977, ENST00000866978, ENST00000866979, ENST00000866980, ENST00000866981, ENST00000866982, ENST00000866983, ENST00000866984, ENST00000866985, ENST00000866986, ENST00000866987, ENST00000929250, ENST00000962042, ENST00000962043, ENST00000962044, ENST00000962045, ENST00000962046, ENST00000962047, ENST00000962048, ENST00000962049, ENST00000962050, ENST00000962051, ENST00000962052, ENST00000962053, ENST00000962054, ENST00000962055, ENST00000962056, ENST00000962057, ENST00000962058, ENST00000962059, ENST00000962060, ENST00000962061, ENST00000962062, ENST00000962063, ENST00000962064, ENST00000962065, ENST00000962066

RefSeq mRNA: 5 — MANE Select: NM_181719 NM_001349112, NM_001349113, NM_001349114, NM_001349115, NM_181719

CCDS: CCDS198

Canonical transcript exons

ENST00000294543 — 16 exons

Exon	Start	End
ENSE00001066123	19745532	19745651
ENSE00001353498	19787026	19787117
ENSE00001372579	19799855	19799916
ENSE00001376551	19798137	19798215
ENSE00001856944	19682240	19683444
ENSE00003507233	19770542	19770569
ENSE00003565615	19747163	19747260
ENSE00003576628	19700768	19700885
ENSE00003590095	19746456	19746599
ENSE00003603268	19694434	19694551
ENSE00003608817	19771308	19771482
ENSE00003622849	19740777	19740941
ENSE00003630185	19739824	19739960
ENSE00003638641	19737372	19737456
ENSE00003672467	19780580	19780766
ENSE00003692252	19755634	19755766

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 90.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.7793 / max 34.5363, expressed in 1365 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10688	2.3567	1262
10686	0.1570	76
10689	0.1378	39
10687	0.0805	40
10690	0.0473	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	90.52	gold quality
sural nerve	UBERON:0015488	88.82	gold quality
granulocyte	CL:0000094	88.28	gold quality
right lobe of thyroid gland	UBERON:0001119	88.09	gold quality
metanephros cortex	UBERON:0010533	87.58	gold quality
left lobe of thyroid gland	UBERON:0001120	87.55	gold quality
prostate gland	UBERON:0002367	87.49	gold quality
mucosa of transverse colon	UBERON:0004991	87.40	gold quality
thyroid gland	UBERON:0002046	87.10	gold quality
body of pancreas	UBERON:0001150	87.02	gold quality
body of stomach	UBERON:0001161	86.89	gold quality
right adrenal gland cortex	UBERON:0035827	86.79	gold quality
pancreatic ductal cell	CL:0002079	86.75	silver quality
left adrenal gland	UBERON:0001234	86.72	gold quality
right adrenal gland	UBERON:0001233	86.70	gold quality
corpus epididymis	UBERON:0004359	86.69	gold quality
left adrenal gland cortex	UBERON:0035825	86.69	gold quality
right uterine tube	UBERON:0001302	86.42	gold quality
minor salivary gland	UBERON:0001830	86.05	gold quality
descending thoracic aorta	UBERON:0002345	85.80	gold quality
popliteal artery	UBERON:0002250	85.53	gold quality
adrenal cortex	UBERON:0001235	85.50	gold quality
duodenum	UBERON:0002114	85.50	gold quality
tibial artery	UBERON:0007610	85.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.49	gold quality
adrenal gland	UBERON:0002369	85.34	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.17	gold quality
aorta	UBERON:0000947	85.01	gold quality
stomach	UBERON:0000945	84.98	gold quality
saliva-secreting gland	UBERON:0001044	84.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting TMCO4, 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-126-5P	100.00	72.71	3180
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-558	97.50	67.16	977
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmco4	ENSDARG00000078924
mus_musculus	Tmco4	ENSMUSG00000041143
rattus_norvegicus	Tmco4	ENSRNOG00000017401
caenorhabditis_elegans		WBGENE00018044

Protein

Protein identifiers

Transmembrane and coiled-coil domain-containing protein 4 — Q5TGY1 (reviewed: Q5TGY1)

All UniProt accessions (2): A0A075B6H3, Q5TGY1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the TMCO4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5TGY1-1	1	yes
Q5TGY1-2	2

RefSeq proteins (5): NP_001336041, NP_001336042, NP_001336043, NP_001336044, NP_859070* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007941	DUF726	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF05277

UniProt features (11 total): transmembrane region 3, sequence variant 2, chain 1, sequence conflict 1, region of interest 1, coiled-coil region 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TGY1-F1	73.10	0.44

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, ROZANOV_MMP14_TARGETS_UP, LIAO_METASTASIS, chr1p36, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, WHITFIELD_CELL_CYCLE_G2_M, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, ESC_V6.5_UP_EARLY.V1_UP, CHAF1B_TARGET_GENES, DLX6_TARGET_GENES, DMRT1_TARGET_GENES, FOXD2_TARGET_GENES, NKX2_2_TARGET_GENES, SFMBT1_TARGET_GENES, TERF1_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMCO4	FAM187B	Q17R55	621
TMCO4	ETDA	Q3ZM63	575
TMCO4	VPS29	Q9UBQ0	510
TMCO4	OR4F16	Q6IEY1	505
TMCO4	LENG9	Q96B70	419
TMCO4	SERPINI1	Q99574	414
TMCO4	MSTO1	Q9BUK6	412
TMCO4	UBXN10	Q96LJ8	400
TMCO4	GIMAP8	Q8ND71	388
TMCO4	SIL1	Q9H173	387
TMCO4	C5orf58	C9J3I9	364
TMCO4	GALNT9	Q9HCQ5	359
TMCO4	FAM8A1	Q9UBU6	356
TMCO4	PSD3	Q9NYI0	347
TMCO4	EML1	O00423	346

IntAct

13 interactions, top by confidence:

A	B	Type	Score
TMCO4	VPS29	psi-mi:“MI:0915”(physical association)	0.560
KPTN	EIF4G3	psi-mi:“MI:0914”(association)	0.530
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350
KPTN	ALDH1A2	psi-mi:“MI:0914”(association)	0.350
SLC37A3	PLXNB2	psi-mi:“MI:0914”(association)	0.350
FLT1	MTCL2	psi-mi:“MI:0914”(association)	0.350
VPS29	TMCO4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): TMCO4 (Affinity Capture-MS), TMCO4 (Affinity Capture-MS), TMCO4 (Affinity Capture-RNA), TMCO4 (Affinity Capture-MS), TMCO4 (Two-hybrid), TMCO4 (Proximity Label-MS), TMCO4 (Proximity Label-MS), TMCO4 (Proximity Label-MS), TMCO4 (Proximity Label-MS), TMCO4 (Proximity Label-MS), TMCO4 (Proximity Label-MS), TMCO4 (Affinity Capture-MS), TMCO4 (Affinity Capture-MS), TMCO4 (Proximity Label-MS), TMCO4 (Proximity Label-MS)

ESM2 similar proteins: A0JMH2, A1L251, A2ARP1, A7Z050, D3ZEY4, E7FCP8, E9QAM5, O00562, O35954, O42412, O95822, P0C644, P0C7A1, P12617, P16386, P40935, P49898, P49899, P52824, P53370, P54310, P70563, Q17QN2, Q2KI24, Q3URQ7, Q499U8, Q5EU90, Q5I0I8, Q5RAR6, Q5RDF1, Q5TGY1, Q5U2N3, Q5XIL6, Q68J42, Q6P5E8, Q6PD24, Q6PFW1, Q80YU0, Q8BX80, Q8CH40

Diamond homologs: O14244, P43564, Q10SS2, Q499U8, Q5TGY1, Q91WU4, Q9US10, Q20035

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2591 predictions. Top by Δscore:

Variant	Effect	Δscore
1:19694430:TCA:T	donor_loss	1.0000
1:19694431:CA:C	donor_loss	1.0000
1:19694432:A:AC	donor_gain	1.0000
1:19694432:A:T	donor_loss	1.0000
1:19694432:AC:A	donor_gain	1.0000
1:19694433:C:CA	donor_gain	1.0000
1:19694433:CC:C	donor_gain	1.0000
1:19694433:CCA:C	donor_gain	1.0000
1:19694433:CCACA:C	donor_gain	1.0000
1:19694547:CTCCC:C	acceptor_gain	1.0000
1:19694549:CCC:C	acceptor_gain	1.0000
1:19694550:CC:C	acceptor_gain	1.0000
1:19694550:CCC:C	acceptor_gain	1.0000
1:19694551:CC:C	acceptor_gain	1.0000
1:19694552:C:A	acceptor_loss	1.0000
1:19694552:C:CC	acceptor_gain	1.0000
1:19694554:G:C	acceptor_gain	1.0000
1:19700741:C:A	donor_gain	1.0000
1:19700763:CAGA:C	donor_loss	1.0000
1:19700764:AGAC:A	donor_loss	1.0000
1:19700765:GAC:G	donor_loss	1.0000
1:19700767:C:CG	donor_loss	1.0000
1:19700886:C:CC	acceptor_gain	1.0000
1:19737367:CTCA:C	donor_loss	1.0000
1:19737368:TCA:T	donor_loss	1.0000
1:19737369:CA:C	donor_loss	1.0000
1:19737370:A:C	donor_loss	1.0000
1:19737371:C:CA	donor_loss	1.0000
1:19737371:CCTTT:C	donor_gain	1.0000
1:19737452:CGCCC:C	acceptor_gain	1.0000

AlphaMissense

4065 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:19737424:G:C	S404R	0.998
1:19737424:G:T	S404R	0.998
1:19737426:T:G	S404R	0.998
1:19739852:A:G	L384P	0.998
1:19746581:G:T	A211D	0.998
1:19740882:A:G	W313R	0.997
1:19740882:A:T	W313R	0.997
1:19740924:A:G	W299R	0.997
1:19740924:A:T	W299R	0.997
1:19746569:A:T	V215D	0.997
1:19747183:A:T	V198D	0.997
1:19747189:G:T	A196E	0.997
1:19737431:C:T	G402D	0.996
1:19739861:C:T	G381D	0.996
1:19739876:C:G	R376P	0.996
1:19740878:T:A	E314V	0.996
1:19746566:G:T	A216D	0.996
1:19747195:C:T	G194D	0.996
1:19737397:A:C	C413W	0.995
1:19739895:A:G	W370R	0.995
1:19739895:A:T	W370R	0.995
1:19739948:G:T	A352D	0.995
1:19745555:C:T	G285E	0.995
1:19745612:A:G	F266S	0.995
1:19746500:G:T	A238D	0.995
1:19747177:C:T	G200D	0.995
1:19694495:G:T	A480D	0.994
1:19694546:T:A	D463V	0.994
1:19700777:C:T	G458D	0.994
1:19700820:A:G	W444R	0.994

dbSNP variants (sampled 300 via entrez): RS1000003725 (1:19681952 C>T), RS1000035066 (1:19681984 G>T), RS1000045182 (1:19758499 C>G), RS1000050094 (1:19761295 C>A,G,T), RS1000057358 (1:19722229 A>T), RS1000074882 (1:19701657 C>A), RS1000075237 (1:19776152 C>G,T), RS1000086732 (1:19681752 C>T), RS1000117437 (1:19757152 G>A,T), RS1000120755 (1:19720254 C>T), RS1000172095 (1:19782025 A>G), RS1000178024 (1:19791078 T>C), RS1000210539 (1:19698549 G>A,T), RS1000224458 (1:19781863 G>A), RS1000236056 (1:19704511 A>C)

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

2 associations (top):

Study	Trait	p-value
GCST003815_97	Late-onset Alzheimer’s disease	7.000000e-06
GCST007565_50	Morning person	3.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	3
Benzo(a)pyrene	decreases expression, increases methylation	2
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
zinc chromate	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Ozone	increases abundance, affects expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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