TMCO2

Summary

TMCO2 (transmembrane and coiled-coil domains 2, HGNC:23312) is a protein-coding gene on chromosome 1p34.2, encoding Transmembrane and coiled-coil domain-containing protein 2 (Q7Z6W1).

Located in nucleus.

Source: NCBI Gene 127391 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_001008740

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23312
Approved symbol	TMCO2
Name	transmembrane and coiled-coil domains 2
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	dJ39G22.2
Ensembl gene	ENSG00000188800
Ensembl biotype	protein_coding
Entrez	127391

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000372766, ENST00000468258

RefSeq mRNA: 1 — MANE Select: NM_001008740 NM_001008740

CCDS: CCDS30684

Canonical transcript exons

ENST00000372766 — 2 exons

Exon	Start	End
ENSE00001458606	40247937	40248230
ENSE00001867105	40251283	40251684

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 99.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2194 / max 230.0533, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2351	0.1845	4
2352	0.0349	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.36	gold quality
left testis	UBERON:0004533	97.32	gold quality
right testis	UBERON:0004534	97.19	gold quality
testis	UBERON:0000473	94.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.63	gold quality
adult organism	UBERON:0007023	88.97	gold quality
tibialis anterior	UBERON:0001385	77.01	silver quality
pancreatic ductal cell	CL:0002079	67.61	silver quality
buccal mucosa cell	CL:0002336	66.47	silver quality
ileal mucosa	UBERON:0000331	61.67	silver quality
deltoid	UBERON:0001476	59.68	silver quality
granulocyte	CL:0000094	56.66	gold quality
epithelial cell of pancreas	CL:0000083	55.57	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
myocardium	UBERON:0002349	50.25	gold quality
quadriceps femoris	UBERON:0001377	48.29	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
metanephros cortex	UBERON:0010533	46.56	gold quality
metanephros	UBERON:0000081	46.36	gold quality
vastus lateralis	UBERON:0001379	45.56	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
oviduct epithelium	UBERON:0004804	43.18	silver quality
amniotic fluid	UBERON:0000173	43.07	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
lower esophagus mucosa	UBERON:0035834	42.43	silver quality
trigeminal ganglion	UBERON:0001675	41.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.27

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmco2	ENSMUSG00000078577
rattus_norvegicus	Tmco2	ENSRNOG00000012340

Protein

Protein identifiers

Transmembrane and coiled-coil domain-containing protein 2 — Q7Z6W1 (reviewed: Q7Z6W1)

All UniProt accessions (2): A0A140VKB8, Q7Z6W1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001008740* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031697	TMCCDC2	Family

Pfam: PF15844

UniProt features (3 total): chain 1, transmembrane region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6W1-F1	61.93	0.04

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): chr1p34, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_UP, SRC_UP.V1_DN, GSE14415_NATURAL_TREG_VS_FOXP3_KO_NATURAL_TREG_UP, GSE13485_DAY1_VS_DAY3_YF17D_VACCINE_PBMC_UP, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_48H_ACT_CD4_TCELL_UP, GSE9946_MATURE_STIMULATORY_VS_LISTERIA_INF_MATURE_DC_UP, GSE12707_AT16L1_HYPOMORPH_VS_WT_THYMUS_DN, GSE12505_WT_VS_E2_2_HET_PDC_UP, GSE1740_UNSTIM_VS_IFNA_STIMULATED_MCSF_DERIVED_MACROPHAGE_DN, GSE8835_HEALTHY_VS_CLL_CD4_TCELL_DN, AAGCACT_MIR520F, GSE31622_WT_VS_KLF3_KO_BCELL_DN, AATGTGA_MIR23A_MIR23B

GO Biological Process (0):

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

GO Cellular Component (2): nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMCO2	TMCO5A	Q8N6Q1	589
TMCO2	CCDC187	A0A096LP49	558
TMCO2	CCDC54	Q8NEL0	543
TMCO2	CXorf65	A6NEN9	541
TMCO2	OR10T2	Q8NGX3	540
TMCO2	C20orf173	Q96LM9	528
TMCO2	FAM209A	Q5JX71	527
TMCO2	ZC3H11D	Q8NA57	507
TMCO2	CIMIP4	O43247	505
TMCO2	FAM81B	Q96LP2	494
TMCO2	GARIN1B	Q96KD3	481
TMCO2	CCDC174	Q6PII3	479
TMCO2	ZFP69	Q49AA0	476
TMCO2	C22orf23	Q9BZE7	475
TMCO2	SPATA31G1	Q5VYM1	472

IntAct

19 interactions, top by confidence:

A	B	Type	Score
TMCO2	TCEANC	psi-mi:“MI:0915”(physical association)	0.560
TMCO2	PBX3	psi-mi:“MI:0915”(physical association)	0.560
PTPN9	TMCO2	psi-mi:“MI:0915”(physical association)	0.560
TMCO2	COQ8A	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	TMCO2	psi-mi:“MI:0915”(physical association)	0.560
UBASH3A	TMCO2	psi-mi:“MI:0915”(physical association)	0.560
TCEANC	TMCO2	psi-mi:“MI:0915”(physical association)	0.000
PBX3	TMCO2	psi-mi:“MI:0915”(physical association)	0.000
UBASH3A	TMCO2	psi-mi:“MI:0915”(physical association)	0.000
PTPN9	TMCO2	psi-mi:“MI:0915”(physical association)	0.000
COQ8A	TMCO2	psi-mi:“MI:0915”(physical association)	0.000
SDCBP	TMCO2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): TMCO2 (Two-hybrid), TMCO2 (Two-hybrid), TMCO2 (Two-hybrid), TMCO2 (Two-hybrid), TMCO2 (Two-hybrid), TMCO2 (Two-hybrid), TMCO2 (Negative Genetic)

ESM2 similar proteins: A1CMP1, A3KQS5, A5HWA8, A6R5Z3, E7Q3U9, O13709, O60071, O74986, O84008, O84512, O84640, O94670, O94707, P0C755, P22469, P25049, P34518, P35198, P39424, P40380, P41993, P97783, Q06324, Q07541, Q09383, Q09599, Q09664, Q0ULD0, Q0VCT1, Q13015, Q1DI23, Q4KMC9, Q5M971, Q5R4W2, Q6CQB7, Q6CS73, Q6FWU4, Q6ZQV5, Q722M0, Q7VKZ7

Diamond homologs: P0C1V4, Q2NKV5, Q7Z6W1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

203 predictions. Top by Δscore:

Variant	Effect	Δscore
1:40248211:G:GT	donor_gain	0.9900
1:40248049:GCACA:G	donor_gain	0.9800
1:40251414:G:A	acceptor_gain	0.9800
1:40248216:ATTC:A	donor_gain	0.9600
1:40251281:A:AG	acceptor_gain	0.9600
1:40251282:G:GG	acceptor_gain	0.9600
1:40251413:T:TA	acceptor_gain	0.9600
1:40248054:G:GG	donor_gain	0.9500
1:40251282:GAA:G	acceptor_gain	0.9500
1:40248073:C:T	donor_gain	0.9400
1:40247967:T:TA	donor_gain	0.9300
1:40247968:A:AA	donor_gain	0.9300
1:40251276:A:AG	acceptor_gain	0.9300
1:40251282:GAAA:G	acceptor_gain	0.9300
1:40251282:GAAAA:G	acceptor_gain	0.9200
1:40248161:G:GT	donor_gain	0.9100
1:40251278:TTTAG:T	acceptor_loss	0.9100
1:40251279:TTAG:T	acceptor_loss	0.9100
1:40251280:TAGAA:T	acceptor_loss	0.9100
1:40251281:AGAA:A	acceptor_loss	0.9100
1:40251270:T:A	acceptor_loss	0.9000
1:40248053:A:AG	donor_gain	0.8900
1:40251276:ATTTT:A	acceptor_gain	0.8800
1:40251282:GA:G	acceptor_gain	0.8800
1:40251277:TTTTA:T	acceptor_gain	0.8500
1:40251321:CAAGA:C	acceptor_gain	0.8000
1:40251322:AAGAA:A	acceptor_gain	0.8000
1:40251423:A:G	acceptor_gain	0.8000
1:40248072:G:GG	donor_gain	0.7900
1:40248084:G:GT	donor_gain	0.7900

AlphaMissense

1178 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:40251443:T:C	L133P	0.970
1:40251577:T:C	F178L	0.934
1:40251579:T:A	F178L	0.934
1:40251579:T:G	F178L	0.934
1:40248189:G:A	G66R	0.923
1:40248189:G:C	G66R	0.923
1:40251328:G:C	G95R	0.921
1:40251295:T:C	F84L	0.916
1:40251297:T:A	F84L	0.916
1:40251297:T:G	F84L	0.916
1:40248059:G:C	W22C	0.904
1:40248059:G:T	W22C	0.904
1:40251317:T:C	L91P	0.900
1:40248190:G:A	G66E	0.899
1:40251443:T:A	L133H	0.898
1:40251431:T:C	I129T	0.896
1:40251473:T:C	L143P	0.894
1:40251455:A:T	E137V	0.891
1:40251308:T:C	L88P	0.884
1:40248183:G:A	G64R	0.882
1:40248183:G:C	G64R	0.882
1:40248213:A:C	S74R	0.880
1:40248215:T:A	S74R	0.880
1:40248215:T:G	S74R	0.880
1:40251299:T:A	V85E	0.875
1:40251423:A:C	Q126H	0.871
1:40251423:A:T	Q126H	0.871
1:40251431:T:G	I129S	0.861
1:40251556:A:C	S171R	0.859
1:40251558:T:A	S171R	0.859

dbSNP variants (sampled 300 via entrez): RS1000115265 (1:40247417 T>C), RS1000230667 (1:40247833 T>C), RS1000643180 (1:40251069 G>A), RS1001122010 (1:40246010 C>G,T), RS1001525655 (1:40251980 G>A,C), RS1001745520 (1:40247350 G>C), RS1003154701 (1:40245979 G>A), RS1003540621 (1:40249307 G>A), RS1003823344 (1:40249655 C>G), RS1003884990 (1:40251053 C>T), RS1004282677 (1:40250531 C>A,T), RS1005004777 (1:40250107 C>T), RS1005384869 (1:40247214 A>G), RS1005460905 (1:40248926 T>C), RS1005895640 (1:40248247 A>G)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	increases expression	1
propionaldehyde	decreases expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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