TMEM268

Summary

TMEM268 (transmembrane protein 268, HGNC:24513) is a protein-coding gene on chromosome 9q32, encoding Transmembrane protein 268 (Q5VZI3). Stabilizes cell surface expression of ITGAM and participates in the adhesion and migration of phagocytes during bacterial clearance.

Predicted to be located in plasma membrane.

Source: NCBI Gene 203197 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_153045

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24513
Approved symbol	TMEM268
Name	transmembrane protein 268
Location	9q32
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp547P234, FLJ38045
Ensembl gene	ENSG00000157693
Ensembl biotype	protein_coding
Entrez	203197

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000288502, ENST00000374049, ENST00000471206, ENST00000482552, ENST00000862170, ENST00000862171, ENST00000862172, ENST00000862173, ENST00000929230, ENST00000929231, ENST00000967746, ENST00000967747, ENST00000967748

RefSeq mRNA: 2 — MANE Select: NM_153045 NM_001330760, NM_153045

CCDS: CCDS6808, CCDS83405

Canonical transcript exons

ENST00000288502 — 9 exons

Exon	Start	End
ENSE00001034424	114624350	114624459
ENSE00001034425	114628101	114628250
ENSE00001091204	114636990	114637070
ENSE00001091208	114638544	114638726
ENSE00001091210	114633768	114633878
ENSE00001953530	114643134	114646422
ENSE00003559851	114626899	114627006
ENSE00003676202	114617118	114617301
ENSE00003846048	114611291	114611564

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 95.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3820 / max 205.5660, expressed in 1663 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98176	5.3584	1514
98177	2.0207	1185
98178	0.0029	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	95.13	gold quality
middle temporal gyrus	UBERON:0002771	90.32	gold quality
prefrontal cortex	UBERON:0000451	90.30	gold quality
pigmented layer of retina	UBERON:0001782	90.04	gold quality
retina	UBERON:0000966	90.02	gold quality
primary visual cortex	UBERON:0002436	88.89	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.01	gold quality
right frontal lobe	UBERON:0002810	87.54	gold quality
frontal cortex	UBERON:0001870	87.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.04	gold quality
monocyte	CL:0000576	86.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.84	gold quality
mononuclear cell	CL:0000842	86.63	gold quality
leukocyte	CL:0000738	86.60	gold quality
neocortex	UBERON:0001950	86.56	gold quality
occipital lobe	UBERON:0002021	85.29	gold quality
cingulate cortex	UBERON:0003027	84.89	gold quality
cerebral cortex	UBERON:0000956	84.87	gold quality
anterior cingulate cortex	UBERON:0009835	84.66	gold quality
spleen	UBERON:0002106	83.71	gold quality
granulocyte	CL:0000094	83.70	gold quality
choroid plexus epithelium	UBERON:0003911	83.70	gold quality
telencephalon	UBERON:0001893	83.09	gold quality
superior frontal gyrus	UBERON:0002661	83.07	gold quality
cortical plate	UBERON:0005343	82.88	gold quality
right adrenal gland	UBERON:0001233	82.20	gold quality
right adrenal gland cortex	UBERON:0035827	82.18	gold quality
prostate gland	UBERON:0002367	82.15	gold quality
Brodmann (1909) area 46	UBERON:0006483	82.13	gold quality
secondary oocyte	CL:0000655	82.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting TMEM268, 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-4673	100.00	66.64	1490
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-544A	99.84	68.66	1965

Literature-anchored findings (GeneRIF, showing 1)

• Deletion of TMEM268 inhibits growth of gastric cancer cells by downregulating the ITGB4 signaling pathway. (PMID:30361615)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000087611
mus_musculus	Tmem268	ENSMUSG00000045917
rattus_norvegicus	Tmem268	ENSRNOG00000008712
drosophila_melanogaster	CG18507	FBGN0028527
caenorhabditis_elegans		WBGENE00016131

Protein

Protein identifiers

Transmembrane protein 268 — Q5VZI3 (reviewed: Q5VZI3)

All UniProt accessions (1): Q5VZI3

UniProt curated annotations — full annotation on UniProt →

Function. Stabilizes cell surface expression of ITGAM and participates in the adhesion and migration of phagocytes during bacterial clearance.

Subunit / interactions. Interacts with ITGAM; this interaction inhibits ITGAM degradation via the endosome-lysosome pathway. Interacts with ITGB4; this interaction prevents ITGB4 degradation.

Subcellular location. Cell membrane.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5VZI3-1	1	yes
Q5VZI3-2	2
Q5VZI3-3	3

RefSeq proteins (2): NP_001317689, NP_694590* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028054	DUF4481	Family

Pfam: PF14800

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VZI3-F1	72.09	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 174 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, BROWNE_HCMV_INFECTION_16HR_UP, WOTTON_RUNX_TARGETS_UP, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, DOUGLAS_BMI1_TARGETS_UP, OSMAN_BLADDER_CANCER_DN, MULLIGHAN_MLL_SIGNATURE_2_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, SWEET_LUNG_CANCER_KRAS_UP, MIKKELSEN_ES_LCP_WITH_H3K4ME3, PANGAS_TUMOR_SUPPRESSION_BY_SMAD1_AND_SMAD5_DN

GO Biological Process (0):

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
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM268	TMEM266	Q2M3C6	618
TMEM268	SLC35F4	A4IF30	614
TMEM268	FIRRM	Q9NSG2	465
TMEM268	GTPBP2	Q9BX10	456
TMEM268	SH3RF1	Q7Z6J0	422
TMEM268	ATP10D	Q9P241	401
TMEM268	KCNE4	Q8WWG9	401
TMEM268	CEP170B	Q9Y4F5	400
TMEM268	CDHR2	Q9BYE9	390
TMEM268	RASGEF1C	Q8N431	374
TMEM268	TMEM68	Q96MH6	370
TMEM268	FAM111B	Q6SJ93	347
TMEM268	AKNA	Q7Z591	343
TMEM268	ZNF618	Q5T7W0	325
TMEM268	KIF12	Q96FN5	310

IntAct

10 interactions, top by confidence:

A	B	Type	Score
TMEM268	REL	psi-mi:“MI:0915”(physical association)	0.370
GCGR	GPR89A	psi-mi:“MI:0914”(association)	0.350
MARCHF4	C2CD2L	psi-mi:“MI:0914”(association)	0.350
OR10H2	ABCD4	psi-mi:“MI:0914”(association)	0.350
AMIGO3	CLGN	psi-mi:“MI:0914”(association)	0.350
TMEM268	ABCC4	psi-mi:“MI:0914”(association)	0.350
SLC6A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC7A1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC7A3	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): C9orf91 (Affinity Capture-MS), C9orf91 (Affinity Capture-MS), C9orf91 (Affinity Capture-MS), C9orf91 (Affinity Capture-MS), C9orf91 (Affinity Capture-MS), C9orf91 (Affinity Capture-MS), C9orf91 (Affinity Capture-MS), RETSAT (Affinity Capture-MS), HMGCR (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), SLC12A9 (Affinity Capture-MS), SREBF1 (Affinity Capture-MS), CDKAL1 (Affinity Capture-MS), SLC27A3 (Affinity Capture-MS)

ESM2 similar proteins: A0JMQ9, A2BD94, A2RRT3, B2RYN2, D3YWQ0, D3ZKV9, F1MAB7, O43147, O43149, O75912, P0DL28, P33279, P59114, P98153, P98154, Q0D2D2, Q0VD00, Q1AE95, Q1L8G6, Q2NKQ1, Q3TQF0, Q4TVR5, Q4VSN4, Q5EA48, Q5EA86, Q5R8D5, Q5SSH7, Q5U3H9, Q5VZI3, Q5XUX0, Q68FS7, Q6XUX2, Q6ZPS6, Q6ZUJ8, Q80TM9, Q80U12, Q8BIA4, Q8BPQ7, Q8C7B8, Q8CAK3

Diamond homologs: Q5EA48, Q5VZI3, Q8R239

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1859 predictions. Top by Δscore:

Variant	Effect	Δscore
9:114612325:G:GT	donor_gain	1.0000
9:114624457:CAGG:C	donor_loss	1.0000
9:114624458:AGGTG:A	donor_loss	1.0000
9:114624460:G:GA	donor_loss	1.0000
9:114624461:T:A	donor_loss	1.0000
9:114626982:GCC:G	donor_gain	1.0000
9:114628095:TTGCA:T	acceptor_loss	1.0000
9:114628096:TGCAG:T	acceptor_loss	1.0000
9:114628097:GCA:G	acceptor_loss	1.0000
9:114628098:CA:C	acceptor_loss	1.0000
9:114628099:AGGTT:A	acceptor_loss	1.0000
9:114628100:G:GT	acceptor_loss	1.0000
9:114636988:A:AG	acceptor_gain	1.0000
9:114636989:G:GG	acceptor_gain	1.0000
9:114636989:GCT:G	acceptor_gain	1.0000
9:114636989:GCTTT:G	acceptor_gain	1.0000
9:114637067:AGAGG:A	donor_loss	1.0000
9:114637068:GAG:G	donor_gain	1.0000
9:114637069:AGGT:A	donor_loss	1.0000
9:114637070:GGTAA:G	donor_loss	1.0000
9:114637071:GTA:G	donor_loss	1.0000
9:114637072:T:A	donor_loss	1.0000
9:114638540:GCA:G	acceptor_loss	1.0000
9:114638542:A:AG	acceptor_gain	1.0000
9:114638543:G:GG	acceptor_gain	1.0000
9:114638543:GT:G	acceptor_gain	1.0000
9:114638543:GTC:G	acceptor_gain	1.0000
9:114638543:GTCC:G	acceptor_gain	1.0000
9:114638543:GTCCT:G	acceptor_gain	1.0000
9:114638715:GC:G	donor_gain	1.0000

AlphaMissense

2217 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:114628119:T:A	W115R	0.995
9:114628119:T:C	W115R	0.995
9:114633837:G:T	G182W	0.982
9:114633793:T:C	L167P	0.980
9:114633837:G:A	G182R	0.979
9:114633837:G:C	G182R	0.979
9:114633838:G:A	G182E	0.979
9:114643254:T:C	C324R	0.978
9:114628203:A:C	S143R	0.977
9:114628205:C:A	S143R	0.977
9:114628205:C:G	S143R	0.977
9:114643150:T:C	L289P	0.976
9:114636991:T:C	L196P	0.975
9:114643180:G:C	R299P	0.974
9:114643248:T:C	C322R	0.974
9:114643255:G:A	C324Y	0.974
9:114637022:T:G	C206W	0.973
9:114643256:C:G	C324W	0.972
9:114637000:T:A	V199D	0.971
9:114628127:T:A	N117K	0.970
9:114628127:T:G	N117K	0.970
9:114637033:T:C	L210S	0.970
9:114637021:G:A	C206Y	0.969
9:114628102:T:A	V109D	0.968
9:114626927:C:A	A82D	0.967
9:114636996:T:C	F198L	0.967
9:114636998:T:A	F198L	0.967
9:114636998:T:G	F198L	0.967
9:114643250:C:G	C322W	0.967
9:114624440:T:C	L66P	0.965

dbSNP variants (sampled 300 via entrez): RS1000047619 (9:114627561 A>G), RS1000082685 (9:114632140 C>T), RS1000260239 (9:114643567 A>G), RS1000291332 (9:114643191 A>C,G), RS1000358830 (9:114614250 C>A,T), RS1000516951 (9:114604863 G>C,T), RS1000559189 (9:114632395 A>G), RS1000586861 (9:114603475 A>G), RS1000592606 (9:114644986 T>C), RS1000614207 (9:114636086 G>C), RS1000627047 (9:114644857 C>T), RS1000645186 (9:114636279 C>A), RS1000660441 (9:114642288 C>T), RS1000697910 (9:114611146 G>A), RS1000751694 (9:114610863 C>A)

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

3 associations (top):

Study	Trait	p-value
GCST007830_9	Anti-thyroid peroxidase (TPOAb) levels in Hashimoto’s thyroiditis	8.000000e-06
GCST009144_34	Disease progression in age-related macular degeneration (adjusted for baseline)	2.000000e-06
GCST012020_20	Serum metabolite levels	5.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
Valproic Acid	affects expression, decreases expression	3
entinostat	increases expression, affects cotreatment	2
Vorinostat	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Estradiol	increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
TL8-506	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	increases expression	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
perfluoro-n-nonanoic acid	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
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Diazinon	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0RF	Ubigene HeLa TMEM268 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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