TMEM220

Summary

TMEM220 (transmembrane protein 220, HGNC:33757) is a protein-coding gene on chromosome 17p13.1, encoding Transmembrane protein 220 (Q6QAJ8).

Predicted to be located in membrane.

Source: NCBI Gene 388335 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_001004313

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33757
Approved symbol	TMEM220
Name	transmembrane protein 220
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187824
Ensembl biotype	protein_coding
Entrez	388335

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000341871, ENST00000455996, ENST00000578345, ENST00000580186, ENST00000580787, ENST00000581949, ENST00000857802, ENST00000857803, ENST00000857804, ENST00000857805, ENST00000857806, ENST00000857807, ENST00000857808

RefSeq mRNA: 3 — MANE Select: NM_001004313 NM_001004313, NM_001330139, NM_001330140

CCDS: CCDS32567, CCDS82074, CCDS82075

Canonical transcript exons

ENST00000341871 — 6 exons

Exon	Start	End
ENSE00001378525	10726204	10726264
ENSE00001379249	10713295	10715588
ENSE00001379595	10729031	10729060
ENSE00003705035	10725011	10725134
ENSE00003710003	10723270	10723329
ENSE00003902664	10729780	10730023

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 96.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2521 / max 74.0620, expressed in 1132 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164617	3.1339	1120
164618	0.1183	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.06	gold quality
ileal mucosa	UBERON:0000331	95.41	gold quality
liver	UBERON:0002107	94.20	gold quality
jejunal mucosa	UBERON:0000399	91.71	gold quality
left testis	UBERON:0004533	90.73	gold quality
right testis	UBERON:0004534	90.49	gold quality
pancreatic ductal cell	CL:0002079	90.16	gold quality
body of pancreas	UBERON:0001150	89.32	gold quality
calcaneal tendon	UBERON:0003701	89.19	gold quality
duodenum	UBERON:0002114	88.85	gold quality
testis	UBERON:0000473	88.70	gold quality
left adrenal gland cortex	UBERON:0035825	88.65	gold quality
left adrenal gland	UBERON:0001234	88.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.72	gold quality
popliteal artery	UBERON:0002250	87.66	gold quality
tibial artery	UBERON:0007610	87.66	gold quality
right adrenal gland	UBERON:0001233	87.50	gold quality
right adrenal gland cortex	UBERON:0035827	87.46	gold quality
small intestine	UBERON:0002108	87.33	gold quality
mucosa of stomach	UBERON:0001199	87.30	gold quality
body of stomach	UBERON:0001161	87.06	gold quality
sperm	CL:0000019	87.03	gold quality
adrenal gland	UBERON:0002369	86.74	gold quality
adrenal cortex	UBERON:0001235	86.61	gold quality
aorta	UBERON:0000947	86.46	gold quality
right coronary artery	UBERON:0001625	86.45	gold quality
right lobe of thyroid gland	UBERON:0001119	85.97	gold quality
descending thoracic aorta	UBERON:0002345	85.82	gold quality
left lobe of thyroid gland	UBERON:0001120	85.81	gold quality
transverse colon	UBERON:0001157	85.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	64.19
E-ANND-3	yes	7.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

140 targeting TMEM220, 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-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 3)

• MAL and TMEM220 were specifically methylated and were down-regulated in human gastric cancer (PMID:27329150)
• Downregulation of TMEM220 promotes tumor progression in Hepatocellular Carcinoma. (PMID:34321624)
• Prognostic signatures and potential pathogenesis of eRNAs-related genes in colon adenocarcinoma. (PMID:34622496)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem220	ENSMUSG00000050270
rattus_norvegicus	Tmem220	ENSRNOG00000003367

Protein

Protein identifiers

Transmembrane protein 220 — Q6QAJ8 (reviewed: Q6QAJ8)

All UniProt accessions (4): Q6QAJ8, J3KSH5, J3KSZ3, J3QRF6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6QAJ8-1	1	yes
Q6QAJ8-2	2

RefSeq proteins (3): NP_001004313, NP_001317068, NP_001317069 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029377	TMEM220	Family

Pfam: PF15071

UniProt features (7 total): transmembrane region 5, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6QAJ8-F1	91.68	0.74

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 49 (showing top): DODD_NASOPHARYNGEAL_CARCINOMA_DN, RAO_BOUND_BY_SALL4, HMG20B_TARGET_GENES, MIR520D_5P, MIR524_5P, MIR5696, MIR340_5P, MIR7_1_3P, MIR7_2_3P, MIR579_3P, MIR664B_3P, MIR1283, MIR33A_3P, MIR664A_3P, MIR4699_3P

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

276 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM220	ADPRM	Q3LIE5	683
TMEM220	KRTAP9-7	A8MTY7	542
TMEM220	RNF222	A6NCQ9	526
TMEM220	ZNF433	Q8N7K0	475
TMEM220	SYNGR4	O95473	450
TMEM220	OR1E2	P47887	445
TMEM220	KRTAP9-8	Q9BYQ0	445
TMEM220	PROSER2	Q86WR7	444
TMEM220	OLFML2B	Q68BL8	435
TMEM220	RCCD1	A6NED2	433
TMEM220	THEM6	Q8WUY1	430
TMEM220	OR1D5	P58170	419
TMEM220	MYH13	Q9UKX3	406
TMEM220	KRTAP9-1	A8MXZ3	400
TMEM220	OR3A2	P47893	400
TMEM220	ZNF334	Q9HCZ1	400

IntAct

8 interactions, top by confidence:

A	B	Type	Score
TMEM220	LRRC3B	psi-mi:“MI:0915”(physical association)	0.560
TMEM220	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TMEM220	GAPDHS	psi-mi:“MI:0914”(association)	0.350
TMEM220	TMEM14B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): ACTA2 (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), COX6B1 (Affinity Capture-MS), PTPN11 (Affinity Capture-MS), SRC (Affinity Capture-MS), TMEM220 (Two-hybrid), TMEM220 (Two-hybrid), COX6B1 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), PTPN11 (Affinity Capture-MS), PACSIN3 (Affinity Capture-MS), GAPDHS (Affinity Capture-MS)

ESM2 similar proteins: A0A194XK05, A0A6A6H402, A0A7L9EZ67, A0A8F4NUZ8, A0A8F4S726, A2XAY1, F5H9N9, F5HE69, G5EEQ9, J7FJH0, O83645, P09716, P0CU77, P0DW86, P0DXW0, P0DXW1, P16733, P32564, P52373, P69334, P69335, P9WEG7, Q10255, Q10436, Q29RQ9, Q2KIB3, Q53FV1, Q55E32, Q5E972, Q5R8X5, Q5RFN8, Q5XH57, Q5ZIU0, Q6K3D8, Q6QAJ8, Q6QI25, Q6SW43, Q74ZU2, Q8BP07, Q8JFB7

Diamond homologs: Q4V7Q8, Q6QAJ8, Q8BP07

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1261 predictions. Top by Δscore:

Variant	Effect	Δscore
17:10704908:A:AG	acceptor_gain	1.0000
17:10704909:G:GG	acceptor_gain	1.0000
17:10706551:GTGA:G	donor_gain	1.0000
17:10706552:TGA:T	donor_gain	1.0000
17:10706553:GA:G	donor_gain	1.0000
17:10706553:GAG:G	donor_gain	1.0000
17:10706555:G:C	donor_loss	1.0000
17:10706555:G:GG	donor_gain	1.0000
17:10706556:T:G	donor_loss	1.0000
17:10710833:GGCC:G	acceptor_gain	1.0000
17:10704908:A:AC	acceptor_loss	0.9900
17:10704909:G:GA	acceptor_loss	0.9900
17:10704909:GA:G	acceptor_gain	0.9900
17:10704909:GAA:G	acceptor_gain	0.9900
17:10705278:AGAG:A	donor_gain	0.9900
17:10706432:TTTCA:T	acceptor_loss	0.9900
17:10706433:TTCA:T	acceptor_loss	0.9900
17:10706434:TCAG:T	acceptor_loss	0.9900
17:10706435:CA:C	acceptor_loss	0.9900
17:10706436:A:AG	acceptor_gain	0.9900
17:10706436:A:T	acceptor_loss	0.9900
17:10706437:G:GA	acceptor_gain	0.9900
17:10706437:GGA:G	acceptor_gain	0.9900
17:10706437:GGAC:G	acceptor_gain	0.9900
17:10706437:GGACT:G	acceptor_gain	0.9900
17:10706543:T:TA	donor_gain	0.9900
17:10706544:G:GA	donor_gain	0.9900
17:10706558:AGTA:A	donor_loss	0.9900
17:10706559:G:C	donor_loss	0.9900
17:10710826:A:G	acceptor_gain	0.9900

AlphaMissense

1030 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:10723298:A:G	W107R	0.989
17:10723298:A:T	W107R	0.989
17:10723329:C:A	R96S	0.982
17:10723329:C:G	R96S	0.982
17:10729036:A:G	W33R	0.982
17:10729036:A:T	W33R	0.982
17:10715521:A:G	W139R	0.974
17:10715521:A:T	W139R	0.974
17:10725123:A:G	W59R	0.972
17:10725123:A:T	W59R	0.972
17:10729034:C:A	W33C	0.972
17:10729034:C:G	W33C	0.972
17:10726248:G:C	P40R	0.971
17:10725011:C:G	R96T	0.969
17:10726248:G:T	P40H	0.965
17:10726258:A:G	Y37H	0.963
17:10729804:G:C	F16L	0.963
17:10729804:G:T	F16L	0.963
17:10729806:A:G	F16L	0.963
17:10725090:A:G	C70R	0.961
17:10729052:G:C	D27E	0.961
17:10729052:G:T	D27E	0.961
17:10729053:T:C	D27G	0.961
17:10715532:G:C	P135R	0.960
17:10725011:C:A	R96M	0.960
17:10723318:C:T	G100D	0.959
17:10725088:A:C	C70W	0.959
17:10723324:A:G	L98P	0.958
17:10726245:G:T	A41E	0.958
17:10729780:C:A	Q24H	0.954

dbSNP variants (sampled 300 via entrez): RS1000033580 (17:10729953 C>T), RS1000274791 (17:10729786 C>A,G,T), RS1000734270 (17:10713546 A>T), RS1000782246 (17:10728026 G>A), RS1000787964 (17:10719622 A>G), RS1000793181 (17:10714218 A>G), RS1000898770 (17:10728205 T>C), RS1000969017 (17:10716061 C>T), RS1001204794 (17:10723511 G>T), RS1001432283 (17:10717757 C>A,T), RS1001443994 (17:10729593 A>G,T), RS1001901809 (17:10713135 G>A), RS1001929930 (17:10713335 T>A,C), RS1002082298 (17:10719091 T>C), RS1002485010 (17:10730688 G>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

1 associations (top):

Study	Trait	p-value
GCST002183_2	Relative hand skill in reading disability	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009902	handedness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	decreases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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