TMEM177

Summary

TMEM177 (transmembrane protein 177, HGNC:28143) is a protein-coding gene on chromosome 2q14.2, encoding Transmembrane protein 177 (Q53S58). Plays a role in the early steps of cytochrome c oxidase subunit II (MT-CO2/COX2) maturation and is required for the stabilization of COX20 and the newly synthesized MT-CO2/COX2 protein.

Located in mitochondrial inner membrane.

Source: NCBI Gene 80775 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 56 total — 2 pathogenic
• MANE Select transcript: NM_030577

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28143
Approved symbol	TMEM177
Name	transmembrane protein 177
Location	2q14.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC10993
Ensembl gene	ENSG00000144120
Ensembl biotype	protein_coding
OMIM	620752
Entrez	80775

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000272521, ENST00000401466, ENST00000409951, ENST00000424086, ENST00000445518, ENST00000496203, ENST00000867107, ENST00000867108, ENST00000867109, ENST00000867110, ENST00000867111, ENST00000921671, ENST00000921672, ENST00000921673, ENST00000921674, ENST00000921675, ENST00000921676, ENST00000921677

RefSeq mRNA: 3 — MANE Select: NM_030577 NM_001105198, NM_001105199, NM_030577

CCDS: CCDS2128

Canonical transcript exons

ENST00000272521 — 2 exons

Exon	Start	End
ENSE00000963676	119680832	119682118
ENSE00001020672	119679201	119679276

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 86.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0442 / max 61.9953, expressed in 1739 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22281	8.7723	1713
22280	3.2719	1466

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	86.31	gold quality
right lobe of liver	UBERON:0001114	86.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.35	gold quality
prefrontal cortex	UBERON:0000451	84.01	gold quality
right uterine tube	UBERON:0001302	83.61	gold quality
liver	UBERON:0002107	82.58	gold quality
cortical plate	UBERON:0005343	82.44	gold quality
metanephros cortex	UBERON:0010533	82.27	gold quality
ganglionic eminence	UBERON:0004023	82.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.90	gold quality
adult mammalian kidney	UBERON:0000082	81.70	gold quality
transverse colon	UBERON:0001157	81.65	gold quality
apex of heart	UBERON:0002098	81.51	gold quality
pituitary gland	UBERON:0000007	80.89	gold quality
gastrocnemius	UBERON:0001388	80.75	gold quality
rectum	UBERON:0001052	80.68	gold quality
adenohypophysis	UBERON:0002196	80.66	gold quality
muscle of leg	UBERON:0001383	80.43	gold quality
right frontal lobe	UBERON:0002810	80.34	gold quality
right adrenal gland cortex	UBERON:0035827	80.05	gold quality
islet of Langerhans	UBERON:0000006	80.04	gold quality
right adrenal gland	UBERON:0001233	80.02	gold quality
ventricular zone	UBERON:0003053	79.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.43	gold quality
frontal cortex	UBERON:0001870	79.40	gold quality
left adrenal gland	UBERON:0001234	79.29	gold quality
duodenum	UBERON:0002114	79.28	gold quality
heart left ventricle	UBERON:0002084	79.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.09	gold quality
neocortex	UBERON:0001950	78.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting TMEM177, 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-4319	99.76	69.83	2586
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-203B-5P	97.24	68.54	543
HSA-MIR-6718-5P	97.24	68.15	553
HSA-MIR-2114-5P	96.00	64.56	617
HSA-MIR-6851-3P	95.73	65.11	688
HSA-MIR-103B	95.51	66.85	441
HSA-MIR-5588-3P	94.96	65.59	500
HSA-MIR-6769A-3P	94.91	61.36	412

Literature-anchored findings (GeneRIF, showing 1)

• data shows that by unbalancing the amount of TMEM177, newly synthesized COX2 accumulates in a COX20-associated state. (PMID:29154948)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem177	ENSDARG00000069301
mus_musculus	Tmem177	ENSMUSG00000036975
rattus_norvegicus	Tmem177	ENSRNOG00000025484
drosophila_melanogaster	CG33506	FBGN0053506
caenorhabditis_elegans		WBGENE00020099
caenorhabditis_elegans		WBGENE00043060

Protein

Protein identifiers

Transmembrane protein 177 — Q53S58 (reviewed: Q53S58)

All UniProt accessions (3): Q53S58, B8ZZT5, C9J6F8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the early steps of cytochrome c oxidase subunit II (MT-CO2/COX2) maturation and is required for the stabilization of COX20 and the newly synthesized MT-CO2/COX2 protein.

Subunit / interactions. Found in a complex with COX20, COA6, MT-CO2/COX2, COX18, SCO1 and SCO2. Interacts with COX20. Interacts with COX1, MT-CO2/COX2, SCO1 and SCO2 in a COX20-dependent manner.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the TMEM177 family.

RefSeq proteins (3): NP_001098668, NP_001098669, NP_085054* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026620	TMEM177	Family

UniProt features (11 total): topological domain 4, sequence variant 3, transmembrane region 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53S58-F1	90.39	0.69

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 95 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, WEI_MYCN_TARGETS_WITH_E_BOX, GOCC_MITOCHONDRIAL_ENVELOPE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, chr2q14, GRYDER_PAX3FOXO1_TOP_ENHANCERS, GOCC_ORGANELLE_INNER_MEMBRANE, BENPORATH_ES_1, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_GREEN_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN

GO Biological Process (0):

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

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

406 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM177	COX20	Q5RI15	775
TMEM177	COX16	Q9P0S2	571
TMEM177	COA6	Q5JTJ3	570
TMEM177	COX18	Q8N8Q8	542
TMEM177	PET117	Q6UWS5	541
TMEM177	MT-CO2	P00403	530
TMEM177	PET100	P0DJ07	507
TMEM177	SCO1	O75880	480
TMEM177	PNKD	Q8N490	448
TMEM177	COX17	Q14061	445
TMEM177	SCO2	O43819	397
TMEM177	ZBED5	Q49AG3	396
TMEM177	COX7C	P15954	373
TMEM177	COX6C	P09669	368
TMEM177	COX7B	P24311	359

IntAct

25 interactions, top by confidence:

A	B	Type	Score
NDUFA13	NDUFS8	psi-mi:“MI:0914”(association)	0.640
TMEM177	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
CPVL	CYB5R3	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	COX7A2L	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
AQP3	RTL8C	psi-mi:“MI:0914”(association)	0.350
PDPN	KIF14	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
ACKR3	PDE2A	psi-mi:“MI:0914”(association)	0.350
FPR1	NBAS	psi-mi:“MI:0914”(association)	0.350
KLK1	PPOX	psi-mi:“MI:0914”(association)	0.350
LCN6	HIGD1C	psi-mi:“MI:0914”(association)	0.350
PTH2R	SPTLC2	psi-mi:“MI:0914”(association)	0.350
RAMP3	TMEM223	psi-mi:“MI:0914”(association)	0.350
VSIG4	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC22A9	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC2A5	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
COA3	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): TMEM177 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), TMEM177 (Synthetic Lethality), TMEM177 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS)

ESM2 similar proteins: A0PJW6, A5PJW2, B3DI94, B5DFG1, O00411, O95382, P49753, Q059A4, Q0V9C9, Q3SX05, Q4KLZ1, Q4KM93, Q4R5Q4, Q4VAE3, Q53S58, Q5EA71, Q5T1A1, Q5XIC2, Q643R3, Q66LN0, Q6DC58, Q6NVG1, Q76MJ5, Q7YS91, Q80YU0, Q863F8, Q8BPE4, Q8BWM0, Q8N159, Q8NFF5, Q8VCA6, Q8VD26, Q921N7, Q96AN5, Q96KR6, Q99MQ3, Q9BQ95, Q9BUB7, Q9BYK8, Q9CQE2

Diamond homologs: Q4KM93, Q53S58, Q66IS8, Q6PBI8, Q8BPE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	49
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
814296	GRCh37/hg19 2q14.1-14.2(chr2:115416190-122399064)x1	Pathogenic
814298	GRCh37/hg19 2q14.2-14.3(chr2:118903294-123099547)x1	Pathogenic

SpliceAI

359 predictions. Top by Δscore:

Variant	Effect	Δscore
2:119680831:GATT:G	acceptor_gain	0.9900
2:119679319:G:GT	donor_gain	0.9700
2:119680100:A:AG	donor_gain	0.9600
2:119680100:A:G	donor_gain	0.9600
2:119680830:A:AG	acceptor_gain	0.9600
2:119680831:G:GG	acceptor_gain	0.9600
2:119679295:G:GT	donor_gain	0.9500
2:119680827:CCCA:C	acceptor_loss	0.9500
2:119680828:CCA:C	acceptor_loss	0.9500
2:119680829:CA:C	acceptor_loss	0.9500
2:119680830:A:C	acceptor_loss	0.9500
2:119680831:G:GT	acceptor_loss	0.9500
2:119680106:ACACC:A	donor_gain	0.9400
2:119680829:CAGA:C	acceptor_gain	0.9100
2:119679272:ACCCG:A	donor_loss	0.9000
2:119679273:CCCG:C	donor_loss	0.9000
2:119679274:CCG:C	donor_loss	0.9000
2:119679275:CG:C	donor_loss	0.9000
2:119679276:GGTAA:G	donor_loss	0.9000
2:119679277:G:GA	donor_loss	0.9000
2:119679278:T:TC	donor_loss	0.9000
2:119679279:A:C	donor_loss	0.9000
2:119680033:G:GA	donor_gain	0.9000
2:119680824:T:A	acceptor_gain	0.9000
2:119679618:G:GG	donor_gain	0.8900
2:119680824:T:TA	acceptor_loss	0.8900
2:119680828:CCAGA:C	acceptor_gain	0.8800
2:119679431:G:T	donor_gain	0.8600
2:119679221:CGGAG:C	donor_loss	0.8500
2:119679223:GAGG:G	donor_loss	0.8500

AlphaMissense

1981 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:119681307:T:C	F152L	0.992
2:119681309:C:A	F152L	0.992
2:119681309:C:G	F152L	0.992
2:119681308:T:C	F152S	0.974
2:119681308:T:G	F152C	0.971
2:119681680:G:T	G276V	0.971
2:119681598:T:C	F249L	0.964
2:119681600:C:A	F249L	0.964
2:119681600:C:G	F249L	0.964
2:119681667:T:G	Y272D	0.964
2:119681684:C:A	N277K	0.960
2:119681684:C:G	N277K	0.960
2:119681100:T:C	F83L	0.959
2:119681102:C:A	F83L	0.959
2:119681102:C:G	F83L	0.959
2:119681316:G:C	A155P	0.958
2:119681737:G:C	R295P	0.957
2:119681109:T:C	F86L	0.956
2:119681111:C:A	F86L	0.956
2:119681111:C:G	F86L	0.956
2:119681680:G:A	G276E	0.956
2:119681679:G:T	G276W	0.953
2:119681170:T:C	I106T	0.949
2:119681635:G:C	R261P	0.944
2:119681181:T:C	F110L	0.942
2:119681183:C:A	F110L	0.942
2:119681183:C:G	F110L	0.942
2:119681599:T:C	F249S	0.942
2:119681298:G:C	A149P	0.940
2:119681317:C:A	A155D	0.937

dbSNP variants (sampled 300 via entrez): RS1000088656 (2:119710622 C>T), RS1000111450 (2:119712555 C>G,T), RS1000228015 (2:119712052 G>A), RS1000360794 (2:119719442 A>G), RS1000365311 (2:119677784 A>G), RS1000394814 (2:119677401 A>C,G), RS1000448211 (2:119711185 C>A,T), RS1000481242 (2:119694280 C>A), RS1000501838 (2:119711018 C>A), RS1000642883 (2:119718072 G>A), RS1000687927 (2:119704410 C>T), RS1000709833 (2:119717524 A>G), RS1000772812 (2:119718932 G>A,C), RS1000814261 (2:119683004 G>T), RS1000879355 (2:119688883 C>T)

Disease associations

OMIM: gene MIM:620752 | 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

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
sodium arsenite	increases expression, decreases expression, increases abundance	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
Formaldehyde	decreases expression	2
Cadmium Chloride	decreases expression	2
tert-Butylhydroperoxide	affects cotreatment, decreases expression, increases expression, decreases reaction	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, increases expression	1
ochratoxin A	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	affects expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
Rosiglitazone	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Pioglitazone	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Troglitazone	affects cotreatment, decreases expression, decreases reaction	1
Acetaminophen	affects response to substance	1
Arsenic	increases expression, increases abundance	1
Hexachlorocyclohexane	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Copper	decreases expression, affects binding	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TS86	HAP1 TMEM177 (-) 1	Cancer cell line	Male
CVCL_TS87	HAP1 TMEM177 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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