TMEM192

Summary

TMEM192 (transmembrane protein 192, HGNC:26775) is a protein-coding gene on chromosome 4q32.3, encoding Transmembrane protein 192 (Q8IY95).

Enables protein homodimerization activity. Located in several cellular components, including late endosome; lysosomal membrane; and perinuclear region of cytoplasm.

Source: NCBI Gene 201931 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_001100389

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26775
Approved symbol	TMEM192
Name	transmembrane protein 192
Location	4q32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38482
Ensembl gene	ENSG00000170088
Ensembl biotype	protein_coding
OMIM	620677
Entrez	201931

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000306480, ENST00000505095, ENST00000506087, ENST00000892790

RefSeq mRNA: 1 — MANE Select: NM_001100389 NM_001100389

CCDS: CCDS43279

Canonical transcript exons

ENST00000306480 — 6 exons

Exon	Start	End
ENSE00001138544	165088468	165088602
ENSE00001263642	165070608	165079796
ENSE00002055482	165112747	165112860
ENSE00003465795	165100628	165100892
ENSE00003607739	165102950	165103096
ENSE00003790226	165085586	165085688

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.4530 / max 84.8237, expressed in 1786 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54705	9.3631	1762
54704	2.8248	1376
54706	1.2652	853

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caput epididymis	UBERON:0004358	97.61	gold quality
corpus epididymis	UBERON:0004359	97.08	gold quality
pigmented layer of retina	UBERON:0001782	96.37	gold quality
retina	UBERON:0000966	96.35	gold quality
kidney epithelium	UBERON:0004819	94.78	gold quality
lower lobe of lung	UBERON:0008949	94.19	gold quality
cauda epididymis	UBERON:0004360	94.12	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.64	gold quality
endothelial cell	CL:0000115	92.63	gold quality
biceps brachii	UBERON:0001507	91.68	gold quality
cartilage tissue	UBERON:0002418	91.01	gold quality
jejunal mucosa	UBERON:0000399	90.90	gold quality
superficial temporal artery	UBERON:0001614	90.62	gold quality
adult organism	UBERON:0007023	90.56	gold quality
bronchial epithelial cell	CL:0002328	90.33	gold quality
bronchus	UBERON:0002185	89.68	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.61	gold quality
liver	UBERON:0002107	89.12	gold quality
colonic mucosa	UBERON:0000317	88.73	gold quality
mammary duct	UBERON:0001765	88.65	gold quality
epithelium of mammary gland	UBERON:0003244	88.56	gold quality
islet of Langerhans	UBERON:0000006	88.09	gold quality
heart right ventricle	UBERON:0002080	88.07	gold quality
skin of hip	UBERON:0001554	87.85	gold quality
oral cavity	UBERON:0000167	87.70	gold quality
postcentral gyrus	UBERON:0002581	87.38	gold quality
kidney	UBERON:0002113	87.17	gold quality
eye	UBERON:0000970	87.11	gold quality
calcaneal tendon	UBERON:0003701	87.09	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.72	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

Literature-anchored findings (GeneRIF, showing 3)

• TMEM192 was found to be strongly expressed in human kidney, liver, lung and pancreas tissue. The widespread tissue distribution could suggest an important role of TMEM192 for lysosomal function. (PMID:20370317)
• TMEM192 deficiency can induce autophagy in tumor cells, and can further activate apoptosis by the mitochondrial pathway through autophagy. (PMID:22736246)
• Authors found that transmembrane protein 192 (TMEM192) interacted with TIG1. Authors also found that both TIG1A and TIG1B isoforms interacted and co-localized with TMEM192 in HtTA cervical cancer cells. The expression of TIG1 induced the expression of autophagy-related proteins. (PMID:27989102)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem192	ENSDARG00000037484
mus_musculus	Tmem192	ENSMUSG00000025521
rattus_norvegicus	Tmem192	ENSRNOG00000030199
drosophila_melanogaster	CG7523	FBGN0038533

Protein

Protein identifiers

Transmembrane protein 192 — Q8IY95 (reviewed: Q8IY95)

All UniProt accessions (2): Q8IY95, D6RAZ6

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Homodimer.

Subcellular location. Lysosome membrane. Late endosome.

Tissue specificity. Strongly expressed in kidney, liver, lung and pancreas.

Post-translational modifications. Not N-glycosylated.

Similarity. Belongs to the TMEM192 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IY95-1	1	yes
Q8IY95-2	2

RefSeq proteins (1): NP_001093859* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029399	TMEM192	Family

Pfam: PF14802

UniProt features (20 total): modified residue 6, topological domain 5, transmembrane region 4, sequence conflict 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IY95-F1	77.22	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 15, 17, 213, 229, 230, 269

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 93 (showing top): chr4q32, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOCC_VACUOLAR_MEMBRANE, WANG_LMO4_TARGETS_DN, NF1_Q6_01, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_PROTEIN_HOMODIMERIZATION_ACTIVITY, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, BRUINS_UVC_RESPONSE_LATE, ARNT2_TARGET_GENES, BARX1_TARGET_GENES, FEV_TARGET_GENES, ZNF354A_TARGET_GENES, ZNF582_TARGET_GENES, MIR3671

GO Biological Process (0):

GO Molecular Function (1): protein homodimerization activity (GO:0042803)

GO Cellular Component (7): nucleoplasm (GO:0005654), lysosome (GO:0005764), lysosomal membrane (GO:0005765), endosome (GO:0005768), late endosome (GO:0005770), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
identical protein binding	1
protein dimerization activity	1
nuclear lumen	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
endomembrane system	1
cytoplasmic vesicle	1
endosome	1
cytoplasm	1

Protein interactions and networks

STRING

2127 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM192	RARRES1	P49788	604
TMEM192	TMA16	Q96EY4	530
TMEM192	LAMP2	P13473	491
TMEM192	BPIFB3	P59826	491
TMEM192	PCP4L1	A6NKN8	473
TMEM192	VRTN	Q9H8Y1	469
TMEM192	AGBL2	Q5U5Z8	459
TMEM192	FBXO27	Q8NI29	452
TMEM192	LAMP1	P11279	428
TMEM192	ARL8A	Q96BM9	411
TMEM192	METAP2	P50579	397
TMEM192	DNAJC8	O75937	386
TMEM192	ARL8B	Q9NVJ2	385
TMEM192	SLC38A9	Q8NBW4	376
TMEM192	FAM218A	Q96MZ4	370

IntAct

87 interactions, top by confidence:

A	B	Type	Score
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
	DDR1	psi-mi:“MI:2364”(proximity)	0.670
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
ASPH	STXBP3	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
GYPA	GOLGA7	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
RPL18	RRP8	psi-mi:“MI:0914”(association)	0.640
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
EVA1C	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TMEM192	STXBP3	psi-mi:“MI:0914”(association)	0.530
CD226	MEN1	psi-mi:“MI:0914”(association)	0.530
HEATR3	SLC27A2	psi-mi:“MI:0914”(association)	0.530
VAMP5	NBAS	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
NTRK3	FAM171A2	psi-mi:“MI:0914”(association)	0.480
vpu	SCAMP3	psi-mi:“MI:0914”(association)	0.460
ICAM3	TMEM192	psi-mi:“MI:0915”(physical association)	0.400
incE	STX7	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
	FAM171A2	psi-mi:“MI:0914”(association)	0.350
ATP6V1A		psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (251): TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS)

ESM2 similar proteins: A4GG66, A4IG66, E1BN97, F1NVK6, F1Q930, F6UF99, O76024, O95772, P28228, P35803, P36383, P56695, P84889, Q0IJ20, Q0VCF5, Q2TBG9, Q3MHM8, Q4QQM5, Q4VBG5, Q5BIY5, Q5BLE2, Q5RCG1, Q5U1Y0, Q5VW38, Q5XJS0, Q66H44, Q6GR21, Q6NRB7, Q6NZH5, Q6PYT3, Q6R4A8, Q7ZWF4, Q7ZXS7, Q80Z96, Q810L4, Q8BG50, Q8IY95, Q8N6S5, Q8NAN2, Q8TAA9

Diamond homologs: Q5EAL6, Q5RCG1, Q5U1Y0, Q66KF2, Q6NYE7, Q8IY95, Q9CXT7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1532 predictions. Top by Δscore:

Variant	Effect	Δscore
4:165079715:A:AC	donor_gain	1.0000
4:165079716:C:CC	donor_gain	1.0000
4:165079720:G:C	donor_gain	1.0000
4:165079792:TAGTT:T	acceptor_gain	1.0000
4:165085684:TTTCA:T	acceptor_gain	1.0000
4:165085685:TTCA:T	acceptor_gain	1.0000
4:165085686:TCA:T	acceptor_gain	1.0000
4:165085687:CA:C	acceptor_gain	1.0000
4:165085687:CAC:C	acceptor_gain	1.0000
4:165085689:C:CC	acceptor_gain	1.0000
4:165085689:CT:C	acceptor_loss	1.0000
4:165085690:T:A	acceptor_loss	1.0000
4:165088462:TCTCA:T	donor_loss	1.0000
4:165088463:CTCAC:C	donor_loss	1.0000
4:165088464:TCACC:T	donor_loss	1.0000
4:165088465:CA:C	donor_loss	1.0000
4:165088466:ACCT:A	donor_loss	1.0000
4:165088467:CCTGT:C	donor_loss	1.0000
4:165100840:T:TC	acceptor_gain	1.0000
4:165207901:GC:G	donor_gain	1.0000
4:165207903:G:GG	donor_gain	1.0000
4:165079617:CT:C	donor_gain	0.9900
4:165079716:CT:C	donor_gain	0.9900
4:165079716:CTCAG:C	donor_gain	0.9900
4:165079719:AG:A	donor_gain	0.9900
4:165079719:AGCAG:A	donor_gain	0.9900
4:165079793:AGTT:A	acceptor_gain	0.9900
4:165079794:GTT:G	acceptor_gain	0.9900
4:165079795:TT:T	acceptor_gain	0.9900
4:165079795:TTC:T	acceptor_loss	0.9900

AlphaMissense

1756 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:165079740:A:G	L245P	0.980
4:165085672:A:C	F197L	0.978
4:165085672:A:T	F197L	0.978
4:165085674:A:G	F197L	0.978
4:165100757:A:G	W104R	0.975
4:165100757:A:T	W104R	0.975
4:165102998:G:C	F42L	0.970
4:165102998:G:T	F42L	0.970
4:165103000:A:G	F42L	0.970
4:165100823:A:G	C82R	0.965
4:165100853:A:G	C72R	0.962
4:165085673:A:G	F197S	0.960
4:165100822:C:G	C82S	0.959
4:165100823:A:T	C82S	0.959
4:165088602:C:T	G147D	0.957
4:165100772:C:G	G99R	0.955
4:165100772:C:T	G99R	0.955
4:165100852:C:G	C72S	0.952
4:165100853:A:T	C72S	0.952
4:165100768:T:A	K100I	0.951
4:165079726:C:G	A250P	0.948
4:165085588:G:C	F225L	0.939
4:165085588:G:T	F225L	0.939
4:165085590:A:G	F225L	0.939
4:165079770:A:T	V235D	0.935
4:165100884:A:C	F61L	0.933
4:165100884:A:T	F61L	0.933
4:165100886:A:G	F61L	0.933
4:165100628:C:G	G147R	0.932
4:165079734:C:G	R247P	0.927

dbSNP variants (sampled 300 via entrez): RS1000029382 (4:165111165 T>A), RS1000061500 (4:165112411 T>G), RS1000092247 (4:165112085 T>G), RS1000205223 (4:165093976 T>A,G), RS1000220211 (4:165087602 G>A), RS1000266656 (4:165086039 G>T), RS10002774 (4:165103359 G>A,T), RS1000294346 (4:165071631 G>A), RS1000342736 (4:165092501 T>C,G), RS1000378517 (4:165078558 C>T), RS1000438743 (4:165098613 G>A), RS1000464925 (4:165110668 G>A), RS1000633790 (4:165105764 G>A), RS10007095 (4:165090509 T>G), RS1000785031 (4:165077444 C>A,T)

Disease associations

OMIM: gene MIM:620677 | 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
GCST003447_4	Neuroticism	4.000000e-08
GCST012167_5	Adiponectin levels	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0004502	adiponectin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
sulforaphane	increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Phthalic Acids	increases methylation	1
Quercetin	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

14 cell lines: 9 induced pluripotent stem cell, 3 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6SR	HEK293 TMEM192-3xHA	Transformed cell line	Female
CVCL_E4JW	HEK293T TetOff-SNCA-A53T EGFP-RNF152-IRES-mScarlet-I TMEM192-3xHA	Transformed cell line	Female
CVCL_F0QI	U2OS-TMEM192-3xHA	Cancer cell line	Female
CVCL_F1KX	HT809-TH-tdTomato-LysoIP-MitoIP	Induced pluripotent stem cell	Male
CVCL_F1KY	HT809-TH-tdTomato-LysoIP-MitoIP-GBA1 KO/KO	Induced pluripotent stem cell	Male
CVCL_F1KZ	HT809-TH-tdTomato-LysoIP-MitoIP-GBA1 WT/WT	Induced pluripotent stem cell	Male
CVCL_F1L0	HT809-TH-tdTomato-LysoIP-MitoIP-GBA1 WT/L444P	Induced pluripotent stem cell	Male
CVCL_F1L1	HT809-TH-tdTomato-LysoIP-MitoIP-GBA1 L444P/L444P	Induced pluripotent stem cell	Male
CVCL_F1L2	HT809-TH-tdTomato-LysoIP-MitoIP-GBA1 KO/KO + GPNMB KO	Induced pluripotent stem cell	Male
CVCL_F1L3	HT809-TH-tdTomato-LysoIP-MitoIP-GBA1 WT/WT + GPNMB KO	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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