TMEM123

Summary

TMEM123 (transmembrane protein 123, HGNC:30138) is a protein-coding gene on chromosome 11q22.2, encoding Porimin (Q8N131). Implicated in oncotic cell death, characterized by cell swelling, organelle swelling, vacuolization and increased membrane permeability.

This gene encodes a highly glycosylated transmembrane protein with a high content of threonine and serine residues in its extracellular domain, similar to a broadly defined category of proteins termed mucins. Exposure of some cell types to anti-PORIMIN (pro-oncosis receptor inducing membrane injury) antibody, crosslinks this protein on the cell surface and induces a type of cell death termed oncosis. Oncosis is distinct from apoptosis and is characterized by a loss of cell membrane integrity without DNA fragmentation. This gene product is proposed to function as a cell surface receptor that mediates cell death.

Source: NCBI Gene 114908 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_052932

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30138
Approved symbol	TMEM123
Name	transmembrane protein 123
Location	11q22.2
Locus type	gene with protein product
Status	Approved
Aliases	PORIMIN, KCT3
Ensembl gene	ENSG00000152558
Ensembl biotype	protein_coding
OMIM	606356
Entrez	114908

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000361236, ENST00000398136, ENST00000525577, ENST00000526676, ENST00000528969, ENST00000529492, ENST00000531103, ENST00000532161, ENST00000969654

RefSeq mRNA: 1 — MANE Select: NM_052932 NM_052932

CCDS: CCDS41702

Canonical transcript exons

ENST00000398136 — 5 exons

Exon	Start	End
ENSE00001005951	102401539	102401692
ENSE00001253924	102452524	102452765
ENSE00002180894	102396332	102398891
ENSE00003466804	102448812	102448868
ENSE00003663302	102401916	102402206

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.7271 / max 1239.7564, expressed in 1819 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121972	42.3606	1816
121971	19.9214	1748
121970	9.8095	1600
121974	7.0328	1580
121973	0.9642	587
121962	0.8421	523
121969	0.7868	256
121976	0.0097	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	99.18	gold quality
epithelium of nasopharynx	UBERON:0001951	99.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.97	gold quality
penis	UBERON:0000989	98.94	gold quality
upper leg skin	UBERON:0004262	98.77	gold quality
adrenal tissue	UBERON:0018303	98.76	gold quality
germinal epithelium of ovary	UBERON:0001304	98.75	gold quality
colonic epithelium	UBERON:0000397	98.71	gold quality
tonsil	UBERON:0002372	98.59	gold quality
nasal cavity mucosa	UBERON:0001826	98.57	gold quality
lymph node	UBERON:0000029	98.48	gold quality
ganglionic eminence	UBERON:0004023	98.43	gold quality
monocyte	CL:0000576	98.41	gold quality
mononuclear cell	CL:0000842	98.41	gold quality
ventricular zone	UBERON:0003053	98.40	gold quality
endometrium	UBERON:0001295	98.39	gold quality
bronchial epithelial cell	CL:0002328	98.35	gold quality
leukocyte	CL:0000738	98.34	gold quality
bone marrow cell	CL:0002092	98.24	gold quality
vermiform appendix	UBERON:0001154	98.16	gold quality
caecum	UBERON:0001153	98.12	gold quality
gall bladder	UBERON:0002110	98.09	gold quality
calcaneal tendon	UBERON:0003701	98.05	gold quality
rectum	UBERON:0001052	98.03	gold quality
skin of hip	UBERON:0001554	98.03	gold quality
body of uterus	UBERON:0009853	98.03	gold quality
saliva-secreting gland	UBERON:0001044	98.01	gold quality
bone marrow	UBERON:0002371	98.00	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.99	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	774.63
E-MTAB-10287	yes	56.64
E-CURD-122	yes	52.71
E-MTAB-6701	yes	9.15
E-GEOD-93593	yes	8.46
E-CURD-112	yes	7.54
E-GEOD-70580	no	1743.85
E-MTAB-8894	no	1249.41
E-CURD-55	no	409.31
E-HCAD-8	no	407.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

172 targeting TMEM123, 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-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6888-3P	99.97	65.95	1170

Literature-anchored findings (GeneRIF, showing 1)

• TMEM123 a key player in immune surveillance of colorectal cancer. (PMID:37426665)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem123	ENSDARG00000095674
mus_musculus	Tmem123	ENSMUSG00000050912
rattus_norvegicus	Tmem123	ENSRNOG00000010584
drosophila_melanogaster	vsg	FBGN0045823

Paralogs (2): CD164 (ENSG00000135535), CD164L2 (ENSG00000174950)

Protein

Protein identifiers

Porimin — Q8N131 (reviewed: Q8N131)

Alternative names: Keratinocytes-associated transmembrane protein 3, Pro-oncosis receptor inducing membrane injury, Transmembrane protein 123

All UniProt accessions (4): Q8N131, E9PJW0, E9PKT4, E9PSB1

UniProt curated annotations — full annotation on UniProt →

Function. Implicated in oncotic cell death, characterized by cell swelling, organelle swelling, vacuolization and increased membrane permeability.

Subcellular location. Membrane.

Tissue specificity. Ubiquitous. Not expressed in ovary. Expressed in keratinocytes.

Similarity. Belongs to the CD164 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N131-1	1	yes
Q8N131-2	2

RefSeq proteins (1): NP_443164* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007947	CD164_MGC24	Family

Pfam: PF05283

UniProt features (23 total): glycosylation site 9, sequence variant 3, compositionally biased region 3, topological domain 2, signal peptide 1, chain 1, splice variant 1, sequence conflict 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N131-F1	59.98	0.09

Functional residue map

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

Glycosylation sites (9): 50, 64, 68, 83, 96, 106, 124, 138, 46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 207 (showing top): HORIUCHI_WTAP_TARGETS_DN, chr11q22, GOCC_CELL_SURFACE, PUJANA_CHEK2_PCC_NETWORK, MORF_CCNI, DOANE_RESPONSE_TO_ANDROGEN_DN, SCHLOSSER_SERUM_RESPONSE_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, VANTVEER_BREAST_CANCER_ESR1_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, RIGGINS_TAMOXIFEN_RESISTANCE_DN, GOCC_SIDE_OF_MEMBRANE, MORF_GNB1, ZHAN_MULTIPLE_MYELOMA_MS_DN, MORF_XRCC5

GO Biological Process (0):

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (3): external side of plasma membrane (GO:0009897), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
molecular transducer activity	1
binding	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM123	CFAP300	Q9BRQ4	447
TMEM123	PSMC6	P49719	422
TMEM123	C5orf15	Q8NC54	403
TMEM123	WFDC13	Q8IUB5	393
TMEM123	ZNF112	Q9UJU3	376
TMEM123	JRKL	Q9Y4A0	370
TMEM123	DHRS4L2	Q6PKH6	365
TMEM123	JAG1	P78504	353
TMEM123	TRAM1	Q15629	347
TMEM123	TMEM129	A0AVI4	344
TMEM123	MMP27	Q9H306	334
TMEM123	TMEM132A	Q24JP5	270
TMEM123	PCNP	Q8WW12	270
TMEM123	SLC25A2	Q9BXI2	269
TMEM123	NIBAN3	Q86XR2	269

IntAct

26 interactions, top by confidence:

A	B	Type	Score
MAGEA11	TMEM123	psi-mi:“MI:0915”(physical association)	0.670
TMEM123	WDFY1	psi-mi:“MI:0915”(physical association)	0.590
MAGEA11	TMEM123	psi-mi:“MI:0915”(physical association)	0.560
TMEM123	MAGEA11	psi-mi:“MI:0915”(physical association)	0.560
TMEM123	SGTB	psi-mi:“MI:0915”(physical association)	0.560
TMEM123	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
TMEM123	ISY1	psi-mi:“MI:0915”(physical association)	0.560
ZHX1-C8orf76	TMEM123	psi-mi:“MI:0915”(physical association)	0.560
SPATA17	TMEM123	psi-mi:“MI:0915”(physical association)	0.560
TMEM123	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
TMEM123	MAGEA11	psi-mi:“MI:0915”(physical association)	0.000
TMEM123	SGTB	psi-mi:“MI:0915”(physical association)	0.000
TMEM123		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): TMEM123 (Two-hybrid), WDFY1 (Affinity Capture-MS), TMEM123 (Two-hybrid), WDFY1 (Affinity Capture-MS), TMEM123 (Two-hybrid), MAGEA11 (Two-hybrid), UBQLN2 (Two-hybrid), SGTB (Two-hybrid), WDFY1 (Affinity Capture-MS), TMEM123 (Affinity Capture-RNA)

ESM2 similar proteins: A0A2R8Y7Y5, O00592, O55145, O57604, P03224, P13838, P14220, P15702, P16150, P20934, P28906, P34910, P59647, P70628, P97525, P97808, Q01036, Q1ECS6, Q28270, Q28645, Q3MIW9, Q3TNW5, Q52S86, Q5HZB0, Q5RFI9, Q5XI99, Q62011, Q64314, Q66676, Q6MG22, Q6R8J2, Q6UXF1, Q7TST5, Q80XH2, Q8BHE4, Q8JZQ0, Q8MJJ2, Q8N131, Q8VD58, Q91Z22

Diamond homologs: Q5HZB0, Q8N131, Q91Z22

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	33
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1155 predictions. Top by Δscore:

Variant	Effect	Δscore
11:102401537:A:AC	donor_gain	1.0000
11:102401538:C:CC	donor_gain	1.0000
11:102401538:CATGG:C	donor_gain	1.0000
11:102401688:TGTGA:T	acceptor_gain	1.0000
11:102401689:GTGA:G	acceptor_gain	1.0000
11:102401690:TGA:T	acceptor_gain	1.0000
11:102401691:GA:G	acceptor_gain	1.0000
11:102401691:GAC:G	acceptor_loss	1.0000
11:102401692:ACTA:A	acceptor_loss	1.0000
11:102401693:C:CC	acceptor_gain	1.0000
11:102401694:T:C	acceptor_loss	1.0000
11:102401699:C:CT	acceptor_gain	1.0000
11:102401911:CATA:C	donor_gain	1.0000
11:102401914:A:AC	donor_gain	1.0000
11:102401915:C:CC	donor_gain	1.0000
11:102402202:AGTCT:A	acceptor_gain	1.0000
11:102402203:GTCT:G	acceptor_gain	1.0000
11:102402205:CT:C	acceptor_gain	1.0000
11:102402207:C:CC	acceptor_gain	1.0000
11:102402207:CT:C	acceptor_loss	1.0000
11:102402208:T:G	acceptor_loss	1.0000
11:102452522:AC:A	donor_gain	1.0000
11:102452523:CC:C	donor_gain	1.0000
11:102401533:ACTT:A	donor_loss	0.9900
11:102401534:CT:C	donor_loss	0.9900
11:102401535:T:TC	donor_loss	0.9900
11:102401536:TA:T	donor_loss	0.9900
11:102401537:A:T	donor_loss	0.9900
11:102401538:CA:C	donor_gain	0.9900
11:102401538:CAT:C	donor_gain	0.9900

AlphaMissense

1316 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:102401637:G:C	S168R	0.999
11:102401637:G:T	S168R	0.999
11:102401639:T:G	S168R	0.999
11:102398871:A:T	I208N	0.998
11:102398874:A:C	I207S	0.998
11:102398874:A:T	I207N	0.998
11:102398878:C:G	A206P	0.998
11:102401627:C:G	G172R	0.998
11:102401634:A:C	F169L	0.998
11:102401634:A:T	F169L	0.998
11:102401636:A:G	F169L	0.998
11:102401649:A:C	F164L	0.998
11:102401649:A:T	F164L	0.998
11:102401651:A:G	F164L	0.998
11:102398874:A:G	I207T	0.997
11:102401584:C:T	G186E	0.997
11:102401608:C:T	G178E	0.997
11:102401609:C:G	G178R	0.997
11:102401609:C:T	G178R	0.997
11:102401629:C:T	G171D	0.997
11:102401632:A:T	V170D	0.997
11:102398871:A:C	I208S	0.996
11:102398880:T:A	D205V	0.996
11:102401549:A:G	Y198H	0.996
11:102401626:C:T	G172D	0.996
11:102401635:A:C	F169C	0.996
11:102401635:A:G	F169S	0.996
11:102398871:A:G	I208T	0.995
11:102398877:G:T	A206D	0.995
11:102401614:G:T	T176K	0.995

dbSNP variants (sampled 300 via entrez): RS1000052128 (11:102452091 A>G), RS1000088859 (11:102414242 AGAGG>A), RS1000089820 (11:102421253 C>A,G,T), RS1000115052 (11:102429358 G>A), RS1000146586 (11:102421442 G>A), RS1000211009 (11:102404260 T>C), RS1000265054 (11:102403920 G>A,T), RS1000321356 (11:102450564 T>C,G), RS1000338205 (11:102409247 C>A,G), RS1000353931 (11:102450197 T>C), RS1000364415 (11:102423338 T>C), RS1000370849 (11:102441694 AGAG>A), RS1000399304 (11:102404088 A>G,T), RS1000427224 (11:102416386 G>A), RS1000450054 (11:102432303 A>G)

Disease associations

OMIM: gene MIM:606356 | 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
GCST001942_2	Prostate cancer	2.000000e-11
GCST002793_6	Vein graft stenosis in coronary artery bypass grafting	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007051	vein graft stenosis

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression	4
bisphenol A	affects expression, affects cotreatment, increases methylation	2
perfluorooctane sulfonic acid	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Irinotecan	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Air Pollutants	increases abundance, decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases expression	1
Cisplatin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Herbicides	decreases expression	1
Hydrogen Peroxide	affects expression	1
Methyl Methanesulfonate	decreases expression	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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