TMEM125

Summary

TMEM125 (transmembrane protein 125, HGNC:28275) is a protein-coding gene on chromosome 1p34.2, encoding Transmembrane protein 125 (Q96AQ2).

Predicted to be located in membrane.

Source: NCBI Gene 128218 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_144626

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28275
Approved symbol	TMEM125
Name	transmembrane protein 125
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC17299
Ensembl gene	ENSG00000179178
Ensembl biotype	protein_coding
Entrez	128218

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 34 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000432792, ENST00000439858, ENST00000442284, ENST00000456751, ENST00000908432, ENST00000908433, ENST00000908434, ENST00000908435, ENST00000908436, ENST00000908437, ENST00000908438, ENST00000908439, ENST00000908440, ENST00000908441, ENST00000908442, ENST00000908443, ENST00000908444, ENST00000908445, ENST00000908446, ENST00000908447, ENST00000908448, ENST00000908449, ENST00000927383, ENST00000927384, ENST00000927385, ENST00000927386, ENST00000964004, ENST00000964005, ENST00000964006, ENST00000964007, ENST00000964008, ENST00000964009, ENST00000964010, ENST00000964011, ENST00000964012

RefSeq mRNA: 2 — MANE Select: NM_144626 NM_001320244, NM_144626

CCDS: CCDS480

Canonical transcript exons

ENST00000439858 — 4 exons

Exon	Start	End
ENSE00001254439	43272184	43272339
ENSE00001593065	43272578	43274002
ENSE00001649813	43270681	43270793
ENSE00001672191	43269983	43270085

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 97.46.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9285 / max 107.4333, expressed in 383 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2502	2.7871	381
2499	0.1013	26
2500	0.0401	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	97.46	gold quality
body of pancreas	UBERON:0001150	97.39	gold quality
pancreatic ductal cell	CL:0002079	97.37	gold quality
right lung	UBERON:0002167	96.92	gold quality
upper lobe of left lung	UBERON:0008952	96.78	gold quality
upper lobe of lung	UBERON:0008948	96.58	gold quality
right lobe of thyroid gland	UBERON:0001119	95.74	gold quality
left lobe of thyroid gland	UBERON:0001120	95.68	gold quality
mucosa of transverse colon	UBERON:0004991	94.49	gold quality
thyroid gland	UBERON:0002046	94.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.62	gold quality
lower lobe of lung	UBERON:0008949	93.58	gold quality
lung	UBERON:0002048	93.49	gold quality
spinal cord	UBERON:0002240	93.03	gold quality
inferior vagus X ganglion	UBERON:0005363	92.94	gold quality
right uterine tube	UBERON:0001302	92.93	gold quality
pancreas	UBERON:0001264	92.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.30	gold quality
duodenum	UBERON:0002114	91.43	gold quality
pituitary gland	UBERON:0000007	91.28	gold quality
bronchial epithelial cell	CL:0002328	91.17	gold quality
nasal cavity epithelium	UBERON:0005384	91.02	gold quality
palpebral conjunctiva	UBERON:0001812	90.81	gold quality
bronchus	UBERON:0002185	90.77	gold quality
adenohypophysis	UBERON:0002196	89.74	gold quality
medial globus pallidus	UBERON:0002477	89.70	gold quality
saliva-secreting gland	UBERON:0001044	89.09	gold quality
metanephros cortex	UBERON:0010533	88.89	gold quality
minor salivary gland	UBERON:0001830	88.84	gold quality
globus pallidus	UBERON:0001875	88.48	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	87.25
E-CURD-114	yes	43.46
E-ANND-3	yes	23.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting TMEM125, 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-4283	100.00	66.42	2097
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-6729-3P	96.91	66.79	703
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-362-5P	95.87	66.02	554
HSA-MIR-500B-5P	95.87	66.04	557
HSA-MIR-1914-3P	95.07	63.37	762

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem125b	ENSDARG00000075980
mus_musculus	Tmem125	ENSMUSG00000050854
rattus_norvegicus	Tmem125	ENSRNOG00000006924

Protein

Protein identifiers

Transmembrane protein 125 — Q96AQ2 (reviewed: Q96AQ2)

All UniProt accessions (2): E5RHB0, Q96AQ2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (2): NP_001307173, NP_653227* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028165	TMEM125	Family

Pfam: PF15109

UniProt features (7 total): transmembrane region 4, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AQ2-F1	66.62	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 70 (showing top): MYOGENIN_Q6, SP3_Q3, AREB6_01, SABATES_COLORECTAL_ADENOMA_SIZE_DN, AP4_Q6, CAGCTG_AP4_Q5, HEN1_01, chr1p34, TGIF_01, ARGGGTTAA_UNKNOWN, TGGAAA_NFAT_Q4_01, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, WGGAATGY_TEF1_Q6, LINDGREN_BLADDER_CANCER_CLUSTER_1_DN, XBP1_01

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (1): molecular_function (GO:0003674)

GO Cellular Component (2): membrane (GO:0016020), cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM125	FRAT2	O75474	475
TMEM125	PLPPR2	Q96GM1	469
TMEM125	CLDN19	Q8N6F1	461
TMEM125	IER2	Q9BTL4	442
TMEM125	KDF1	Q8NAX2	431
TMEM125	SEL1L2	Q5TEA6	408
TMEM125	ZNF442	Q9H7R0	398
TMEM125	TAL1	P17542	396
TMEM125	COL9A2	Q14055	396
TMEM125	FZD10	Q9ULW2	388
TMEM125	PHLDA1	Q8WV24	388
TMEM125	TMEM42	Q69YG0	373
TMEM125	SMIM8	Q96KF7	370
TMEM125	ZSWIM1	Q9BR11	365
TMEM125	ADNP	Q9H2P0	362

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GUA5, A0A1B0GVQ0, A0A286YF18, A0JNN8, A2VDX9, A5PK62, A6NGB7, A9CBA0, O09800, P04488, P06480, P06764, P07646, P0C171, P0DJK0, P0DJK1, P0DMQ5, P13291, P22389, P36342, P46695, P98162, Q08102, Q1RMT9, Q2HJ59, Q3TYP4, Q5BIR3, Q5EAA5, Q5JTB6, Q5NRQ0, Q6F5E0, Q6VUC0, Q6VUP9, Q703F0, Q765Z5, Q867A9, Q867D0, Q89448, Q8MJW9, Q8TEF2

Diamond homologs: Q2HJ59, Q8CHQ6, Q96AQ2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

759 predictions. Top by Δscore:

Variant	Effect	Δscore
1:43272345:GGCC:G	donor_gain	0.9900
1:43272952:T:A	acceptor_gain	0.9900
1:43272182:A:AG	acceptor_gain	0.9800
1:43272183:G:GG	acceptor_gain	0.9800
1:43270794:G:GG	donor_gain	0.9700
1:43272183:GCT:G	acceptor_gain	0.9700
1:43272183:GCTC:G	acceptor_gain	0.9700
1:43272335:GAGAG:G	donor_gain	0.9700
1:43272338:AG:A	donor_loss	0.9700
1:43272339:GGTCA:G	donor_loss	0.9700
1:43272340:G:GA	donor_loss	0.9700
1:43272961:T:A	acceptor_gain	0.9700
1:43270079:G:T	donor_gain	0.9600
1:43272337:GAG:G	donor_gain	0.9600
1:43270083:G:GT	donor_gain	0.9500
1:43272179:CACA:C	acceptor_loss	0.9500
1:43272181:CA:C	acceptor_loss	0.9500
1:43272182:AGCT:A	acceptor_loss	0.9500
1:43272183:G:GT	acceptor_loss	0.9500
1:43272256:T:A	acceptor_gain	0.9500
1:43272332:G:GT	donor_gain	0.9400
1:43272713:T:TA	acceptor_gain	0.9400
1:43270033:G:GT	donor_gain	0.9300
1:43270081:TGGAG:T	donor_loss	0.9300
1:43270083:GAGGT:G	donor_loss	0.9300
1:43270084:AGG:A	donor_loss	0.9300
1:43270085:GG:G	donor_loss	0.9300
1:43270086:G:GA	donor_loss	0.9300
1:43270087:T:A	donor_loss	0.9300
1:43271082:G:GT	donor_gain	0.9300

AlphaMissense

1360 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:43272918:T:A	W66R	0.994
1:43272918:T:C	W66R	0.994
1:43272920:G:C	W66C	0.994
1:43272920:G:T	W66C	0.994
1:43273080:A:C	S120R	0.994
1:43273082:T:A	S120R	0.994
1:43273082:T:G	S120R	0.994
1:43272945:T:C	C75R	0.991
1:43272974:A:C	K84N	0.989
1:43272974:A:T	K84N	0.989
1:43273004:G:A	M94I	0.989
1:43273004:G:C	M94I	0.989
1:43273004:G:T	M94I	0.989
1:43272803:G:C	W27C	0.987
1:43272803:G:T	W27C	0.987
1:43272933:G:C	G71R	0.987
1:43272984:A:C	S88R	0.987
1:43272986:C:A	S88R	0.987
1:43272986:C:G	S88R	0.987
1:43272973:A:T	K84I	0.986
1:43273104:G:C	G128R	0.986
1:43272934:G:A	G71D	0.985
1:43273000:A:C	D93A	0.985
1:43273083:G:C	G121R	0.985
1:43272979:T:C	L86P	0.984
1:43273000:A:T	D93V	0.984
1:43272868:G:A	G49D	0.983
1:43273194:G:C	G158R	0.983
1:43272864:T:C	C48R	0.982
1:43272877:G:A	G52D	0.982

dbSNP variants (sampled 300 via entrez): RS1000558724 (1:43271112 A>T), RS1000611000 (1:43270741 C>A,T), RS1002115261 (1:43271585 G>A,T), RS1002189948 (1:43269683 C>T), RS1002243760 (1:43270103 G>A), RS1002255048 (1:43271794 A>G), RS1003928583 (1:43268284 A>G), RS1004453393 (1:43270631 G>A,C), RS1005506144 (1:43271804 C>T), RS1005647027 (1:43270154 G>A,T), RS1006401952 (1:43271879 G>GA), RS1006782859 (1:43270711 G>A,C), RS1006961352 (1:43272198 C>G), RS1007920131 (1:43273354 C>T), RS1008450620 (1:43272223 G>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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	4
sodium arsenite	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Estradiol	affects cotreatment, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
trichostatin A	increases expression	1
tobacco tar	decreases expression	1
hydroquinone	increases expression	1
tebuconazole	decreases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	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
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Folic Acid	decreases expression	1
Hydrogen Peroxide	affects expression	1
Mustard Gas	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Tretinoin	increases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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