TMEM254

Summary

TMEM254 (transmembrane protein 254, HGNC:25804) is a protein-coding gene on chromosome 10q22.3, encoding Transmembrane protein 254 (Q8TBM7).

Predicted to be located in membrane.

Source: NCBI Gene 80195 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_025125

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25804
Approved symbol	TMEM254
Name	transmembrane protein 254
Location	10q22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13263, bA369J21.6
Ensembl gene	ENSG00000133678
Ensembl biotype	protein_coding
Entrez	80195

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000372273, ENST00000372274, ENST00000372275, ENST00000372277, ENST00000372281, ENST00000450179, ENST00000463029, ENST00000463209, ENST00000467529, ENST00000472622, ENST00000476173, ENST00000483732, ENST00000613758, ENST00000896381

RefSeq mRNA: 9 — MANE Select: NM_025125 NM_001270367, NM_001270368, NM_001270369, NM_001270370, NM_001270371, NM_001270372, NM_001270373, NM_001270374, NM_025125

CCDS: CCDS58086, CCDS58087, CCDS73157, CCDS7363

Canonical transcript exons

ENST00000372281 — 4 exons

Exon	Start	End
ENSE00000909271	80078665	80078786
ENSE00003534950	80082145	80082204
ENSE00003545276	80081841	80081944
ENSE00003845654	80090797	80092551

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 96.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.5398 / max 143.1427, expressed in 1774 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105838	13.7338	1748
105840	4.1827	1482
105839	0.6233	193

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.58	gold quality
skin of abdomen	UBERON:0001416	94.86	gold quality
lower esophagus mucosa	UBERON:0035834	94.56	gold quality
skin of leg	UBERON:0001511	93.40	gold quality
esophagus mucosa	UBERON:0002469	92.80	gold quality
zone of skin	UBERON:0000014	92.66	gold quality
right testis	UBERON:0004534	91.70	gold quality
rectum	UBERON:0001052	91.53	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.33	gold quality
left testis	UBERON:0004533	91.18	gold quality
bronchial epithelial cell	CL:0002328	90.33	gold quality
upper arm skin	UBERON:0004263	90.23	gold quality
right lobe of liver	UBERON:0001114	90.17	gold quality
upper leg skin	UBERON:0004262	89.82	gold quality
mammalian vulva	UBERON:0000997	89.65	gold quality
testis	UBERON:0000473	89.36	gold quality
ventricular zone	UBERON:0003053	89.21	gold quality
gall bladder	UBERON:0002110	89.16	gold quality
right adrenal gland cortex	UBERON:0035827	89.15	gold quality
right adrenal gland	UBERON:0001233	88.94	gold quality
esophagus	UBERON:0001043	88.84	gold quality
epithelium of bronchus	UBERON:0002031	88.63	gold quality
vagina	UBERON:0000996	88.15	gold quality
body of pancreas	UBERON:0001150	87.98	gold quality
minor salivary gland	UBERON:0001830	87.82	gold quality
bronchus	UBERON:0002185	87.81	gold quality
left adrenal gland	UBERON:0001234	87.61	gold quality
corpus epididymis	UBERON:0004359	87.60	gold quality
mouth mucosa	UBERON:0003729	87.26	gold quality
ganglionic eminence	UBERON:0004023	87.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting TMEM254, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem254	ENSDARG00000109902
mus_musculus	Tmem254	ENSMUSG00000072676
rattus_norvegicus	Tmem254	ENSRNOG00000011276

Protein

Protein identifiers

Transmembrane protein 254 — Q8TBM7 (reviewed: Q8TBM7)

All UniProt accessions (4): A0A087WZM8, Q8TBM7, H0Y376, H0Y4Q8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TBM7-1	1	yes
Q8TBM7-2	2
Q8TBM7-3	3

RefSeq proteins (9): NP_001257296, NP_001257297, NP_001257298, NP_001257299, NP_001257300, NP_001257301, NP_001257302, NP_001257303, NP_079401* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028110	TMEM254	Domain

Pfam: PF14934

UniProt features (11 total): sequence conflict 3, transmembrane region 3, splice variant 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBM7-F1	90.37	0.79

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 43 (showing top): WANG_TUMOR_INVASIVENESS_DN, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GCM_USP6, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, KRIEG_KDM3A_TARGETS_NOT_HYPOXIA, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, ZNF407_TARGET_GENES, ZNF768_TARGET_GENES, MIR6809_3P, MIR2052, MIR12131, MIR1276, MIR12132, MIR140_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

1696 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM254	PLAC9	Q5JTB6	608
TMEM254	OR4D9	Q8NGE8	578
TMEM254	GPHB5	Q86YW7	522
TMEM254	SLC9A8	Q9Y2E8	490
TMEM254	KBTBD12	Q3ZCT8	445
TMEM254	SH2D4B	Q5SQS7	433
TMEM254	CIMIP2B	A8MTA8	431
TMEM254	DYDC1	Q8WWB3	423
TMEM254	GP6	Q9HCN6	407
TMEM254	ANKLE1	Q8NAG6	396
TMEM254	D6RAR5	D6RAR5	395
TMEM254	DYDC2	Q96IM9	381
TMEM254	B4GALNT4	Q76KP1	377
TMEM254	FNDC4	Q9H6D8	373
TMEM254	CRCP	O75575	370
TMEM254	HAGHL	Q6PII5	370

IntAct

125 interactions, top by confidence:

A	B	Type	Score
TMEM254	TMX2	psi-mi:“MI:0915”(physical association)	0.560
TMEM254	MTIF3	psi-mi:“MI:0915”(physical association)	0.560
TMEM254	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
TMEM254	AQP6	psi-mi:“MI:0915”(physical association)	0.560
TMEM254	BCL2L13	psi-mi:“MI:0915”(physical association)	0.560
STX1A	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
TMEM254	TMEM79	psi-mi:“MI:0915”(physical association)	0.560
TMEM254	MFF	psi-mi:“MI:0915”(physical association)	0.560
FKBP8	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
CD74	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
TMED8	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
BIK	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
TMEM254	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0E1	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
PAGE1	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
ARL13B	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
IFNGR2	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
FNDC9	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
EBP	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
TMEM254	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
TMEM254	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
SYT1	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
TMEM254	GPR152	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (47): TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid), TMEM254 (Two-hybrid)

ESM2 similar proteins: A0A067DFU5, A0A0E3D8L0, A0A0E3D8M3, A0A0U5GIU9, A0A140JWS9, A0A194XJW1, A0A1V6NYL5, E2RDM9, E3UBL5, F5HGH8, F5HHT6, O82245, O94327, O94440, P09723, P0CU77, P0DXH1, P0DXW0, P0DXW1, P16257, P30535, P50637, P58872, P58873, P97689, P9WEQ3, Q07764, Q0C8A7, Q0C9L5, Q0D2G3, Q10255, Q13336, Q2KIB3, Q5AR23, Q5R9A6, Q5RFN8, Q5TGU0, Q5U4Q2, Q6GNM0, Q6TEK3

Diamond homologs: P0DN89, Q0D2G3, Q5R9A6, Q5U220, Q8TBM7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1239 predictions. Top by Δscore:

Variant	Effect	Δscore
10:80078787:G:GG	donor_gain	1.0000
10:80078877:G:GT	donor_gain	1.0000
10:80078877:G:T	donor_gain	1.0000
10:80080335:T:G	donor_gain	1.0000
10:80081839:AGTG:A	acceptor_gain	1.0000
10:80081840:GTGG:G	acceptor_gain	1.0000
10:80082201:GCAA:G	donor_gain	1.0000
10:80082205:G:GG	donor_gain	1.0000
10:80078848:GACC:G	donor_gain	0.9900
10:80078924:G:T	donor_gain	0.9900
10:80078991:GGCCC:G	donor_gain	0.9900
10:80080392:T:G	donor_gain	0.9900
10:80081839:AGT:A	acceptor_gain	0.9900
10:80081840:GT:G	acceptor_gain	0.9900
10:80081840:GTG:G	acceptor_gain	0.9900
10:80086368:G:GG	donor_gain	0.9900
10:80078951:C:T	donor_gain	0.9800
10:80081839:A:AG	acceptor_gain	0.9800
10:80081839:AGTGG:A	acceptor_gain	0.9800
10:80081840:G:GA	acceptor_gain	0.9800
10:80081840:GTGGG:G	acceptor_gain	0.9800
10:80082038:T:TA	donor_gain	0.9800
10:80082039:A:AA	donor_gain	0.9800
10:80082204:AGTAA:A	donor_loss	0.9800
10:80082205:G:C	donor_loss	0.9800
10:80082206:T:A	donor_loss	0.9800
10:80082207:A:AG	donor_loss	0.9800
10:80082208:AG:A	donor_loss	0.9800
10:80082209:G:C	donor_loss	0.9800
10:80082572:A:AG	acceptor_gain	0.9800

AlphaMissense

795 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:80078769:A:C	S24R	0.963
10:80078771:C:A	S24R	0.963
10:80078771:C:G	S24R	0.963
10:80078727:T:C	F10L	0.940
10:80078729:T:A	F10L	0.940
10:80078729:T:G	F10L	0.940
10:80090834:T:A	W97R	0.931
10:80090834:T:C	W97R	0.931
10:80090859:G:A	G105E	0.916
10:80090880:T:C	L112S	0.912
10:80090808:T:C	I88T	0.900
10:80082158:T:A	W69R	0.889
10:80082158:T:C	W69R	0.889
10:80082178:G:C	E75D	0.884
10:80082178:G:T	E75D	0.884
10:80090859:G:T	G105V	0.881
10:80082167:C:G	H72D	0.877
10:80090858:G:T	G105W	0.870
10:80082169:T:A	H72Q	0.869
10:80082169:T:G	H72Q	0.869
10:80090858:G:A	G105R	0.867
10:80090858:G:C	G105R	0.867
10:80082202:C:G	C83W	0.862
10:80082189:C:A	A79D	0.861
10:80081893:G:A	G47D	0.857
10:80081892:G:C	G47R	0.848
10:80081841:T:A	W30R	0.846
10:80081841:T:C	W30R	0.846
10:80090836:G:C	W97C	0.845
10:80090836:G:T	W97C	0.845

dbSNP variants (sampled 300 via entrez): RS1000074625 (10:80089500 G>T), RS1000428633 (10:80078739 A>C,G,T), RS1001749771 (10:80077987 C>A,G), RS1002135010 (10:80077185 C>T), RS1002331003 (10:80082699 A>G), RS1002392803 (10:80088497 C>G), RS1002521404 (10:80090973 G>A), RS1002623121 (10:80082938 CTA>C), RS1002826828 (10:80078973 T>C), RS1002885518 (10:80080220 G>C), RS1003093159 (10:80085293 C>T), RS1003215813 (10:80081515 A>G), RS1003397826 (10:80087147 A>G), RS1003425329 (10:80086877 T>C,G), RS1003987141 (10:80081874 C>A,G)

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, increases expression, affects cotreatment	8
Nickel	decreases expression	2
Cyclosporine	decreases expression	2
bisphenol F	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Bortezomib	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation, decreases methylation	1
Catechin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Phthalic Acids	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	increases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Isotretinoin	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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