TMEM154

Summary

TMEM154 (transmembrane protein 154, HGNC:26489) is a protein-coding gene on chromosome 4q31.3, encoding Transmembrane protein 154 (Q6P9G4).

Predicted to be located in membrane.

Source: NCBI Gene 201799 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_152680

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26489
Approved symbol	TMEM154
Name	transmembrane protein 154
Location	4q31.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32028
Ensembl gene	ENSG00000170006
Ensembl biotype	protein_coding
Entrez	201799

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000304385, ENST00000504064, ENST00000510252, ENST00000705347, ENST00000705348, ENST00000705349, ENST00000869041

RefSeq mRNA: 1 — MANE Select: NM_152680 NM_152680

CCDS: CCDS3779

Canonical transcript exons

ENST00000304385 — 7 exons

Exon	Start	End
ENSE00001130838	152640928	152640985
ENSE00001130844	152652667	152652927
ENSE00001151857	152643088	152643173
ENSE00001151862	152644415	152644442
ENSE00001151871	152652538	152652576
ENSE00001200471	152618628	152628561
ENSE00002041662	152679870	152679997

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 98.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5589 / max 1886.8924, expressed in 1270 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54396	8.4077	895
54397	6.1435	1013
54395	0.7898	185
54398	0.2180	76

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	98.44	gold quality
gingival epithelium	UBERON:0001949	97.11	gold quality
gingiva	UBERON:0001828	95.95	gold quality
esophagus squamous epithelium	UBERON:0006920	95.16	gold quality
oral cavity	UBERON:0000167	94.64	gold quality
blood	UBERON:0000178	94.61	gold quality
upper leg skin	UBERON:0004262	93.90	gold quality
monocyte	CL:0000576	93.66	gold quality
penis	UBERON:0000989	93.65	gold quality
leukocyte	CL:0000738	93.46	gold quality
mammalian vulva	UBERON:0000997	92.71	gold quality
esophagus mucosa	UBERON:0002469	91.36	gold quality
pharyngeal mucosa	UBERON:0000355	90.43	gold quality
skin of hip	UBERON:0001554	90.39	gold quality
secondary oocyte	CL:0000655	90.19	gold quality
bone marrow cell	CL:0002092	89.64	gold quality
nasal cavity epithelium	UBERON:0005384	89.37	silver quality
skin of abdomen	UBERON:0001416	88.88	gold quality
bone marrow	UBERON:0002371	88.68	gold quality
zone of skin	UBERON:0000014	88.54	gold quality
trabecular bone tissue	UBERON:0002483	87.69	gold quality
bronchial epithelial cell	CL:0002328	87.64	gold quality
oocyte	CL:0000023	87.41	gold quality
lower esophagus mucosa	UBERON:0035834	87.37	gold quality
epithelium of nasopharynx	UBERON:0001951	87.15	gold quality
skin of leg	UBERON:0001511	87.14	gold quality
nasopharynx	UBERON:0001728	87.13	gold quality
bronchus	UBERON:0002185	86.72	gold quality
vermiform appendix	UBERON:0001154	86.36	gold quality
calcaneal tendon	UBERON:0003701	85.72	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-109979	yes	306.02
E-ANND-3	yes	18.18
E-MTAB-9067	yes	12.63
E-MTAB-9801	yes	9.62
E-MTAB-6678	yes	5.29
E-CURD-112	no	2.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting TMEM154, 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-3163	100.00	77.23	8605
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-548AC	99.84	70.77	4351

Literature-anchored findings (GeneRIF, showing 2)

• the diabetogenic impact of the C-allele of TMEM154-rs6813195 is mediated through reduced beta cell function. (PMID:25799151)
• Genetic associations of TMEM154, PRC1 and ZFAND6 loci with type 2 diabetes in an endogamous business community of North India. (PMID:37738238)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem154	ENSMUSG00000056498
rattus_norvegicus	Tmem154	ENSRNOG00000010866

Protein

Protein identifiers

Transmembrane protein 154 — Q6P9G4 (reviewed: Q6P9G4)

All UniProt accessions (4): Q6P9G4, A0A994J4V3, A0A994J5I7, A0A994J7E6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_689893* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028064	TMEM154	Family
IPR053087	TMEM154-like	Family

Pfam: PF15102

UniProt features (8 total): topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P9G4-F1	63.14	0.10

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): 179

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 148 (showing top): AGGAAGC_MIR5163P, BILD_HRAS_ONCOGENIC_SIGNATURE, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, RYTTCCTG_ETS2_B, SENESE_HDAC1_TARGETS_UP, GATA4_Q3, NUYTTEN_EZH2_TARGETS_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, MGGAAGTG_GABP_B, E4BP4_01, NUYTTEN_NIPP1_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MIKKELSEN_ES_ICP_WITH_H3K4ME3

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

556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM154	TMEM38A	Q9H6F2	579
TMEM154	SYTL3	Q4VX76	574
TMEM154	ZSCAN16	Q9H4T2	536
TMEM154	ARFIP1	P53367	532
TMEM154	DPPA2	Q7Z7J5	532
TMEM154	PRR16	Q569H4	487
TMEM154	TMEM223	A0PJW6	486
TMEM154	LACTBL1	A8MY62	480
TMEM154	SMIM7	Q9BQ49	478
TMEM154	TMEM53	Q6P2H8	473
TMEM154	RPP14	O95059	447
TMEM154	CCR5	P51681	413
TMEM154	TMEM238	C9JI98	413
TMEM154	APOB	P04114	409
TMEM154	DPPA4	Q7L190	403

IntAct

38 interactions, top by confidence:

A	B	Type	Score
SGTA	TMEM154	psi-mi:“MI:0915”(physical association)	0.560
PPGB	TMEM154	psi-mi:“MI:0915”(physical association)	0.560
	TMEM154	psi-mi:“MI:0915”(physical association)	0.560
CYB561D2	TMEM154	psi-mi:“MI:0915”(physical association)	0.560
TMEM154	FXYD6	psi-mi:“MI:0915”(physical association)	0.560
GET3	TMEM154	psi-mi:“MI:0915”(physical association)	0.560
MIP	TMEM154	psi-mi:“MI:0915”(physical association)	0.560
GYPA	TMEM154	psi-mi:“MI:0915”(physical association)	0.560
TMEM154	SLC35A4	psi-mi:“MI:0915”(physical association)	0.560
TMEM154	FUNDC2	psi-mi:“MI:0915”(physical association)	0.560
SMIM1	TMEM154	psi-mi:“MI:0915”(physical association)	0.560
TMEM154	rep	psi-mi:“MI:0915”(physical association)	0.370
TMEM154	VPS26A	psi-mi:“MI:0914”(association)	0.350
TMEM154	RPSA2	psi-mi:“MI:0914”(association)	0.350
TMEM154	SMCHD1	psi-mi:“MI:0914”(association)	0.350
SGTA	TMEM154	psi-mi:“MI:0915”(physical association)	0.000
	TMEM154	psi-mi:“MI:0915”(physical association)	0.000
CYB561D2	TMEM154	psi-mi:“MI:0915”(physical association)	0.000
FXYD6	TMEM154	psi-mi:“MI:0915”(physical association)	0.000
GET3	TMEM154	psi-mi:“MI:0915”(physical association)	0.000
MIP	TMEM154	psi-mi:“MI:0915”(physical association)	0.000
SMIM1	TMEM154	psi-mi:“MI:0915”(physical association)	0.000
PPGB	TMEM154	psi-mi:“MI:0915”(physical association)	0.000
GYPA	TMEM154	psi-mi:“MI:0915”(physical association)	0.000
SLC35A4	TMEM154	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): TMEM154 (Two-hybrid), TMEM154 (Two-hybrid), TMEM154 (Two-hybrid), TMEM154 (Two-hybrid), TMEM154 (Two-hybrid), TMEM154 (Two-hybrid), TMEM154 (Two-hybrid), GYPA (Two-hybrid), SLC35A4 (Two-hybrid), ASNA1 (Two-hybrid), SMIM1 (Two-hybrid), TMEM192 (Affinity Capture-MS), GIT2 (Affinity Capture-MS), TMEM68 (Affinity Capture-MS), ARHGEF7 (Affinity Capture-MS)

ESM2 similar proteins: A0A5F4BST2, A5PJC7, A8MWV9, D3ZZP4, O14836, P0CAN6, P11911, P11912, P14753, Q01114, Q07303, Q13113, Q2KI80, Q2KL21, Q3TS39, Q3URD2, Q4V9L6, Q5F267, Q5FVJ4, Q5FVQ7, Q5RA41, Q5T1S8, Q6P9G4, Q6UWJ8, Q6UX34, Q80VJ8, Q810F0, Q86XR5, Q8BRJ3, Q8BX43, Q8K064, Q8K5A9, Q8N112, Q8N4K4, Q8N6L0, Q8NBR0, Q8NC24, Q8QZT4, Q8R138, Q923S2

Diamond homologs: Q6P9G4, Q8C4Q9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1493 predictions. Top by Δscore:

Variant	Effect	Δscore
4:152640923:AGTAC:A	donor_loss	1.0000
4:152640924:GTACC:G	donor_loss	1.0000
4:152640925:TAC:T	donor_loss	1.0000
4:152640926:A:T	donor_loss	1.0000
4:152640981:GTCGG:G	acceptor_gain	1.0000
4:152640982:TCGG:T	acceptor_gain	1.0000
4:152640983:CGG:C	acceptor_gain	1.0000
4:152640983:CGGC:C	acceptor_gain	1.0000
4:152640984:GG:G	acceptor_gain	1.0000
4:152640985:GCTAG:G	acceptor_loss	1.0000
4:152640986:C:CC	acceptor_gain	1.0000
4:152640987:T:C	acceptor_loss	1.0000
4:152640992:C:CT	acceptor_gain	1.0000
4:152643169:TAGGG:T	acceptor_gain	1.0000
4:152643171:GGG:G	acceptor_gain	1.0000
4:152643172:GG:G	acceptor_gain	1.0000
4:152643174:C:CC	acceptor_gain	1.0000
4:152644230:CACG:C	donor_gain	1.0000
4:152668447:C:CA	donor_gain	1.0000
4:152679868:ACC:A	donor_gain	1.0000
4:152679869:CCC:C	donor_gain	1.0000
4:152640984:G:T	acceptor_gain	0.9900
4:152640993:A:T	acceptor_gain	0.9900
4:152640996:A:AC	acceptor_gain	0.9900
4:152642953:T:C	donor_gain	0.9900
4:152643083:CATA:C	donor_loss	0.9900
4:152643085:T:TG	donor_loss	0.9900
4:152643086:A:AC	donor_gain	0.9900
4:152643086:A:AG	donor_loss	0.9900
4:152643087:C:CC	donor_gain	0.9900

AlphaMissense

1204 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:152643120:A:G	L149P	0.996
4:152643164:A:C	F134L	0.996
4:152643164:A:T	F134L	0.996
4:152643166:A:G	F134L	0.996
4:152643110:C:A	W152C	0.995
4:152643110:C:G	W152C	0.995
4:152643112:A:G	W152R	0.995
4:152643112:A:T	W152R	0.995
4:152643144:A:T	V141D	0.994
4:152643157:C:G	D137H	0.993
4:152643165:A:C	F134C	0.993
4:152643156:T:G	D137A	0.992
4:152643156:T:A	D137V	0.990
4:152643132:T:A	E145V	0.989
4:152643165:A:G	F134S	0.986
4:152643156:T:C	D137G	0.985
4:152643120:A:T	L149H	0.984
4:152643135:A:C	I144S	0.984
4:152643155:A:C	D137E	0.984
4:152643155:A:T	D137E	0.984
4:152643132:T:C	E145G	0.982
4:152643144:A:C	V141G	0.980
4:152643148:A:G	S140P	0.979
4:152643138:T:A	E143V	0.978
4:152652744:G:C	P83R	0.978
4:152643132:T:G	E145A	0.977
4:152643140:C:A	M142I	0.977
4:152643140:C:G	M142I	0.977
4:152643140:C:T	M142I	0.977
4:152643111:C:G	W152S	0.976

dbSNP variants (sampled 300 via entrez): RS1000058502 (4:152679031 T>C), RS1000093515 (4:152672507 T>C), RS1000197552 (4:152633437 T>G), RS1000216403 (4:152646931 C>T), RS1000293602 (4:152669730 C>T), RS10003323 (4:152649301 A>T), RS1000399071 (4:152665927 A>C,G), RS1000445113 (4:152663562 T>A), RS1000452029 (4:152660007 C>T), RS1000511780 (4:152628655 G>A,T), RS10005426 (4:152618205 T>C), RS1000641930 (4:152635519 G>A), RS1000685290 (4:152669268 C>A,T), RS1000809509 (4:152635034 T>A,G), RS10008259 (4:152668713 G>T)

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

12 associations (top):

Study	Trait	p-value
GCST002352_41	Type 2 diabetes	4.000000e-14
GCST004894_126	Type 2 diabetes	2.000000e-15
GCST004894_51	Type 2 diabetes	7.000000e-09
GCST005050_2	Obstructive sleep apnea during REM sleep (apnea hypopnea index)	5.000000e-07
GCST005414_10	Type 2 diabetes	8.000000e-06
GCST006867_36	Type 2 diabetes	2.000000e-10
GCST007847_15	Type 2 diabetes	4.000000e-13
GCST007847_25	Type 2 diabetes	3.000000e-17
GCST008162_98	Hip circumference	6.000000e-06
GCST009379_267	Type 2 diabetes	1.000000e-14
GCST010118_39	Type 2 diabetes	1.000000e-27
GCST90006995_3	Gut microbiota relative abundance (unclassified genus belonging to family Lachnospiraceae)	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008455	sleep apnea measurement during REM sleep
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
trichostatin A	increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	increases methylation, affects response to substance, increases expression, affects methylation, decreases expression	3
mercuric bromide	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
triphenyl phosphate	affects expression	1
titanium dioxide	increases expression	1
3,4-dichloroaniline	increases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
diallyl trisulfide	increases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	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
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MT19c compound	increases expression	1

Clinical trials (associated diseases)

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