TMEM158

Summary

TMEM158 (transmembrane protein 158, HGNC:30293) is a protein-coding gene on chromosome 3p21.31, encoding Transmembrane protein 158 (Q8WZ71). Receptor for brain injury-derived neurotrophic peptide (BINP), a synthetic 13-mer peptide.

Constitutive activation of the Ras pathway triggers an irreversible proliferation arrest reminiscent of replicative senescence. Transcription of this gene is upregulated in response to activation of the Ras pathway, but not under other conditions that induce senescence. The encoded protein is similar to a rat cell surface receptor proposed to function in a neuronal survival pathway. An allelic polymorphism in this gene results in both functional and non-functional (frameshifted) alleles; the reference genome represents the functional allele.

Source: NCBI Gene 25907 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_015444

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30293
Approved symbol	TMEM158
Name	transmembrane protein 158
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	RIS1, p40BBp
Ensembl gene	ENSG00000249992
Ensembl biotype	protein_coding
OMIM	620257
Entrez	25907

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000503771

RefSeq mRNA: 1 — MANE Select: NM_015444 NM_015444

CCDS: CCDS54573

Canonical transcript exons

ENST00000503771 — 1 exons

Exon	Start	End
ENSE00002028020	45224466	45226287

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 96.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.2762 / max 1025.1256, expressed in 1589 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41895	46.3038	1586
41894	0.4285	195
41892	0.3492	162
41893	0.1947	92

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	96.58	gold quality
nucleus accumbens	UBERON:0001882	95.25	gold quality
putamen	UBERON:0001874	94.18	gold quality
caudate nucleus	UBERON:0001873	94.15	gold quality
ganglionic eminence	UBERON:0004023	93.97	gold quality
myometrium	UBERON:0001296	93.20	gold quality
periodontal ligament	UBERON:0008266	92.60	gold quality
cauda epididymis	UBERON:0004360	91.92	gold quality
entorhinal cortex	UBERON:0002728	91.23	gold quality
body of uterus	UBERON:0009853	90.47	gold quality
stromal cell of endometrium	CL:0002255	89.99	gold quality
cartilage tissue	UBERON:0002418	89.83	gold quality
lateral globus pallidus	UBERON:0002476	89.06	silver quality
lower esophagus mucosa	UBERON:0035834	88.44	gold quality
temporal lobe	UBERON:0001871	88.36	gold quality
ventricular zone	UBERON:0003053	87.86	gold quality
amygdala	UBERON:0001876	87.77	gold quality
CA1 field of hippocampus	UBERON:0003881	86.91	gold quality
olfactory bulb	UBERON:0002264	86.33	gold quality
hypothalamus	UBERON:0001898	86.27	gold quality
adult organism	UBERON:0007023	86.03	gold quality
superior frontal gyrus	UBERON:0002661	85.95	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.76	gold quality
telencephalon	UBERON:0001893	85.74	gold quality
Ammon’s horn	UBERON:0001954	85.70	gold quality
middle frontal gyrus	UBERON:0002702	85.60	gold quality
postcentral gyrus	UBERON:0002581	85.22	gold quality
forebrain	UBERON:0001890	85.10	gold quality
Brodmann (1909) area 10	UBERON:0013541	85.00	gold quality
type B pancreatic cell	CL:0000169	84.87	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.90
E-MTAB-10290	no	433.69
E-MTAB-6075	no	63.07

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1

miRNA regulators (miRDB)

50 targeting TMEM158, 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-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-544A	99.84	68.66	1965
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-548A-3P	99.76	70.58	3524
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-3120-3P	99.54	70.28	2669

Literature-anchored findings (GeneRIF, showing 7)

• Suggested role of Ris-1 as tumor suppressor gene is not evident, at least in breast cancer. (PMID:16280139)
• RIS1 exhibits frameshift mutations in high-frequency microsatellite instability tumors, and its alteration is correlated with mutations in two target genes BAX and TGFBR2, linking it to the mutator pathway in colorectal carcinogenesis. (PMID:16737913)
• Silencing of TMEM158 Inhibits Tumorigenesis and Multidrug Resistance in Colorectal Cancer. (PMID:31389251)
• TMEM158 promotes pancreatic cancer aggressiveness by activation of TGFbeta1 and PI3K/AKT signaling pathway. (PMID:31531884)
• TMEM158 May Serve as a Diagnostic Biomarker for Anaplastic Thyroid Carcinoma: An Integrated Bioinformatic Analysis. (PMID:33428142)
• TMEM158 promotes the proliferation and migration of glioma cells via STAT3 signaling in glioblastomas. (PMID:34992215)
• TMEM158 functions as an oncogene and promotes lung adenocarcinoma progression through the PI3K/AKT pathway via interaction with TWIST1. (PMID:38508329)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem158	ENSMUSG00000054871
rattus_norvegicus	Tmem158	ENSRNOG00000072779

Protein

Protein identifiers

Transmembrane protein 158 — Q8WZ71 (reviewed: Q8WZ71)

Alternative names: 40 kDa BINP-binding protein, Ras-induced senescence protein 1

All UniProt accessions (1): Q8WZ71

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for brain injury-derived neurotrophic peptide (BINP), a synthetic 13-mer peptide.

Subcellular location. Membrane.

Post-translational modifications. N-glycosylated.

Induction. Up-regulated during Ras-induced senescence.

Similarity. Belongs to the TMEM158 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WZ71-1	1	yes
Q8WZ71-2	2

RefSeq proteins (1): NP_056259* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038962	TMEM158	Family

UniProt features (7 total): transmembrane region 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WZ71-F1	58.36	0.07

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 (1): 75

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 181 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WALLACE_PROSTATE_CANCER_RACE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MODULE_118, BILD_E2F3_ONCOGENIC_SIGNATURE, RIGGI_EWING_SARCOMA_PROGENITOR_DN, DASU_IL6_SIGNALING_UP, MODULE_544, SENESE_HDAC1_TARGETS_UP, HAN_SATB1_TARGETS_DN

GO Biological Process (0):

GO Molecular Function (1): peptide binding (GO:0042277)

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

500 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM158	TMEM45A	Q9NWC5	578
TMEM158	C2CD2	Q9Y426	469
TMEM158	TSR3	Q9UJK0	458
TMEM158	EBPL	Q9BY08	455
TMEM158	SLC35G2	Q8TBE7	440
TMEM158	TMEM98	Q9Y2Y6	421
TMEM158	TMEM88	Q6PEY1	419
TMEM158	TMEM14A	Q9Y6G1	408
TMEM158	TAF10	Q12962	407
TMEM158	NDC1	Q9BTX1	391
TMEM158	COL8A2	P25067	387
TMEM158	CMPK2	Q5EBM0	381
TMEM158	TMEM213	A2RRL7	380
TMEM158	CCDC71	Q8IV32	378
TMEM158	RTP3	Q9BQQ7	373

IntAct

4 interactions, top by confidence:

A	B	Type	Score
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): TMEM158 (Affinity Capture-MS), TMEM158 (Affinity Capture-MS), TMEM158 (Affinity Capture-RNA), TMEM158 (Affinity Capture-MS), TMEM158 (Affinity Capture-MS)

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: A2VDX9, Q6F5E0, Q8WZ71, Q91XV7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

43 predictions. Top by Δscore:

Variant	Effect	Δscore
3:45225265:C:CT	acceptor_gain	0.4700
3:45225335:C:CT	acceptor_gain	0.4300
3:45225326:C:CT	acceptor_gain	0.3600
3:45225709:C:CT	acceptor_gain	0.3600
3:45225377:A:AC	donor_gain	0.3100
3:45225378:C:CC	donor_gain	0.3100
3:45225427:C:CC	acceptor_gain	0.3100
3:45225703:CG:C	acceptor_gain	0.2800
3:45225373:G:GA	donor_gain	0.2700
3:45225451:C:CA	acceptor_gain	0.2700
3:45225704:G:C	acceptor_gain	0.2700
3:45225265:C:T	acceptor_gain	0.2600
3:45225432:C:A	acceptor_gain	0.2600
3:45225612:T:TA	donor_gain	0.2600
3:45225369:ATGGG:A	donor_gain	0.2500
3:45225137:C:CT	donor_gain	0.2400
3:45225781:G:C	donor_gain	0.2400
3:45225136:C:CT	donor_gain	0.2300
3:45225321:C:CT	acceptor_gain	0.2300
3:45225336:A:T	acceptor_gain	0.2300
3:45225379:G:C	donor_gain	0.2300
3:45225424:AGTCT:A	acceptor_gain	0.2300
3:45225686:G:T	acceptor_gain	0.2300
3:45225200:C:CA	donor_gain	0.2200
3:45225297:G:T	acceptor_gain	0.2200
3:45225736:A:AC	donor_gain	0.2200
3:45225737:C:CC	donor_gain	0.2200
3:45225435:C:A	acceptor_gain	0.2100
3:45225449:C:T	acceptor_gain	0.2100
3:45225707:CGCGT:C	acceptor_gain	0.2100

AlphaMissense

1871 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:45225275:G:C	F251L	1.000
3:45225275:G:T	F251L	1.000
3:45225276:A:C	F251C	1.000
3:45225277:A:G	F251L	1.000
3:45225285:A:T	I248N	1.000
3:45225301:A:G	W243R	1.000
3:45225301:A:T	W243R	1.000
3:45225306:A:T	L241H	1.000
3:45225312:G:T	A239D	1.000
3:45225317:G:C	S237R	1.000
3:45225317:G:T	S237R	1.000
3:45225319:T:G	S237R	1.000
3:45225322:A:G	W236R	1.000
3:45225322:A:T	W236R	1.000
3:45225330:A:T	I233N	1.000
3:45225341:C:A	M229I	1.000
3:45225341:C:G	M229I	1.000
3:45225341:C:T	M229I	1.000
3:45225342:A:T	M229K	1.000
3:45225349:A:G	C227R	1.000
3:45225389:C:A	W213C	1.000
3:45225389:C:G	W213C	1.000
3:45225423:A:C	F202C	1.000
3:45225423:A:G	F202S	1.000
3:45225758:C:A	W90C	1.000
3:45225758:C:G	W90C	1.000
3:45225276:A:G	F251S	0.999
3:45225282:G:T	A249D	0.999
3:45225285:A:C	I248S	0.999
3:45225288:A:G	I247T	0.999

dbSNP variants (sampled 300 via entrez): RS1002375286 (3:45227695 T>C), RS1002404270 (3:45228118 G>A), RS1003338694 (3:45226420 G>A), RS1003409116 (3:45226597 G>C), RS1003575968 (3:45226931 G>C,T), RS1004448572 (3:45224177 G>T), RS1005448403 (3:45227751 G>A,C), RS1006567878 (3:45227001 G>T), RS1007256103 (3:45226854 C>G,T), RS1007740541 (3:45227215 G>A), RS1008331765 (3:45224853 G>A,T), RS1008677730 (3:45224339 A>G), RS1009022433 (3:45226347 C>G), RS1009277676 (3:45225522 GTGGCGGCGGCGGCGC>G), RS1009384397 (3:45226456 C>T)

Disease associations

OMIM: gene MIM:620257 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002481_7	Acne (severe)	3.000000e-06
GCST002740_80	Inflammatory skin disease	5.000000e-07
GCST006947_43	Feeling fed-up	1.000000e-08
GCST007001_3	Cerebrospinal AB1-42 levels in normal cognition	5.000000e-07
GCST009391_1946	Metabolite levels	2.000000e-06
GCST011065_8	Levodopa-induced dyskinesia in levodopa treated Parkinson’s disease	4.000000e-06
GCST012501_1	Achilles tendon injury	2.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0009588	feeling “fed-up” measurement
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0010462	aspartate measurement
EFO:0010747	response to levodopa
EFO:0600078	Achilles tendon injury

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
trichostatin A	affects cotreatment, decreases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment	3
Temozolomide	affects response to substance, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	affects expression, increases expression	2
Doxorubicin	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Progesterone	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tamoxifen	affects expression, affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
lead acetate	increases expression	1
sodium arsenate	increases abundance, increases expression	1
hydroxyhydroquinone	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
nickel chloride	increases expression	1
diallyl trisulfide	increases expression	1
beta-methylcholine	affects expression	1

Clinical trials (associated diseases)

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