TMEM238L

Summary

TMEM238L (transmembrane protein 238 like, HGNC:44356) is a protein-coding gene on chromosome 17p13.1-p12, encoding Transmembrane protein 238-like (A6NJY4). May play a role in inducing apoptosis during endoplasmic reticulum (ER) stress and in the inhibition of proliferation and tumorigenicity.

Involved in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress. Located in endoplasmic reticulum membrane.

Source: NCBI Gene 100289255 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001388428

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44356
Approved symbol	TMEM238L
Name	transmembrane protein 238 like
Location	17p13.1-p12
Locus type	gene with protein product
Status	Approved
Aliases	FORCP
Ensembl gene	ENSG00000263429
Ensembl biotype	protein_coding
Entrez	100289255

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000578763, ENST00000581851

RefSeq mRNA: 1 — MANE Select: NM_001388428 NM_001388428

CCDS: CCDS92258

Canonical transcript exons

ENST00000581851 — 2 exons

Exon	Start	End
ENSE00002727053	10803606	10804099
ENSE00003978267	10794908	10795948

Expression profiles

Bgee: expression breadth broad, 99 present calls, max score 95.72.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2227 / max 60.8745, expressed in 45 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164624	0.1443	34
164625	0.0423	18
164623	0.0156	5
164621	0.0150	5
164622	0.0055	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.72	gold quality
rectum	UBERON:0001052	93.26	gold quality
duodenum	UBERON:0002114	89.07	gold quality
transverse colon	UBERON:0001157	83.17	gold quality
body of stomach	UBERON:0001161	80.43	gold quality
stomach	UBERON:0000945	79.39	gold quality
small intestine	UBERON:0002108	74.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.26	gold quality
lower esophagus mucosa	UBERON:0035834	71.92	gold quality
fundus of stomach	UBERON:0001160	70.48	gold quality
gall bladder	UBERON:0002110	70.45	gold quality
colonic epithelium	UBERON:0000397	70.03	gold quality
esophagus mucosa	UBERON:0002469	68.84	gold quality
intestine	UBERON:0000160	68.18	gold quality
colon	UBERON:0001155	65.79	gold quality
vermiform appendix	UBERON:0001154	64.99	gold quality
urinary bladder	UBERON:0001255	63.37	gold quality
right lobe of liver	UBERON:0001114	58.77	gold quality
smooth muscle tissue	UBERON:0001135	58.55	gold quality
mucosa of stomach	UBERON:0001199	56.75	gold quality
liver	UBERON:0002107	54.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	54.51	gold quality
skin of abdomen	UBERON:0001416	52.34	gold quality
sural nerve	UBERON:0015488	52.00	gold quality
esophagus	UBERON:0001043	51.70	gold quality
zone of skin	UBERON:0000014	51.29	gold quality
metanephros cortex	UBERON:0010533	51.12	gold quality
skin of leg	UBERON:0001511	50.48	gold quality
muscle tissue	UBERON:0002385	49.47	gold quality
adult mammalian kidney	UBERON:0000082	47.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.77

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 9)

• Linc00675 may function as an oncogene during pancreatic ductal adenocarcinoma development, and its expression is an independent predictor of unfavorable prognosis in patients with PDAC. (PMID:26309360)
• LINC00675 interacted with vimentin, a protein involved in cell metastasis, and enhanced its phosphorylation level on Ser83 to result in the collapse of vimentin filament in GC cells, thereby reducing cell metastasis. (PMID:29107103)
• Overexpression of Linc00675 inhibited the proliferation, invasion and migration of colorectal cancer cells. (PMID:29524886)
• LINC00675 acts as a tumor promoter in glioma progression.Levels of LINC00675 expression are increased in glioma tissues. (PMID:30061182)
• LINC00675 promoted cancer cell proliferation, migration, and invasion, and inhibit apoptosis likely by modulating the Wnt/beta-catenin pathway. (PMID:30372871)
• Long non-coding RNA LINC00675 is associated with bladder cancer metastasis and patient survival. (PMID:32367602)
• A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells. (PMID:33112233)
• Investigation of Long Non-coding RNAs H19 and LINC00675 in Colorectal Cancers in Terms of Histopathological Features and Correlations With Plasma Markers. (PMID:35220220)
• Long noncoding RNA LINC00675 drives malignancy in acute myeloid leukemia via the miR-6809 -CDK6 axis. (PMID:38422911)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem238l	ENSMUSG00000085683
rattus_norvegicus	Tmem238l	ENSRNOG00000069550

Protein

Protein identifiers

Transmembrane protein 238-like — A6NJY4 (reviewed: A6NJY4)

Alternative names: FOXA1-regulated conserved small protein

All UniProt accessions (1): A6NJY4

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in inducing apoptosis during endoplasmic reticulum (ER) stress and in the inhibition of proliferation and tumorigenicity.

Subunit / interactions. Interacts with BRI3BP.

Subcellular location. Endoplasmic reticulum membrane.

Induction. Induced by FOXA1 in well-differentiated colorectal cancer (CRC) cells.

Miscellaneous. The TMEM238L transcript is unstable, and this instability is partly mediated through a conserved region containing AU-rich sequences in the TMEM238L 3’UTR. Cancer cells lacking this conserved region display decreased proliferation and clonogenicity.

RefSeq proteins (1): NP_001375357* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029365	TMEM238	Family

Pfam: PF15125

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NJY4-F1	84.63	0.59

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): chr17p12, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_DN, KRAS.LUNG_UP.V1_UP, NKX2_3_TARGET_GENES, FAN_EMBRYONIC_CTX_BIG_GROUPS_CAJAL_RETZIUS, BUSSLINGER_GASTRIC_METALLOTHIONEIN_CELLS, DESCARTES_MAIN_FETAL_GOBLET_CELLS, DESCARTES_FETAL_KIDNEY_URETERIC_BUD_CELLS

GO Biological Process (1): intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to endoplasmic reticulum stress	1
intrinsic apoptotic signaling pathway	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM238L	TRIP6	Q15654	435
TMEM238L	ARHGAP9	Q9BRR9	308
TMEM238L	FEZF1	A0PJY2	297
TMEM238L	SULT6B1	Q6IMI4	296
TMEM238L	TMEM238	C9JI98	295
TMEM238L	UBL4B	Q8N7F7	294
TMEM238L	TMEM167B	Q9NRX6	247
TMEM238L	VTI1A	Q96AJ9	244
TMEM238L	NKX2-3	Q8TAU0	234
TMEM238L	NXN	Q6DKJ4	222
TMEM238L	PITX1	P78337	216
TMEM238L	AFAP1	Q8N556	209
TMEM238L	SLCO2A1	Q92959	207
TMEM238L	ARHGDIB	P52566	206
TMEM238L	ANKZF1	Q9H8Y5	206
TMEM238L	PRICKLE1	Q96MT3	206

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TMEM238L	BRI3BP	psi-mi:“MI:0915”(physical association)	0.500
TMEM238L	REEP5	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A1B0GTI8, A0A2Z2U4G9, A0A494BA31, A5D6W6, A6NC51, A6NDP7, A6NFC5, A6NH21, A6NJY4, A8WCG0, B0BNG2, B1AQL3, E9Q9H8, O43246, P43219, P48546, Q1HG43, Q1HG44, Q2KIG8, Q32L10, Q497B3, Q49LS0, Q49LS7, Q4VV71, Q53RY4, Q58CW5, Q5REM8, Q5XK03, Q658P3, Q6PEY1, Q6UW68, Q80SU6, Q8C0T0, Q8K177, Q8K4R8, Q8K4V2, Q8N130, Q8VE49, Q91XE8, Q923Z0

Diamond homologs: A6NJY4, A9JSM3, C9JI98

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:10803790:G:C	S58R	0.980
17:10803790:G:T	S58R	0.980
17:10803792:T:G	S58R	0.980
17:10803858:C:G	G36R	0.963
17:10803858:C:T	G36R	0.963
17:10803857:C:T	G36E	0.951
17:10803812:C:T	G51D	0.947
17:10803791:C:A	S58I	0.946
17:10803879:C:G	G29R	0.946
17:10803780:A:G	W62R	0.945
17:10803780:A:T	W62R	0.945
17:10803813:C:G	G51R	0.940
17:10803888:C:G	D26H	0.940
17:10803858:C:A	G36W	0.938
17:10803878:C:T	G29D	0.932
17:10803771:A:G	W65R	0.929
17:10803771:A:T	W65R	0.929
17:10803813:C:A	G51C	0.929
17:10803887:T:A	D26V	0.916
17:10803887:T:G	D26A	0.915
17:10803857:C:A	G36V	0.901
17:10803791:C:T	S58N	0.898
17:10803866:A:G	L33S	0.896
17:10803886:G:C	D26E	0.895
17:10803886:G:T	D26E	0.895
17:10803812:C:A	G51V	0.884
17:10803888:C:T	D26N	0.884
17:10803809:G:T	A52D	0.880
17:10803887:T:C	D26G	0.880
17:10803778:C:A	W62C	0.876

dbSNP variants (sampled 300 via entrez): RS1000483015 (17:10804932 T>C,G), RS1001141758 (17:10798676 TGTGA>T), RS1001192266 (17:10806011 T>C), RS1001218789 (17:10796736 C>T), RS1001475182 (17:10799861 C>T), RS1001706758 (17:10805676 G>A), RS1001816075 (17:10796076 C>G), RS1001934035 (17:10796318 A>G), RS1002020169 (17:10795904 A>G), RS1002024905 (17:10801937 A>G), RS1002243679 (17:10801444 C>G,T), RS1002501877 (17:10802227 C>T), RS1002707279 (17:10799283 C>T), RS1002866175 (17:10804849 A>T), RS1003145276 (17:10801171 C>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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Methapyrilene	increases methylation	1
Tretinoin	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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