TRAM1L1

Summary

TRAM1L1 (translocation associated membrane protein 1 like 1, HGNC:28371) is a protein-coding gene on chromosome 4q26, encoding Translocating chain-associated membrane protein 1-like 1 (Q8N609). Stimulatory or required for the translocation of secretory proteins across the ER membrane.

Predicted to be involved in protein insertion into ER membrane. Predicted to be located in endoplasmic reticulum and membrane. Predicted to be active in endoplasmic reticulum membrane.

Source: NCBI Gene 133022 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_152402

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28371
Approved symbol	TRAM1L1
Name	translocation associated membrane protein 1 like 1
Location	4q26
Locus type	gene with protein product
Status	Approved
Aliases	MGC26568
Ensembl gene	ENSG00000174599
Ensembl biotype	protein_coding
OMIM	617505
Entrez	133022

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000310754

RefSeq mRNA: 1 — MANE Select: NM_152402 NM_152402

CCDS: CCDS3707

Canonical transcript exons

ENST00000310754 — 1 exons

Exon	Start	End
ENSE00001201956	117083554	117085576

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 87.78.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1095 / max 57.4145, expressed in 823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53722	1.2580	589
53721	0.8515	482

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	87.78	gold quality
upper arm skin	UBERON:0004263	86.79	silver quality
epithelial cell of pancreas	CL:0000083	86.04	silver quality
kidney epithelium	UBERON:0004819	85.22	silver quality
corpus epididymis	UBERON:0004359	84.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.69	gold quality
oviduct epithelium	UBERON:0004804	82.26	gold quality
pons	UBERON:0000988	81.65	gold quality
Brodmann (1909) area 23	UBERON:0013554	81.33	gold quality
middle temporal gyrus	UBERON:0002771	81.23	gold quality
cortical plate	UBERON:0005343	80.77	gold quality
corpus callosum	UBERON:0002336	79.82	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.46	gold quality
pancreatic ductal cell	CL:0002079	79.31	silver quality
germinal epithelium of ovary	UBERON:0001304	78.92	gold quality
pigmented layer of retina	UBERON:0001782	78.79	gold quality
retina	UBERON:0000966	78.77	gold quality
subthalamic nucleus	UBERON:0001906	78.28	gold quality
metanephros	UBERON:0000081	78.19	gold quality
inferior vagus X ganglion	UBERON:0005363	77.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.77	gold quality
prefrontal cortex	UBERON:0000451	77.55	gold quality
spinal cord	UBERON:0002240	77.50	gold quality
superior vestibular nucleus	UBERON:0007227	77.42	gold quality
renal medulla	UBERON:0000362	77.39	gold quality
substantia nigra	UBERON:0002038	76.86	gold quality
midbrain	UBERON:0001891	76.80	gold quality
putamen	UBERON:0001874	76.72	gold quality
ganglionic eminence	UBERON:0004023	76.64	gold quality
dorsal plus ventral thalamus	UBERON:0001897	76.58	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting TRAM1L1, 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-4682	100.00	68.89	1258
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tram1	ENSDARG00000019137
mus_musculus	Tram1l1	ENSMUSG00000044528
rattus_norvegicus	Tram1l1	ENSRNOG00000087014
drosophila_melanogaster	TRAM	FBGN0040340
caenorhabditis_elegans		WBGENE00007696

Paralogs (2): TRAM2 (ENSG00000065308), TRAM1 (ENSG00000067167)

Protein

Protein identifiers

Translocating chain-associated membrane protein 1-like 1 — Q8N609 (reviewed: Q8N609)

All UniProt accessions (1): Q8N609

UniProt curated annotations — full annotation on UniProt →

Function. Stimulatory or required for the translocation of secretory proteins across the ER membrane.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the TRAM family.

RefSeq proteins (1): NP_689615* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006634	TLC-dom	Domain
IPR016447	Translocation_assoc_membrane	Family

Pfam: PF03798

UniProt features (23 total): topological domain 9, transmembrane region 8, sequence conflict 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N609-F1	80.64	0.39

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): TGCGCANK_UNKNOWN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_PROTEIN_TARGETING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_TRANSMEMBRANE_TRANSPORT, GOBP_MEMBRANE_ORGANIZATION, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_PROTEIN_INSERTION_INTO_MEMBRANE, GOBP_TRANSMEMBRANE_TRANSPORT

GO Biological Process (3): SRP-dependent cotranslational protein targeting to membrane, translocation (GO:0006616), protein insertion into ER membrane (GO:0045048), protein transport (GO:0015031)

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
SRP-dependent cotranslational protein targeting to membrane	1
intracellular protein transmembrane transport	1
endoplasmic reticulum organization	1
protein localization to organelle	1
protein insertion into membrane	1
transport	1
intracellular protein localization	1
establishment of protein localization	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

360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAM1L1	NDST4	Q9H3R1	447
TRAM1L1	KLHL8	Q9P2G9	446
TRAM1L1	TLCD1	Q96CP7	435
TRAM1L1	CCDC47	Q96A33	407
TRAM1L1	POM121L2	Q96KW2	398
TRAM1L1	NKAIN3	Q8N8D7	380
TRAM1L1	NDST3	O95803	379
TRAM1L1	FAM174A	Q8TBP5	379
TRAM1L1	QRFPR	Q96P65	372
TRAM1L1	TM4SF20	Q53R12	371
TRAM1L1	H2AL3	A0A3B3IU63	370
TRAM1L1	RUNDC3B	Q96NL0	365
TRAM1L1	ZFP28	Q8NHY6	351
TRAM1L1	ZNF804B	A4D1E1	348
TRAM1L1	SEC63	Q9UGP8	348

IntAct

80 interactions, top by confidence:

A	B	Type	Score
TRAM1L1	CD99L2	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	MUC1	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	EVI2B	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	MFF	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	CLEC1A	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	TMEM79	psi-mi:“MI:0915”(physical association)	0.560
BSCL2	TRAM1L1	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	LRRC59	psi-mi:“MI:0915”(physical association)	0.560
ASGR2	TRAM1L1	psi-mi:“MI:0915”(physical association)	0.560
TMED8	TRAM1L1	psi-mi:“MI:0915”(physical association)	0.560
MUC1	TRAM1L1	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
CD53	TRAM1L1	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	FKBP7	psi-mi:“MI:0915”(physical association)	0.560
CD79A	TRAM1L1	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	TMX2	psi-mi:“MI:0915”(physical association)	0.560
PLEKHO1	TRAM1L1	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	CYBC1	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	GPX8	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	TRAM1L1	psi-mi:“MI:0915”(physical association)	0.560
TMEM52B	TRAM1L1	psi-mi:“MI:0915”(physical association)	0.560
EVI2B	TRAM1L1	psi-mi:“MI:0915”(physical association)	0.560
PLPP2	TRAM1L1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (30): TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid), TRAM1L1 (Two-hybrid)

ESM2 similar proteins: A2AKM2, A4FUY9, A5D6V4, A7YY55, A8WGS4, Q01685, Q0P5C7, Q15629, Q3T124, Q4R8A8, Q4V8U5, Q5BJF2, Q5GH60, Q5GH61, Q5GH68, Q5HZE5, Q5ND56, Q5NVQ2, Q5R7Z3, Q5U2T1, Q5VWC8, Q5XI41, Q5ZM57, Q60457, Q6DED0, Q6GLX2, Q6GNB5, Q6P4N1, Q6PP77, Q6YWS8, Q7SY06, Q84QC0, Q86X19, Q8CGF5, Q8K0U3, Q8K2C9, Q8N609, Q8QZR0, Q8R000, Q8VZB2

Diamond homologs: Q01685, Q15035, Q15629, Q5E9R6, Q5R7Z3, Q5XI41, Q6DED0, Q8N609, Q8QZR0, Q91V04, Q924Z5, Q9GKZ4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

149 predictions. Top by Δscore:

Variant	Effect	Δscore
4:117084577:C:T	acceptor_gain	0.6500
4:117085415:A:AC	donor_gain	0.5700
4:117085416:C:CC	donor_gain	0.5700
4:117085408:GATAC:G	donor_loss	0.5600
4:117085409:ATACT:A	donor_loss	0.5600
4:117085410:TACT:T	donor_loss	0.5600
4:117085411:ACT:A	donor_loss	0.5600
4:117085412:CT:C	donor_loss	0.5600
4:117085413:T:TC	donor_loss	0.5600
4:117085414:C:CC	donor_loss	0.5600
4:117085416:C:CA	donor_loss	0.5600
4:117085021:A:C	donor_gain	0.5400
4:117085326:TGATT:T	acceptor_gain	0.5400
4:117085331:C:CC	acceptor_gain	0.5300
4:117085416:CCGG:C	donor_gain	0.5200
4:117085329:TT:T	acceptor_gain	0.4900
4:117084578:A:T	acceptor_gain	0.4600
4:117085407:GGATA:G	donor_loss	0.4400
4:117085096:ATT:A	donor_gain	0.4200
4:117084566:CAGG:C	acceptor_gain	0.4100
4:117084842:G:C	acceptor_gain	0.4000
4:117085227:CTGTG:C	acceptor_gain	0.3900
4:117085328:ATT:A	acceptor_loss	0.3900
4:117085329:TTC:T	acceptor_loss	0.3900
4:117085330:TCTGC:T	acceptor_loss	0.3900
4:117085331:C:A	acceptor_loss	0.3900
4:117085332:TG:T	acceptor_loss	0.3900
4:117085333:G:C	acceptor_loss	0.3800
4:117085334:CAGGA:C	acceptor_loss	0.3800
4:117085338:A:C	acceptor_loss	0.3800

AlphaMissense

2431 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:117084482:A:C	S304R	0.993
4:117084482:A:T	S304R	0.993
4:117084484:T:G	S304R	0.993
4:117084988:C:G	G136R	0.986
4:117085158:T:G	D79A	0.986
4:117085159:C:G	D79H	0.985
4:117084481:A:G	C305R	0.983
4:117084896:C:A	K166N	0.980
4:117084896:C:G	K166N	0.980
4:117085340:G:C	F18L	0.980
4:117085340:G:T	F18L	0.980
4:117085342:A:G	F18L	0.980
4:117084873:G:T	A174D	0.974
4:117084987:C:T	G136D	0.974
4:117085158:T:C	D79G	0.972
4:117085026:C:T	G123D	0.971
4:117085157:A:C	D79E	0.971
4:117085157:A:T	D79E	0.971
4:117085158:T:A	D79V	0.971
4:117084868:A:G	W176R	0.970
4:117084868:A:T	W176R	0.970
4:117085111:C:G	A95P	0.970
4:117084739:C:G	G219R	0.969
4:117084739:C:T	G219R	0.969
4:117085016:A:C	S126R	0.969
4:117085016:A:T	S126R	0.969
4:117085018:T:G	S126R	0.969
4:117084498:G:T	A299D	0.968
4:117084783:A:G	L204P	0.967
4:117084898:T:C	K166E	0.966

dbSNP variants (sampled 300 via entrez): RS1000472812 (4:117085781 C>T), RS1000988899 (4:117083991 C>A), RS1001298765 (4:117086696 T>C), RS1001718299 (4:117083310 A>G), RS1002252107 (4:117085614 G>A,C), RS1002324448 (4:117085005 A>C), RS1002678497 (4:117085377 T>C,G), RS1003264873 (4:117086615 A>T), RS1005818862 (4:117086222 G>A), RS1006181139 (4:117086542 C>A,G), RS1006401887 (4:117084534 A>C), RS1006798448 (4:117084159 G>C), RS1007388812 (4:117085648 G>A,T), RS1007916962 (4:117085868 T>A), RS1007926107 (4:117084054 A>G)

Disease associations

OMIM: gene MIM:617505 | 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
GCST000426_7	Obesity (extreme)	3.000000e-06
GCST001523_43	Visceral adipose tissue adjusted for BMI	8.000000e-06
GCST002104_19	Bronchopulmonary dysplasia	1.000000e-06
GCST003830_43	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	7.000000e-07
GCST005286_1	Lateral ventricle volume in trauma-exposed individuals	2.000000e-07
GCST009391_1184	Metabolite levels	9.000000e-06
GCST011767_7	Bipolar disorder	5.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005921	FEV change measurement
EFO:0008483	response to trauma exposure
EFO:0008487	lateral ventricle volume measurement
EFO:0010454	adenosine monophosphate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation	5
Air Pollutants	decreases expression, increases abundance	2
Nickel	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
methylparaben	decreases expression	1
avobenzone	decreases expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Resveratrol	affects cotreatment, decreases expression, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Malathion	increases expression	1
Plant Extracts	affects cotreatment, decreases expression, increases expression	1
Quercetin	decreases expression	1
Smoke	increases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	increases expression	1
Permethrin	increases expression	1

Clinical trials (associated diseases)

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