TMEM108

Summary

TMEM108 (transmembrane protein 108, HGNC:28451) is a protein-coding gene on chromosome 3q22.1, encoding Transmembrane protein 108 (Q6UXF1). Transmembrane protein required for proper cognitive functions.

Predicted to be involved in several processes, including cellular response to brain-derived neurotrophic factor stimulus; nervous system development; and regulation of signal transduction. Predicted to be located in somatodendritic compartment. Predicted to be active in several cellular components, including endosome; glutamatergic synapse; and postsynaptic density membrane.

Source: NCBI Gene 66000 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_023943

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28451
Approved symbol	TMEM108
Name	transmembrane protein 108
Location	3q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC3040, CT124
Ensembl gene	ENSG00000144868
Ensembl biotype	protein_coding
OMIM	617361
Entrez	66000

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 23 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000321871, ENST00000393130, ENST00000508711, ENST00000510183, ENST00000511388, ENST00000511555, ENST00000512137, ENST00000512662, ENST00000514529, ENST00000514894, ENST00000515826, ENST00000930512, ENST00000930513, ENST00000930514, ENST00000930515, ENST00000930516, ENST00000930517, ENST00000930518, ENST00000930519, ENST00000930520, ENST00000968854, ENST00000968855, ENST00000968856, ENST00000968857, ENST00000968858

RefSeq mRNA: 3 — MANE Select: NM_023943 NM_001136469, NM_001282865, NM_023943

CCDS: CCDS33858, CCDS75012

Canonical transcript exons

ENST00000321871 — 6 exons

Exon	Start	End
ENSE00001223724	133379752	133381161
ENSE00001363298	133038391	133038435
ENSE00001495835	133045902	133046020
ENSE00002059602	133395864	133397775
ENSE00003542740	133390180	133390334
ENSE00003560653	133229266	133229351

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 98.42.

FANTOM5 (CAGE): breadth broad, TPM avg 5.0854 / max 393.0664, expressed in 621 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38644	2.6678	507
38643	1.7058	441
38642	0.3169	193
38645	0.3110	91
38646	0.0839	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.42	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.87	gold quality
ganglionic eminence	UBERON:0004023	92.52	gold quality
middle temporal gyrus	UBERON:0002771	91.95	gold quality
ventricular zone	UBERON:0003053	91.34	gold quality
endothelial cell	CL:0000115	89.96	gold quality
biceps brachii	UBERON:0001507	89.72	gold quality
vastus lateralis	UBERON:0001379	89.42	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.45	gold quality
quadriceps femoris	UBERON:0001377	87.50	silver quality
skeletal muscle tissue	UBERON:0001134	86.60	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.07	gold quality
entorhinal cortex	UBERON:0002728	85.85	gold quality
decidua	UBERON:0002450	85.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.68	gold quality
secondary oocyte	CL:0000655	85.48	gold quality
muscle tissue	UBERON:0002385	85.22	gold quality
lateral nuclear group of thalamus	UBERON:0002736	84.86	gold quality
superior frontal gyrus	UBERON:0002661	84.79	gold quality
primary visual cortex	UBERON:0002436	83.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.40	gold quality
right testis	UBERON:0004534	83.07	gold quality
right adrenal gland	UBERON:0001233	82.88	gold quality
left testis	UBERON:0004533	82.75	gold quality
right adrenal gland cortex	UBERON:0035827	82.68	gold quality
left adrenal gland cortex	UBERON:0035825	82.45	gold quality
left adrenal gland	UBERON:0001234	82.28	gold quality
postcentral gyrus	UBERON:0002581	82.28	gold quality
neocortex	UBERON:0001950	82.16	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	89.64
E-ANND-3	yes	4.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting TMEM108, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3941	99.86	70.54	2735

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem108	ENSDARG00000090230
mus_musculus	Tmem108	ENSMUSG00000042757
rattus_norvegicus	Tmem108	ENSRNOG00000010911

Protein

Protein identifiers

Transmembrane protein 108 — Q6UXF1 (reviewed: Q6UXF1)

Alternative names: Retrolinkin

All UniProt accessions (8): Q6UXF1, B3KT64, D6R911, D6R9I6, D6RFH6, D6RGJ9, D6RIE1, E9PB58

UniProt curated annotations — full annotation on UniProt →

Function. Transmembrane protein required for proper cognitive functions. Involved in the development of dentate gyrus (DG) neuron circuitry, is necessary for AMPA receptors surface expression and proper excitatory postsynaptic currents of DG granule neurons. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Through the interaction with DST, mediates the docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport. In hippocampal neurons, required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2 and recruits the WAVE1 complex to facilitate actin-dependent BDNF:NTRK2 early endocytic trafficking and mediate signaling from early endosomes.

Subunit / interactions. Interacts with DST (isoform 1). Interacts with SH3GL2. Interacts (via N-terminus) with CYFIP1 and CYFIP2; the interactions associate TMEM108 with the WAVE1 complex.

Subcellular location. Membrane. Postsynaptic density. Endosome membrane. Cell projection. Axon. Dendrite. Early endosome.

Post-translational modifications. Glycosylated.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UXF1-1	1	yes
Q6UXF1-2	2

RefSeq proteins (3): NP_001129941, NP_001269794, NP_076432* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031508	TMEM108	Family

Pfam: PF15759

UniProt features (19 total): compositionally biased region 8, region of interest 4, transmembrane region 2, splice variant 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXF1-F1	45.75	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 244 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, E2F_Q4, GOBP_DENTATE_GYRUS_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_NEURON_PROJECTION_EXTENSION, E2F4DP1_01, GOBP_GROWTH, TATTATA_MIR374, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, USF_C, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CELL_CELL_SIGNALING

GO Biological Process (10): receptor-mediated endocytosis (GO:0006898), retrograde axonal transport (GO:0008090), dentate gyrus development (GO:0021542), neuron projection development (GO:0031175), positive regulation of neurotrophin TRK receptor signaling pathway (GO:0051388), postsynaptic density organization (GO:0097106), dendrite extension (GO:0097484), regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696), modulation of excitatory postsynaptic potential (GO:0098815), cellular response to brain-derived neurotrophic factor stimulus (GO:1990416)

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

GO Cellular Component (13): early endosome (GO:0005769), endosome membrane (GO:0010008), postsynaptic density (GO:0014069), axon (GO:0030424), dendrite (GO:0030425), somatodendritic compartment (GO:0036477), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), axon cytoplasm (GO:1904115), endosome (GO:0005768), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
endosome	2
neuron projection	2
endocytosis	1
axonal transport	1
axon cytoplasm	1
hippocampus development	1
anatomical structure development	1
neuron development	1
plasma membrane bounded cell projection organization	1
positive regulation of signal transduction	1
neurotrophin TRK receptor signaling pathway	1
regulation of neurotrophin TRK receptor signaling pathway	1
postsynaptic specialization organization	1
neuron projection extension	1
regulation of biological quality	1
neurotransmitter receptor localization to postsynaptic specialization membrane	1
regulation of protein localization to synapse	1
regulation of receptor localization to synapse	1
regulation of protein localization to cell periphery	1
regulation of protein localization to membrane	1
regulation of signal transduction	1
regulation of nervous system process	1
regulation of membrane potential	1
modulation of chemical synaptic transmission	1
excitatory postsynaptic potential	1
cellular response to nerve growth factor stimulus	1
binding	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
asymmetric synapse	1
postsynaptic specialization	1
dendritic tree	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
synapse	1
axon	1
neuron projection cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM108	SH3GL2	Q99962	792
TMEM108	DST	Q03001	695
TMEM108	DYNC1H1	Q14204	690
TMEM108	DCTN1	Q14203	655
TMEM108	DLX3	O60479	547
TMEM108	GAS2	O43903	521
TMEM108	MSX2	P35548	514
TMEM108	SYNDIG1L	A6NDD5	489
TMEM108	CDV3	Q9UKY7	453
TMEM108	Q3SXR2	Q3SXR2	435
TMEM108	WDR64	B1ANS9	430
TMEM108	SYNDIG1	Q9H7V2	426
TMEM108	DLX5	P56178	424
TMEM108	TBX6	O95947	397
TMEM108	RYK	P34925	389

IntAct

15 interactions, top by confidence:

A	B	Type	Score
TMEM108	FKBP7	psi-mi:“MI:0915”(physical association)	0.560
TMEM108	SGTB	psi-mi:“MI:0915”(physical association)	0.560
FHL3	TMEM108	psi-mi:“MI:0915”(physical association)	0.560
TMEM108	TCAF2	psi-mi:“MI:0914”(association)	0.530
TMEM108	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
TMEM108	ARHGEF6	psi-mi:“MI:0915”(physical association)	0.370
TMEM108	SH3GL2	psi-mi:“MI:0915”(physical association)	0.370
TMEM108	FHL3	psi-mi:“MI:0915”(physical association)	0.000
FKBP7	TMEM108	psi-mi:“MI:0915”(physical association)	0.000
TMEM108	SGTB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (49): TMEM108 (Reconstituted Complex), RRN3 (Affinity Capture-MS), FAM115C (Affinity Capture-MS), POU2F2 (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), MTFP1 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), PDXDC1 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), ACAD10 (Affinity Capture-MS), BRAT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Y7Y5, A1KXC4, A6QLF8, J3KML8, O00592, O35188, O55145, O57604, P06484, P07141, P13838, P14220, P15702, P16150, P18827, P20934, P26260, P34740, P47951, P59647, P78423, P97808, Q08DZ5, Q1ECS6, Q28270, Q28645, Q29RT9, Q3MIW9, Q3TNW5, Q52S86, Q58Y74, Q5RAF8, Q62170, Q64314, Q6MG22, Q6P9X9, Q6UWI2, Q6UXF1, Q86YL7, Q8BHE4

Diamond homologs: A6QLF8, Q6UXF1, Q8BHE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4053 predictions. Top by Δscore:

Variant	Effect	Δscore
3:133038433:GAG:G	donor_gain	1.0000
3:133038436:G:GG	donor_gain	1.0000
3:133038437:T:G	donor_loss	1.0000
3:133041783:T:G	acceptor_gain	1.0000
3:133229264:A:AG	acceptor_gain	1.0000
3:133229265:G:GG	acceptor_gain	1.0000
3:133229265:GAC:G	acceptor_gain	1.0000
3:133229265:GACA:G	acceptor_gain	1.0000
3:133229347:GTTAA:G	donor_gain	1.0000
3:133229348:T:G	donor_gain	1.0000
3:133229348:TTAA:T	donor_gain	1.0000
3:133229351:AG:A	donor_loss	1.0000
3:133229352:G:C	donor_loss	1.0000
3:133229352:G:GG	donor_gain	1.0000
3:133229353:TAA:T	donor_loss	1.0000
3:133381159:GCT:G	donor_gain	1.0000
3:133381162:G:GG	donor_gain	1.0000
3:133390178:A:AG	acceptor_gain	1.0000
3:133390179:G:GA	acceptor_gain	1.0000
3:133390179:GC:G	acceptor_gain	1.0000
3:133390179:GCT:G	acceptor_gain	1.0000
3:133390179:GCTGT:G	acceptor_gain	1.0000
3:133390332:GAGGT:G	donor_loss	1.0000
3:133390333:AGGTA:A	donor_loss	1.0000
3:133390335:GT:G	donor_loss	1.0000
3:133390336:T:A	donor_loss	1.0000
3:133045900:A:AG	acceptor_gain	0.9900
3:133045900:AGTT:A	acceptor_gain	0.9900
3:133045901:G:GG	acceptor_gain	0.9900
3:133045901:GTTG:G	acceptor_gain	0.9900

AlphaMissense

3664 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:133381140:A:C	S477R	0.999
3:133381142:C:A	S477R	0.999
3:133381142:C:G	S477R	0.999
3:133390278:T:C	F517L	0.997
3:133390280:C:A	F517L	0.997
3:133390280:C:G	F517L	0.997
3:133395936:T:C	F560L	0.997
3:133395938:C:A	F560L	0.997
3:133395938:C:G	F560L	0.997
3:133395954:T:C	F566L	0.997
3:133395956:T:A	F566L	0.997
3:133395956:T:G	F566L	0.997
3:133381147:C:G	P479R	0.996
3:133390253:G:C	W508C	0.996
3:133390253:G:T	W508C	0.996
3:133390279:T:C	F517S	0.996
3:133395932:C:A	N558K	0.996
3:133395932:C:G	N558K	0.996
3:133390183:T:A	V485D	0.995
3:133395955:T:G	F566C	0.995
3:133390279:T:G	F517C	0.994
3:133395925:T:C	L556P	0.994
3:133395937:T:G	F560C	0.994
3:133395946:A:T	E563V	0.994
3:133381147:C:A	P479H	0.993
3:133381158:T:C	C483R	0.993
3:133395928:T:A	V557D	0.993
3:133380997:T:G	F429C	0.992
3:133381122:T:A	W471R	0.992
3:133381122:T:C	W471R	0.992

dbSNP variants (sampled 300 via entrez): RS1000018591 (3:133178063 A>G), RS1000032053 (3:133146693 G>A), RS1000051906 (3:133339237 A>G), RS1000069744 (3:133045929 A>T), RS1000070370 (3:133089513 CAT>C), RS1000076805 (3:133290454 C>T), RS1000085751 (3:133213365 C>T), RS1000088785 (3:133097097 G>T), RS1000117428 (3:133073502 CTCTCTCTCTATATATA>C), RS1000120477 (3:133220393 C>T), RS1000126697 (3:133096553 T>C), RS1000127087 (3:133140161 G>T), RS1000145520 (3:133239999 G>A), RS1000149361 (3:133190046 T>C), RS1000153731 (3:133082665 G>C)

Disease associations

OMIM: gene MIM:617361 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000880_27	Menarche (age at onset)	1.000000e-08
GCST001303_7	IgE grass sensitization	3.000000e-06
GCST003993_15	Menarche (age at onset)	4.000000e-06
GCST004571_3	Iron status biomarkers (total iron binding capacity)	4.000000e-08
GCST004571_6	Iron status biomarkers (total iron binding capacity)	1.000000e-08
GCST004572_13	Iron status biomarkers (transferrin saturation)	4.000000e-08
GCST004572_16	Iron status biomarkers (transferrin saturation)	1.000000e-08
GCST006624_1	Systolic blood pressure	2.000000e-11
GCST007267_106	Systolic blood pressure	2.000000e-11
GCST007576_81	Chronotype	4.000000e-11
GCST008151_58	Waist circumference	8.000000e-06
GCST008160_17	Waist circumference	8.000000e-06
GCST011101_1	Bipolar disorder	2.000000e-08
GCST011176_24	Stroke	6.000000e-08
GCST011494_8	Daytime nap	1.000000e-09
GCST011823_9	Parkinson’s disease progression (cognitive)	2.000000e-08
GCST012490_257	Femur bone mineral density x serum urate levels interaction	1.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0006334	total iron binding capacity
EFO:0006335	systolic blood pressure
EFO:0008328	chronotype measurement
EFO:0007828	daytime rest measurement
EFO:0008336	disease progression measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	6
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
sodium arsenite	decreases expression, increases abundance	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Aldehydes	increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Tobacco Smoke Pollution	increases methylation	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1
Tunicamycin	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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