TMEM170A

Summary

TMEM170A (transmembrane protein 170A, HGNC:29577) is a protein-coding gene on chromosome 16q23.1, encoding Transmembrane protein 170A (Q8WVE7). Acts as a regulator of endoplasmic reticulum (ER) and nuclear envelope (NE) morphogenesis.

Involved in endoplasmic reticulum tubular network organization; nuclear envelope organization; and nuclear pore complex assembly. Located in endoplasmic reticulum membrane and nuclear envelope.

Source: NCBI Gene 124491 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_145254

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29577
Approved symbol	TMEM170A
Name	transmembrane protein 170A
Location	16q23.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ37611
Ensembl gene	ENSG00000166822
Ensembl biotype	protein_coding
OMIM	620630
Entrez	124491

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000357613, ENST00000561878, ENST00000566980, ENST00000567796, ENST00000568559, ENST00000569276, ENST00000569540, ENST00000897719, ENST00000921541

RefSeq mRNA: 4 — MANE Select: NM_145254 NM_001304996, NM_001304997, NM_001304998, NM_145254

CCDS: CCDS10917, CCDS76899, CCDS76900, CCDS76901

Canonical transcript exons

ENST00000561878 — 3 exons

Exon	Start	End
ENSE00001106968	75451669	75451839
ENSE00001422109	75464468	75464689
ENSE00001425660	75443054	75447688

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 98.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.0458 / max 138.6221, expressed in 1796 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158170	12.1327	1777
158168	2.3137	1082
158167	1.4359	878
158169	0.1634	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	98.12	gold quality
ileal mucosa	UBERON:0000331	97.73	gold quality
epithelial cell of pancreas	CL:0000083	95.80	gold quality
oviduct epithelium	UBERON:0004804	92.92	gold quality
jejunal mucosa	UBERON:0000399	92.03	gold quality
colonic mucosa	UBERON:0000317	91.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.76	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.14	gold quality
ventricular zone	UBERON:0003053	91.03	gold quality
adrenal tissue	UBERON:0018303	90.07	gold quality
pigmented layer of retina	UBERON:0001782	89.30	gold quality
renal medulla	UBERON:0000362	89.28	gold quality
duodenum	UBERON:0002114	89.04	gold quality
sperm	CL:0000019	88.50	gold quality
germinal epithelium of ovary	UBERON:0001304	88.33	gold quality
epithelium of nasopharynx	UBERON:0001951	87.88	gold quality
placenta	UBERON:0001987	87.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.75	gold quality
parietal pleura	UBERON:0002400	87.45	gold quality
endothelial cell	CL:0000115	87.18	gold quality
mucosa of transverse colon	UBERON:0004991	87.12	gold quality
palpebral conjunctiva	UBERON:0001812	86.74	gold quality
visceral pleura	UBERON:0002401	86.69	gold quality
spinal cord	UBERON:0002240	86.68	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.45	gold quality
kidney epithelium	UBERON:0004819	86.41	silver quality
trigeminal ganglion	UBERON:0001675	86.28	gold quality
corpus callosum	UBERON:0002336	86.18	gold quality
superior vestibular nucleus	UBERON:0007227	86.18	gold quality
ganglionic eminence	UBERON:0004023	86.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

189 targeting TMEM170A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4650-5P	99.98	64.69	999

Literature-anchored findings (GeneRIF, showing 2)

• This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of carotid intima-media thickness and coronary artery disease risk. (PMID:23152477)
• this paper shows that that downregulation of TMEM170A specifically induces tubular endoplasmic reticulum formation, whereas overexpression of TMEM170A induces endoplasmic reticulum sheet formation. (PMID:26906412)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem170a	ENSDARG00000056628
mus_musculus	Tmem170	ENSMUSG00000031953
rattus_norvegicus		ENSRNOG00000087558
drosophila_melanogaster	CG12341	FBGN0033550
caenorhabditis_elegans	F43G9.13	WBGENE00009673

Paralogs (1): TMEM170B (ENSG00000205269)

Protein

Protein identifiers

Transmembrane protein 170A — Q8WVE7 (reviewed: Q8WVE7)

All UniProt accessions (5): Q8WVE7, B3KT46, H3BQT8, H3BRD7, H3BS26

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a regulator of endoplasmic reticulum (ER) and nuclear envelope (NE) morphogenesis. Affects the ratio between tubular ER and ER sheets by promoting sheet formation at the expense of tubules. Influences NE expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins.

Subunit / interactions. Interacts with RTN4.

Subcellular location. Endoplasmic reticulum membrane. Nucleus envelope.

Similarity. Belongs to the TMEM170 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WVE7-1	1	yes
Q8WVE7-2	2

RefSeq proteins (4): NP_001291925, NP_001291926, NP_001291927, NP_660297* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019334	TMEM170A/B/YPR153W-like	Family

Pfam: PF10190

UniProt features (11 total): topological domain 4, transmembrane region 3, glycosylation site 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVE7-F1	82.53	0.46

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 (2): 30, 36

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_NUCLEAR_PORE_ORGANIZATION, GOBP_NUCLEUS_ORGANIZATION, GOBP_PORE_COMPLEX_ASSEMBLY, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, BENPORATH_NOS_TARGETS, GOBP_NUCLEAR_PORE_COMPLEX_ASSEMBLY, GOBP_NUCLEAR_ENVELOPE_ORGANIZATION, GOBP_MEMBRANE_ORGANIZATION, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, RASHI_RESPONSE_TO_IONIZING_RADIATION_5, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_NUCLEAR_ENVELOPE, BENPORATH_OCT4_TARGETS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK

GO Biological Process (3): nuclear envelope organization (GO:0006998), nuclear pore complex assembly (GO:0051292), endoplasmic reticulum tubular network organization (GO:0071786)

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

GO Cellular Component (5): nuclear envelope (GO:0005635), endoplasmic reticulum membrane (GO:0005789), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
intracellular membrane-bounded organelle	2
nucleus organization	1
endomembrane system organization	1
membrane organization	1
nuclear pore organization	1
pore complex assembly	1
endoplasmic reticulum organization	1
binding	1
nucleus	1
organelle envelope	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM170A	CFDP1	Q9UEE9	849
TMEM170A	BCAR1	P56945	782
TMEM170A	ZDHHC11B	P0C7U3	507
TMEM170A	SLC17A4	Q9Y2C5	506
TMEM170A	ZHX2	Q9Y6X8	482
TMEM170A	BTBD6	Q96KE9	445
TMEM170A	TMEM236	Q5W0B7	405
TMEM170A	CHST6	Q9GZX3	386
TMEM170A	MCPH1	Q8NEM0	383
TMEM170A	PGPEP1	Q9NXJ5	377
TMEM170A	RTN1	Q16799	372
TMEM170A	TMEM147	Q9BVK8	364
TMEM170A	TMEM117	Q9H0C3	358
TMEM170A	RCCD1	A6NED2	357
TMEM170A	TMEM229B	Q8NBD8	348

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TMEM170A	CDIPT	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): TMEM170A (Affinity Capture-RNA), LMAN2L (Affinity Capture-MS), REEP5 (Affinity Capture-MS), GCC1 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), GPR56 (Affinity Capture-MS), SRC (Affinity Capture-MS), C4orf32 (Affinity Capture-MS), C10orf35 (Affinity Capture-MS), CDIPT (Affinity Capture-MS), REEP6 (Affinity Capture-MS), IFITM1 (Affinity Capture-MS), TMEM170A (Affinity Capture-RNA), TMEM170A (Affinity Capture-RNA)

ESM2 similar proteins: A1L3G9, A2ARJ3, A3KPL7, A4IFE9, A5WVU6, A9UY97, B9X187, E7FE40, E9Q9H8, F4HW17, F4JY11, O15321, O22752, O23693, O43073, O64761, P23290, P35801, P35803, P36963, P36965, P79826, Q05005, Q06537, Q0P4G7, Q12016, Q13491, Q28EH9, Q3T110, Q5R603, Q5R8F1, Q5W0B7, Q5ZM31, Q641M3, Q66HF2, Q6DDK3, Q6DF87, Q8BI36, Q8L928, Q8NFJ5

Diamond homologs: A3KPL7, P86050, Q5T4T1, Q5ZM31, Q6DF87, Q7TQ79, Q8WVE7, Q9D342

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

765 predictions. Top by Δscore:

Variant	Effect	Δscore
16:75447165:CT:C	donor_gain	0.9900
16:75447165:CTCTG:C	donor_gain	0.9900
16:75447590:C:CT	donor_gain	0.9900
16:75451835:CATCT:C	acceptor_gain	0.9900
16:75451840:C:CC	acceptor_gain	0.9900
16:75460660:C:CT	donor_gain	0.9900
16:75447591:C:CT	donor_gain	0.9800
16:75447699:A:AC	acceptor_gain	0.9800
16:75447699:A:C	acceptor_gain	0.9800
16:75447707:A:AC	acceptor_gain	0.9700
16:75449161:T:A	donor_gain	0.9700
16:75451838:CT:C	acceptor_gain	0.9700
16:75464462:CCGTA:C	donor_loss	0.9700
16:75464463:CGTA:C	donor_loss	0.9700
16:75464464:GTA:G	donor_loss	0.9700
16:75464465:TA:T	donor_loss	0.9700
16:75464466:AC:A	donor_loss	0.9700
16:75464467:CCTGG:C	donor_loss	0.9700
16:75447164:A:AC	donor_gain	0.9600
16:75447165:C:CC	donor_gain	0.9600
16:75447707:A:C	acceptor_gain	0.9600
16:75464463:CGTAC:C	donor_loss	0.9600
16:75464466:A:C	donor_loss	0.9600
16:75464467:C:G	donor_loss	0.9600
16:75447689:C:CA	acceptor_loss	0.9500
16:75447690:T:C	acceptor_loss	0.9500
16:75451787:A:C	acceptor_gain	0.9500
16:75464587:C:A	donor_gain	0.9500
16:75451838:CTCT:C	acceptor_loss	0.9400
16:75451839:TC:T	acceptor_loss	0.9400

AlphaMissense

910 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:75447676:G:T	A106D	0.995
16:75451816:A:G	W53R	0.995
16:75451816:A:T	W53R	0.995
16:75447687:A:C	S102R	0.994
16:75447687:A:T	S102R	0.994
16:75451669:T:G	S102R	0.994
16:75451705:C:G	G90R	0.994
16:75447619:C:T	G125D	0.993
16:75447620:C:G	G125R	0.992
16:75447682:G:T	A104D	0.992
16:75447602:A:G	C131R	0.991
16:75451834:A:G	W47R	0.991
16:75451834:A:T	W47R	0.991
16:75451671:G:T	T101K	0.990
16:75447620:C:A	G125C	0.988
16:75451737:C:T	G79D	0.988
16:75451755:A:G	L73P	0.988
16:75447646:A:G	M116T	0.987
16:75451696:C:G	G93R	0.987
16:75451696:C:T	G93R	0.987
16:75451767:G:T	A69D	0.987
16:75447688:C:A	S102I	0.986
16:75451692:G:C	P94R	0.986
16:75451718:G:C	S85R	0.986
16:75451718:G:T	S85R	0.986
16:75451720:T:G	S85R	0.986
16:75447613:C:T	G127E	0.985
16:75451671:G:A	T101I	0.985
16:75451671:G:C	T101R	0.985
16:75447614:C:G	G127R	0.984

dbSNP variants (sampled 300 via entrez): RS1000009800 (16:75464189 C>G,T), RS1000098741 (16:75459546 C>A,G), RS1000100254 (16:75456914 G>T), RS1000118170 (16:75456712 G>A,C), RS1000369283 (16:75455041 A>C), RS1000396720 (16:75455265 G>A), RS1000412310 (16:75450499 G>T), RS1000425461 (16:75447657 T>C,G), RS1000597071 (16:75445326 T>G), RS1000976576 (16:75454119 C>A,G,T), RS1001103852 (16:75458407 A>G), RS1001122199 (16:75455885 C>T), RS1001122917 (16:75461968 T>A,C), RS1001211285 (16:75444606 C>A), RS1001263382 (16:75444322 G>A)

Disease associations

OMIM: gene MIM:620630 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002553_10	Pancreatic cancer	1.000000e-10
GCST004858_22	Dupuytren’s disease	5.000000e-10
GCST007435_4	Carotid plaque	9.000000e-11
GCST007611_5	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	3.000000e-11
GCST007612_2	Chronic obstructive pulmonary disease or coronary artery disease (pleiotropy)	4.000000e-08
GCST010397_99	Gut microbiota (bacterial taxa, rank normal transformation method)	1.000000e-07
GCST90002400_181	Plateletcrit	5.000000e-22
GCST90002402_463	Platelet count	1.000000e-15

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture
EFO:0009783	carotid atherosclerosis
EFO:0007874	gut microbiome measurement
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
bisphenol A	decreases methylation	1
resorcinol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Gallic Acid	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Nickel	increases expression	1
Plant Oils	increases expression	1
Urethane	increases expression	1
Zinc	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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