TMEM74

Summary

TMEM74 (transmembrane protein 74, HGNC:26409) is a protein-coding gene on chromosome 8q23.1, encoding Transmembrane protein 74 (Q96NL1). Plays an essential role in autophagy.

Predicted to enable transmembrane transporter binding activity. Involved in macroautophagy. Predicted to be located in cytoplasmic vesicle; plasma membrane; and vacuolar membrane.

Source: NCBI Gene 157753 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_153015

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26409
Approved symbol	TMEM74
Name	transmembrane protein 74
Location	8q23.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30668, NET36
Ensembl gene	ENSG00000164841
Ensembl biotype	protein_coding
OMIM	613935
Entrez	157753

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000297459, ENST00000518838, ENST00000899500, ENST00000899501, ENST00000919625

RefSeq mRNA: 1 — MANE Select: NM_153015 NM_153015

CCDS: CCDS6310

Canonical transcript exons

ENST00000297459 — 2 exons

Exon	Start	End
ENSE00001087929	108778974	108785137
ENSE00001289495	108787476	108787594

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 86.32.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8939 / max 123.6232, expressed in 657 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94403	1.3973	438
94405	1.1663	268
94404	0.3304	140

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	86.32	gold quality
oocyte	CL:0000023	85.09	gold quality
cortical plate	UBERON:0005343	83.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.70	gold quality
ganglionic eminence	UBERON:0004023	75.62	gold quality
buccal mucosa cell	CL:0002336	71.58	silver quality
prefrontal cortex	UBERON:0000451	70.29	gold quality
corpus callosum	UBERON:0002336	69.37	gold quality
spinal cord	UBERON:0002240	66.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.12	gold quality
frontal cortex	UBERON:0001870	65.82	gold quality
frontal lobe	UBERON:0016525	65.82	gold quality
cerebellum	UBERON:0002037	65.80	gold quality
cerebellar cortex	UBERON:0002129	65.66	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	65.61	gold quality
cerebellar hemisphere	UBERON:0002245	65.54	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	65.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	65.34	gold quality
lower lobe of lung	UBERON:0008949	65.29	gold quality
neocortex	UBERON:0001950	65.25	gold quality
Ammon’s horn	UBERON:0001954	65.12	gold quality
cerebral cortex	UBERON:0000956	64.71	gold quality
anterior cingulate cortex	UBERON:0009835	63.57	gold quality
postcentral gyrus	UBERON:0002581	63.38	silver quality
hindlimb stylopod muscle	UBERON:0004252	62.85	gold quality
superior frontal gyrus	UBERON:0002661	62.56	gold quality
amygdala	UBERON:0001876	62.48	gold quality
Brodmann (1909) area 46	UBERON:0006483	62.09	gold quality
parietal lobe	UBERON:0001872	61.73	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

180 targeting TMEM74, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-498-3P	99.91	71.27	1114

Literature-anchored findings (GeneRIF, showing 5)

• These findings demonstrate that TMEM74 may be involved in promoting functional autophagy during cell starvation and other stress conditions. (PMID:18294959)
• the results revealed the autophagy modulator TMEM74 interrelates with apoptosis inducer BIK and inhibits its function. (PMID:28412412)
• TMEM74 promotes tumor cell survival by inducing autophagy via interactions with ATG16L1 and ATG9A. (PMID:29048433)
• The results suggested that TMEM74 acts as an oncogene and a potential diagnostic marker and a therapeutic target for liver cancer and lung cancer. (PMID:29629952)
• Genome-wide association study detected novel susceptibility genes for social cognition impairment in people with schizophrenia. (PMID:34132174)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem74	ENSMUSG00000054409
rattus_norvegicus	Tmem74	ENSRNOG00000065300

Paralogs (1): TMEM74B (ENSG00000125895)

Protein

Protein identifiers

Transmembrane protein 74 — Q96NL1 (reviewed: Q96NL1)

All UniProt accessions (1): Q96NL1

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role in autophagy. TMEM74-induced autophagy may involve PI3K signal transduction.

Subcellular location. Lysosome membrane. Cytoplasmic vesicle. Autophagosome membrane.

Tissue specificity. Expressed in heart, lung, and placenta.

Similarity. Belongs to the TMEM74 family.

RefSeq proteins (1): NP_694560* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029695	TMEM74-like	Family

Pfam: PF14927

UniProt features (6 total): transmembrane region 2, region of interest 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NL1-F1	56.82	0.06

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, RNGTGGGC_UNKNOWN, GOBP_BEHAVIOR, GOCC_VACUOLAR_MEMBRANE, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, GOBP_MACROAUTOPHAGY, GOCC_AUTOPHAGOSOME, TCCCRNNRTGC_UNKNOWN, GOCC_AUTOPHAGOSOME_MEMBRANE, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, GOMF_TRANSMEMBRANE_TRANSPORTER_BINDING, GSE13887_HEALTHY_VS_LUPUS_RESTING_CD4_TCELL_UP, MARTENS_TRETINOIN_RESPONSE_UP, HOELZEL_NF1_TARGETS_UP

GO Biological Process (3): macroautophagy (GO:0016236), general adaptation syndrome, behavioral process (GO:0051867), autophagy (GO:0006914)

GO Molecular Function (2): transmembrane transporter binding (GO:0044325), protein binding (GO:0005515)

GO Cellular Component (6): autophagosome membrane (GO:0000421), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), lysosome (GO:0005764), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
autophagosome assembly	1
autophagy	1
behavior	1
general adaptation syndrome	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
protein binding	1
binding	1
vacuolar membrane	1
autophagosome	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
cytoplasm	1
intracellular vesicle	1
lytic vacuole	1
cellular anatomical structure	1

Protein interactions and networks

STRING

510 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM74	ATG16L1	Q676U5	741
TMEM74	ATG9A	Q7Z3C6	669
TMEM74	ATG9B	Q674R7	598
TMEM74	BIRC5	O15392	533
TMEM74	ATIC	P31939	507
TMEM74	DAPK2	Q9UIK4	496
TMEM74	TM9SF1	O15321	482
TMEM74	ATG16L2	Q8NAA4	464
TMEM74	HSPB8	Q9UJY1	434
TMEM74	PAK1IP1	Q9NWT1	432
TMEM74	CDADC1	Q9BWV3	428
TMEM74	DCAF13	Q9NV06	428
TMEM74	RAB3GAP2	Q9H2M9	420
TMEM74	MAP1LC3C	Q9BXW4	419
TMEM74	NRG3	P56975	418

IntAct

22 interactions, top by confidence:

A	B	Type	Score
FATE1	TMEM74	psi-mi:“MI:0915”(physical association)	0.560
TMEM74	FATE1	psi-mi:“MI:0915”(physical association)	0.560
MS4A13	TMEM74	psi-mi:“MI:0915”(physical association)	0.560
TMEM42	TMEM74	psi-mi:“MI:0915”(physical association)	0.560
	TMEM74	psi-mi:“MI:0915”(physical association)	0.560
AQP6	TMEM74	psi-mi:“MI:0915”(physical association)	0.560
TMEM74	LIME1	psi-mi:“MI:0915”(physical association)	0.560
TMEM74	CALML3	psi-mi:“MI:0915”(physical association)	0.400
TMEM74	KLRG2	psi-mi:“MI:0914”(association)	0.350
TMEM74	MGAM	psi-mi:“MI:0914”(association)	0.350
MS4A13	TMEM74	psi-mi:“MI:0915”(physical association)	0.000
TMEM74	TMEM42	psi-mi:“MI:0915”(physical association)	0.000
TMEM74	LIME1	psi-mi:“MI:0915”(physical association)	0.000
TMEM74		psi-mi:“MI:0915”(physical association)	0.000
TMEM74	AQP6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (125): TMEM74 (Two-hybrid), TMEM74 (Two-hybrid), TMEM74 (Affinity Capture-Western), ATG16L1 (Affinity Capture-Western), TMEM74 (Affinity Capture-Western), TMEM74 (Two-hybrid), TMEM74 (Two-hybrid), TMEM42 (Two-hybrid), LIME1 (Two-hybrid), MS4A13 (Two-hybrid), FAM216A (Affinity Capture-MS), SEC62 (Affinity Capture-MS), TAB2 (Affinity Capture-MS), FAR2 (Affinity Capture-MS), GTSE1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMD2, A2ANU3, A7J1T0, A7J1T2, B0S6S9, D3ZJ47, F1M5M3, F1MJR8, M0R5D6, O14544, O43283, P57773, Q02223, Q06190, Q08DM6, Q14CH0, Q1HKZ5, Q1X8D7, Q2PFD7, Q3TEL6, Q3UVY1, Q4R532, Q58DZ9, Q5R8X7, Q5RA75, Q5RCM6, Q5RD34, Q5RJX2, Q5SW75, Q5TZE2, Q5VUB5, Q60610, Q6IRN6, Q6NRK3, Q6P995, Q6PUR7, Q76I76, Q86SP6, Q8BIA3, Q8BQU7

Diamond homologs: Q8BQU7, Q96NL1, Q9NUR3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

331 predictions. Top by Δscore:

Variant	Effect	Δscore
8:108787471:CTCA:C	donor_loss	1.0000
8:108787472:TCACC:T	donor_loss	1.0000
8:108787473:CACCT:C	donor_loss	1.0000
8:108787475:CCTT:C	donor_gain	1.0000
8:108787474:A:AC	donor_gain	0.9900
8:108787474:AC:A	donor_gain	0.9900
8:108787475:C:CA	donor_gain	0.9900
8:108787475:CC:C	donor_gain	0.9900
8:108787475:CCT:C	donor_gain	0.9900
8:108787474:ACCTT:A	donor_gain	0.9800
8:108787475:CCTTC:C	donor_gain	0.9800
8:108785138:C:CC	acceptor_gain	0.9700
8:108786325:T:A	donor_gain	0.9400
8:108785136:GT:G	acceptor_gain	0.9100
8:108785356:A:C	donor_gain	0.9100
8:108785412:G:GA	donor_gain	0.9100
8:108785135:AGTCT:A	acceptor_loss	0.9000
8:108785136:GTCT:G	acceptor_loss	0.9000
8:108785137:TCT:T	acceptor_loss	0.9000
8:108785138:CTGCC:C	acceptor_loss	0.9000
8:108785139:T:A	acceptor_loss	0.9000
8:108785140:G:C	acceptor_loss	0.8900
8:108786916:C:CA	donor_gain	0.8900
8:108785134:AAGT:A	acceptor_gain	0.8700
8:108785135:AGT:A	acceptor_gain	0.8700
8:108787180:TGA:T	donor_gain	0.8400
8:108785355:A:AC	donor_gain	0.8300
8:108787181:G:T	donor_gain	0.8300
8:108786324:TTCC:T	donor_gain	0.8000
8:108787210:G:GT	donor_gain	0.8000

AlphaMissense

1995 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:108784559:G:C	S180R	0.992
8:108784559:G:T	S180R	0.992
8:108784561:T:G	S180R	0.992
8:108784537:C:A	G188W	0.991
8:108784537:C:G	G188R	0.990
8:108784537:C:T	G188R	0.990
8:108784383:A:T	L239H	0.988
8:108784390:A:G	C237R	0.988
8:108784392:A:G	L236P	0.988
8:108784536:C:T	G188E	0.988
8:108784383:A:G	L239P	0.987
8:108784395:C:T	G235E	0.987
8:108784396:C:G	G235R	0.987
8:108784396:C:T	G235R	0.987
8:108784375:C:G	G242R	0.986
8:108784375:C:T	G242R	0.986
8:108784380:G:T	T240K	0.986
8:108784374:C:T	G242E	0.984
8:108784413:T:A	D229V	0.984
8:108784396:C:A	G235W	0.983
8:108784413:T:G	D229A	0.983
8:108784380:G:C	T240R	0.982
8:108784557:G:T	A181D	0.982
8:108784371:C:T	G243D	0.979
8:108784386:A:G	L238P	0.979
8:108784392:A:T	L236H	0.978
8:108784372:C:G	G243R	0.977
8:108784357:A:G	C248R	0.976
8:108784383:A:C	L239R	0.976
8:108784375:C:A	G242W	0.975

dbSNP variants (sampled 300 via entrez): RS1000010465 (8:108698710 A>G,T), RS1000028390 (8:108734108 C>T), RS1000044768 (8:108776338 C>T), RS1000065466 (8:108741809 G>A), RS1000068837 (8:108656804 C>T), RS1000107693 (8:108642087 A>T), RS1000111448 (8:108747750 T>A,C), RS1000164744 (8:108609448 T>C,G), RS1000169233 (8:108650320 C>T), RS1000181602 (8:108740489 C>A,T), RS1000217289 (8:108647407 C>A), RS1000221137 (8:108650612 T>C), RS1000233898 (8:108666447 T>C), RS1000234744 (8:108693914 A>G), RS1000240014 (8:108705098 T>C)

Disease associations

OMIM: gene MIM:613935 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003983_17	Male-pattern baldness	4.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	8
trichostatin A	affects cotreatment, decreases expression, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Vorinostat	decreases expression, increases expression, affects cotreatment	2
Panobinostat	decreases expression, affects cotreatment	2
Copper	affects cotreatment, decreases expression, affects binding	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	2
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation, affects cotreatment	1
butyraldehyde	increases expression	1
pentanal	increases expression	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
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Fluorouracil	increases expression	1
Methotrexate	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	affects expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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