TMEM69

Summary

TMEM69 (transmembrane protein 69, HGNC:28035) is a protein-coding gene on chromosome 1p34.1, encoding Transmembrane protein 69 (Q5SWH9).

Located in mitochondrion.

Source: NCBI Gene 51249 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_016486

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28035
Approved symbol	TMEM69
Name	transmembrane protein 69
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21029
Ensembl gene	ENSG00000159596
Ensembl biotype	protein_coding
Entrez	51249

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 16 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000372025, ENST00000496366, ENST00000871190, ENST00000871191, ENST00000871192, ENST00000871193, ENST00000871194, ENST00000871195, ENST00000871196, ENST00000871197, ENST00000937789, ENST00000937790, ENST00000937791, ENST00000937792, ENST00000937793, ENST00000937794, ENST00000960165

RefSeq mRNA: 1 — MANE Select: NM_016486 NM_016486

CCDS: CCDS41325

Canonical transcript exons

ENST00000372025 — 3 exons

Exon	Start	End
ENSE00001456726	45693204	45694436
ENSE00001456727	45690974	45691110
ENSE00001923758	45688181	45688275

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.6438 / max 313.1952, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2705	47.1004	1817
2704	2.5434	754

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.28	gold quality
secondary oocyte	CL:0000655	98.18	gold quality
epithelial cell of pancreas	CL:0000083	96.29	gold quality
left ventricle myocardium	UBERON:0006566	94.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.74	gold quality
gingival epithelium	UBERON:0001949	93.59	gold quality
myocardium	UBERON:0002349	93.11	gold quality
germinal epithelium of ovary	UBERON:0001304	92.73	gold quality
esophagus squamous epithelium	UBERON:0006920	92.55	gold quality
rectum	UBERON:0001052	92.38	gold quality
ileal mucosa	UBERON:0000331	92.28	gold quality
gingiva	UBERON:0001828	92.28	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.13	gold quality
vastus lateralis	UBERON:0001379	92.03	gold quality
palpebral conjunctiva	UBERON:0001812	91.97	gold quality
quadriceps femoris	UBERON:0001377	91.81	gold quality
deltoid	UBERON:0001476	91.73	gold quality
penis	UBERON:0000989	91.53	gold quality
biceps brachii	UBERON:0001507	91.31	gold quality
monocyte	CL:0000576	91.12	gold quality
islet of Langerhans	UBERON:0000006	91.08	gold quality
leukocyte	CL:0000738	90.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.67	gold quality
esophagus mucosa	UBERON:0002469	90.64	gold quality
cortical plate	UBERON:0005343	90.50	gold quality
right adrenal gland	UBERON:0001233	90.39	gold quality
pigmented layer of retina	UBERON:0001782	90.23	gold quality
right adrenal gland cortex	UBERON:0035827	90.22	gold quality
metanephros	UBERON:0000081	90.13	gold quality
lower esophagus mucosa	UBERON:0035834	89.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1

miRNA regulators (miRDB)

42 targeting TMEM69, 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-656-3P	100.00	72.15	2788
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-6088	99.29	68.45	1284

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem69	ENSDARG00000076017
mus_musculus	Tmem69	ENSMUSG00000055900
rattus_norvegicus	Tmem69	ENSRNOG00000029152

Protein

Protein identifiers

Transmembrane protein 69 — Q5SWH9 (reviewed: Q5SWH9)

All UniProt accessions (1): Q5SWH9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_057570* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021836	DUF3429	Family

Pfam: PF11911

UniProt features (7 total): transmembrane region 5, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SWH9-F1	73.68	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): AAAYRNCTG_UNKNOWN, YY1_Q6, MYOD_01, chr1p34, LYF1_01, DODD_NASOPHARYNGEAL_CARCINOMA_UP, RYTTCCTG_ETS2_B, YY1_01, ACTWSNACTNY_UNKNOWN, GCCATNTTG_YY1_Q6, MYB_Q6, SMAD4_Q6, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_DN, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3

GO Biological Process (0):

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

GO Cellular Component (2): mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM69	GPBP1L1	Q9HC44	741
TMEM69	CCDC137	Q6PK04	649
TMEM69	ZC3H10	Q96K80	601
TMEM69	CBLN3	Q6UW01	581
TMEM69	CLEC19A	Q6UXS0	549
TMEM69	C1QTNF7	Q9BXJ2	531
TMEM69	PECR	Q9BY49	521
TMEM69	DNLZ	Q5SXM8	479
TMEM69	ENTR1	Q96C92	477
TMEM69	METAP1	P53582	476
TMEM69	TXNDC12	O95881	473
TMEM69	LRRC20	Q8TCA0	464
TMEM69	MRGPRX3	Q96LB0	464
TMEM69	PURG	Q9UJV8	464
TMEM69	MAST2	Q6P0Q8	461

IntAct

11 interactions, top by confidence:

A	B	Type	Score
TUSC5	TMEM69	psi-mi:“MI:0915”(physical association)	0.560
TMEM69	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
AQP6	TMEM69	psi-mi:“MI:0915”(physical association)	0.560
TMEM69	ACOX3	psi-mi:“MI:0914”(association)	0.350
TUSC5	TMEM69	psi-mi:“MI:0915”(physical association)	0.000
TMEM14B	TMEM69	psi-mi:“MI:0915”(physical association)	0.000
TMEM69	AQP6	psi-mi:“MI:0915”(physical association)	0.000
TMEM69	TMEM14B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): TMEM69 (Two-hybrid), TMEM69 (Two-hybrid), TUSC5 (Two-hybrid), IMPACT (Affinity Capture-MS), ACOX3 (Affinity Capture-MS), PKLR (Affinity Capture-MS), PBK (Affinity Capture-MS), KLK3 (Affinity Capture-MS), PRTN3 (Affinity Capture-MS), PPP2CA (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), RTFDC1 (Affinity Capture-MS), SMEK1 (Affinity Capture-MS), TPP2 (Affinity Capture-MS), S100A2 (Affinity Capture-MS)

ESM2 similar proteins: A1XQS5, A6H666, A8XDX2, B0VYY5, B3DHU2, G5EDB8, O14046, P00842, P05496, P07926, P10175, P11432, P16000, P16221, P17605, P23968, P32876, P48201, P48772, P56383, P56384, Q01931, Q03672, Q06055, Q06056, Q06645, Q06646, Q0V9J0, Q0VCH8, Q2LCR3, Q2TA24, Q37315, Q3ZC75, Q53CG1, Q59550, Q5RAP9, Q5RFL2, Q5SWH9, Q71S46, Q7JX57

Diamond homologs: Q0V9J0, Q3KQJ0, Q5SWH9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

358 predictions. Top by Δscore:

Variant	Effect	Δscore
1:45688259:TCTCA:T	donor_gain	0.9800
1:45693198:TTGTA:T	acceptor_loss	0.9800
1:45693199:TGTAG:T	acceptor_loss	0.9800
1:45693201:TA:T	acceptor_loss	0.9800
1:45693202:A:AG	acceptor_gain	0.9800
1:45693202:AGAT:A	acceptor_loss	0.9800
1:45693203:G:C	acceptor_loss	0.9800
1:45693203:G:GG	acceptor_gain	0.9800
1:45693203:GAT:G	acceptor_gain	0.9700
1:45693192:T:G	acceptor_gain	0.9300
1:45690972:A:AG	acceptor_gain	0.9200
1:45690973:G:GG	acceptor_gain	0.9200
1:45693203:GATA:G	acceptor_gain	0.9200
1:45688255:C:T	donor_gain	0.9100
1:45688309:T:TA	donor_gain	0.9100
1:45688310:A:AA	donor_gain	0.9100
1:45688158:G:GT	donor_gain	0.8900
1:45688189:G:GT	donor_gain	0.8900
1:45690973:GAAAC:G	acceptor_gain	0.8900
1:45693203:GA:G	acceptor_gain	0.8800
1:45688226:T:TA	donor_gain	0.8700
1:45693203:GATAC:G	acceptor_gain	0.8200
1:45693184:T:TA	acceptor_gain	0.8100
1:45689000:TTC:T	donor_gain	0.7800
1:45689067:C:G	donor_gain	0.7600
1:45693191:A:AG	acceptor_gain	0.7400
1:45690973:GA:G	acceptor_gain	0.7300
1:45691105:TCAAA:T	donor_loss	0.7200
1:45691106:CAAAG:C	donor_loss	0.7200
1:45691107:AAAG:A	donor_loss	0.7200

AlphaMissense

1603 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:45693564:A:C	S135R	0.988
1:45693566:T:A	S135R	0.988
1:45693566:T:G	S135R	0.988
1:45693594:T:A	W145R	0.979
1:45693594:T:C	W145R	0.979
1:45693654:A:C	S165R	0.978
1:45693656:T:A	S165R	0.978
1:45693656:T:G	S165R	0.978
1:45693678:T:A	W173R	0.970
1:45693678:T:C	W173R	0.970
1:45693600:T:C	F147L	0.961
1:45693602:T:A	F147L	0.961
1:45693602:T:G	F147L	0.961
1:45693789:T:A	W210R	0.951
1:45693789:T:C	W210R	0.951
1:45693576:T:C	F139L	0.950
1:45693578:C:A	F139L	0.950
1:45693578:C:G	F139L	0.950
1:45693438:A:C	S93R	0.947
1:45693440:C:A	S93R	0.947
1:45693440:C:G	S93R	0.947
1:45693735:G:C	G192R	0.946
1:45693596:G:C	W145C	0.938
1:45693596:G:T	W145C	0.938
1:45693555:T:G	Y132D	0.936
1:45693736:G:A	G192D	0.935
1:45693505:T:G	M115R	0.928
1:45693597:G:C	G146R	0.927
1:45693685:C:A	A175D	0.924
1:45693559:G:A	G133E	0.920

dbSNP variants (sampled 300 via entrez): RS1000154561 (1:45687547 G>C,T), RS1000540441 (1:45692377 A>AT), RS1000574232 (1:45691411 C>T), RS1000658036 (1:45692115 C>A,G,T), RS1001023908 (1:45686704 A>G), RS1001855994 (1:45686965 C>G,T), RS1001990501 (1:45686767 G>A,C), RS1002451210 (1:45692975 G>A), RS1002646293 (1:45689034 G>A), RS1002920718 (1:45691569 G>A), RS1003030075 (1:45691820 G>A), RS1003088194 (1:45686325 C>A,T), RS1003477400 (1:45686984 C>T), RS1003532308 (1:45688027 G>C), RS1003668178 (1:45687853 G>A,C,T)

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

10 associations (top):

Study	Trait	p-value
GCST005951_37	Body mass index	8.000000e-10
GCST009391_1592	Metabolite levels	5.000000e-06
GCST010696_7	Cortical thickness (min-P)	3.000000e-08
GCST010697_28	Cortical surface area (min-P)	2.000000e-08
GCST010698_30	Subcortical volume (min-P)	3.000000e-08
GCST010699_45	Brain morphology (min-P)	3.000000e-08
GCST010700_23	Cortical thickness (MOSTest)	1.000000e-10
GCST010701_9	Cortical surface area (MOSTest)	2.000000e-08
GCST010702_139	Subcortical volume (MOSTest)	4.000000e-14
GCST010703_258	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010376	phosphatidylcholine 34:2 measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
Air Pollutants	decreases expression, affects expression, increases abundance	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Nickel	decreases expression	1
Ozone	affects expression, increases abundance	1
Asbestos, Crocidolite	decreases expression	1
Antirheumatic Agents	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2IU	Abcam HeLa TMEM69 KO	Cancer cell line	Female
CVCL_B5L4	HAP1 TMEM69 (-) 2	Cancer cell line	Male
CVCL_XU53	HAP1 TMEM69 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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