TMEM40

Summary

TMEM40 (transmembrane protein 40, HGNC:25620) is a protein-coding gene on chromosome 3p25.2, encoding Transmembrane protein 40 (Q8WWA1).

Predicted to be located in membrane.

Source: NCBI Gene 55287 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_018306

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25620
Approved symbol	TMEM40
Name	transmembrane protein 40
Location	3p25.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11036
Ensembl gene	ENSG00000088726
Ensembl biotype	protein_coding
Entrez	55287

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264728, ENST00000314124, ENST00000428020, ENST00000435218, ENST00000435575, ENST00000476331, ENST00000480698, ENST00000485124

RefSeq mRNA: 4 — MANE Select: NM_018306 NM_001284406, NM_001284407, NM_001284408, NM_018306

CCDS: CCDS2613, CCDS68347, CCDS68348

Canonical transcript exons

ENST00000314124 — 12 exons

Exon	Start	End
ENSE00000746746	12742454	12742507
ENSE00000746783	12748655	12748792
ENSE00001213633	12743900	12743989
ENSE00001816212	12759191	12759259
ENSE00001869777	12733528	12734793
ENSE00003498769	12749760	12749840
ENSE00003539441	12736764	12736835
ENSE00003548738	12736578	12736652
ENSE00003657490	12738553	12738588
ENSE00003664914	12738136	12738168
ENSE00003669655	12735555	12735617
ENSE00003670493	12737707	12737754

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 99.44.

FANTOM5 (CAGE): breadth broad, TPM avg 9.6928 / max 521.9939, expressed in 436 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41136	5.4588	397
41135	4.0707	280
202683	0.1467	74
202682	0.0166	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.44	gold quality
esophagus mucosa	UBERON:0002469	97.76	gold quality
gingiva	UBERON:0001828	96.88	gold quality
gingival epithelium	UBERON:0001949	96.65	gold quality
oral cavity	UBERON:0000167	95.83	gold quality
skin of abdomen	UBERON:0001416	95.33	gold quality
esophagus squamous epithelium	UBERON:0006920	95.08	gold quality
skin of leg	UBERON:0001511	94.51	gold quality
pharyngeal mucosa	UBERON:0000355	93.53	gold quality
zone of skin	UBERON:0000014	93.38	gold quality
monocyte	CL:0000576	93.25	gold quality
mononuclear cell	CL:0000842	92.85	gold quality
upper leg skin	UBERON:0004262	92.84	gold quality
mammalian vulva	UBERON:0000997	92.76	gold quality
epithelium of esophagus	UBERON:0001976	92.60	gold quality
amniotic fluid	UBERON:0000173	92.56	gold quality
penis	UBERON:0000989	92.44	gold quality
leukocyte	CL:0000738	92.20	gold quality
squamous epithelium	UBERON:0006914	91.05	gold quality
placenta	UBERON:0001987	89.02	gold quality
buccal mucosa cell	CL:0002336	88.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.43	gold quality
vagina	UBERON:0000996	87.76	gold quality
granulocyte	CL:0000094	85.21	gold quality
upper arm skin	UBERON:0004263	83.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.07	gold quality
body of tongue	UBERON:0011876	80.55	gold quality
blood	UBERON:0000178	80.50	gold quality
palpebral conjunctiva	UBERON:0001812	79.78	gold quality
bronchial epithelial cell	CL:0002328	79.68	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	1877.46
E-MTAB-8142	yes	1758.11
E-ANND-5	yes	515.71
E-HCAD-1	yes	231.02
E-CURD-114	yes	55.22
E-MTAB-6701	yes	50.52
E-HCAD-4	yes	31.37
E-CURD-122	yes	22.64
E-MTAB-9221	yes	19.28
E-HCAD-10	yes	18.37
E-ANND-3	yes	11.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting TMEM40, 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-4533	100.00	69.48	2758
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-3085-5P	97.72	65.43	544
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-6741-5P	93.86	63.06	437

Literature-anchored findings (GeneRIF, showing 2)

• TMEM40 represents a potential oncogene, which exert a crucial role in the proliferation and apoptosis via the p53 signaling pathway in bladder cancer. (PMID:29351801)
• Study found that TMEM40 expression was increased in tongue squamous cell carcinoma (TSCC) tissues and associated with clinicopathological parameters. Further results indicated that TMEM40 promoted TSCC development and progression via regulation of p53, Bax and MMP9. (PMID:30320346)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem40	ENSMUSG00000059900
rattus_norvegicus	Tmem40	ENSRNOG00000010430

Protein

Protein identifiers

Transmembrane protein 40 — Q8WWA1 (reviewed: Q8WWA1)

All UniProt accessions (2): Q8WWA1, H7BZY7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WWA1-1	1	yes
Q8WWA1-2	2
Q8WWA1-3	3

RefSeq proteins (4): NP_001271335, NP_001271336, NP_001271337, NP_060776* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026181	TMEM40	Family

Pfam: PF15817

UniProt features (13 total): compositionally biased region 4, transmembrane region 2, splice variant 2, modified residue 2, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWA1-F1	50.95	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 1, 137

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 119 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, COUP_01, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, HNF4_01, TGANTCA_AP1_C, RYTTCCTG_ETS2_B, LE_EGR2_TARGETS_DN, CERVERA_SDHB_TARGETS_1_UP, MODULE_48, MODULE_95, SENESE_HDAC3_TARGETS_DN, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

462 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM40	SMIM3	Q9BZL3	480
TMEM40	RTL8B	Q17RB0	446
TMEM40	ZBTB8B	Q8NAP8	434
TMEM40	CRABP2	P29373	433
TMEM40	TMEM62	Q0P6H9	381
TMEM40	GRIFIN	A4D1Z8	373
TMEM40	GP1BB	P13224	372
TMEM40	POGLUT3	Q7Z4H8	366
TMEM40	DNAJC1	Q96KC8	360
TMEM40	TMEM164	Q5U3C3	356
TMEM40	GARNL3	Q5VVW2	345
TMEM40	LY6G6F	Q5SQ64	337
TMEM40	PPP1R14C	Q8TAE6	330
TMEM40	DHX32	Q7L7V1	326
TMEM40	PRTFDC1	Q9NRG1	317
TMEM40	NT5DC3	Q86UY8	317

IntAct

22 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	TMEM40	psi-mi:“MI:0915”(physical association)	0.630
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
GUCY1A1	SULT2B1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
RNF115	IGLC7	psi-mi:“MI:0914”(association)	0.350
C18orf21	A2ML1	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PHF11	A2ML1	psi-mi:“MI:0914”(association)	0.350
PACC1	IPO5	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
SSTR2	PJA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): TMEM40 (Affinity Capture-MS), TMEM40 (Affinity Capture-MS), TMEM40 (Affinity Capture-MS), TMEM40 (Affinity Capture-MS), TMEM40 (Affinity Capture-MS), TMEM40 (Affinity Capture-MS), TMEM40 (Affinity Capture-MS), TMEM40 (Affinity Capture-MS), TMEM40 (Affinity Capture-MS), TMEM40 (Affinity Capture-MS), TMEM40 (Affinity Capture-MS), TMEM40 (Positive Genetic), TMEM40 (PCA), TMEM40 (Proximity Label-MS), TMEM40 (Affinity Capture-MS)

ESM2 similar proteins: A6NKL6, A6NNE9, A6P320, D3ZHS6, P0C1G7, P0C7U0, P0DPB3, P0DPB4, P53349, P56975, P78524, Q0P496, Q13233, Q3TZ87, Q49LS4, Q4ZIN3, Q52L14, Q5GH59, Q5GH67, Q5GH76, Q5R3F8, Q62925, Q62985, Q63085, Q66JB6, Q68FM6, Q80TE3, Q86XL3, Q86YJ5, Q8BGW2, Q8C8T7, Q8CBH7, Q8R554, Q8TC41, Q8TE49, Q8WWA1, Q8WY54, Q924W7, Q92560, Q96EP1

Diamond homologs: Q4FJU9, Q8WWA1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1634 predictions. Top by Δscore:

Variant	Effect	Δscore
3:12735616:CA:C	acceptor_gain	1.0000
3:12736572:GCTTA:G	donor_loss	1.0000
3:12736573:CTTA:C	donor_loss	1.0000
3:12736574:TTAC:T	donor_loss	1.0000
3:12736575:TA:T	donor_loss	1.0000
3:12736648:CCAGT:C	acceptor_gain	1.0000
3:12736649:CAGT:C	acceptor_gain	1.0000
3:12736649:CAGTC:C	acceptor_gain	1.0000
3:12736650:AGT:A	acceptor_gain	1.0000
3:12736650:AGTCT:A	acceptor_loss	1.0000
3:12736651:GT:G	acceptor_gain	1.0000
3:12736651:GTCT:G	acceptor_loss	1.0000
3:12736652:TCT:T	acceptor_loss	1.0000
3:12736653:C:CC	acceptor_gain	1.0000
3:12736653:CTG:C	acceptor_loss	1.0000
3:12736654:T:A	acceptor_loss	1.0000
3:12736662:C:CT	acceptor_gain	1.0000
3:12736663:A:T	acceptor_gain	1.0000
3:12736664:G:C	acceptor_gain	1.0000
3:12749632:T:TA	donor_gain	1.0000
3:12749758:A:AC	donor_gain	1.0000
3:12749759:C:CC	donor_gain	1.0000
3:12749759:CAGT:C	donor_gain	1.0000
3:12735618:C:CC	acceptor_gain	0.9900
3:12735623:C:CT	acceptor_gain	0.9900
3:12736576:A:AC	donor_gain	0.9900
3:12736577:C:CC	donor_gain	0.9900
3:12736580:AGT:A	donor_gain	0.9900
3:12736664:G:GC	acceptor_gain	0.9900
3:12737756:T:C	acceptor_gain	0.9900

AlphaMissense

1498 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:12736809:A:G	C167R	0.996
3:12736603:T:A	E198D	0.992
3:12736603:T:G	E198D	0.992
3:12736615:G:C	F194L	0.991
3:12736615:G:T	F194L	0.991
3:12736617:A:G	F194L	0.991
3:12736828:A:C	F160L	0.991
3:12736828:A:T	F160L	0.991
3:12736830:A:G	F160L	0.991
3:12736607:A:G	L197P	0.990
3:12736625:A:G	L191P	0.990
3:12736797:C:G	G171R	0.990
3:12736797:C:T	G171R	0.990
3:12736596:C:G	G201R	0.989
3:12736604:T:A	E198V	0.989
3:12736613:G:T	A195D	0.989
3:12736629:C:G	G190R	0.989
3:12736796:C:T	G171E	0.989
3:12736595:C:T	G201D	0.988
3:12737712:T:A	K156I	0.988
3:12736628:C:T	G190D	0.987
3:12736635:C:G	G188R	0.987
3:12736635:C:T	G188R	0.987
3:12736825:G:C	F161L	0.985
3:12736825:G:T	F161L	0.985
3:12736827:A:G	F161L	0.985
3:12736616:A:G	F194S	0.984
3:12736817:A:T	V164D	0.984
3:12736829:A:G	F160S	0.984
3:12736819:G:C	F163L	0.983

dbSNP variants (sampled 300 via entrez): RS1000140898 (3:12764452 A>C), RS1000147868 (3:12733762 T>G), RS1000176740 (3:12749628 T>A), RS1000193591 (3:12764739 G>A), RS1000259730 (3:12735989 G>A), RS1000339656 (3:12758400 C>T), RS1000387468 (3:12766347 G>C), RS1000402617 (3:12761202 G>C), RS1000450117 (3:12738743 C>T), RS1000603888 (3:12746555 T>A), RS1000658429 (3:12740071 A>G), RS1000706777 (3:12744089 G>A,C,T), RS1000708903 (3:12740503 C>A), RS1000861742 (3:12734564 A>C), RS1000989445 (3:12765098 C>A,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

13 associations (top):

Study	Trait	p-value
GCST005956_72	Waist-to-hip ratio adjusted for BMI	1.000000e-07
GCST005957_11	Waist-to-hip ratio adjusted for BMI (age <50)	9.000000e-06
GCST005958_19	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-06
GCST005962_29	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	9.000000e-09
GCST010151_8	Carotid intima media thickness x smoking interaction	8.000000e-06
GCST010617_2	Left ventricular ejection fraction	3.000000e-08
GCST90020025_1933	Waist-to-hip ratio adjusted for BMI	8.000000e-10
GCST90020025_1934	Waist-to-hip ratio adjusted for BMI	8.000000e-09
GCST90020025_1935	Waist-to-hip ratio adjusted for BMI	2.000000e-09
GCST90020027_163	Waist-hip index	3.000000e-10
GCST90020027_164	Waist-hip index	7.000000e-09
GCST90020027_165	Waist-hip index	4.000000e-08
GCST90020027_166	Waist-hip index	1.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0006527	smoking status measurement
EFO:0008373	left ventricular ejection fraction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Silicon Dioxide	increases expression	2
Aflatoxin B1	increases expression	2
Genistein	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
3,4-dichloroaniline	decreases expression	1
ferrous chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
diallyl trisulfide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	increases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzene	decreases expression	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diuron	decreases expression	1

Clinical trials (associated diseases)

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