TMEM14A

Summary

TMEM14A (transmembrane protein 14A, HGNC:21076) is a protein-coding gene on chromosome 6p12.2, encoding Transmembrane protein 14A (Q9Y6G1). Inhibits apoptosis via negative regulation of the mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway.

Involved in negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway. Located in endoplasmic reticulum membrane and mitochondrial membrane.

Source: NCBI Gene 28978 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_014051

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21076
Approved symbol	TMEM14A
Name	transmembrane protein 14A
Location	6p12.2
Locus type	gene with protein product
Status	Approved
Aliases	PTD011, C6orf73
Ensembl gene	ENSG00000096092
Ensembl biotype	protein_coding
OMIM	616870
Entrez	28978

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000211314, ENST00000872503, ENST00000872504, ENST00000872505, ENST00000872506, ENST00000872507, ENST00000872508, ENST00000872509, ENST00000872510, ENST00000924643, ENST00000949406

RefSeq mRNA: 1 — MANE Select: NM_014051 NM_014051

CCDS: CCDS4943

Canonical transcript exons

ENST00000211314 — 5 exons

Exon	Start	End
ENSE00000619446	52681813	52681914
ENSE00000850474	52677087	52677172
ENSE00000850475	52684078	52684165
ENSE00001015280	52671113	52671245
ENSE00001015281	52686010	52686588

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5365 / max 413.8624, expressed in 1725 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68242	28.5365	1725

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.07	gold quality
secondary oocyte	CL:0000655	98.46	gold quality
choroid plexus epithelium	UBERON:0003911	98.26	gold quality
pigmented layer of retina	UBERON:0001782	98.08	gold quality
pons	UBERON:0000988	98.07	gold quality
retina	UBERON:0000966	98.05	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.84	gold quality
middle temporal gyrus	UBERON:0002771	97.62	gold quality
esophagus squamous epithelium	UBERON:0006920	97.52	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.14	gold quality
endothelial cell	CL:0000115	97.13	gold quality
prefrontal cortex	UBERON:0000451	97.09	gold quality
cortical plate	UBERON:0005343	97.04	gold quality
superior frontal gyrus	UBERON:0002661	96.98	gold quality
hypothalamus	UBERON:0001898	96.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.85	gold quality
epithelium of esophagus	UBERON:0001976	96.84	gold quality
superior vestibular nucleus	UBERON:0007227	96.77	gold quality
postcentral gyrus	UBERON:0002581	96.72	gold quality
orbitofrontal cortex	UBERON:0004167	96.59	gold quality
anterior cingulate cortex	UBERON:0009835	96.47	gold quality
cingulate cortex	UBERON:0003027	96.44	gold quality
adult organism	UBERON:0007023	96.41	gold quality
frontal cortex	UBERON:0001870	96.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.39	gold quality
frontal lobe	UBERON:0016525	96.39	gold quality
nephron tubule	UBERON:0001231	96.38	gold quality
parietal lobe	UBERON:0001872	96.36	gold quality
neocortex	UBERON:0001950	96.34	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	14.42
E-ANND-3	yes	10.15
E-HCAD-10	yes	4.31
E-CURD-10	no	286.07
E-HCAD-5	no	12.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting TMEM14A, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-5007-3P	99.51	68.14	1242

Literature-anchored findings (GeneRIF, showing 3)

• findings show for the first time that TMEM14A inhibits apoptosis by blocking the mitochondrial permeability transition and stabilizing mitochondrial membrane potential (PMID:21723035)
• MiR-1179 is sponged by circular RNA circ_0003645 and TMEM14A is a target of miR-1179. (PMID:30853176)
• AXL transcriptionally up-regulates TMEM14A expression to mediate cell proliferation in non-small-cell lung cancer cells. (PMID:37839105)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem14a	ENSDARG00000095157
mus_musculus	Tmem14a	ENSMUSG00000025933
rattus_norvegicus	Tmem14a	ENSRNOG00000013238

Paralogs (2): TMEM14C (ENSG00000111843), TMEM14B (ENSG00000137210)

Protein

Protein identifiers

Transmembrane protein 14A — Q9Y6G1 (reviewed: Q9Y6G1)

All UniProt accessions (1): Q9Y6G1

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits apoptosis via negative regulation of the mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway.

Subcellular location. Mitochondrion membrane. Endoplasmic reticulum membrane.

Tissue specificity. Expressed at significantly higher levels in ovarian cancer tissues than in normal tissues (at protein level).

Similarity. Belongs to the TMEM14 family.

RefSeq proteins (1): NP_054770* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005349	TMEM14	Family
IPR044890	TMEM14_sf	Homologous_superfamily

Pfam: PF03647

UniProt features (11 total): helix 4, transmembrane region 3, strand 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2LOO	SOLUTION NMR
2LOP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6G1-F1	56.93	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, PRAMOONJAGO_SOX4_TARGETS_DN, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, chr6p12, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOCC_MITOCHONDRIAL_ENVELOPE, PARK_HSC_VS_MULTIPOTENT_PROGENITORS_UP, TIEN_INTESTINE_PROBIOTICS_24HR_UP, MODULE_544, GOBP_NEGATIVE_REGULATION_OF_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_MITOCHONDRIAL_OUTER_MEMBRANE_PERMEABILIZATION_INVOLVED_IN_APOPTOTIC_SIGNALING_PATHWAY, GOBP_MEMBRANE_ORGANIZATION

GO Biological Process (3): apoptotic process (GO:0006915), negative regulation of apoptotic process (GO:0043066), negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway (GO:1901029)

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

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), mitochondrial membrane (GO:0031966), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle membrane	2
cytoplasm	2
intracellular membrane-bounded organelle	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
negative regulation of organelle organization	1
negative regulation of mitochondrial membrane permeability	1
mitochondrial outer membrane permeabilization	1
regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	1
negative regulation of apoptotic signaling pathway	1
binding	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
mitochondrion	1
mitochondrial envelope	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM14A	TMEM205	Q6UW68	637
TMEM14A	TMEM45A	Q9NWC5	599
TMEM14A	PPM1N	Q8N819	568
TMEM14A	FGD6	Q6ZV73	549
TMEM14A	GCSAM	Q8N6F7	536
TMEM14A	TMEM164	Q5U3C3	506
TMEM14A	AKR7A2	O43488	494
TMEM14A	CLNK	Q7Z7G1	493
TMEM14A	GGT5	P36269	491
TMEM14A	SERTM1	A2A2V5	490
TMEM14A	FAM91A1	Q658Y4	476
TMEM14A	DDIAS	Q8IXT1	474
TMEM14A	UPK3A	O75631	469
TMEM14A	TRAM2	Q15035	463
TMEM14A	PRAM1	Q96QH2	456

IntAct

94 interactions, top by confidence:

A	B	Type	Score
TMEM14A	LXN	psi-mi:“MI:0915”(physical association)	0.560
LXN	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
TMEM14A	ERMAP	psi-mi:“MI:0915”(physical association)	0.560
LRCH1	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
CREB3L1	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
CXCR3	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
NEMP1	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
PDZK1IP1	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
ERMAP	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
ERGIC3	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
SLC7A1	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
CPLX4	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
SLC18A1	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
SLC10A6	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
SSMEM1	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
AQP6	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
TMEM51	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
TMEM80	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
TMEM179B	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
TMEM14B	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
SCN3B	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
MMGT1	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
IER3IP1	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
MUC1	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (42): LXN (Two-hybrid), TMEM14A (Two-hybrid), TMEM14A (Two-hybrid), TMEM14A (Two-hybrid), TMEM14A (Two-hybrid), TMEM14A (Two-hybrid), TMEM14A (Affinity Capture-MS), TMEM14A (Two-hybrid), TMEM14A (Two-hybrid), ERGIC3 (Two-hybrid), IER3IP1 (Two-hybrid), SLC19A3 (Two-hybrid), LRCH1 (Two-hybrid), TMEM14B (Two-hybrid), SLC7A1 (Two-hybrid)

ESM2 similar proteins: A1CKG4, A1D708, A2XSY1, A4K2N5, A4K2W1, A4R2N5, A6RRF7, A7EMV1, B0XXU1, O43934, O80594, O81214, O95214, O95427, P56982, P56983, P56984, P57758, Q0CNZ5, Q0JDK9, Q1RMQ3, Q32PD8, Q3ZBX1, Q3ZCG8, Q4WXT2, Q56P28, Q5BJW3, Q5PQQ4, Q5RCQ5, Q5RDE9, Q5RFE0, Q5ZLL0, Q62302, Q68EU8, Q6GLC5, Q6P0F0, Q6PDU4, Q6UWH6, Q78S06, Q7ZUA6

Diamond homologs: A8MWL7, O64847, P47131, P56982, P56983, P56984, Q0P436, Q3ZCI1, Q5R751, Q6UXP3, Q75JB5, Q924P2, Q9C6T7, Q9CQN6, Q9LJU6, Q9NUH8, Q9P0S9, Q9W1K0, Q9Y6G1, Q8LPG1, Q94A32, Q9P7G3, Q93V66, Q9ZVH7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

800 predictions. Top by Δscore:

Variant	Effect	Δscore
6:52681807:TTCCA:T	acceptor_loss	1.0000
6:52681808:TCCA:T	acceptor_loss	1.0000
6:52681809:CCAG:C	acceptor_loss	1.0000
6:52681810:CAGGT:C	acceptor_loss	1.0000
6:52681811:AGGT:A	acceptor_gain	1.0000
6:52681812:G:GC	acceptor_loss	1.0000
6:52681812:GGTG:G	acceptor_gain	1.0000
6:52681913:GT:G	donor_gain	1.0000
6:52681915:G:GA	donor_loss	1.0000
6:52681915:G:GG	donor_gain	1.0000
6:52681916:TAA:T	donor_loss	1.0000
6:52681917:AAG:A	donor_loss	1.0000
6:52681918:AGT:A	donor_loss	1.0000
6:52681919:G:GG	donor_gain	1.0000
6:52677085:A:AG	acceptor_gain	0.9900
6:52677086:G:GG	acceptor_gain	0.9900
6:52677086:GA:G	acceptor_gain	0.9900
6:52677086:GAATT:G	acceptor_gain	0.9900
6:52677168:GAGAG:G	donor_gain	0.9900
6:52677169:AGAGG:A	donor_loss	0.9900
6:52677170:GAG:G	donor_gain	0.9900
6:52677171:AG:A	donor_loss	0.9900
6:52677172:GG:G	donor_loss	0.9900
6:52677173:G:GA	donor_loss	0.9900
6:52677174:T:TT	donor_loss	0.9900
6:52681811:A:AG	acceptor_gain	0.9900
6:52681811:AGGTG:A	acceptor_gain	0.9900
6:52681812:G:GG	acceptor_gain	0.9900
6:52681812:GGT:G	acceptor_gain	0.9900
6:52681812:GGTGG:G	acceptor_gain	0.9900

AlphaMissense

627 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:52684116:T:C	F71L	0.952
6:52684118:T:A	F71L	0.952
6:52684118:T:G	F71L	0.952
6:52681848:G:A	G36R	0.940
6:52681848:G:C	G36R	0.940
6:52677128:C:A	A9E	0.935
6:52684107:G:C	G68R	0.935
6:52681849:G:A	G36E	0.930
6:52684108:G:A	G68D	0.923
6:52684147:G:A	G81D	0.921
6:52677115:G:C	G5R	0.908
6:52684158:G:C	G85R	0.906
6:52684106:G:A	M67I	0.901
6:52684106:G:C	M67I	0.901
6:52684106:G:T	M67I	0.901
6:52677148:A:C	S16R	0.898
6:52677150:C:A	S16R	0.898
6:52677150:C:G	S16R	0.898
6:52681866:G:A	G42R	0.897
6:52681866:G:C	G42R	0.897
6:52677106:G:C	D2H	0.895
6:52684156:C:A	A84E	0.892
6:52681869:G:C	A43P	0.889
6:52681867:G:A	G42E	0.888
6:52681870:C:A	A43D	0.887
6:52681861:G:A	G40D	0.886
6:52684159:G:A	G85D	0.883
6:52681858:C:A	A39D	0.881
6:52677127:G:C	A9P	0.878
6:52684165:G:T	S87I	0.875

dbSNP variants (sampled 300 via entrez): RS1000104917 (6:52671846 G>T), RS1000273540 (6:52669767 C>T), RS1000281278 (6:52678687 T>C), RS1000287029 (6:52682530 T>C), RS1000580535 (6:52676138 A>G,T), RS1000589956 (6:52682193 A>C), RS1000809 (6:52670476 A>G,T), RS1000810 (6:52670133 C>A,G,T), RS1000990193 (6:52670714 C>A,T), RS1001107971 (6:52670419 A>C,T), RS1001213212 (6:52670690 C>T), RS1001279055 (6:52670957 G>A), RS1001558906 (6:52680022 G>A), RS1001642416 (6:52683768 T>A), RS1002368715 (6:52685533 C>T)

Disease associations

OMIM: gene MIM:616870 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005606_8	Response to hepatitis B vaccine	8.000000e-06
GCST008764_11	Perceived intensity of neohesperidin dihydrochalcone	9.000000e-06
GCST009391_1308	Metabolite levels	8.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0010517	oxalate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
trichostatin A	affects expression, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
didecyldimethylammonium	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Am 580	decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
MT19c compound	increases expression	1
Rosiglitazone	decreases expression	1
Temozolomide	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1

Clinical trials (associated diseases)

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