TMEM86A

Summary

TMEM86A (transmembrane protein 86A, HGNC:26890) is a protein-coding gene on chromosome 11p15.1, encoding Lysoplasmalogenase TMEM86A (Q8N2M4). Catalyzes the hydrolysis of the vinyl ether bond of choline or ethanolamine lysoplasmalogens, forming fatty aldehyde and glycerophosphocholine or glycerophosphoethanolamine, respectively and is specific for the sn-2-deacylated (lyso) form of plasmalogen.

Enables alkenylglycerophosphocholine hydrolase activity. Predicted to be involved in lipid metabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in membrane.

Source: NCBI Gene 144110 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_153347

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26890
Approved symbol	TMEM86A
Name	transmembrane protein 86A
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90119
Ensembl gene	ENSG00000151117
Ensembl biotype	protein_coding
Entrez	144110

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000280734, ENST00000524888, ENST00000527002, ENST00000529240, ENST00000533987

RefSeq mRNA: 1 — MANE Select: NM_153347 NM_153347

CCDS: CCDS7844

Canonical transcript exons

ENST00000280734 — 3 exons

Exon	Start	End
ENSE00001220407	18701573	18704785
ENSE00002151117	18698779	18698907
ENSE00003601095	18700933	18701197

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 89.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.9174 / max 119.9135, expressed in 990 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113356	2.4406	875
113357	0.4768	248

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	89.54	gold quality
kidney epithelium	UBERON:0004819	89.29	gold quality
pancreatic ductal cell	CL:0002079	87.81	silver quality
adrenal tissue	UBERON:0018303	84.23	gold quality
skin of leg	UBERON:0001511	83.17	gold quality
tibialis anterior	UBERON:0001385	81.13	silver quality
zone of skin	UBERON:0000014	80.48	gold quality
left ventricle myocardium	UBERON:0006566	79.32	gold quality
buccal mucosa cell	CL:0002336	79.29	gold quality
skin of abdomen	UBERON:0001416	79.24	gold quality
cardiac muscle of right atrium	UBERON:0003379	78.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.43	gold quality
nasal cavity epithelium	UBERON:0005384	78.16	gold quality
lower esophagus mucosa	UBERON:0035834	78.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.05	gold quality
metanephros	UBERON:0000081	77.72	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	77.39	gold quality
adult mammalian kidney	UBERON:0000082	76.81	gold quality
myocardium	UBERON:0002349	76.81	gold quality
metanephros cortex	UBERON:0010533	76.65	gold quality
gall bladder	UBERON:0002110	75.87	gold quality
pigmented layer of retina	UBERON:0001782	75.68	gold quality
parotid gland	UBERON:0001831	75.65	gold quality
kidney	UBERON:0002113	75.15	gold quality
islet of Langerhans	UBERON:0000006	74.18	gold quality
deltoid	UBERON:0001476	74.17	silver quality
right ovary	UBERON:0002118	73.56	gold quality
left ovary	UBERON:0002119	73.45	gold quality
heart right ventricle	UBERON:0002080	73.24	silver quality
spleen	UBERON:0002106	72.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

126 targeting TMEM86A, 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-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-4283	100.00	66.42	2097
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 1)

• Sterol-regulated transmembrane protein TMEM86a couples LXR signaling to regulation of lysoplasmalogens in macrophages. (PMID:36592658)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem86a	ENSDARG00000044034
mus_musculus	Tmem86a	ENSMUSG00000010307
rattus_norvegicus	Tmem86a	ENSRNOG00000013663
drosophila_melanogaster	CG7582	FBGN0039681

Paralogs (1): TMEM86B (ENSG00000180089)

Protein

Protein identifiers

Lysoplasmalogenase TMEM86A — Q8N2M4 (reviewed: Q8N2M4)

Alternative names: Transmembrane protein 86A

All UniProt accessions (1): Q8N2M4

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of the vinyl ether bond of choline or ethanolamine lysoplasmalogens, forming fatty aldehyde and glycerophosphocholine or glycerophosphoethanolamine, respectively and is specific for the sn-2-deacylated (lyso) form of plasmalogen. Plays an important role in lysoplasmalogen metabolism in the adipocyte tissue and macrophages.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in the macrophages.

Induction. Sterol-inducible in the macrophages and the induction is mediated by the liver X receptor (LXR).

Similarity. Belongs to the TMEM86 family.

RefSeq proteins (1): NP_699178* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012506	TMEM86B-like	Family

Pfam: PF07947

Catalyzed reactions (Rhea), 2 shown:

• a 1-O-(1Z-alkenyl)-sn-glycero-3-phosphoethanolamine + H2O = a 2,3-saturated aldehyde + sn-glycero-3-phosphoethanolamine (RHEA:16905)
• a 1-O-(1Z-alkenyl)-sn-glycero-3-phosphocholine + H2O = a 2,3-saturated aldehyde + sn-glycerol 3-phosphocholine (RHEA:22544)

UniProt features (19 total): topological domain 9, transmembrane region 8, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N2M4-F1	89.98	0.78

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 153 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, RACCACAR_AML_Q6, CAGCTG_AP4_Q5, CREB_Q4, AML_Q6, ATF1_Q6, CAATGCA_MIR33, GOBP_LIPID_METABOLIC_PROCESS, ATF4_Q2, WHN_B, AML1_01, AR_Q2, WGGAATGY_TEF1_Q6, USF2_Q6, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK

GO Biological Process (1): lipid metabolic process (GO:0006629)

GO Molecular Function (3): hydrolase activity (GO:0016787), alkenylglycerophosphocholine hydrolase activity (GO:0047408), protein binding (GO:0005515)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
catalytic activity	1
ether hydrolase activity	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM86A	NXPH2	O95156	514
TMEM86A	LRRC3C	A6NJW4	485
TMEM86A	PPP1R14B	Q96C90	466
TMEM86A	LHFPL2	Q6ZUX7	463
TMEM86A	CLCA2	Q9UQC9	459
TMEM86A	TSPAN2	O60636	457
TMEM86A	GET3	O43681	456
TMEM86A	DLST	P36957	446
TMEM86A	PRODH	O43272	445
TMEM86A	PRODH	O43272	439
TMEM86A	TMEM51	Q9NW97	437
TMEM86A	MAGEA9B	P43362	433
TMEM86A	C11orf52	Q96A22	417
TMEM86A	VIPR1	P32241	410
TMEM86A	LZTS2	Q9BRK4	410

IntAct

142 interactions, top by confidence:

A	B	Type	Score
TMEM86A	AQP3	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	NCAPH2	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	HAVCR2	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	GJB4	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
KCNA1	TMEM86A	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	RNF185	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	BCL2L13	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS2	TMEM86A	psi-mi:“MI:0915”(physical association)	0.560
	TMEM86A	psi-mi:“MI:0915”(physical association)	0.560
PI16	TMEM86A	psi-mi:“MI:0915”(physical association)	0.560
MS4A2	TMEM86A	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	FKBP7	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	TMEM86A	psi-mi:“MI:0915”(physical association)	0.560
GPR37L1	TMEM86A	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	FNDC9	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (50): TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid), TMEM86A (Two-hybrid)

ESM2 similar proteins: A0JNU3, A4K526, O18765, O88202, O88407, P0DXN1, P0DXN2, P0DXN3, P16257, P30535, P30536, P31213, P39619, P50637, Q0P436, Q1LZ71, Q2KI29, Q32L10, Q32LG5, Q3MHQ7, Q49VD3, Q4L3Q9, Q568J8, Q58CW5, Q5F285, Q5HRG3, Q5R4I4, Q5REM8, Q5RKL5, Q658P3, Q6GPW4, Q6UN27, Q6UW68, Q71KT5, Q86U10, Q8CI59, Q8CTQ5, Q8K0E7, Q8N2M4, Q8N2U0

Diamond homologs: B0BNF0, F1RMN2, Q3MHQ7, Q3T0W0, Q497J1, Q8N2M4, Q8N661, Q9D8N3, Q5ZU17

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

951 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18698905:GTG:G	donor_gain	1.0000
11:18698908:G:GG	donor_gain	0.9900
11:18698908:GTGA:G	donor_loss	0.9900
11:18698909:TGAG:T	donor_loss	0.9900
11:18698910:G:GG	donor_loss	0.9900
11:18698912:G:GG	donor_gain	0.9900
11:18699149:G:GT	donor_gain	0.9900
11:18700928:TCCAG:T	acceptor_loss	0.9900
11:18700929:CCA:C	acceptor_loss	0.9900
11:18700930:CA:C	acceptor_loss	0.9900
11:18700931:A:AG	acceptor_gain	0.9900
11:18700931:A:C	acceptor_loss	0.9900
11:18700932:G:GA	acceptor_loss	0.9900
11:18700932:G:GG	acceptor_gain	0.9900
11:18701183:GA:G	donor_gain	0.9900
11:18701193:GCATG:G	donor_gain	0.9900
11:18701198:G:GG	donor_gain	0.9900
11:18701568:CCCA:C	acceptor_loss	0.9900
11:18701569:CCAGG:C	acceptor_loss	0.9900
11:18701570:CA:C	acceptor_loss	0.9900
11:18701571:AGG:A	acceptor_loss	0.9900
11:18701572:G:T	acceptor_loss	0.9900
11:18704539:C:CC	acceptor_gain	0.9900
11:18698911:A:AG	donor_gain	0.9800
11:18698978:C:T	donor_gain	0.9800
11:18699260:G:GT	donor_gain	0.9800
11:18699261:G:T	donor_gain	0.9800
11:18700932:GGTGA:G	acceptor_gain	0.9800
11:18701212:T:TA	donor_gain	0.9800
11:18701213:A:AA	donor_gain	0.9800

AlphaMissense

1528 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:18701584:T:C	F100L	0.997
11:18701586:T:A	F100L	0.997
11:18701586:T:G	F100L	0.997
11:18701156:A:C	D82A	0.995
11:18701156:A:T	D82V	0.995
11:18701040:G:C	K43N	0.994
11:18701040:G:T	K43N	0.994
11:18701132:G:A	G74E	0.994
11:18700963:T:C	F18L	0.993
11:18700965:C:A	F18L	0.993
11:18700965:C:G	F18L	0.993
11:18701048:C:A	P46H	0.993
11:18701156:A:G	D82G	0.993
11:18701761:T:A	W159R	0.993
11:18701761:T:C	W159R	0.993
11:18701855:A:C	D190A	0.993
11:18701855:A:T	D190V	0.993
11:18701878:T:C	F198L	0.993
11:18701880:C:A	F198L	0.993
11:18701880:C:G	F198L	0.993
11:18701585:T:G	F100C	0.992
11:18700978:T:C	C23R	0.991
11:18701153:G:A	G81D	0.991
11:18701155:G:C	D82H	0.991
11:18701157:C:A	D82E	0.991
11:18701157:C:G	D82E	0.991
11:18701585:T:C	F100S	0.991
11:18701048:C:G	P46R	0.990
11:18701056:T:C	C49R	0.990
11:18701856:C:A	D190E	0.990

dbSNP variants (sampled 300 via entrez): RS1000613868 (11:18699299 A>G), RS1000724287 (11:18706153 G>A,C), RS1001103026 (11:18708581 T>C), RS1001155316 (11:18705859 C>T), RS1001396426 (11:18703020 A>G), RS1001686025 (11:18697155 G>C), RS1001759657 (11:18697554 G>A), RS1001790798 (11:18697963 C>T), RS1002317556 (11:18697558 G>A,C), RS1002692164 (11:18698722 C>A,T), RS1002754319 (11:18698979 A>G), RS1002984130 (11:18705376 C>A,T), RS1003117390 (11:18701373 T>C), RS1003334448 (11:18705113 T>C,G), RS1003728420 (11:18699946 A>G)

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

1 associations (top):

Study	Trait	p-value
GCST001330_4	Ovarian reserve	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004770	ovarian reserve

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
sodium arsenate	decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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