TMEM186

Summary

TMEM186 (transmembrane protein 186, HGNC:24530) is a protein-coding gene on chromosome 16p13.2, encoding Transmembrane protein 186 (Q96B77). As part of the MCIA complex, required for efficient assembly of the mitochondrial complex I.

This gene encodes a potential transmembrane protein.

Source: NCBI Gene 25880 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_015421

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24530
Approved symbol	TMEM186
Name	transmembrane protein 186
Location	16p13.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564K2062
Ensembl gene	ENSG00000184857
Ensembl biotype	protein_coding
OMIM	620433
Entrez	25880

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000333050, ENST00000564869, ENST00000872296

RefSeq mRNA: 1 — MANE Select: NM_015421 NM_015421

CCDS: CCDS10535

Canonical transcript exons

ENST00000333050 — 2 exons

Exon	Start	End
ENSE00001311751	8795180	8796590
ENSE00001412007	8797612	8797639

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 89.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.7687 / max 30.1615, expressed in 1504 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156161	2.7687	1504

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	89.62	silver quality
mucosa of transverse colon	UBERON:0004991	87.70	gold quality
tongue squamous epithelium	UBERON:0006919	86.17	silver quality
right lobe of liver	UBERON:0001114	86.11	gold quality
gastrocnemius	UBERON:0001388	86.00	gold quality
islet of Langerhans	UBERON:0000006	85.82	gold quality
squamous epithelium	UBERON:0006914	85.67	gold quality
esophagus squamous epithelium	UBERON:0006920	85.42	gold quality
muscle of leg	UBERON:0001383	85.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.32	gold quality
epithelium of esophagus	UBERON:0001976	85.29	gold quality
endometrium epithelium	UBERON:0004811	85.27	silver quality
hair follicle	UBERON:0002073	84.38	silver quality
muscle organ	UBERON:0001630	83.99	gold quality
pancreas	UBERON:0001264	83.95	gold quality
right adrenal gland cortex	UBERON:0035827	83.84	gold quality
body of pancreas	UBERON:0001150	83.74	gold quality
tendon of biceps brachii	UBERON:0008188	83.74	gold quality
right adrenal gland	UBERON:0001233	83.72	gold quality
apex of heart	UBERON:0002098	83.63	gold quality
body of tongue	UBERON:0011876	83.57	gold quality
heart left ventricle	UBERON:0002084	83.45	gold quality
cardiac ventricle	UBERON:0002082	83.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.21	gold quality
left adrenal gland	UBERON:0001234	82.66	gold quality
deltoid	UBERON:0001476	82.55	gold quality
palpebral conjunctiva	UBERON:0001812	82.55	gold quality
vena cava	UBERON:0004087	82.37	silver quality
left adrenal gland cortex	UBERON:0035825	82.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting TMEM186, 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-6764-5P	99.75	67.89	2304
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-346	97.01	66.97	662
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-345-5P	96.40	66.43	663

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem186	ENSDARG00000109974
mus_musculus	Tmem186	ENSMUSG00000043140
rattus_norvegicus	AABR07057217.1	ENSRNOG00000025487
rattus_norvegicus	Tmem186	ENSRNOG00000027087
drosophila_melanogaster	CG4627	FBGN0033808

Protein

Protein identifiers

Transmembrane protein 186 — Q96B77 (reviewed: Q96B77)

All UniProt accessions (1): Q96B77

UniProt curated annotations — full annotation on UniProt →

Function. As part of the MCIA complex, required for efficient assembly of the mitochondrial complex I.

Subunit / interactions. Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186. Interacts with MT-ND3.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the TMEM186 family.

RefSeq proteins (1): NP_056236* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026571	Tmem186	Family
IPR045325	TMEM70/TMEM186/TMEM223	Family

Pfam: PF06979

UniProt features (7 total): topological domain 3, transmembrane region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96B77-F1	60.13	0.02

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-611105	Respiratory electron transport
R-HSA-6799198	Complex I biogenesis

MSigDB gene sets: 94 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOCC_MITOCHONDRIAL_ENVELOPE, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, TCCCRNNRTGC_UNKNOWN, GOCC_ORGANELLE_INNER_MEMBRANE, GOCC_INNER_MITOCHONDRIAL_MEMBRANE_PROTEIN_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, SANSOM_APC_TARGETS_REQUIRE_MYC, GOCC_MITOCHONDRIAL_PROTEIN_CONTAINING_COMPLEX, SCGGAAGY_ELK1_02, GOCC_ORGANELLE_ENVELOPE, MARTENS_TRETINOIN_RESPONSE_DN

GO Biological Process (1): mitochondrial respiratory chain complex I assembly (GO:0032981)

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

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
NADH dehydrogenase complex assembly	1
mitochondrial respiratory chain complex assembly	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM186	TMEM126B	Q8IUX1	896
TMEM186	NDUFAF1	Q9Y375	822
TMEM186	ECSIT	Q9BQ95	794
TMEM186	ACAD9	Q9H845	775
TMEM186	DMAC2	Q9NW81	715
TMEM186	TMEM70	Q9BUB7	690
TMEM186	TIMMDC1	Q9NPL8	670
TMEM186	FOXRED1	Q96CU9	647
TMEM186	COA1	Q9GZY4	597
TMEM186	ZNF277	Q9NRM2	517
TMEM186	HAPSTR1	Q14CZ0	514
TMEM186	TMEM259	Q4ZIN3	514
TMEM186	NDUFAF6	Q330K2	506
TMEM186	NDUFAF4	Q9P032	501
TMEM186	TMEM258	P61165	487

IntAct

127 interactions, top by confidence:

A	B	Type	Score
TUBGCP5	TUBG1	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
HEATR3	TMEM186	psi-mi:“MI:0914”(association)	0.730
RANBP6	SLC27A2	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
TMEM186	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
TMEM186	GFAP	psi-mi:“MI:0915”(physical association)	0.560
	TMEM186	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	TMEM186	psi-mi:“MI:0915”(physical association)	0.560
TMEM186	JPH3	psi-mi:“MI:0915”(physical association)	0.560
TMEM186		psi-mi:“MI:0915”(physical association)	0.560
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
TMEM171	THAP12	psi-mi:“MI:0914”(association)	0.530
TMEM186	POTEE	psi-mi:“MI:0914”(association)	0.530

BioGRID (102): TMEM186 (Two-hybrid), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), POTEE (Affinity Capture-MS)

ESM2 similar proteins: A5GZW8, A6H773, A6QPI4, D3ZAW2, O14521, O75208, P09925, Q05B67, Q08BI9, Q12887, Q15070, Q15526, Q2KHV4, Q2NL34, Q3B8P0, Q3SYV3, Q3TD49, Q4KLZ1, Q5EA03, Q5G2C6, Q5PQL3, Q5R460, Q5R5H4, Q5R7D0, Q5RC29, Q5RE99, Q5T6X4, Q5XIJ4, Q5XJY4, Q5ZIS0, Q5ZLJ4, Q68FN7, Q68FT1, Q6AZR3, Q6AZV0, Q6DGM2, Q6P355, Q6PCT8, Q800L1, Q8BSF4

Diamond homologs: B3DI94, Q059A4, Q4KLZ1, Q5EA03, Q96B77, Q9CR76

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 148 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SLC transporter disorders	8	17.2×	5e-06
R-HSA-425366	7	13.4×	9e-05
Disorders of transmembrane transporters	9	13.2×	5e-06
SLC-mediated transmembrane transport	11	6.8×	7e-05
Transport of small molecules	13	3.4×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

450 predictions. Top by Δscore:

Variant	Effect	Δscore
16:8796407:C:CT	acceptor_gain	0.9700
16:8796891:CAAA:C	acceptor_gain	0.9500
16:8781450:G:GG	donor_gain	0.9400
16:8782406:C:G	acceptor_gain	0.9400
16:8797622:C:CT	donor_gain	0.9400
16:8781449:A:AG	donor_gain	0.9300
16:8782396:T:TA	acceptor_gain	0.9200
16:8782405:A:AG	acceptor_gain	0.9200
16:8796591:C:CC	acceptor_gain	0.9200
16:8797623:C:CT	donor_gain	0.9200
16:8796587:CAGC:C	acceptor_gain	0.9100
16:8796892:A:T	acceptor_gain	0.9100
16:8796588:AGCCT:A	acceptor_loss	0.9000
16:8796589:GCCTG:G	acceptor_loss	0.9000
16:8796590:CCTG:C	acceptor_loss	0.9000
16:8796592:T:G	acceptor_loss	0.9000
16:8796408:A:T	acceptor_gain	0.8900
16:8796593:G:C	acceptor_loss	0.8700
16:8797609:TAC:T	donor_loss	0.8700
16:8797610:A:T	donor_loss	0.8700
16:8797611:C:CG	donor_loss	0.8700
16:8796898:A:C	acceptor_gain	0.8400
16:8796890:CCAAA:C	acceptor_gain	0.8300
16:8797610:A:AC	donor_gain	0.8200
16:8797611:C:CC	donor_gain	0.8200
16:8796430:TTCTC:T	acceptor_gain	0.8000
16:8796891:C:T	acceptor_gain	0.8000
16:8796898:A:AC	acceptor_gain	0.8000
16:8797621:A:AC	donor_gain	0.7900
16:8781308:GGT:G	acceptor_gain	0.7800

AlphaMissense

1375 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:8796231:G:C	S121R	0.973
16:8796231:G:T	S121R	0.973
16:8796233:T:G	S121R	0.973
16:8796426:G:C	F56L	0.970
16:8796426:G:T	F56L	0.970
16:8796428:A:G	F56L	0.970
16:8796369:C:A	K75N	0.963
16:8796369:C:G	K75N	0.963
16:8796153:G:C	F147L	0.956
16:8796153:G:T	F147L	0.956
16:8796155:A:G	F147L	0.956
16:8796167:C:G	A143P	0.946
16:8796061:A:G	I178T	0.945
16:8796193:T:A	N134I	0.944
16:8796028:A:T	V189D	0.943
16:8796149:C:G	G149R	0.941
16:8796172:C:G	R141P	0.934
16:8796208:C:T	G129D	0.931
16:8796371:T:C	K75E	0.929
16:8796033:G:C	F187L	0.925
16:8796033:G:T	F187L	0.925
16:8796035:A:G	F187L	0.925
16:8795988:G:C	F202L	0.922
16:8795988:G:T	F202L	0.922
16:8795990:A:G	F202L	0.922
16:8796148:C:A	G149V	0.918
16:8796166:G:T	A143D	0.918
16:8796211:A:T	V128D	0.912
16:8796256:G:T	A113D	0.910
16:8796209:C:G	G129R	0.909

dbSNP variants (sampled 300 via entrez): RS1000111351 (16:8797159 G>C), RS1000578780 (16:8798240 A>G), RS1000941675 (16:8797363 G>A,C), RS1001617262 (16:8798717 G>A,T), RS1002218256 (16:8795264 G>C), RS1002344814 (16:8797789 G>A,C,T), RS1002651206 (16:8799611 A>C,G), RS1002737669 (16:8795073 C>T), RS1003342085 (16:8798210 A>G), RS1004348600 (16:8799518 G>A,T), RS1004386707 (16:8797828 G>A,C,T), RS1004691426 (16:8795284 C>A,G,T), RS1004697397 (16:8797330 A>G), RS1004802196 (16:8796876 T>A,C), RS1004869644 (16:8797671 C>A,T)

Disease associations

OMIM: gene MIM:620433 | disease phenotypes: MIM:613163, MIM:212065

GenCC curated gene-disease

Mondo (2): GABA aminotransaminase deficiency (MONDO:0013166), PMM2-congenital disorder of glycosylation (MONDO:0008907)

Orphanet (2): Gamma-aminobutyric acid transaminase deficiency (Orphanet:2066), PMM2-CDG (Orphanet:79318)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C535739	Congenital disorder of glycosylation type 1A (supp.)
C535407	Gamma aminobutyric acid transaminase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Urethane	decreases expression	1
Vitamin E	increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04925960	PHASE3	TERMINATED	Oral Epalrestat Therapy in Pediatric Subjects With PMM2-CDG
NCT05549219	PHASE2	COMPLETED	24-Week Study to Assess the PD, Safety, Tolerability, and PK of GLM101 in Participants With PMM2-CDG
NCT06657859	PHASE2	ENROLLING_BY_INVITATION	Open-Label Extension Study to Assess GLM101 in PMM2-CDG Patients
NCT04679389	PHASE2/PHASE3	TERMINATED	Acetazolamide Efficacy in Ataxia in PMM2-CDG
NCT06892288	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study to Assess the Efficacy and Safety of Weekly Doses of GLM101 in Participants With PMM2-CDG
NCT03173300	Not specified	ACTIVE_NOT_RECRUITING	Natural History Study Protocol in PMM2-CDG (CDG-Ia)