MTCH2

Summary

MTCH2 (mitochondrial carrier 2, HGNC:17587) is a protein-coding gene on chromosome 11p11.2, encoding Mitochondrial carrier homolog 2 (Q9Y6C9). Protein insertase that mediates insertion of transmembrane proteins into the mitochondrial outer membrane. It is a selective cancer dependency (DepMap: 11.8% of cell lines).

This gene encodes a member of the SLC25 family of nuclear-encoded transporters that are localized in the inner mitochondrial membrane. Members of this superfamily are involved in many metabolic pathways and cell functions. Genome-wide association studies in human have identified single-nucleotide polymorphisms in several loci associated with obesity. This gene is one such locus, which is highly expressed in white adipose tissue and adipocytes, and thought to play a regulatory role in adipocyte differentiation and biology. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study showed this gene to be an authentic stop codon readthrough target that can produce two isoforms from the same mRNA by use of alternative in-frame translation termination codons.

Source: NCBI Gene 23788 — RefSeq curated summary.

At a glance

• GWAS associations: 50
• Clinical variants (ClinVar): 61 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 11.8% of screened cell lines
• MANE Select transcript: NM_014342

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17587
Approved symbol	MTCH2
Name	mitochondrial carrier 2
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Aliases	SLC25A50, MIMP
Ensembl gene	ENSG00000109919
Ensembl biotype	protein_coding
OMIM	613221
Entrez	23788

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000302503, ENST00000525649, ENST00000530428, ENST00000533571, ENST00000534074, ENST00000539759, ENST00000864069, ENST00000864070, ENST00000864071, ENST00000864072, ENST00000864073, ENST00000864074, ENST00000864075, ENST00000920958, ENST00000920959, ENST00000920960, ENST00000920961, ENST00000920962, ENST00000920963, ENST00000920964, ENST00000920965, ENST00000947886, ENST00000947887

RefSeq mRNA: 4 — MANE Select: NM_014342 NM_001317231, NM_001317232, NM_001317233, NM_014342

CCDS: CCDS7943

Canonical transcript exons

ENST00000302503 — 13 exons

Exon	Start	End
ENSE00001180228	47642379	47642559
ENSE00001267224	47617317	47618919
ENSE00003487086	47631654	47631711
ENSE00003488685	47635545	47635571
ENSE00003507307	47638967	47639051
ENSE00003550408	47627080	47627127
ENSE00003573606	47634672	47634734
ENSE00003578384	47625674	47625741
ENSE00003586972	47631036	47631087
ENSE00003626323	47638699	47638805
ENSE00003627864	47628953	47629046
ENSE00003635465	47630555	47630614
ENSE00003650577	47622701	47622776

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 98.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 92.2980 / max 440.4787, expressed in 1826 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119662	60.6892	1826
119661	30.7486	1817
119664	0.5135	307
119663	0.3467	181

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.56	gold quality
right testis	UBERON:0004534	98.54	gold quality
testis	UBERON:0000473	98.09	gold quality
mucosa of transverse colon	UBERON:0004991	97.78	gold quality
rectum	UBERON:0001052	97.61	gold quality
right lobe of liver	UBERON:0001114	97.30	gold quality
duodenum	UBERON:0002114	97.27	gold quality
liver	UBERON:0002107	97.24	gold quality
cortical plate	UBERON:0005343	96.98	gold quality
stromal cell of endometrium	CL:0002255	96.96	gold quality
islet of Langerhans	UBERON:0000006	96.90	gold quality
gastrocnemius	UBERON:0001388	96.87	gold quality
muscle of leg	UBERON:0001383	96.65	gold quality
skeletal muscle organ	UBERON:0014892	96.62	gold quality
adult mammalian kidney	UBERON:0000082	96.51	gold quality
adrenal tissue	UBERON:0018303	96.22	gold quality
smooth muscle tissue	UBERON:0001135	96.19	gold quality
esophagus mucosa	UBERON:0002469	95.92	gold quality
skeletal muscle tissue	UBERON:0001134	95.87	gold quality
muscle tissue	UBERON:0002385	95.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.73	gold quality
right adrenal gland	UBERON:0001233	95.73	gold quality
kidney	UBERON:0002113	95.64	gold quality
heart left ventricle	UBERON:0002084	95.62	gold quality
right adrenal gland cortex	UBERON:0035827	95.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.47	gold quality
ganglionic eminence	UBERON:0004023	95.21	gold quality
embryo	UBERON:0000922	95.20	gold quality
transverse colon	UBERON:0001157	95.18	gold quality
left adrenal gland	UBERON:0001234	95.15	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10596	no	608.61
E-GEOD-81383	no	336.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting MTCH2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-520F-3P	99.82	71.32	1216

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 21)

• Mtch2 is a mitochondrial target of tBID and possibly participates in the mitochondrial apoptotic program. (PMID:15899861)
• MTCH2 rs 10838738 is associated with higher body mass index. (PMID:19910938)
• MTCH2 may play a role in cellular processes underlying obesity (PMID:21795451)
• Gene-treatment interactions were observed for short-term weight loss. (MTCH2 rs10838738, Plifestyle*SNP = 0.022) (PMID:22179955)
• Molecular basis of the interaction between proapoptotic truncated BID (tBID) protein and mitochondrial carrier homologue 2 (MTCH2) protein (PMID:22416135)
• Our study supports earlier reports of SH2B1 to be of importance in insulin sensitivity and, in addition, suggests potential roles of NEGR1 and MTCH2. (PMID:22443470)
• Results imply a regulatory role for TMEM18, BDNF, MTCH2 and NEGR1 in adipocyte differentiation and biology. In addition, we show a variation of MAF expression during adipogenesis, while NPC1, PTER and SH2B1 were not regulated. (PMID:23229156)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• Data indicate that Mtch2 accelerated conformational change in membrane-bound tBid (Bid) enables it to activate Bax. (PMID:23744079)
• MTCH2 and cardiolipin participate in the recruitment and integration of tBID into the mitochondrial outer membrane. (PMID:26794447)
• The BID-MTCH2 axis regulates the differentiation/apoptosis of stem cells and mitochondrial metabolism. (Review) (PMID:26827940)
• study identified Cav1 and MTCH2 as the molecular targets of DHA and revealed a new link between the upstream Cav1/MTCH2 upregulation and the downstream activation of the cell death pathway involved in the DHA-mediated inhibition of cell viability. (PMID:28498397)
• MARCH5 requires MTCH2 to coordinate proteasomal turnover of the MCL1:NOXA complex. (PMID:32094511)
• Mitochondrial carrier homolog 2 is necessary for AML survival. (PMID:32299104)
• Stop codon read-through of mammalian MTCH2 leading to an unstable isoform regulates mitochondrial membrane potential. (PMID:33028634)
• Inhibition of mitochondrial carrier homolog 2 (MTCH2) suppresses tumor invasion and enhances sensitivity to temozolomide in malignant glioma. (PMID:33509092)
• The modified mitochondrial outer membrane carrier MTCH2 links mitochondrial fusion to lipogenesis. (PMID:34586346)
• Opposing effects of genetic variation in MTCH2 for obesity versus heart failure. (PMID:35904451)
• The biology of mitochondrial carrier homolog 2. (PMID:38158152)
• MTCH2 cooperates with MFN2 and lysophosphatidic acid synthesis to sustain mitochondrial fusion. (PMID:38177900)
• The mitochondrial carrier homolog 2 is involved in down-regulation of influenza A virus replication. (PMID:38727866)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtch2	ENSDARG00000019732
mus_musculus	Mtch2	ENSMUSG00000027282
rattus_norvegicus	Mtch2	ENSRNOG00000058658
drosophila_melanogaster	Mtch	FBGN0027786
drosophila_melanogaster	CG10920	FBGN0029963
caenorhabditis_elegans		WBGENE00018395
caenorhabditis_elegans		WBGENE00018397

Paralogs (1): MTCH1 (ENSG00000137409)

Protein

Protein identifiers

Mitochondrial carrier homolog 2 — Q9Y6C9 (reviewed: Q9Y6C9)

Alternative names: Met-induced mitochondrial protein

All UniProt accessions (2): Q9Y6C9, E9PIE4

UniProt curated annotations — full annotation on UniProt →

Function. Protein insertase that mediates insertion of transmembrane proteins into the mitochondrial outer membrane. Catalyzes insertion of proteins with alpha-helical transmembrane regions, such as signal-anchored, tail-anchored and multi-pass membrane proteins. Does not mediate insertion of beta-barrel transmembrane proteins. Also acts as a receptor for the truncated form of pro-apoptotic BH3-interacting domain death agonist (p15 BID) and has therefore a critical function in apoptosis. Regulates the quiescence/cycling of hematopoietic stem cells (HSCs). Acts as a regulator of mitochondrial fusion, essential for the naive-to-primed interconversion of embryonic stem cells (ESCs). Acts as a regulator of lipid homeostasis and has a regulatory role in adipocyte differentiation and biology.

Subunit / interactions. Interacts with p15BID. Interacts with MUL1/MAPL.

Subcellular location. Mitochondrion outer membrane.

Similarity. Belongs to the mitochondrial carrier (TC 2.A.29) family.

RefSeq proteins (4): NP_001304160, NP_001304161, NP_001304162, NP_055157* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018108	MCP_transmembrane	Repeat
IPR023395	MCP_dom_sf	Homologous_superfamily

Pfam: PF00153

UniProt features (21 total): topological domain 6, transmembrane region 6, repeat 2, sequence variant 2, mutagenesis site 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
12PB	ELECTRON MICROSCOPY	3.1
12OZ	ELECTRON MICROSCOPY	3.3
12OY	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6C9-F1	86.47	0.58

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 (1): 2

Mutagenesis-validated functional residues (2):

Position	Phenotype
25	hyperactive mutant with enhanced protein insertase activity.
189	abolished protein insertase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 285 (showing top): TAATAAT_MIR126, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, CMYB_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_LIPID_HOMEOSTASIS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, WEI_MYCN_TARGETS_WITH_E_BOX

GO Biological Process (19): lactate metabolic process (GO:0006089), regulation of mitochondrial fusion (GO:0010635), negative regulation of mitochondrial membrane potential (GO:0010917), hematopoietic stem cell migration (GO:0035701), mitochondrial ATP synthesis coupled electron transport (GO:0042775), positive regulation of apoptotic process (GO:0043065), protein insertion into mitochondrial outer membrane (GO:0045040), negative regulation of glycolytic process (GO:0045820), lipid homeostasis (GO:0055088), hematopoietic stem cell homeostasis (GO:0061484), protein localization to mitochondrion (GO:0070585), cellular response to radiation (GO:0071478), obsolete establishment of protein localization to mitochondrial membrane involved in mitochondrial fission (GO:0090152), hepatocyte apoptotic process (GO:0097284), regulation of mitochondrial membrane permeability involved in apoptotic process (GO:1902108), positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902231), positive regulation of stem cell differentiation (GO:2000738), mitochondrial transport (GO:0006839), obsolete establishment of protein localization to mitochondrial membrane (GO:0090151)

GO Molecular Function (2): membrane insertase activity (GO:0032977), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	2
intracellular membrane-bounded organelle	2
monocarboxylic acid metabolic process	1
mitochondrial fusion	1
regulation of mitochondrion organization	1
regulation of anatomical structure morphogenesis	1
negative regulation of membrane potential	1
regulation of mitochondrial membrane potential	1
cell migration	1
mitochondrion	1
ATP synthesis coupled electron transport	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
outer mitochondrial membrane organization	1
protein insertion into mitochondrial membrane	1
glycolytic process	1
regulation of glycolytic process	1
negative regulation of purine nucleotide catabolic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of ATP metabolic process	1
chemical homeostasis	1
homeostasis of number of cells	1
protein localization to organelle	1
response to radiation	1
cellular response to abiotic stimulus	1
epithelial cell apoptotic process	1
apoptotic mitochondrial changes	1
regulation of mitochondrial membrane permeability	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
positive regulation of intrinsic apoptotic signaling pathway	1
positive regulation of cell differentiation	1
stem cell differentiation	1
regulation of stem cell differentiation	1
intracellular transport	1
establishment of protein localization to membrane	1
protein carrier activity	1
binding	1
cytoplasm	1
mitochondrial membrane	1

Protein interactions and networks

STRING

1656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTCH2	KCTD15	Q96SI1	917
MTCH2	GNPDA2	Q8TDQ7	913
MTCH2	TMEM18	Q96B42	906
MTCH2	NEGR1	Q7Z3B1	893
MTCH2	SH2B1	Q9NRF2	870
MTCH2	SLC25A17	O43808	830
MTCH2	SLC25A3	Q00325	813
MTCH2	FTO	Q9C0B1	800
MTCH2	F6RGN5	F6RGN5	799
MTCH2	SLC25A10	Q9UBX3	799
MTCH2	MC4R	P32245	793
MTCH2	SLC25A16	P16260	782
MTCH2	SLC25A33	Q9BSK2	770
MTCH2	SEC16B	Q96JE7	766
MTCH2	BID	P55957	710

IntAct

156 interactions, top by confidence:

A	B	Type	Score
RFX3	RFX1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
BCAM	LAMA5	psi-mi:“MI:0914”(association)	0.640
MP68	MTCH2	psi-mi:“MI:0915”(physical association)	0.560
APOC1	MTCH2	psi-mi:“MI:0915”(physical association)	0.560
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
WNT4	TOMM40	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
vpr	AGPS	psi-mi:“MI:0914”(association)	0.460
MTCH2	AMY1A	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
TK	AP3B1	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	TAF4	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (581): MTCH2 (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), ALDH3A2 (Co-fractionation), ATP1A1 (Co-fractionation), ATP2A2 (Co-fractionation), ATP5C1 (Co-fractionation)

ESM2 similar proteins: A0JN87, A6QR09, B6ZJZ9, O22261, O43808, O70579, O77792, O97562, O97649, P55851, P55916, P56499, P56501, P70406, Q08DK4, Q1LZB3, Q287T7, Q3SZI5, Q3TZX3, Q4V9P0, Q5R5A8, Q5R5M0, Q5RD81, Q5RFB7, Q5U680, Q5ZKP7, Q641C8, Q66H23, Q6DG32, Q6GLA2, Q6IZB5, Q70HW3, Q8BMG8, Q920G8, Q922G0, Q95J75, Q96CQ1, Q9BQT8, Q9BSK2, Q9D6D0

Diamond homologs: A5D9W9, G3YD89, O13660, O22261, O59674, P38127, P39953, P40556, Q12482, Q1LZB3, Q3TZX3, Q54BM3, Q54FE6, Q54FU9, Q54MZ4, Q54QN2, Q54S10, Q5HZE0, Q5R5M0, Q5ZKP7, Q641C8, Q6DG32, Q6IZB5, Q791V5, Q7S2H8, Q7XA87, Q8BMG8, Q8N8R3, Q8R0Z5, Q8RWA5, Q922G0, Q94AG6, Q95J75, Q96A46, Q96CQ1, Q9BSK2, Q9H2D1, Q9LV81, Q9N285, Q9P6L7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MTCH2	up-regulates	BID	relocalization
MTCH2	up-regulates	BID	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 167 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
RAS processing	5	21.2×	8e-04
FCERI mediated MAPK activation	5	15.4×	1e-03
Signaling by SCF-KIT	5	11.1×	4e-03
Regulation of RAS by GAPs	5	8.6×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1859 predictions. Top by Δscore:

Variant	Effect	Δscore
11:47622777:C:CC	acceptor_gain	1.0000
11:47625742:C:CC	acceptor_gain	1.0000
11:47627078:A:AC	donor_gain	1.0000
11:47627078:ACT:A	donor_gain	1.0000
11:47627078:ACTC:A	donor_gain	1.0000
11:47627079:C:CC	donor_gain	1.0000
11:47627079:CT:C	donor_gain	1.0000
11:47627079:CTC:C	donor_gain	1.0000
11:47627079:CTCC:C	donor_gain	1.0000
11:47627125:AACCT:A	acceptor_loss	1.0000
11:47627126:ACCT:A	acceptor_loss	1.0000
11:47627127:CCT:C	acceptor_loss	1.0000
11:47627129:T:A	acceptor_loss	1.0000
11:47630553:A:AC	donor_gain	1.0000
11:47630554:C:CC	donor_gain	1.0000
11:47630554:CG:C	donor_gain	1.0000
11:47630615:C:CC	acceptor_gain	1.0000
11:47630619:G:C	acceptor_gain	1.0000
11:47630622:C:CT	acceptor_gain	1.0000
11:47631088:C:CC	acceptor_gain	1.0000
11:47634667:CTTA:C	donor_loss	1.0000
11:47634668:TTACC:T	donor_loss	1.0000
11:47634669:TACC:T	donor_loss	1.0000
11:47634670:A:AG	donor_loss	1.0000
11:47634670:ACCT:A	donor_gain	1.0000
11:47634671:C:CA	donor_loss	1.0000
11:47634671:CCTC:C	donor_gain	1.0000
11:47634673:T:TA	donor_gain	1.0000
11:47638801:CTGAG:C	acceptor_gain	1.0000
11:47638806:C:CC	acceptor_gain	1.0000

AlphaMissense

1966 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:47618903:C:T	G281E	1.000
11:47618904:C:G	G281R	1.000
11:47618904:C:T	G281R	1.000
11:47631075:C:G	R147T	1.000
11:47618903:C:A	G281V	0.999
11:47622722:A:C	C268W	0.999
11:47622733:A:G	W265R	0.999
11:47622733:A:T	W265R	0.999
11:47625734:G:T	A230E	0.999
11:47629006:A:G	W194R	0.999
11:47629006:A:T	W194R	0.999
11:47629035:G:C	P184R	0.999
11:47629035:G:T	P184H	0.999
11:47629044:C:T	G181D	0.999
11:47629045:C:G	G181R	0.999
11:47631059:G:C	F152L	0.999
11:47631059:G:T	F152L	0.999
11:47631061:A:G	F152L	0.999
11:47631074:T:A	R147S	0.999
11:47631074:T:G	R147S	0.999
11:47631075:C:A	R147I	0.999
11:47631662:G:T	P140H	0.999
11:47638761:C:G	G73R	0.999
11:47639047:C:T	G31E	0.999
11:47642386:A:G	L27P	0.999
11:47618885:C:G	R287P	0.998
11:47622711:A:G	L272P	0.998
11:47625686:A:T	V246D	0.998
11:47625707:A:G	L239P	0.998
11:47627087:A:T	V225D	0.998

dbSNP variants (sampled 300 via entrez): RS1000040260 (11:47638235 A>G), RS1000113549 (11:47637849 A>C,G), RS1000149005 (11:47626712 C>A,T), RS1000179993 (11:47610391 A>G), RS1000290449 (11:47617694 G>A), RS1000333357 (11:47631391 A>C), RS1000415873 (11:47624885 C>T), RS1000537486 (11:47625553 T>A,C), RS1000969599 (11:47632645 A>G), RS1001071239 (11:47639451 T>C), RS1001103455 (11:47632466 G>A), RS1001215537 (11:47618134 T>C), RS1001365560 (11:47606278 A>G), RS1001462465 (11:47614207 A>G), RS1001551800 (11:47610401 T>C)

Disease associations

OMIM: gene MIM:613221 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

50 associations (top):

Study	Trait	p-value
GCST000298_11	Body mass index	5.000000e-09
GCST000830_15	Body mass index	2.000000e-12
GCST002783_110	Body mass index	2.000000e-11
GCST002783_198	Body mass index	5.000000e-17
GCST002783_353	Body mass index	1.000000e-17
GCST002783_593	Body mass index	2.000000e-10
GCST004495_52	BMI (adjusted for smoking behaviour)	2.000000e-06
GCST004495_53	BMI (adjusted for smoking behaviour)	1.000000e-11
GCST004495_54	BMI (adjusted for smoking behaviour)	1.000000e-07
GCST004497_10	Body mass index (joint analysis main effects and smoking interaction)	4.000000e-07
GCST004497_11	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-06
GCST004497_9	Body mass index (joint analysis main effects and smoking interaction)	7.000000e-12
GCST004499_81	BMI in non-smokers	1.000000e-08
GCST004499_82	BMI in non-smokers	6.000000e-06
GCST004557_102	Body mass index	2.000000e-06
GCST004557_138	Body mass index	1.000000e-07
GCST004557_20	Body mass index	1.000000e-11
GCST004557_203	Body mass index	3.000000e-06
GCST004557_232	Body mass index	5.000000e-12
GCST004557_64	Body mass index	3.000000e-07
GCST004558_135	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-06
GCST004558_152	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-11
GCST004558_17	Body mass index (joint analysis main effects and physical activity interaction)	5.000000e-11
GCST004559_15	Body mass index in physically active individuals	3.000000e-08
GCST004559_193	Body mass index in physically active individuals	5.000000e-06
GCST004559_97	Body mass index in physically active individuals	7.000000e-09
GCST004904_237	Body mass index	1.000000e-24
GCST005232_56	Neuroticism	1.000000e-16
GCST006269_686	General cognitive ability	9.000000e-10
GCST006802_19	Body mass index	2.000000e-13

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0007660	neuroticism measurement
EFO:0004337	intelligence
EFO:0007865	loneliness measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0008475	mood instability measurement
EFO:0010089	bitter beverage consumption measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523511 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Miscellaneous SLC25 mitochondrial transporters

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.55	Kd	27.95	nM	CHEMBL3752910
7.55	ED50	27.95	nM	CHEMBL3752910
6.88	Kd	130.5	nM	CHEMBL5653589
6.88	ED50	130.5	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 8 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148790: Binding affinity to human MTCH2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0279	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148790: Binding affinity to human MTCH2 incubated for 45 mins by Kinobead based pull down assay	kd	0.1305	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	3
Cyclosporine	decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	affects expression, decreases expression	2
Valproic Acid	decreases expression, increases expression	2
bisphenol F	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
corosolic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Atrazine	decreases expression	1
Cisplatin	increases expression	1
Cycloheximide	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ketoconazole	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4341389	Binding	Binding affinity to MTCH2 in human A549 cells lysates grown on SILAC media at 10 uM incubated for 1 hr by LC-MS/MS analysis	Profiling withanolide A for therapeutic targets in neurodegenerative diseases. — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 3 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3BD	Abcam HEK293T MTCH2 KO	Transformed cell line	Female
CVCL_D4DC	HEK-MTCH2-KO-c1	Transformed cell line	Female
CVCL_D4DD	HEK-MTCH2-KO-c10	Transformed cell line	Female
CVCL_E2CU	HAP1 MTCH2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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