MTX2

Summary

MTX2 (metaxin 2, HGNC:7506) is a protein-coding gene on chromosome 2q31.1, encoding Metaxin-2 (O75431). Involved in transport of proteins into the mitochondrion.

The protein encoded by this gene is highly similar to the metaxin 2 protein from mouse, which has been shown to interact with the mitochondrial membrane protein metaxin 1. Because of this similarity, it is thought that the encoded protein is peripherally associated with the cytosolic face of the outer mitochondrial membrane, and that it is involved in the import of proteins into the mitochondrion. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 7.

Source: NCBI Gene 10651 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mandibuloacral dysplasia progeroid syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 17
• Clinical variants (ClinVar): 61 total — 6 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 60
• Druggable target: yes
• MANE Select transcript: NM_006554

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7506
Approved symbol	MTX2
Name	metaxin 2
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000128654
Ensembl biotype	protein_coding
OMIM	608555
Entrez	10651

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 nonsense_mediated_decay

ENST00000249442, ENST00000420864, ENST00000423461, ENST00000443241, ENST00000452865, ENST00000894532, ENST00000894533, ENST00000926925, ENST00000926926, ENST00000926927, ENST00000926928, ENST00000926929, ENST00000954016, ENST00000954017

RefSeq mRNA: 4 — MANE Select: NM_006554 NM_001006635, NM_001319097, NM_001319098, NM_006554

CCDS: CCDS2272

Canonical transcript exons

ENST00000249442 — 10 exons

Exon	Start	End
ENSE00001945422	176269442	176269669
ENSE00003465325	176329301	176329426
ENSE00003515606	176323392	176323464
ENSE00003566854	176297849	176297895
ENSE00003577197	176296860	176296907
ENSE00003585610	176326825	176326901
ENSE00003612612	176337493	176338025
ENSE00003659334	176330584	176330660
ENSE00003668124	176328874	176328912
ENSE00003668386	176328293	176328385

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 95.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.1978 / max 183.3162, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23875	32.7017	1812
23876	1.4961	896

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	95.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.63	gold quality
cortical plate	UBERON:0005343	94.71	gold quality
oocyte	CL:0000023	94.68	gold quality
right testis	UBERON:0004534	94.67	gold quality
left testis	UBERON:0004533	94.54	gold quality
right uterine tube	UBERON:0001302	94.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.22	gold quality
muscle of leg	UBERON:0001383	94.19	gold quality
mucosa of transverse colon	UBERON:0004991	94.15	gold quality
testis	UBERON:0000473	94.14	gold quality
right adrenal gland cortex	UBERON:0035827	94.14	gold quality
rectum	UBERON:0001052	94.11	gold quality
gastrocnemius	UBERON:0001388	94.04	gold quality
adult organism	UBERON:0007023	93.93	gold quality
heart left ventricle	UBERON:0002084	93.87	gold quality
prefrontal cortex	UBERON:0000451	93.86	gold quality
right adrenal gland	UBERON:0001233	93.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.82	gold quality
biceps brachii	UBERON:0001507	93.79	gold quality
cardiac ventricle	UBERON:0002082	93.73	gold quality
ventricular zone	UBERON:0003053	93.71	gold quality
right atrium auricular region	UBERON:0006631	93.52	gold quality
ganglionic eminence	UBERON:0004023	93.49	gold quality
left adrenal gland	UBERON:0001234	93.42	gold quality
heart right ventricle	UBERON:0002080	93.22	gold quality
muscle organ	UBERON:0001630	93.18	gold quality
adrenal tissue	UBERON:0018303	93.09	gold quality
left adrenal gland cortex	UBERON:0035825	93.09	gold quality
cardiac atrium	UBERON:0002081	93.08	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.27
E-MTAB-4850	no	690.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting MTX2, 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-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
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-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481

Literature-anchored findings (GeneRIF, showing 4)

• The pathway of Voltage-dependent anion-selective channel biogenesis in human mitochondria involves the TOM complex, Sam50 and metaxins, and that it is evolutionarily conserved. (PMID:17510655)
• mitofilin helps regulate mitochondrial morphology and at least four of the associated proteins (metaxins 1 and 2, SAM50 and CHCHD3) have been implicated in protein import (PMID:17624330)
• Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology. (PMID:32917887)
• Loss of MTX2 causes mitochondrial dysfunction, podocyte injury, nephrotic proteinuria and glomerulopathy in mice and patients. (PMID:38250156)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtx2	ENSDARG00000029415
mus_musculus	Mtx2	ENSMUSG00000027099
rattus_norvegicus	Mtx2	ENSRNOG00000001559
drosophila_melanogaster	CG5662	FBGN0030620
drosophila_melanogaster	CG8004	FBGN0036920
caenorhabditis_elegans		WBGENE00022516

Paralogs (3): FAXC (ENSG00000146267), MTX1 (ENSG00000173171), MTX3 (ENSG00000177034)

Protein

Protein identifiers

Metaxin-2 — O75431 (reviewed: O75431)

Alternative names: Mitochondrial outer membrane import complex protein 2

All UniProt accessions (5): O75431, C9JAZ1, C9JNK6, F8WCW1, F8WE26

UniProt curated annotations — full annotation on UniProt →

Function. Involved in transport of proteins into the mitochondrion.

Subunit / interactions. Interacts with MTX1/metaxin-1. Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex.

Subcellular location. Mitochondrion outer membrane. Mitochondrion.

Disease relevance. Mandibuloacral dysplasia progeroid syndrome (MDPS) [MIM:619127] A form of mandibuloacral dysplasia, a rare progeroid disorder with clinical and genetic heterogeneity, characterized by growth retardation, craniofacial dysmorphic features due to distal bone resorption, musculoskeletal and skin abnormalities associated with lipodystrophy. MDPS is an autosomal recessive disorder. Clinical features include poor growth, osteoporosis, osteopenia, acroosteolysis of distal phalanges, arterial calcification, renal glomerulosclerosis and severe hypertension. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the metaxin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75431-1	1	yes
O75431-2	2

RefSeq proteins (4): NP_001006636, NP_001306026, NP_001306027, NP_006545* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019564	Sam37/metaxin_N	Domain
IPR033468	Metaxin_GST	Domain
IPR036282	Glutathione-S-Trfase_C_sf	Homologous_superfamily
IPR040079	Glutathione_S-Trfase	Family
IPR050931	Mito_Protein_Transport_Metaxin	Family

Pfam: PF10568, PF17171

UniProt features (4 total): initiator methionine 1, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75431-F1	92.54	0.88

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

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-8949613	Cristae formation
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-9609507	Protein localization

MSigDB gene sets: 359 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, TGACCTY_ERR1_Q2, MORF_HDAC2, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MITOCHONDRIAL_TRANSPORT, PUJANA_CHEK2_PCC_NETWORK, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, WTGAAAT_UNKNOWN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, MORF_RFC4, GOCC_MITOCHONDRIAL_ENVELOPE, APPIERTO_RESPONSE_TO_FENRETINIDE_DN

GO Biological Process (5): mitochondrial transport (GO:0006839), mitochondrion organization (GO:0007005), inner mitochondrial membrane organization (GO:0007007), protein transport (GO:0015031), protein insertion into mitochondrial outer membrane (GO:0045040)

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

GO Cellular Component (6): SAM complex (GO:0001401), nucleolus (GO:0005730), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), MIB complex (GO:0140275), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Protein localization	1
Mitochondrial biogenesis	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular transport	1
organelle organization	1
mitochondrial membrane organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
outer mitochondrial membrane organization	1
protein insertion into mitochondrial membrane	1
binding	1
mitochondrial outer membrane translocase complex	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
inner mitochondrial membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1510 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTX2	SAMM50	Q9Y512	983
MTX2	MTX1	Q13505	958
MTX2	LNPK	Q9C0E8	942
MTX2	MTX3	Q5HYI7	849
MTX2	EVX2	Q03828	837
MTX2	HOXD3	P31249	774
MTX2	CHCHD6	Q9BRQ6	770
MTX2	MICOS13	Q5XKP0	756
MTX2	CHCHD3	Q9NX63	756
MTX2	IMMT	Q16891	708
MTX2	DNAJC11	Q9NVH1	699
MTX2	APOOL	Q6UXV4	684
MTX2	APOO	Q9BUR5	681
MTX2	MICOS10	Q5TGZ0	667
MTX2	HOXD1	Q9GZZ0	657

IntAct

101 interactions, top by confidence:

A	B	Type	Score
TUBA1C	TXNDC9	psi-mi:“MI:0914”(association)	0.730
IMMT	MTX2	psi-mi:“MI:0914”(association)	0.730
KASH5	MTX2	psi-mi:“MI:0915”(physical association)	0.720
MTX2	KASH5	psi-mi:“MI:0915”(physical association)	0.720
MTX2	TADA2A	psi-mi:“MI:0915”(physical association)	0.560
TADA2A	MTX2	psi-mi:“MI:0915”(physical association)	0.560
MTX2	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.560
MTX2	RHOH	psi-mi:“MI:0915”(physical association)	0.560
MTX2	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
RPS14	MAGEB2	psi-mi:“MI:0914”(association)	0.560
APOOL	MTX2	psi-mi:“MI:0914”(association)	0.530
FAM3B	LRP5	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
TRAK2	OGT	psi-mi:“MI:0914”(association)	0.530
TRAK1	MTX2	psi-mi:“MI:0914”(association)	0.530
CD244	MTX2	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
MTX2	EED	psi-mi:“MI:0915”(physical association)	0.400
MTX1	MTX2	psi-mi:“MI:0915”(physical association)	0.400
MTX2		psi-mi:“MI:0914”(association)	0.350
K8.1	EXOC5	psi-mi:“MI:0914”(association)	0.350
SCARB2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
VMP1	TPM3	psi-mi:“MI:0914”(association)	0.350

BioGRID (213): MTX2 (Two-hybrid), CCDC155 (Two-hybrid), MTX2 (Affinity Capture-RNA), MTX2 (Affinity Capture-MS), MTX2 (Affinity Capture-MS), IMMT (Co-fractionation), MTX2 (Synthetic Lethality), PHB (Affinity Capture-MS), PPP1CA (Affinity Capture-MS), TPD52 (Affinity Capture-MS), VDAC2 (Affinity Capture-MS), EIF2B4 (Affinity Capture-MS), YWHAQ (Affinity Capture-MS), IMMT (Affinity Capture-MS), PHB2 (Affinity Capture-MS)

ESM2 similar proteins: A4FUF0, A5HK05, B0K012, O43324, O43929, O75431, O94955, O95453, P20135, P42694, P47802, P69341, P70102, P78417, Q2L969, Q3U2J5, Q3UFS0, Q49A26, Q4R8V9, Q562D5, Q5R6Z7, Q5R7T2, Q5RC51, Q5RDU9, Q5RKH0, Q5ZIA0, Q5ZLS2, Q5ZLS7, Q6AXV9, Q6DC64, Q6DFV5, Q6GR37, Q6NYU2, Q7SXV1, Q7Z624, Q8IX04, Q8K2D3, Q8K2Q2, Q8R5L3, Q8VE33

Diamond homologs: A8XWD1, O45503, O75431, P47802, Q13505, Q27HK4, Q2TBS1, Q3KPT9, Q4R3I0, Q4VBW0, Q5HYI7, Q9VHB6, O88441, P34599, Q2L969

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AREL1	“down-regulates quantity by destabilization”	MTX2	ubiquitination
MTX2	“form complex”	“SAM complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 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
Cristae formation	6	28.4×	2e-05
Mitochondrial biogenesis	6	13.8×	9e-04
Organelle biogenesis and maintenance	8	7.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cristae formation	6	61.4×	3e-07
inner mitochondrial membrane organization	6	49.1×	6e-07
mitochondrion organization	6	8.8×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	32
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
4294092	NM_006554.5(MTX2):c.136-1G>C	Pathogenic
805937	NM_006554.5(MTX2):c.2T>A (p.Met1Lys)	Pathogenic
805938	NM_006554.5(MTX2):c.208+3_208+6del	Pathogenic
805939	NM_006554.5(MTX2):c.544-1G>C	Pathogenic
805940	NM_006554.5(MTX2):c.603del (p.Tyr202fs)	Pathogenic
827676	NM_006554.5(MTX2):c.295_296del (p.Ser98_Leu99insTer)	Pathogenic
2627385	NM_006554.5(MTX2):c.135+2T>C	Likely pathogenic

SpliceAI

1596 predictions. Top by Δscore:

Variant	Effect	Δscore
2:176295158:G:GT	donor_gain	1.0000
2:176295159:A:T	donor_gain	1.0000
2:176296856:A:AG	acceptor_gain	1.0000
2:176296857:T:G	acceptor_gain	1.0000
2:176296858:A:AG	acceptor_gain	1.0000
2:176296858:AGCT:A	acceptor_gain	1.0000
2:176296859:G:GG	acceptor_gain	1.0000
2:176296859:GC:G	acceptor_gain	1.0000
2:176296859:GCT:G	acceptor_gain	1.0000
2:176296859:GCTG:G	acceptor_gain	1.0000
2:176296859:GCTGC:G	acceptor_gain	1.0000
2:176296903:GAAAG:G	donor_gain	1.0000
2:176296906:AG:A	donor_gain	1.0000
2:176296907:GG:G	donor_gain	1.0000
2:176296908:G:GG	donor_gain	1.0000
2:176296909:T:A	donor_loss	1.0000
2:176297847:A:AG	acceptor_gain	1.0000
2:176297847:AG:A	acceptor_gain	1.0000
2:176297847:AGG:A	acceptor_gain	1.0000
2:176297848:G:GG	acceptor_gain	1.0000
2:176297848:GG:G	acceptor_gain	1.0000
2:176297848:GGG:G	acceptor_gain	1.0000
2:176328291:AG:A	acceptor_gain	1.0000
2:176328292:GG:G	acceptor_gain	1.0000
2:176328292:GGGCC:G	acceptor_gain	1.0000
2:176328381:CAGAG:C	donor_loss	1.0000
2:176328382:AGAGG:A	donor_loss	1.0000
2:176328383:GAG:G	donor_gain	1.0000
2:176328383:GAGGT:G	donor_loss	1.0000
2:176328384:AGGTA:A	donor_loss	1.0000

AlphaMissense

1725 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:176328886:T:A	W131R	0.999
2:176328886:T:C	W131R	0.999
2:176337522:G:A	G217D	0.998
2:176326834:C:A	P73H	0.997
2:176328888:G:C	W131C	0.997
2:176328888:G:T	W131C	0.997
2:176296871:T:A	W18R	0.996
2:176296871:T:C	W18R	0.996
2:176296873:G:C	W18C	0.996
2:176296873:G:T	W18C	0.996
2:176330608:T:C	C190R	0.996
2:176330618:T:C	L193P	0.996
2:176337510:C:A	A213E	0.996
2:176337518:T:C	F216L	0.996
2:176337520:T:A	F216L	0.996
2:176337520:T:G	F216L	0.996
2:176337528:T:C	L219P	0.996
2:176326834:C:G	P73R	0.995
2:176326879:T:A	I88K	0.995
2:176329403:T:A	W174R	0.995
2:176329403:T:C	W174R	0.995
2:176330618:T:A	L193H	0.995
2:176337506:G:C	D212H	0.995
2:176337521:G:C	G217R	0.995
2:176330620:T:C	S194P	0.994
2:176337522:G:T	G217V	0.994
2:176323392:G:C	A46P	0.993
2:176328345:C:A	A113D	0.993
2:176328360:T:A	V118D	0.993
2:176328381:C:A	A125E	0.993

dbSNP variants (sampled 300 via entrez): RS1000008573 (2:176303902 A>G), RS1000064740 (2:176296824 T>C,G), RS1000142252 (2:176312292 C>A,T), RS1000149025 (2:176333675 T>C), RS1000158806 (2:176333424 G>A,C), RS1000178445 (2:176267813 T>C), RS1000179448 (2:176309065 G>C), RS1000252091 (2:176267542 T>A), RS1000301541 (2:176283698 T>C), RS1000332929 (2:176327481 C>T), RS1000411630 (2:176277525 C>T), RS1000422797 (2:176320314 C>A,T), RS1000435430 (2:176280222 G>T), RS1000480351 (2:176319831 C>T), RS1000517530 (2:176320567 T>C)

Disease associations

OMIM: gene MIM:608555 | disease phenotypes: MIM:619127

GenCC curated gene-disease

Disease	Classification	Inheritance
mandibuloacral dysplasia progeroid syndrome	Strong	Autosomal recessive
mandibuloacral dysplasia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mandibuloacral dysplasia progeroid syndrome	Definitive	AR

Mondo (4): mandibuloacral dysplasia progeroid syndrome (MONDO:0030880), hypertensive disorder (MONDO:0005044), megacolon (MONDO:0001273), mandibuloacral dysplasia (MONDO:0016584)

Orphanet (1): Mandibuloacral dysplasia associated to MTX2 (Orphanet:647667)

HPO phenotypes

60 total (30 of 60 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000160	Narrow mouth
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000270	Delayed cranial suture closure
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000414	Bulbous nose
HP:0000418	Narrow nasal ridge
HP:0000430	Underdeveloped nasal alae
HP:0000520	Proptosis
HP:0000586	Shallow orbits
HP:0000668	Hypodontia
HP:0000767	Pectus excavatum
HP:0000883	Thin ribs
HP:0000938	Osteopenia
HP:0000972	Palmoplantar hyperkeratosis
HP:0001029	Poikiloderma
HP:0001290	Generalized hypotonia
HP:0001371	Flexion contracture
HP:0001387	Joint stiffness
HP:0001403	Macrovesicular hepatic steatosis
HP:0001620	Abnormally high-pitched voice
HP:0001653	Mitral regurgitation
HP:0001655	Patent foramen ovale

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST003983_42	Male-pattern baldness	4.000000e-08
GCST003989_13	Chin dimples	2.000000e-19
GCST003996_11	Monobrow	9.000000e-12
GCST006105_6	Eye morphology	9.000000e-07
GCST006107_1	Upper eyelid morphology	2.000000e-07
GCST006107_10	Upper eyelid morphology	4.000000e-06
GCST006107_13	Upper eyelid morphology	1.000000e-07
GCST006107_15	Upper eyelid morphology	4.000000e-09
GCST006107_4	Upper eyelid morphology	9.000000e-08
GCST006107_8	Upper eyelid morphology	7.000000e-09
GCST006661_59	Male-pattern baldness	4.000000e-09
GCST006661_61	Male-pattern baldness	4.000000e-09
GCST006988_32	Blond vs. brown/black hair color	2.000000e-10
GCST008062_126	Blood urea nitrogen levels	3.000000e-08
GCST008064_47	Chronic kidney disease	8.000000e-07
GCST008745_36	Estimated glomerular filtration rate in non-diabetics	7.000000e-11
GCST008972_238	Urate levels	1.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007906	synophrys measurement
EFO:0003924	hair color
EFO:0004531	urate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006973	Hypertension	C14.907.489
D008531	Megacolon	C06.405.469.158.701

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066373 (SINGLE PROTEIN)

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

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
8.00	Kd	10.11	nM	CHEMBL3752910
8.00	ED50	10.11	nM	CHEMBL3752910
5.75	Kd	1772	nM	CHEMBL5653589
5.75	ED50	1772	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 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	2148800: Binding affinity to human MTX2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0101	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148800: Binding affinity to human MTX2 incubated for 45 mins by Kinobead based pull down assay	kd	1.7718	uM

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, decreases methylation	1
dicrotophos	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Ivermectin	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Rotenone	decreases expression	1
Valproic Acid	decreases methylation, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651842	Binding	Binding affinity to human MTX2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8QW	Ubigene HCT 116 MTX2 KO	Cancer cell line	Male
CVCL_E0IG	Ubigene HeLa MTX2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000521	PHASE4	COMPLETED	Sodium-Potassium Blood Pressure Trial in Children
NCT00018759	PHASE4	COMPLETED	Treatment Effects on Platelet Calcium in Hypertensive and Depressed Patients
NCT00034840	PHASE4	COMPLETED	Telmisartan vs. Valsartan in Patients With Mild to Moderate Hypertension Following a Missed Dose
NCT00044265	PHASE4	COMPLETED	Treatment of Pediatric Hypertension With Altace Trial
NCT00060918	PHASE4	COMPLETED	Glycemic Control Of Carvedilol Versus Metoprolol In Patients With Type II Diabetes Mellitus And Hypertension
NCT00060931	PHASE4	COMPLETED	Effect Of Carvedilol Versus Metoprolol On Glycemic Control In Patients With Type II Diabetes And Hypertension
NCT00110422	PHASE4	COMPLETED	Irbesartan in the Treatment of Hypertensive Patients With Metabolic Syndrome
NCT00115726	PHASE4	COMPLETED	Trial Assessing the Effect of Preoperative Furosemide on Intraoperative Blood Pressure
NCT00120380	PHASE4	TERMINATED	Combination Therapy of Bosentan and Aerosolized Iloprost in Idiopathic Pulmonary Arterial Hypertension (IPAH)
NCT00122811	PHASE4	UNKNOWN	The Hypertension in the Very Elderly Trial (HYVET)
NCT00123045	PHASE4	COMPLETED	Patient-Physician Partnership to Improve High Blood Pressure Adherence
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00126516	PHASE4	COMPLETED	Angiotensin II Receptor Blockers (ARB) and ACE Inhibitors (ACEI) on Silent Brain Infarction and Cognitive Decline
NCT00127348	PHASE4	COMPLETED	Effect of Continuous Positive Airway Pressure (CPAP) on Hypertension and Cardiovascular Morbidity-Mortality in Patients With Sleep Apnea and no Daytime Sleepiness
NCT00128518	PHASE4	COMPLETED	IDEAL Study: Identification of the Determinants of the Efficacy of Arterial Blood Pressure Lowering Drugs
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00129909	PHASE4	COMPLETED	STITCH (Simplified Therapeutic Intervention To Control Hypertension)
NCT00130156	PHASE4	COMPLETED	Effects of Combination Therapy With Alpha-1 Blocker (Bunazosin or Doxazosin) in the Treatment of Patients With Mild to Moderate Essential Hypertension
NCT00131846	PHASE4	COMPLETED	Diuretics In the Management of Essential Hypertension (DIME) Study
NCT00133068	PHASE4	COMPLETED	Collaboration to Reduce Disparities in Hypertension
NCT00133328	PHASE4	UNKNOWN	A Morbidity-Mortality and Remodeling Study With Valsartan
NCT00133692	PHASE4	COMPLETED	INVEST: INternational VErapamil SR Trandolapril STudy
NCT00134160	PHASE4	COMPLETED	OlmeSartan and Calcium Antagonists Randomized (OSCAR) Study
NCT00136851	PHASE4	COMPLETED	Study Comparing the Efficacy of Amlodipine Besylate/Benazepril Versus Amlodipine in the Treatment of Severe Hypertension
NCT00139386	PHASE4	COMPLETED	Candesartan for Prevention of Cardiovascular Events After Cypher or Taxus Coronary Stenting (4C) Trial
NCT00139555	PHASE4	COMPLETED	Effects of Amlodipine/Benazepril in Reducing Left Ventricular Hypertrophy in Patients With High Risk Hypertension
NCT00139984	PHASE4	COMPLETED	Ambulatory Blood Pressure Monitoring for Antihypertensive Treatment Guidance
NCT00140790	PHASE4	TERMINATED	Valsartan in Cardiovascular Disease With Renal Dysfunction (The V-CARD) Study
NCT00140907	PHASE4	COMPLETED	ALLOGRAFT, A Study to Evaluate the Renal Protective Effects of Losartan (0954-222)(COMPLETED)
NCT00140959	PHASE4	COMPLETED	Losartan and HCTZ and Amlodipine vs Atenolol and Amlodipine (0954A-309)(COMPLETED)
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00144937	PHASE4	UNKNOWN	Multifactorial Intervention on Cardiovascular Risk Factors in Subjects With Peripheral Arterial Disease
NCT00147251	PHASE4	COMPLETED	Stop Atherosclerosis in Native Diabetics Study
NCT00147524	PHASE4	COMPLETED	Non-Comparative Study To Evaluate Changes In FMD After Quinapril Therapy In Hypertensive Women
NCT00147563	PHASE4	COMPLETED	Compare Effectiveness of Eplerenone vs Atenolol in Reversing the Remodelling Resistance Arteries in Subjects With HT
NCT00149227	PHASE4	COMPLETED	Add-on Effects of Valsartan on Morbi- Mortality (KYOTO HEART Study)
NCT00150358	PHASE4	COMPLETED	To Yield Further Information On The Efficacy And Safety Of Viagra Among Subjects With Arterial Hypertension .
NCT00150384	PHASE4	COMPLETED	Clinical Utility of Caduet in Achieving Blood Pressure and Lipid Endpoints in a Specific Patient Population
NCT00153023	PHASE4	COMPLETED	1 Year Trial Telmisartan 80 mg Versus Valsartan 160 mg in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy
NCT00154271	PHASE4	COMPLETED	Effects of Blood Pressure Reduction on High Sensitivity C-Reactive Protein (hsCRP)