MTSS1

Summary

MTSS1 (MTSS I-BAR domain containing 1, HGNC:20443) is a protein-coding gene on chromosome 8q24.13, encoding Protein MTSS 1 (O43312). May be related to cancer progression or tumor metastasis in a variety of organ sites, most likely through an interaction with the actin cytoskeleton.

Enables actin monomer binding activity; identical protein binding activity; and signaling receptor binding activity. Predicted to be involved in several processes, including adherens junction maintenance; positive regulation of actin filament bundle assembly; and renal tubule development. Predicted to act upstream of or within several processes, including actin filament polymerization; bone mineralization; and magnesium ion homeostasis. Located in actin cytoskeleton.

Source: NCBI Gene 9788 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 152 total
• MANE Select transcript: NM_014751

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20443
Approved symbol	MTSS1
Name	MTSS I-BAR domain containing 1
Location	8q24.13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0429, MIMA, MIMB, MIM
Ensembl gene	ENSG00000170873
Ensembl biotype	protein_coding
OMIM	608486
Entrez	9788

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 17 protein_coding, 6 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000325064, ENST00000378017, ENST00000431961, ENST00000472084, ENST00000518547, ENST00000519168, ENST00000519226, ENST00000519671, ENST00000520094, ENST00000520771, ENST00000522118, ENST00000522162, ENST00000522722, ENST00000523179, ENST00000523587, ENST00000524090, ENST00000524243, ENST00000529463, ENST00000898433, ENST00000898434, ENST00000898435, ENST00000898436, ENST00000898437, ENST00000898438, ENST00000898439, ENST00000898440

RefSeq mRNA: 12 — MANE Select: NM_014751 NM_001282971, NM_001282974, NM_001363294, NM_001363295, NM_001363296, NM_001363297, NM_001363298, NM_001363299, NM_001363300, NM_001363301, NM_001363302, NM_014751

CCDS: CCDS6353, CCDS64968, CCDS64969

Canonical transcript exons

ENST00000518547 — 14 exons

Exon	Start	End
ENSE00001698444	124565662	124565759
ENSE00001713684	124567071	124567178
ENSE00002126518	124727884	124728473
ENSE00003525499	124556232	124556405
ENSE00003534591	124704130	124704191
ENSE00003546303	124562782	124562992
ENSE00003556975	124589620	124589711
ENSE00003577666	124557681	124557875
ENSE00003582257	124585087	124585161
ENSE00003593114	124591151	124591235
ENSE00003625537	124555742	124555904
ENSE00003658265	124568379	124568536
ENSE00003673092	124699526	124699599
ENSE00003901315	124550784	124553692

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.7231 / max 524.7310, expressed in 1501 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94772	10.5367	1331
94773	3.5759	984
94774	1.0303	507
94759	0.5448	95
94776	0.5244	258
94775	0.2858	125
94760	0.2820	120
94757	0.2711	79
94758	0.2675	79
94777	0.2364	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	98.68	gold quality
renal glomerulus	UBERON:0000074	98.61	gold quality
metanephric glomerulus	UBERON:0004736	98.51	gold quality
hair follicle	UBERON:0002073	98.38	gold quality
subthalamic nucleus	UBERON:0001906	98.34	gold quality
renal medulla	UBERON:0000362	98.24	gold quality
skin of hip	UBERON:0001554	98.18	gold quality
inferior vagus X ganglion	UBERON:0005363	98.01	gold quality
upper leg skin	UBERON:0004262	98.00	gold quality
bronchial epithelial cell	CL:0002328	97.70	gold quality
cortical plate	UBERON:0005343	97.69	gold quality
gingival epithelium	UBERON:0001949	97.66	gold quality
ventral tegmental area	UBERON:0002691	97.63	gold quality
endothelial cell	CL:0000115	97.51	gold quality
synovial joint	UBERON:0002217	97.50	gold quality
esophagus squamous epithelium	UBERON:0006920	97.47	gold quality
epithelium of bronchus	UBERON:0002031	97.44	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.42	gold quality
bronchus	UBERON:0002185	97.41	gold quality
penis	UBERON:0000989	97.39	gold quality
superior vestibular nucleus	UBERON:0007227	97.38	gold quality
calcaneal tendon	UBERON:0003701	97.36	gold quality
gingiva	UBERON:0001828	97.35	gold quality
epithelium of nasopharynx	UBERON:0001951	97.35	gold quality
mammalian vulva	UBERON:0000997	97.32	gold quality
pons	UBERON:0000988	97.18	gold quality
medulla oblongata	UBERON:0001896	97.12	gold quality
pericardium	UBERON:0002407	97.07	gold quality
kidney epithelium	UBERON:0004819	97.07	gold quality
epithelium of esophagus	UBERON:0001976	96.97	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	84.15
E-CURD-114	yes	58.10
E-CURD-122	yes	34.94
E-CURD-119	yes	27.30
E-GEOD-93593	yes	18.66
E-MTAB-6678	yes	10.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT3B, NR1I2, TBX5

miRNA regulators (miRDB)

149 targeting MTSS1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-381-3P	99.93	71.87	2854

Literature-anchored findings (GeneRIF, showing 40)

• a potential metastasis suppressor gene in bladder cancer; data suggest that it may be involved in cytoskeletal organization (PMID:12082544)
• missing in metastasis protein and insulin receptor tyrosine kinase substrate p53 have a conserved novel actin bundling/filopodium-forming domain (PMID:14752106)
• Our data indicate that down-regulation of MIM and/or MIM-B expression can occur in bladder cancer cell lines but is not associated with increased invasive behaviour. (PMID:15488640)
• MTSS1, also known as MIM, is a hedgehog inducible protein expressed in carcinomas that potentiates Gli transcription factor activity (PMID:15545630)
• MTSS1, also known as MIM, is a modular hedgehog inducible protein that contains a dimerization domain and a distinct activation/scaffolding domain that binds RPTPdelta and induces membrane projections. (PMID:15684034)
• MIM-B is unlikely to be a metastasis suppressor but acts as a scaffold protein that interacts with Rac, actin and actin-associated proteins to modulate lamellipodia formation. (PMID:16280553)
• The expression of metastasis suppressor MIM is regulated by DNA methylation of a CpG island within its promoter region. (PMID:16921485)
• Elevated MIM-B expression may influence the development of hepatocellular carcinoma and may possibly be a powerful indicator for the disease at an early stage. (PMID:17442377)
• MTSS1 is a prognostic indicator of disease-free survival in breast cancer patients and demonstrates the ability to play a role in governing the metastatic nature of breast cancer cells. (PMID:19328678)
• Downregulation of metastasis suppressor 1 is associated with nodal metastasis and gastric cancer. (PMID:20712855)
• the current knowledge of MTSS1’s role in cancer metastasis, carcinogenesis, and development is discussed. (PMID:21196400)
• MTSS1 serves as a potential prognostic indicator in human oesophageal squamous cell carcinoma and may be an important target for cancer therapy. (PMID:21696600)
• MTSS1 was characterized as a novel tumor suppressor gene in hepatocellular carcinoma (PMID:21909138)
• at high cell densities, Mtss1 impacts negatively on EGF signaling and this suggests why it inhibits metastasis. (PMID:21927027)
• MTSS1 is expressed at low levels or is absent from human bladder cancer cells. (PMID:21965727)
• Anthrax edema toxin induced transendothelial cell tunnels are resealed by MIM via Arp2/3-driven actin polymerization. (PMID:22100162)
• MiR-23a expression promotes colon carcinoma cell growth, invasion and metastasis through inhibition of the MTSS1 gene. (PMID:22455847)
• Data show that Mtss1 drives enhanced junction formation specifically by elevating Rac-GTP. (PMID:22479308)
• Compared with normal tissue, miR-182 was up-reg’d and MTSS1 was down-reg’d in HCC tissues. Over-expression of miR-182 was correlated with intrahepatic metastasis. There was a negative correlation between miR-182 and MTSS1 expression in both HCC tissues. (PMID:22681717)
• the dimeric configuration is essential for MIM-mediated membrane remodelling and serves as a proper target to develop antagonists specifically against an I-BAR-domain-containing protein. (PMID:22721729)
• Data show that the expression of the metastasis suppressor 1 (MTSS1) gene was regulated by miR-135a overexpression and knockdown. (PMID:23017832)
• Loww MTSS1 expression is associated with kidney cancer. (PMID:23350348)
• MicroRNA-182-5p promotes cell invasion and proliferation by down regulating FOXF2, RECK and MTSS1 genes in human prostate cancer. (PMID:23383207)
• In breast tumor samples, miR-182 induction is linked to downregulation of MIM, RhoA activation and poor prognosis. (PMID:23474751)
• MTSS1 expression was analyzed in normal and cancerous tissue specimens from Chinese patients with Hilar cholangiocarcinoma. (PMID:23852458)
• Study provides a novel molecular mechanism for the negative regulation of MTSS1 by beta-TRCP in cancer cells. (PMID:24318128)
• MTSS1 is a metastasis driver in a subset of human melanomas. (PMID:24632752)
• The absence of MIM led to PTPdelta-mediated activation of SRC. (PMID:25287652)
• These results implicate that the role of MTSS1 suppresses cell migration and invasion by inhibiting expression of CTTN and as a prognosis biomarker in Glioblastomas (PMID:25385572)
• Data shows that MTSS1 is highly expressed in non-small-cell lung carcinomas compared with non-neoplastic lung tissues and may serve as an independent prognostic factor. (PMID:25625275)
• EGF induces microRNAs that target suppressors of cell migration: miR-15b targets MTSS1 in breast cancer. (PMID:25783158)
• our findings suggest that MTSS1 might have a context-dependent function and could act as a tumor suppressor, which is pharmacologically targetable in AML patients. (PMID:25996952)
• human breast tumors data sets the MTSS1/p63 co-expression is a negative prognostic factor on patient survival, suggesting that the MTSS1/p63 axis might be functionally important to regulate breast tumor progression (PMID:26119942)
• Down-regulation of MTSS1 expression is associated with lymph node metastasis in Pancreatic Cancer. (PMID:26198729)
• MTSS1 plays an essential inhibitory role in the development and progression of ovarian cancers (PMID:26316204)
• Low expression of Mtss1 is associated with Chronic myeloid leukemia. (PMID:26621336)
• MTSS1 is a new authentic target of miR-96 in prostate carcinoma. (PMID:27164937)
• Data suggest that overexpression of MAEL, caused by gene amplification and/or decreased miR-186, has a critical oncogenic role in UCB pathogenesis by downregulation of MTSS1. (PMID:27181205)
• MTSS1 suppressed H1299 cell migration and invasion, and its expression level can be used as a new independent factor for determining the prognosis of non-small cell lung cancer. (PMID:27634022)
• in contrast to MIM, which is a prototype of I-BAR proteins and does not contain an SH3 domain, IRTKS promoted serum-induced cell migration along with enhanced phosphorylation of mitogen activated kinases Erk1/2 and p38 (PMID:27693783)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mtss1	ENSMUSG00000022353
rattus_norvegicus	Mtss1	ENSRNOG00000009001
drosophila_melanogaster	mim	FBGN0053558
caenorhabditis_elegans	M04F3.5	WBGENE00019771

Paralogs (1): MTSS2 (ENSG00000132613)

Protein

Protein identifiers

Protein MTSS 1 — O43312 (reviewed: O43312)

Alternative names: Metastasis suppressor YGL-1, Metastasis suppressor protein 1, Missing in metastasis protein

All UniProt accessions (6): O43312, E5RJX3, E7EWW5, H0YAZ8, H0YB53, H0YBL3

UniProt curated annotations — full annotation on UniProt →

Function. May be related to cancer progression or tumor metastasis in a variety of organ sites, most likely through an interaction with the actin cytoskeleton.

Subunit / interactions. Binds to actin. Binds to the cytoplasmic domain of receptor protein tyrosine phosphatase delta.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed in many tissues, including spleen, thymus, prostate, testis, uterus, colon, and peripheral blood.

Domain organisation. The WH2 motif at the C-terminus binds to actin monomers.

Similarity. Belongs to the MTSS family.

Isoforms (4)

UniProt ID	Names	Canonical?
O43312-1	1	yes
O43312-2	2
O43312-4	3
O43312-5	4

RefSeq proteins (12): NP_001269900, NP_001269903, NP_001350223, NP_001350224, NP_001350225, NP_001350226, NP_001350227, NP_001350228, NP_001350229, NP_001350230, NP_001350231, NP_055566* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003124	WH2_dom	Domain
IPR013606	I-BAR_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR030127	MTSS1/MTSS2	Family

Pfam: PF02205, PF08397

UniProt features (31 total): modified residue 9, region of interest 6, splice variant 4, compositionally biased region 3, domain 2, sequence variant 2, sequence conflict 2, chain 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2D1K	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43312-F1	62.20	0.32

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 (9): 258, 261, 262, 271, 322, 425, 603, 644, 647

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 453 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, TTTGTAG_MIR520D, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS, GOZGIT_ESR1_TARGETS_DN, AAGCCAT_MIR135A_MIR135B, GEORGES_CELL_CYCLE_MIR192_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PLASMA_MEMBRANE_ORGANIZATION, IVANOVA_HEMATOPOIESIS_MATURE_CELL

GO Biological Process (13): plasma membrane organization (GO:0007009), cell adhesion (GO:0007155), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), microspike assembly (GO:0030035), actin cytoskeleton organization (GO:0030036), positive regulation of actin filament bundle assembly (GO:0032233), adherens junction maintenance (GO:0034334), negative regulation of epithelial cell proliferation (GO:0050680), renal tubule morphogenesis (GO:0061333), cellular response to fluid shear stress (GO:0071498), glomerulus morphogenesis (GO:0072102), nephron tubule epithelial cell differentiation (GO:0072160), epithelial cell proliferation involved in renal tubule morphogenesis (GO:2001013)

GO Molecular Function (6): actin binding (GO:0003779), actin monomer binding (GO:0003785), signaling receptor binding (GO:0005102), phospholipid binding (GO:0005543), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (6): ruffle (GO:0001726), cytoplasm (GO:0005737), cytoplasmic side of plasma membrane (GO:0009898), actin cytoskeleton (GO:0015629), endocytic vesicle (GO:0030139), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
epithelial cell proliferation	2
protein binding	2
endomembrane system organization	1
membrane organization	1
cellular process	1
enzyme-linked receptor protein signaling pathway	1
plasma membrane bounded cell projection assembly	1
cytoskeleton organization	1
actin filament-based process	1
regulation of actin filament bundle assembly	1
positive regulation of cellular component biogenesis	1
actin filament bundle assembly	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
adherens junction organization	1
cell-cell junction maintenance	1
negative regulation of cell population proliferation	1
regulation of epithelial cell proliferation	1
epithelial tube morphogenesis	1
renal tubule development	1
cellular response to stress	1
response to fluid shear stress	1
anatomical structure morphogenesis	1
glomerulus development	1
epithelial cell differentiation involved in kidney development	1
nephron tubule development	1
renal tubule morphogenesis	1
cytoskeletal protein binding	1
actin binding	1
lipid binding	1
binding	1
cell leading edge	1
plasma membrane bounded cell projection	1
intracellular anatomical structure	1
cellular anatomical structure	1
plasma membrane	1
cytoplasmic side of membrane	1
cytoskeleton	1
cytoplasmic vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTSS1	CTTN	Q14247	807
MTSS1	HCLS1	P14317	801
MTSS1	GLI1	P08151	754
MTSS1	SUFU	Q9UMX1	725
MTSS1	WAS	P42768	706
MTSS1	GLI2	P10070	615
MTSS1	PTPRD	P23468	611
MTSS1	AKT1	P31749	594
MTSS1	CLPTM1	O96005	549
MTSS1	SHH	Q15465	545
MTSS1	HTRA1	Q92743	491
MTSS1	BRMS1L	Q5PSV4	483
MTSS1	BRMS1	Q9HCU9	483
MTSS1	AMPH	P49418	475
MTSS1	WASL	O00401	454

IntAct

14 interactions, top by confidence:

A	B	Type	Score
MTSS1	MTSS1	psi-mi:“MI:0407”(direct interaction)	0.540
MTSS1	MTSS1	psi-mi:“MI:0915”(physical association)	0.540
Cttn	MTSS1	psi-mi:“MI:0915”(physical association)	0.520
ACTA1	MTSS1	psi-mi:“MI:0407”(direct interaction)	0.440
MTSS1	CTTN	psi-mi:“MI:0915”(physical association)	0.400
HTT	MTSS1	psi-mi:“MI:0915”(physical association)	0.370
CUL4B	GGTLC3	psi-mi:“MI:0914”(association)	0.350
MTSS2	CHEK1	psi-mi:“MI:0914”(association)	0.350
MTSS1		psi-mi:“MI:0915”(physical association)	0.000
RECQL5	MTSS1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (42): MTSS1 (Affinity Capture-MS), MTSS1 (Affinity Capture-Western), CXCR4 (Affinity Capture-Western), ITCH (Affinity Capture-Western), RAB5A (Affinity Capture-Western), RAB7A (Affinity Capture-Western), MTSS1 (Affinity Capture-Western), MTSS1 (Affinity Capture-Western), MTSS1 (Affinity Capture-MS), MTSS1 (Two-hybrid), MTSS1 (Affinity Capture-RNA), MZF1 (Protein-RNA), MTSS1 (Affinity Capture-MS), ACTBL2 (Affinity Capture-Western), MTSS1 (Affinity Capture-Western)

ESM2 similar proteins: A2A690, A2AWP8, A6QL63, F1LTE0, O08873, O14795, O43312, O70585, P0C7A6, P84060, Q08BT5, Q0VGY8, Q14161, Q15139, Q1LVW0, Q3KR37, Q5T6S3, Q62101, Q66H91, Q68FF6, Q6DFZ1, Q6GQW0, Q6IQ26, Q6P6Y1, Q6PAL8, Q6ZWH5, Q80TI0, Q80U28, Q80YA9, Q86UE8, Q8BG18, Q8BIE6, Q8R1S4, Q8WXG6, Q8WXI2, Q92538, Q9BZ71, Q9C0D5, Q9D2N4, Q9ESB5

Diamond homologs: O43312, Q6P9S0, Q765P7, Q8R1S4

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
MTSS1	up-regulates	GLI1	binding
MTSS1	up-regulates	SUFU	binding
MTSS1	up-regulates	RAC1	binding
TBX5	“up-regulates quantity by expression”	MTSS1	“transcriptional regulation”
SCF-betaTRCP	“down-regulates quantity by destabilization”	MTSS1	ubiquitination
CSNK1D	“down-regulates quantity by destabilization”	MTSS1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	111
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3622 predictions. Top by Δscore:

Variant	Effect	Δscore
8:124553663:CACT:C	acceptor_gain	1.0000
8:124553666:T:C	acceptor_gain	1.0000
8:124553666:T:TC	acceptor_gain	1.0000
8:124553688:TGAAA:T	acceptor_loss	1.0000
8:124553691:AACT:A	acceptor_loss	1.0000
8:124553692:AC:A	acceptor_loss	1.0000
8:124553694:T:C	acceptor_loss	1.0000
8:124555900:CCAGG:C	acceptor_gain	1.0000
8:124555901:CAGGC:C	acceptor_gain	1.0000
8:124555903:GG:G	acceptor_gain	1.0000
8:124555905:C:CC	acceptor_gain	1.0000
8:124555908:C:CT	acceptor_gain	1.0000
8:124555909:A:T	acceptor_gain	1.0000
8:124555911:G:GC	acceptor_gain	1.0000
8:124555912:T:C	acceptor_gain	1.0000
8:124555912:T:TC	acceptor_gain	1.0000
8:124556275:T:TA	donor_gain	1.0000
8:124556281:G:C	donor_gain	1.0000
8:124562990:CTG:C	acceptor_gain	1.0000
8:124567066:CCTA:C	donor_loss	1.0000
8:124567067:CTA:C	donor_loss	1.0000
8:124567069:ACC:A	donor_loss	1.0000
8:124567070:C:CA	donor_loss	1.0000
8:124567178:CCTG:C	acceptor_loss	1.0000
8:124568373:A:C	donor_gain	1.0000
8:124568374:CTTA:C	donor_loss	1.0000
8:124568376:TACA:T	donor_loss	1.0000
8:124568377:A:AC	donor_gain	1.0000
8:124568377:AC:A	donor_loss	1.0000
8:124568378:C:CC	donor_gain	1.0000

AlphaMissense

4928 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:124553056:A:T	I735N	1.000
8:124553494:A:C	I589S	1.000
8:124553494:A:G	I589T	1.000
8:124553494:A:T	I589N	1.000
8:124562845:G:C	F324L	1.000
8:124562845:G:T	F324L	1.000
8:124562847:A:G	F324L	1.000
8:124565670:A:C	S272R	1.000
8:124565670:A:T	S272R	1.000
8:124565672:T:G	S272R	1.000
8:124567077:A:C	S240R	1.000
8:124567077:A:T	S240R	1.000
8:124567079:T:G	S240R	1.000
8:124567090:A:G	L236P	1.000
8:124567120:A:G	L226P	1.000
8:124567141:A:G	L219P	1.000
8:124568443:C:G	R185P	1.000
8:124568446:A:T	V184D	1.000
8:124568450:C:G	A183P	1.000
8:124568491:A:T	V169D	1.000
8:124568504:C:G	A165P	1.000
8:124585097:T:A	K150N	1.000
8:124585097:T:G	K150N	1.000
8:124585099:T:C	K150E	1.000
8:124585100:C:A	K149N	1.000
8:124585100:C:G	K149N	1.000
8:124585102:T:C	K149E	1.000
8:124585107:A:G	L147P	1.000
8:124585109:T:A	K146N	1.000
8:124585109:T:G	K146N	1.000

dbSNP variants (sampled 300 via entrez): RS1000007681 (8:124698148 A>T), RS1000010520 (8:124660522 C>T), RS1000015823 (8:124583129 C>T), RS1000097333 (8:124579076 A>T), RS1000115498 (8:124705314 T>C), RS1000130440 (8:124715231 C>A), RS1000150842 (8:124615245 G>C,T), RS1000159692 (8:124654342 T>A,C), RS1000160617 (8:124615606 T>A), RS1000174871 (8:124633493 G>A), RS1000185011 (8:124586106 A>C), RS1000189967 (8:124693195 A>G), RS1000211411 (8:124570926 G>A), RS1000222529 (8:124693514 A>G), RS1000239451 (8:124571351 G>A)

Disease associations

OMIM: gene MIM:608486 | disease phenotypes: MIM:618245

GenCC curated gene-disease

Mondo (1): mitochondrial complex I deficiency, nuclear type 24 (MONDO:0032628)

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST002386_13	Cognitive function	6.000000e-06
GCST004655_1	Left ventricle diastolic internal dimension	2.000000e-13
GCST005173_26	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	2.000000e-06
GCST005174_30	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	8.000000e-07
GCST005175_16	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	1.000000e-06
GCST006061_10	Atrial fibrillation	3.000000e-09
GCST006061_11	Atrial fibrillation	3.000000e-09
GCST006304_8	Irritable bowel syndrome	2.000000e-06
GCST009395_1	Left ventricular ejection fraction	7.000000e-11
GCST009678_1	Cognitive performance in schizophrenia or bipolar disorder	1.000000e-07
GCST010125_3	Left ventricular ejection fraction	1.000000e-07
GCST010130_3	Left ventricular end-systolic volume	3.000000e-13
GCST010796_1476	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-11
GCST010796_1477	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-10
GCST010796_1478	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_1479	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-12
GCST011198_6	Left ventricular end-systolic volume	4.000000e-12
GCST011202_8	Dilated cardiomyopathy (MTAG)	2.000000e-11
GCST011209_4	Left ventricular ejection fraction	6.000000e-11
GCST011217_7	Left ventricular global circumferential strain	2.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0003925	cognition
EFO:0008205	left ventricular structural measurement
EFO:0004723	coronary artery calcification
EFO:0008373	left ventricular ejection fraction measurement
EFO:0008354	cognitive function measurement
EFO:0008206	left ventricular systolic function measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance, increases expression	6
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	5
Decitabine	affects methylation, affects expression, decreases expression, decreases reaction, increases expression	3
bisphenol A	decreases expression, increases expression	2
trichostatin A	increases expression	2
nickel sulfate	increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression, affects cotreatment	2
Doxorubicin	decreases expression, affects response to substance	2
Estradiol	increases expression, affects expression, affects cotreatment	2
Valproic Acid	decreases methylation, increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
testosterone undecanoate	affects cotreatment, increases expression	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1

Clinical trials (associated diseases)

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