OMA1

Summary

OMA1 (OMA1 zinc metallopeptidase, HGNC:29661) is a protein-coding gene on chromosome 1p32.2-p32.1, encoding Metalloendopeptidase OMA1, mitochondrial (Q96E52). Metalloprotease that is part of the quality control system in the inner membrane of mitochondria.

Enables metalloendopeptidase activity. Involved in several processes, including HRI-mediated signaling; proteolysis; and regulation of mitochondrion organization. Located in mitochondrial inner membrane. Is active in mitochondrial intermembrane space.

Source: NCBI Gene 115209 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_145243

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29661
Approved symbol	OMA1
Name	OMA1 zinc metallopeptidase
Location	1p32.2-p32.1
Locus type	gene with protein product
Status	Approved
Aliases	MPRP-1, YKR087C, ZMPOMA1, FLJ33782
Ensembl gene	ENSG00000162600
Ensembl biotype	protein_coding
OMIM	617081
Entrez	115209

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 31 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000371226, ENST00000419242, ENST00000421528, ENST00000426139, ENST00000453710, ENST00000456980, ENST00000460671, ENST00000467063, ENST00000467509, ENST00000476933, ENST00000482274, ENST00000906297, ENST00000906298, ENST00000906299, ENST00000906300, ENST00000906301, ENST00000906302, ENST00000906303, ENST00000906304, ENST00000906305, ENST00000906306, ENST00000906307, ENST00000906308, ENST00000906309, ENST00000906310, ENST00000929571, ENST00000929572, ENST00000929573, ENST00000929574, ENST00000963342, ENST00000963343, ENST00000963344, ENST00000963345, ENST00000963346, ENST00000963347

RefSeq mRNA: 1 — MANE Select: NM_145243 NM_145243

CCDS: CCDS608

Canonical transcript exons

ENST00000371226 — 9 exons

Exon	Start	End
ENSE00001066711	58533953	58534060
ENSE00001066717	58530601	58530729
ENSE00001454682	58480719	58481174
ENSE00001860692	58546703	58546726
ENSE00003541330	58538795	58539310
ENSE00003548836	58536513	58536741
ENSE00003571426	58534158	58534331
ENSE00003589509	58527261	58527335
ENSE00003620771	58506060	58506209

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 94.92.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0900 / max 4.3907, expressed in 25 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12565	9.9520	1738
12564	0.0900	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	94.92	gold quality
bronchus	UBERON:0002185	94.57	gold quality
calcaneal tendon	UBERON:0003701	94.45	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.22	gold quality
bone marrow cell	CL:0002092	93.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.93	gold quality
right uterine tube	UBERON:0001302	92.76	gold quality
kidney epithelium	UBERON:0004819	92.02	gold quality
colonic epithelium	UBERON:0000397	91.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.63	gold quality
corpus callosum	UBERON:0002336	91.63	gold quality
caput epididymis	UBERON:0004358	91.37	gold quality
renal medulla	UBERON:0000362	91.27	gold quality
epithelium of nasopharynx	UBERON:0001951	90.43	gold quality
right adrenal gland	UBERON:0001233	90.40	gold quality
superior surface of tongue	UBERON:0007371	90.24	gold quality
right adrenal gland cortex	UBERON:0035827	90.16	gold quality
rectum	UBERON:0001052	89.77	gold quality
lymph node	UBERON:0000029	89.67	gold quality
islet of Langerhans	UBERON:0000006	89.40	gold quality
adrenal cortex	UBERON:0001235	89.40	gold quality
tonsil	UBERON:0002372	89.35	gold quality
prostate gland	UBERON:0002367	89.32	gold quality
left adrenal gland cortex	UBERON:0035825	89.29	gold quality
skeletal muscle tissue	UBERON:0001134	89.26	gold quality
left adrenal gland	UBERON:0001234	89.22	gold quality
deltoid	UBERON:0001476	89.21	gold quality
corpus epididymis	UBERON:0004359	89.06	gold quality
adrenal tissue	UBERON:0018303	89.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

38 targeting OMA1, 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-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631

Literature-anchored findings (GeneRIF, showing 26)

• These results provide evidence for different substrate specificities of m-AAA proteases composed of different subunits and reveal a striking evolutionary switch of proteases involved in the proteolytic processing of dynamin-like GTPases in mitochondria. (PMID:17615298)
• OMA1 controls OPA1 cleavage and function. (PMID:20038677)
• Cleavage of the inner membrane fusion factor L-OPA1 is prevented due to the failure to activate the inner membrane protease OMA1 in mitochondria that have a collapsed membrane potential. (PMID:24634514)
• OMA1 is cleaved to a short form (S-OMA1) by itself upon mitochondrial membrane depolarization; S-OMA1 is degraded quickly but could be stabilized by CCCP treatment or Prohibitin knockdown in cells. (PMID:24719224)
• These findings demonstrate that (a) p53 and Oma1 mediate L-Opa1 processing, (b) mitochondrial fragmentation is involved in CDDP-induced apoptosis in OVCA and CECA cells, and (c) dysregulated mitochondrial dynamics (PMID:25112877)
• The mitochondrial metalloprotease OMA1 was activated in a Bax- and Bak-dependent fashion. (PMID:25275009)
• differential stress-induced degradation of YME1L and OMA1 as a mechanism for sensitively adapting mitochondrial inner membrane protease activity and function in response to distinct types of cellular insults. (PMID:26923599)
• we identify AFG3L2 [matrix (m)-AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. (PMID:29545505)
• leptin targeting the GSK3/OMA1/OPA1 signaling pathway can optimize hMSCs therapy for cardiovascular diseases such (PMID:29748581)
• Studies present evidence that OMA1 activation promotes cell death and its inhibition is protective against it. OMA1 activation on gene expression and protein levels is regulated by many tumor proteins. [review] (PMID:30714136)
• Mitochondrial membrane potential loss-dependent PINK1 import arrest does not result solely from Tim23 inactivation but also through an actively regulated “tug of war” between Tom7 and OMA1. (PMID:30733118)
• Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells. (PMID:31611601)
• Overexpression of ROMO1 and OMA1 are Potentially Biomarkers and Predict Unfavorable Prognosis in Gastric Cancer. (PMID:31729644)
• mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway; the OMA1-DELE1-HRI pathway represents a potential therapeutic target that could enable fine-tuning of the integrated stress response for beneficial outcomes in diseases that involve mitochondrial dysfunction (PMID:32132707)
• A Common Missense Variant in OMA1 Associated with the Prognosis of Heart Failure. (PMID:32236861)
• OMA1-An integral membrane protease? (PMID:33130089)
• Mitochondrial Safeguard: a stress response that offsets extreme fusion and protects respiratory function via flickering-induced Oma1 activation. (PMID:33200421)
• Tau phosphorylation and OPA1 proteolysis are unrelated events: Implications for Alzheimer’s Disease. (PMID:34400172)
• Circular RNA OMA1 regulates the progression of breast cancer via modulation of the miR1276/SIRT4 axis. (PMID:34414449)
• The Mitochondrial PHB2/OMA1/DELE1 Pathway Cooperates with Endoplasmic Reticulum Stress to Facilitate the Response to Chemotherapeutics in Ovarian Cancer. (PMID:35163244)
• Long Noncoding RNA PCGEM1 Facilitates Tumor Growth and Metastasis of Osteosarcoma by Sponging miR-433-3p and Targeting OMA1. (PMID:36782343)
• The mitochondrial protease OMA1 acts as a metabolic safeguard upon nuclear DNA damage. (PMID:37002921)
• OMA1 protease eliminates arrested protein import intermediates upon mitochondrial depolarization. (PMID:38530280)
• OMA1 competitively binds to HSPA9 to promote mitophagy and activate the cGAS-STING pathway to mediate GBM immune escape. (PMID:38604814)
• Melatonin Rescues Influenza A Virus-Induced Cellular Energy Exhaustion via OMA1-OPA1-S in Acute Exacerbation of COPD. (PMID:39039850)
• Mitochondrial metallopeptidase OMA1 in cancer. (PMID:39069370)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	oma1	ENSDARG00000090503
mus_musculus	Oma1	ENSMUSG00000035069
rattus_norvegicus	Oma1	ENSRNOG00000007214

Protein

Protein identifiers

Metalloendopeptidase OMA1, mitochondrial — Q96E52 (reviewed: Q96E52)

Alternative names: Metalloprotease-related protein 1, Overlapping with the m-AAA protease 1 homolog

All UniProt accessions (7): Q96E52, H7BZX2, S4R3A3, X6RD49, X6RDQ1, X6RIG5, X6RL62

UniProt curated annotations — full annotation on UniProt →

Function. Metalloprotease that is part of the quality control system in the inner membrane of mitochondria. Activated in response to various mitochondrial stress, leading to the proteolytic cleavage of target proteins, such as OPA1, UQCC3 and DELE1. Involved in the fusion of the mitochondrial inner membranes by mediating cleavage of OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which cooperates with the membrane form (L-OPA1) to coordinate the fusion of mitochondrial inner membranes. Following stress conditions that induce loss of mitochondrial membrane potential, mediates cleavage of OPA1, leading to excess production of soluble OPA1 (S-OPA1) and negative regulation of mitochondrial fusion. Involved in mitochondrial safeguard in response to transient mitochondrial membrane depolarization (flickering) by catalyzing cleavage of OPA1, leading to excess production of S-OPA1, preventing mitochondrial hyperfusion. Also acts as a regulator of apoptosis: upon BAK and BAX aggregation, mediates cleavage of OPA1, leading to the remodeling of mitochondrial cristae and allowing the release of cytochrome c from mitochondrial cristae. In depolarized mitochondria, may also act as a backup protease for PINK1 by mediating PINK1 cleavage and promoting its subsequent degradation by the proteasome. May also cleave UQCC3 in response to mitochondrial depolarization. Also acts as an activator of the integrated stress response (ISR): in response to mitochondrial stress, mediates cleavage of DELE1 to generate the processed form of DELE1 (S-DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to trigger the ISR. Its role in mitochondrial quality control is essential for regulating lipid metabolism as well as to maintain body temperature and energy expenditure under cold-stress conditions. Binds cardiolipin, possibly regulating its protein turnover. Required for the stability of the respiratory supercomplexes.

Subunit / interactions. Homooligomer.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Widely expressed, with strong expression in the heart, skeletal muscle, kidney and liver.

Post-translational modifications. May form a redox-dependent disulfide bond. Exists in a semi-oxidized state and is activated by prolonged hypoxia. Autocatalytically cleaved in response to mitochondrial depolarization both at the N-terminus and C-terminus to generate the short active form (S-OMA1). Autocatalytic processing at the C-terminus takes place at residues 447-456. The S-OMA1 form is unstable. OMA1 pre-processing by AFG3L2 may participate in maturation before OMA1 autocatalytic cleavage. Degraded by YMEL1 in response to membrane depolarization. Protein turnover is regulated by prohibitin (PHB and PHB2), which promotes degradation of OMA1 in a cardiolipin-binding manner.

Activity regulation. Protease activity is activated upon autocatalytic cleavage in response to mitochondrial depolarization.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The stress-sensor region regulates proteolysis and activation.

Similarity. Belongs to the peptidase M48 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96E52-1	1	yes
Q96E52-2	2

RefSeq proteins (1): NP_660286* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001915	Peptidase_M48	Domain
IPR051156	Mito/Outer_Membr_Metalloprot	Family

Pfam: PF01435

UniProt features (25 total): sequence variant 8, binding site 3, propeptide 2, mutagenesis site 2, topological domain 2, region of interest 2, transit peptide 1, disulfide bond 1, splice variant 1, chain 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96E52-F1	71.49	0.42

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 328

Ligand- & substrate-binding residues (3): 327; 331; 392

Disulfide bonds (1): 407–465

Mutagenesis-validated functional residues (2):

Position	Phenotype
328	abolished protease activity and ability to mediate cleavage of dele1 in response to mitochondrial stress. abolished abil
331	abolishes ability to cleave opa1 at s1 position.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-169911	Regulation of Apoptosis
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-9840373	Cellular response to mitochondrial stress

MSigDB gene sets: 186 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_RESPONSE_TO_DIETARY_EXCESS, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TAL1ALPHAE47_01, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GOBP_CRISTAE_FORMATION, EFC_Q6, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, CEBP_Q2, GOBP_PROTEIN_MATURATION, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, GOBP_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (23): diet induced thermogenesis (GO:0002024), glucose metabolic process (GO:0006006), protein quality control for misfolded or incompletely synthesized proteins (GO:0006515), lipid metabolic process (GO:0006629), negative regulation of mitochondrial fusion (GO:0010637), protein autoprocessing (GO:0016540), zymogen activation (GO:0031638), mitochondrial respiratory chain complex assembly (GO:0033108), cellular response to stress (GO:0033554), mitochondrial protein processing (GO:0034982), cristae formation (GO:0042407), positive regulation of apoptotic process (GO:0043065), energy homeostasis (GO:0097009), positive regulation of cold-induced thermogenesis (GO:0120162), integrated stress response signaling (GO:0140467), HRI-mediated signaling (GO:0140468), regulation of cristae formation (GO:1903850), mitophagy (GO:0000423), translational initiation (GO:0006413), proteolysis (GO:0006508), mitochondrion organization (GO:0007005), protein localization to mitochondrion (GO:0070585), positive regulation of mitophagy (GO:1901526)

GO Molecular Function (6): metalloendopeptidase activity (GO:0004222), lipid binding (GO:0008289), metal ion binding (GO:0046872), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial membrane (GO:0031966), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Apoptosis	1
Metabolism of proteins	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein processing	3
mitochondrion	3
mitochondrial envelope	2
response to dietary excess	1
adaptive thermogenesis	1
hexose metabolic process	1
protein catabolic process	1
primary metabolic process	1
mitochondrial fusion	1
regulation of mitochondrial fusion	1
negative regulation of organelle organization	1
negative regulation of developmental process	1
mitochondrion organization	1
protein-containing complex assembly	1
response to stress	1
cellular response to stimulus	1
inner mitochondrial membrane organization	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
multicellular organismal-level homeostasis	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
cellular response to stress	1
intracellular signaling cassette	1
integrated stress response signaling	1
regulation of mitochondrion organization	1
cristae formation	1
autophagy of mitochondrion	1
macroautophagy	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
protein metabolic process	1
endopeptidase activity	1
metallopeptidase activity	1
binding	1
cation binding	1
hydrolase activity	1

Protein interactions and networks

STRING

2168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OMA1	YME1L1	Q96TA2	916
OMA1	PARL	Q9H300	779
OMA1	A0A1W2PP11	A0A1W2PP11	773
OMA1	DELE1	Q14154	758
OMA1	AFG3L2	Q9Y4W6	748
OMA1	MFN2	O95140	743
OMA1	MFN1	Q8IWA4	741
OMA1	SPG7	Q9UQ90	702
OMA1	OPA1	O60313	693
OMA1	FIS1	Q9Y3D6	677
OMA1	CLPP	Q16740	665
OMA1	DNM1L	O00429	658
OMA1	LONP1	P36776	646
OMA1	MIEF2	Q96C03	643
OMA1	MFF	Q9GZY8	628

IntAct

104 interactions, top by confidence:

A	B	Type	Score
SIL1	HSPA5	psi-mi:“MI:0914”(association)	0.740
ADCY9	NEMP1	psi-mi:“MI:0914”(association)	0.640
BZW2	ENDOD1	psi-mi:“MI:0914”(association)	0.640
NRAS	RGL2	psi-mi:“MI:0914”(association)	0.550
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
NCR3LG1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
UST	GOLIM4	psi-mi:“MI:0914”(association)	0.530
IFNA8	IFIT3	psi-mi:“MI:0914”(association)	0.530
CNPPD1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
BZW2	SLC27A2	psi-mi:“MI:0914”(association)	0.530
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530
TBC1D25	GABARAP	psi-mi:“MI:0914”(association)	0.530
P2RX1	ATE1	psi-mi:“MI:0914”(association)	0.530
AMIGO3	CANX	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
IRGC	RAP1GDS1	psi-mi:“MI:0914”(association)	0.530
SIDT2	AP3D1	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
OMA1	ATP1A1	psi-mi:“MI:0915”(physical association)	0.400
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
SLC4A8	ABCC4	psi-mi:“MI:0914”(association)	0.350
EDEM2	HACD1	psi-mi:“MI:0914”(association)	0.350
FAM8A1	SDCBP	psi-mi:“MI:0914”(association)	0.350

BioGRID (186): OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A077K8G3, A0A077K9K6, A0A0B4ZTQ2, A0A0B5A051, A0A0B5L778, A0A0U5CJV1, A0A1Y0BRF7, A0A3G9GNJ4, A0A455LLV4, A0A455ZJC3, A0A8D5M7V9, B9A1Q4, D3ZS74, E5RP65, F1DBA7, F4IQV7, F4JPW1, G0LET6, G1XTZ7, G3Y418, G5DBJ0, O22780, O80899, P9WEQ7, P9WEW7, P9WEX2, Q09701, Q0C8A6, Q2N2K0, Q3KQJ0, Q3SZN3, Q4R690, Q4WBI5, Q5AR21, Q5NVB9, Q67YT8, Q67ZM7, Q8IUH4, Q8TFH4, Q8VY13

Diamond homologs: D3ZS74, E9QBI7, Q3SZN3, Q96E52, Q9D8H7, Q9FLI5, Q9P7G4, P36163

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
OMA1	“up-regulates activity”	OPA1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 141 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
Ion transport by P-type ATPases	5	11.7×	6e-03
SLC transporter disorders	5	11.5×	6e-03
R-HSA-425366	5	10.2×	9e-03
SLC-mediated transmembrane transport	11	7.3×	6e-05
Transport of small molecules	21	5.9×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
sodium ion transmembrane transport	7	11.4×	1e-03
ERAD pathway	7	10.2×	1e-03
transport across blood-brain barrier	7	10.0×	1e-03
transmembrane transport	7	9.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1941 predictions. Top by Δscore:

Variant	Effect	Δscore
1:58527331:ATATA:A	acceptor_gain	1.0000
1:58527332:TATA:T	acceptor_gain	1.0000
1:58527333:ATA:A	acceptor_gain	1.0000
1:58527334:TA:T	acceptor_gain	1.0000
1:58527336:C:CC	acceptor_gain	1.0000
1:58533951:A:AC	donor_gain	1.0000
1:58533952:C:CC	donor_gain	1.0000
1:58533952:CAG:C	donor_gain	1.0000
1:58534067:C:CT	acceptor_gain	1.0000
1:58534152:A:AC	donor_gain	1.0000
1:58534152:ACTT:A	donor_loss	1.0000
1:58534153:C:CC	donor_gain	1.0000
1:58534153:CT:C	donor_loss	1.0000
1:58534153:CTTA:C	donor_gain	1.0000
1:58534154:TTAC:T	donor_loss	1.0000
1:58534155:TAC:T	donor_loss	1.0000
1:58534156:A:AC	donor_gain	1.0000
1:58534156:AC:A	donor_loss	1.0000
1:58534157:C:CT	donor_gain	1.0000
1:58534157:CT:C	donor_gain	1.0000
1:58534157:CTG:C	donor_gain	1.0000
1:58534157:CTGG:C	donor_gain	1.0000
1:58534157:CTGGA:C	donor_gain	1.0000
1:58534327:ATCCA:A	acceptor_gain	1.0000
1:58534328:TCCA:T	acceptor_gain	1.0000
1:58534329:CCA:C	acceptor_gain	1.0000
1:58534329:CCAC:C	acceptor_gain	1.0000
1:58534330:CA:C	acceptor_gain	1.0000
1:58534330:CAC:C	acceptor_gain	1.0000
1:58534332:C:CC	acceptor_gain	1.0000

AlphaMissense

3481 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:58506186:A:C	S413R	0.993
1:58506186:A:T	S413R	0.993
1:58506188:T:G	S413R	0.993
1:58527293:C:G	A395P	0.992
1:58527266:C:G	A404P	0.988
1:58534192:A:T	V290D	0.988
1:58538798:C:T	G166D	0.987
1:58530666:A:G	W359R	0.985
1:58530666:A:T	W359R	0.985
1:58534208:A:G	W285R	0.984
1:58534208:A:T	W285R	0.984
1:58481160:T:A	R460S	0.982
1:58481160:T:G	R460S	0.982
1:58506091:C:G	R445P	0.979
1:58534046:A:C	F306L	0.978
1:58534046:A:T	F306L	0.978
1:58534048:A:G	F306L	0.978
1:58536732:C:A	R170S	0.978
1:58536732:C:G	R170S	0.978
1:58506176:A:G	W417R	0.977
1:58506176:A:T	W417R	0.977
1:58506192:T:A	R411S	0.977
1:58506192:T:G	R411S	0.977
1:58527277:A:G	L400P	0.976
1:58536733:C:G	R170T	0.976
1:58481146:C:G	C465S	0.974
1:58481147:A:T	C465S	0.974
1:58506122:A:G	W435R	0.974
1:58506122:A:T	W435R	0.974
1:58506193:C:A	R411I	0.974

dbSNP variants (sampled 300 via entrez): RS1000044898 (1:58482464 A>G), RS1000050618 (1:58513119 T>C), RS1000072592 (1:58482848 G>A), RS1000161572 (1:58481132 T>C,G), RS1000282826 (1:58529100 C>A,T), RS1000353116 (1:58522225 C>T), RS1000388369 (1:58515719 T>C), RS1000446172 (1:58535115 A>G), RS1000502202 (1:58540911 A>G), RS1000519628 (1:58511164 C>A,T), RS1000552135 (1:58511561 C>G,T), RS1000569903 (1:58497834 T>C), RS1000641134 (1:58509722 G>A), RS1000685612 (1:58484763 G>T), RS1000730483 (1:58516426 C>G)

Disease associations

OMIM: gene MIM:617081 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	5
entinostat	increases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
quercitrin	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Am 580	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Rosiglitazone	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Phenobarbital	affects expression	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9LV	Ubigene HEK293 OMA1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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