MECR

Summary

MECR (mitochondrial trans-2-enoyl-CoA reductase, HGNC:19691) is a protein-coding gene on chromosome 1p35.3, encoding Enoyl-[acyl-carrier-protein] reductase, mitochondrial (Q9BV79). Catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters in mitochondrial fatty acid synthesis (fatty acid synthesis type II).

The protein encoded by this gene is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis. Defects in this gene are a cause of childhood-onset dystonia and optic atrophy.

Source: NCBI Gene 51102 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 357 total — 23 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 56
• MANE Select transcript: NM_016011

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19691
Approved symbol	MECR
Name	mitochondrial trans-2-enoyl-CoA reductase
Location	1p35.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-63, NRBF1, FASN2B, ETR1
Ensembl gene	ENSG00000116353
Ensembl biotype	protein_coding
OMIM	608205
Entrez	51102

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding_CDS_not_defined, 5 protein_coding, 1 nonsense_mediated_decay

ENST00000263702, ENST00000373791, ENST00000453185, ENST00000463052, ENST00000463412, ENST00000464511, ENST00000464915, ENST00000473030, ENST00000474946, ENST00000475773, ENST00000475861, ENST00000478505, ENST00000482610, ENST00000483435, ENST00000484012, ENST00000489248, ENST00000490529, ENST00000493928, ENST00000883815, ENST00000883816, ENST00000944953

RefSeq mRNA: 9 — MANE Select: NM_016011 NM_001024732, NM_001349711, NM_001349712, NM_001349713, NM_001349714, NM_001349715, NM_001349716, NM_001349717, NM_016011

CCDS: CCDS30659, CCDS30660

Canonical transcript exons

ENST00000263702 — 10 exons

Exon	Start	End
ENSE00001897993	29230731	29230934
ENSE00003463736	29192657	29194179
ENSE00003514783	29201943	29202045
ENSE00003541531	29216588	29216685
ENSE00003555300	29200516	29200589
ENSE00003576980	29203131	29203233
ENSE00003606944	29196198	29196258
ENSE00003614856	29216005	29216136
ENSE00003657858	29206762	29206905
ENSE00003671182	29195941	29196013

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 95.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.4471 / max 147.4246, expressed in 1779 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11381	20.1951	1779
11380	0.2520	120

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	95.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.26	gold quality
gastrocnemius	UBERON:0001388	94.87	gold quality
muscle of leg	UBERON:0001383	94.24	gold quality
prefrontal cortex	UBERON:0000451	93.70	gold quality
anterior cingulate cortex	UBERON:0009835	93.69	gold quality
heart left ventricle	UBERON:0002084	93.65	gold quality
cingulate cortex	UBERON:0003027	93.58	gold quality
right frontal lobe	UBERON:0002810	93.24	gold quality
cardiac ventricle	UBERON:0002082	93.19	gold quality
right atrium auricular region	UBERON:0006631	92.68	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.55	gold quality
right adrenal gland	UBERON:0001233	92.45	gold quality
left adrenal gland	UBERON:0001234	92.27	gold quality
left adrenal gland cortex	UBERON:0035825	92.06	gold quality
right lobe of liver	UBERON:0001114	92.05	gold quality
skin of leg	UBERON:0001511	91.99	gold quality
muscle organ	UBERON:0001630	91.99	gold quality
skeletal muscle organ	UBERON:0014892	91.99	gold quality
nucleus accumbens	UBERON:0001882	91.98	gold quality
right adrenal gland cortex	UBERON:0035827	91.96	gold quality
heart	UBERON:0000948	91.57	gold quality
skin of abdomen	UBERON:0001416	91.55	gold quality
amygdala	UBERON:0001876	91.43	gold quality
cardiac atrium	UBERON:0002081	91.43	gold quality
minor salivary gland	UBERON:0001830	91.17	gold quality
caudate nucleus	UBERON:0001873	91.16	gold quality
omental fat pad	UBERON:0010414	91.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.07	gold quality
peritoneum	UBERON:0002358	91.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting MECR, 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-3925-3P	100.00	69.95	1237
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-1227-5P	98.65	65.32	1549

Literature-anchored findings (GeneRIF, showing 7)

• The crystal structure of this dimeric enzyme (at 2.4 A resolution) suggests that the binding site for the recognition helix of the acyl carrier protein is in a groove between the two adjacent monomers. (PMID:18479707)
• overexpression of MECR, the last step in the mitochondrial fatty acid synthesis (mtFASII) pathway, causes modulation of gene expression through the PPAR pathway. (PMID:24161390)
• results suggest that mutations in MECR cause a distinct human disorder of the mitochondrial fatty acid synthesis pathway; the observation of decreased lipoylation raises the possibility of a potential therapeutic strategy (PMID:27817865)
• MECR is involved in mitochondrial fatty acid synthesis, and overexpression of this gene increases peroxisome proliferator-activated receptor alpha (PPARalpha) activity. (PMID:27845578)
• Whole exome sequencing identifies a novel homozygous MECR mutation in a Chinese patient with childhood-onset dystonia and basal ganglia abnormalities, without optic atrophy. (PMID:33401012)
• Alternative splicing liberates a cryptic cytoplasmic isoform of mitochondrial MECR that antagonizes influenza virus. (PMID:36542656)
• Recessive MECR pathogenic variants cause an LHON-like optic neuropathy. (PMID:37734847)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mecr	ENSDARG00000032326
mus_musculus	Mecr	ENSMUSG00000028910
rattus_norvegicus	Mecr	ENSRNOG00000028047
drosophila_melanogaster	CG16935	FBGN0033883
caenorhabditis_elegans		WBGENE00012375

Paralogs (17): PTGR1 (ENSG00000106853), VAT1 (ENSG00000108828), TP53I3 (ENSG00000115129), CRYZ (ENSG00000116791), RTN4IP1 (ENSG00000130347), PTGR2 (ENSG00000140043), SORD (ENSG00000140263), VAT1L (ENSG00000171724), ADH6 (ENSG00000172955), PTGR3 (ENSG00000180011), ADH1A (ENSG00000187758), ADH7 (ENSG00000196344), ADH1B (ENSG00000196616), ADH5 (ENSG00000197894), ADH4 (ENSG00000198099), CRYZL1 (ENSG00000205758), ADH1C (ENSG00000248144)

Protein

Protein identifiers

Enoyl-[acyl-carrier-protein] reductase, mitochondrial — Q9BV79 (reviewed: Q9BV79)

Alternative names: 2-enoyl thioester reductase, Nuclear receptor-binding factor 1

All UniProt accessions (2): Q9BV79, H3BM30

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters in mitochondrial fatty acid synthesis (fatty acid synthesis type II). Fatty acid chain elongation in mitochondria uses acyl carrier protein (ACP) as an acyl group carrier, but the enzyme accepts both ACP and CoA thioesters as substrates in vitro. Displays a preference for medium-chain over short- and long-chain substrates. May provide the octanoyl chain used for lipoic acid biosynthesis, regulating protein lipoylation and mitochondrial respiratory activity particularly in Purkinje cells. Involved in iron homeostasis; affecting Fe-S cluster assembly and ceramide metabolism. Required for proper morphology and bioenergetic functions of mitochondria. Required for maintenance of neurons.

Subunit / interactions. Homodimer. Isoform 2 interacts with PPARA in the nucleus and increases its activity.

Subcellular location. Mitochondrion Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in skeletal and heart muscle. Expressed at lower level in placenta, liver, kidney and pancreas. Weakly or not expressed in lung.

Disease relevance. Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities (DYTOABG) [MIM:617282] An autosomal recessive neurologic disorder characterized by childhood-onset dystonia, basal ganglia degeneration and optic atrophy with decreased visual acuity. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTOABG severity is variable, and some patients lose independent ambulation. The disease is caused by variants affecting the gene represented in this entry. Optic atrophy 16 (OPA16) [MIM:620629] A disease characterized by visual impairment in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA16 is an autosomal recessive form. Patients also show mild sensorineural hearing impairment. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BV79-1	1	yes
Q9BV79-2	2, cMECR

RefSeq proteins (9): NP_001019903, NP_001336640, NP_001336641, NP_001336642, NP_001336643, NP_001336644, NP_001336645, NP_001336646, NP_057095* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011032	GroES-like_sf	Homologous_superfamily
IPR013149	ADH-like_C	Domain
IPR013154	ADH-like_N	Domain
IPR020843	ER	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR051034	Mito_Enoyl-ACP_Reductase	Family

Pfam: PF00107, PF08240

Catalyzed reactions (Rhea), 8 shown:

• a 2,3-saturated acyl-[ACP] + NADP(+) = a (2E)-enoyl-[ACP] + NADPH + H(+) (RHEA:22564)
• (2E)-butenoyl-[ACP] + NADPH + H(+) = butanoyl-[ACP] + NADP(+) (RHEA:41812)
• (2E)-hexenoyl-[ACP] + NADPH + H(+) = hexanoyl-[ACP] + NADP(+) (RHEA:41832)
• (2E)-octenoyl-[ACP] + NADPH + H(+) = octanoyl-[ACP] + NADP(+) (RHEA:41848)
• (2E)-decenoyl-[ACP] + NADPH + H(+) = decanoyl-[ACP] + NADP(+) (RHEA:41864)
• (2E)-dodecenoyl-[ACP] + NADPH + H(+) = dodecanoyl-[ACP] + NADP(+) (RHEA:41880)
• (2E)-tetradecenoyl-[ACP] + NADPH + H(+) = tetradecanoyl-[ACP] + NADP(+) (RHEA:41896)
• (2E)-hexadecenoyl-[ACP] + NADPH + H(+) = hexadecanoyl-[ACP] + NADP(+) (RHEA:41912)

UniProt features (69 total): strand 20, helix 15, mutagenesis site 8, modified residue 7, sequence variant 7, binding site 6, sequence conflict 2, transit peptide 1, chain 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1ZSY	X-RAY DIFFRACTION	1.75
7AYB	X-RAY DIFFRACTION	1.85
7AYC	X-RAY DIFFRACTION	2.02
2VCY	X-RAY DIFFRACTION	2.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV79-F1	90.55	0.86

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): 94 (proton donor)

Ligand- & substrate-binding residues (6): 167; 193–196; 216–218; 285–288; 310–312; 368

Post-translational modifications (7): 61, 252, 252, 267, 267, 316, 61

Mutagenesis-validated functional residues (8):

Position	Phenotype
85	reduces catalytic activity by 68%.
94	reduces catalytic activity by 95%. strongly reduces affinity for trans-oct-2-enoyl-coa.
129	strongly increases activity with trans-oct-2-enoyl-coa. no effect on activity with trans-tetradec-2-enoyl-coa. decreases
165	strongly increases activity with trans-oct-2-enoyl-coa. decreases activity with trans-tetradec-2-enoyl-coa by 73%. decre
170	reduces catalytic activity by 69%.
311	reduces catalytic activity by 98%. strongly reduces affinity for trans-oct-2-enoyl-coa.
311	reduces catalytic activity by 87%. strongly reduces affinity for trans-oct-2-enoyl-coa.
324	strongly increases activity with trans-oct-2-enoyl-coa. decreases activity with trans-tetradec-2-enoyl-coa by 25%. decre

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-77346	Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-77286	mitochondrial fatty acid beta-oxidation of saturated fatty acids
R-HSA-77289	Mitochondrial Fatty Acid Beta-Oxidation
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 247 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_FATTY_ACID_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_CERAMIDE_METABOLIC_PROCESS

GO Biological Process (5): fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633), intracellular iron ion homeostasis (GO:0006879), ceramide biosynthetic process (GO:0046513), lipid metabolic process (GO:0006629)

GO Molecular Function (2): enoyl-[acyl-carrier-protein] reductase (NADPH) activity (GO:0141148), oxidoreductase activity (GO:0016491)

GO Cellular Component (5): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), membrane (GO:0016020), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
mitochondrial fatty acid beta-oxidation of saturated fatty acids	1
Metabolism	1
Mitochondrial Fatty Acid Beta-Oxidation	1
Fatty acid metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
ceramide metabolic process	1
sphingolipid biosynthetic process	1
primary metabolic process	1
enoyl-[acyl-carrier-protein] reductase [NAD(P)H] activity	1
catalytic activity	1
cytoplasm	1
mitochondrion	1
intracellular organelle lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MECR	OXSM	Q9NWU1	779
MECR	GDPD4	Q6W3E5	670
MECR	MCAT	Q8IVS2	666
MECR	LIAS	O43766	614
MECR	LIPT2	A6NK58	592
MECR	LIPT1	Q9Y234	576
MECR	HSD17B8	Q92506	567
MECR	TXNRD2	Q9NNW7	543
MECR	RARA	P10276	461
MECR	HNF4A	P41235	451
MECR	ECHS1	P30084	442
MECR	AFG3L2	Q9Y4W6	428
MECR	UQCRB	P14927	419
MECR	NDUFAB1	O14561	408
MECR	ACAA1	P09110	382

IntAct

15 interactions, top by confidence:

A	B	Type	Score
TAS2R41	YKT6	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
AURKA	CTNNB1	psi-mi:“MI:0914”(association)	0.350
Yap1	GEMIN2	psi-mi:“MI:0914”(association)	0.350
PPA2	H1-3	psi-mi:“MI:0914”(association)	0.350
LAMP1	DST	psi-mi:“MI:0914”(association)	0.350
NCKAP1	ENAH	psi-mi:“MI:0914”(association)	0.350
WASF2	HSBP1	psi-mi:“MI:0914”(association)	0.350
MECR	SNX4	psi-mi:“MI:0914”(association)	0.350
RNF133	CD14	psi-mi:“MI:0914”(association)	0.350
NR2E1	DCAF6	psi-mi:“MI:0914”(association)	0.350
DMRT1	ATE1	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): MECR (Affinity Capture-RNA), MECR (Affinity Capture-MS), MECR (Co-fractionation), MECR (Co-fractionation), MECR (Co-fractionation), MECR (Affinity Capture-MS), MECR (Affinity Capture-MS), MECR (Affinity Capture-MS), MECR (Affinity Capture-MS), MECR (Synthetic Lethality), Ppara (Two-hybrid), Rxra (Two-hybrid), Hnf4a (Two-hybrid), Thrb (Two-hybrid), PPARA (Reconstituted Complex)

ESM2 similar proteins: A9JS71, D4A2H2, F1NB38, F1R6N4, O15269, O35459, O35704, O54695, P11172, P13439, P23965, P31754, P42125, P42126, P51398, P82922, Q13011, Q28C91, Q28DB5, Q2HJD5, Q3MIE0, Q5E9H9, Q5HZQ8, Q5R4W0, Q5R514, Q5R9T5, Q5REX5, Q5RFG0, Q5XIC0, Q60HD1, Q62651, Q6AYG5, Q6DIS1, Q6GM82, Q6NYL5, Q6PE15, Q86WA6, Q8BGT5, Q8R164, Q8TD30

Diamond homologs: A0A0D2YG03, B0BNC9, K4BW79, O23939, O45903, O57380, O74822, P38071, P72324, P80175, P9WQB8, P9WQB9, Q10488, Q28GQ2, Q3MIE4, Q54YT4, Q62465, Q6BLV6, Q6BV30, Q6CBE4, Q6CIR6, Q6FXN7, Q6GQN8, Q757U3, Q7YS70, Q8JFV8, Q8LCU7, Q8NJJ9, Q8WZM3, Q8WZM4, Q99536, Q9BV79, Q9DCS3, Q9V6U9, Q9XXC8, Q9Z311, S0DRW9, S3D9F1, W7NCN7, A0A098D8A0

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MECR	“down-regulates quantity”	trans-dec-2-enoyl-CoA	“chemical modification”
MECR	“down-regulates quantity”	NADPH(4-)	“chemical modification”
MECR	“up-regulates quantity”	decanoyl-CoA	“chemical modification”
MECR	“up-regulates quantity”	NADP(3-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	7
Uncertain significance	97
Likely benign	183
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1173961	NM_016011.5(MECR):c.910G>T (p.Asp304Tyr)	Pathogenic
2090545	NM_016011.5(MECR):c.646C>T (p.Arg216Ter)	Pathogenic
2717811	NM_016011.5(MECR):c.46C>T (p.Gln16Ter)	Pathogenic
2725088	NM_016011.5(MECR):c.331C>T (p.Gln111Ter)	Pathogenic
2778848	NM_016011.5(MECR):c.319G>T (p.Glu107Ter)	Pathogenic
2790814	NM_016011.5(MECR):c.890_891del (p.Val297fs)	Pathogenic
2799762	NM_016011.5(MECR):c.5G>A (p.Trp2Ter)	Pathogenic
2814279	NM_016011.5(MECR):c.696_697dup (p.Ala233fs)	Pathogenic
2829450	NM_016011.5(MECR):c.604C>T (p.Gln202Ter)	Pathogenic
2836545	NC_000001.11:g.29195999_29196014A[5]TGAGCAGGCTCGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAATGAGCAGGCTC[1]	Pathogenic
2840857	NM_016011.5(MECR):c.449dup (p.Gln151fs)	Pathogenic
2845237	NM_016011.5(MECR):c.544del (p.Gln182fs)	Pathogenic
2867130	NM_016011.5(MECR):c.202del (p.Ala67_Val68insTer)	Pathogenic
2870640	NM_016011.5(MECR):c.676dup (p.Asp226fs)	Pathogenic
2881617	NM_016011.5(MECR):c.44_57del (p.Arg15fs)	Pathogenic
2963153	NM_016011.5(MECR):c.861dup (p.Met288fs)	Pathogenic
3248003	NC_000001.10:g.(?29527008)(29527121_?)del	Pathogenic
3248004	NC_000001.10:g.(?29520534)(29543217_?)del	Pathogenic
3248005	NC_000001.10:g.(?29542497)(29543217_?)del	Pathogenic
374879	NM_016011.5(MECR):c.855T>G (p.Tyr285Ter)	Pathogenic
374883	NM_016011.5(MECR):c.247_250del (p.Asn83fs)	Pathogenic
4797605	NM_016011.5(MECR):c.39dup (p.Ala14fs)	Pathogenic
807442	NC_000001.11:g.29203234del	Pathogenic
2801751	NM_016011.5(MECR):c.831-2A>G	Likely pathogenic
2859873	NM_016011.5(MECR):c.654-1G>T	Likely pathogenic
2905705	NM_016011.5(MECR):c.830+1G>A	Likely pathogenic
3008945	NM_016011.5(MECR):c.830+1del	Likely pathogenic
3583631	NM_016011.5(MECR):c.176+1G>A	Likely pathogenic
4277683	NM_016011.5(MECR):c.410C>T (p.Thr137Ile)	Likely pathogenic
4292104	NM_016011.5(MECR):c.831-2_831-1insT	Likely pathogenic

SpliceAI

1954 predictions. Top by Δscore:

Variant	Effect	Δscore
1:29201974:AGCT:A	donor_gain	1.0000
1:29201975:G:C	donor_gain	1.0000
1:29202041:CAGGT:C	acceptor_gain	1.0000
1:29202042:AGGT:A	acceptor_gain	1.0000
1:29202043:GGT:G	acceptor_gain	1.0000
1:29202044:GT:G	acceptor_gain	1.0000
1:29202046:C:CC	acceptor_gain	1.0000
1:29203126:CGCA:C	donor_loss	1.0000
1:29203127:GCA:G	donor_loss	1.0000
1:29203128:CACC:C	donor_loss	1.0000
1:29203129:A:AT	donor_loss	1.0000
1:29203130:C:CA	donor_loss	1.0000
1:29203231:CCC:C	acceptor_gain	1.0000
1:29203232:CCC:C	acceptor_gain	1.0000
1:29203243:C:CT	acceptor_gain	1.0000
1:29203244:A:T	acceptor_gain	1.0000
1:29206758:CTA:C	donor_loss	1.0000
1:29206759:TACCT:T	donor_loss	1.0000
1:29206761:C:T	donor_loss	1.0000
1:29206761:CCTGG:C	donor_gain	1.0000
1:29216000:CTCA:C	donor_loss	1.0000
1:29216001:TCACC:T	donor_loss	1.0000
1:29216002:CA:C	donor_loss	1.0000
1:29216003:A:C	donor_loss	1.0000
1:29216133:TTTC:T	acceptor_gain	1.0000
1:29216134:TTC:T	acceptor_gain	1.0000
1:29216134:TTCCT:T	acceptor_loss	1.0000
1:29216135:TCCTG:T	acceptor_loss	1.0000
1:29216136:CCTGA:C	acceptor_loss	1.0000
1:29216137:C:A	acceptor_loss	1.0000

AlphaMissense

2403 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:29195999:A:C	F302L	0.997
1:29195999:A:T	F302L	0.997
1:29196001:A:G	F302L	0.997
1:29200560:G:C	N262K	0.997
1:29200560:G:T	N262K	0.997
1:29206900:A:G	W138R	0.997
1:29206900:A:T	W138R	0.997
1:29200557:A:C	C263W	0.996
1:29203214:A:C	N190K	0.995
1:29203214:A:T	N190K	0.995
1:29203145:A:C	N213K	0.994
1:29203145:A:T	N213K	0.994
1:29203202:G:C	S194R	0.994
1:29203202:G:T	S194R	0.994
1:29203204:T:G	S194R	0.994
1:29203224:A:T	V187D	0.994
1:29206811:A:C	N167K	0.994
1:29206811:A:T	N167K	0.994
1:29216613:A:C	N83K	0.994
1:29216613:A:T	N83K	0.994
1:29195975:A:C	F310L	0.993
1:29195975:A:T	F310L	0.993
1:29195977:A:G	F310L	0.993
1:29200567:G:T	A260D	0.993
1:29203195:C:A	G197W	0.993
1:29206800:G:T	A171D	0.993
1:29196232:C:T	G286E	0.992
1:29206788:A:G	L175S	0.992
1:29206827:G:T	A162D	0.991
1:29216091:T:A	E107V	0.991

dbSNP variants (sampled 300 via entrez): RS1000016378 (1:29232164 A>C), RS1000141829 (1:29198266 TG>T,TGG), RS1000153670 (1:29186016 A>G), RS1000194742 (1:29180675 A>G), RS1000204303 (1:29207926 G>A), RS1000220318 (1:29182416 C>T), RS1000220986 (1:29180913 G>A), RS1000222474 (1:29226031 T>A), RS1000264341 (1:29223621 C>G), RS1000309883 (1:29216350 C>G), RS1000363566 (1:29176974 G>C), RS1000472568 (1:29212909 C>G,T), RS1000479729 (1:29176569 T>C,G), RS1000480497 (1:29218724 A>G), RS1000497013 (1:29192971 G>C)

Disease associations

OMIM: gene MIM:608205 | disease phenotypes: MIM:617282, MIM:620629

GenCC curated gene-disease

Disease	Classification	Inheritance
dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Leigh syndrome	Moderate	AR

Mondo (4): dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities (MONDO:0015003), optic atrophy 16 (MONDO:0957978), optic atrophy (MONDO:0003608), mitochondrial disease (MONDO:0044970)

Orphanet (2): MEPAN syndrome (Orphanet:508093), Mitochondrial disease (Orphanet:68380)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000505	Visual impairment
HP:0000514	Slow saccadic eye movements
HP:0000543	Optic disc pallor
HP:0000572	Visual loss
HP:0000580	Pigmentary retinopathy
HP:0000603	Central scotoma
HP:0000639	Nystagmus
HP:0000643	Blepharospasm
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0002015	Dysphagia
HP:0002059	Cerebral atrophy
HP:0002063	Rigidity
HP:0002072	Chorea
HP:0002194	Delayed gross motor development
HP:0002305	Athetosis

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003190_1	Schizophrenia	2.000000e-06
GCST006630_83	Diastolic blood pressure	1.000000e-11
GCST007277_1	Tourette syndrome	2.000000e-06
GCST010204_31	Low density lipoprotein cholesterol levels	2.000000e-08
GCST010536_11	Carotid plaque maximum area	1.000000e-06
GCST010537_9	Mean area of carotid plaque	5.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0006501	carotid plaque build

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, affects cotreatment, decreases expression	2
Air Pollutants	increases abundance, increases expression, affects expression, affects cotreatment	2
Ozone	increases expression, increases abundance, affects expression, affects cotreatment	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
GW 4064	affects cotreatment, decreases expression	1
GW 7647	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
jinfukang	increases expression	1
Decitabine	increases expression	1
Acrolein	increases abundance, affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cannabidiol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Isoniazid	increases expression	1
Methotrexate	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Thiram	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2BZ	HAP1 MECR (-) 2	Cancer cell line	Male
CVCL_E2C0	HAP1 MECR (-) 3	Cancer cell line	Male
CVCL_XQ39	HAP1 MECR (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01834079	PHASE1/PHASE2	UNKNOWN	Study the Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Optic Nerve Disease
NCT04680143	PHASE1/PHASE2	COMPLETED	Systemic Erythropoietin Injection in Patients Having Optic Atrophy
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT04580979	Not specified	COMPLETED	Natural History Study of FDXR Mutation-related Mitochondriopathy
NCT04594590	Not specified	COMPLETED	Natural History Study of SLC25A46 Mutation-related Mitochondriopathy
NCT04723160	Not specified	COMPLETED	Computer Aided Diagnosis of Multiple Eye Fundus Diseases From Color Fundus Photograph
NCT06390579	Not specified	COMPLETED	Building Research With Artificial Intelligence in Neuro-Ophthalmology