MECR

mitochondrial trans-2-enoyl-CoA reductase

Basic information

Region (hg38): 1:29192657-29230942

Links

ENSG00000116353 ∙ NCBI:51102 ∙ OMIM:608205 ∙ HGNC:19691 ∙ Uniprot:Q9BV79 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities (Strong), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities; Optic atrophy 16	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Neurologic; Ophthalmologic	27817865; 37734847

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MECR gene.

• not provided (17 variants)
• Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities (4 variants)
• Childhood Onset Dystonias;Optic atrophy (2 variants)
• Optic atrophy 16 (1 variants)
• Optic atrophy;Childhood Onset Dystonias (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MECR gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				90	1	91
missense	1	1	52	6	2	62
nonsense	7		1			8
start loss						0
frameshift	10					10
inframe indel						0
splice donor/acceptor (+/-2bp)		5				5
splice region			5	18		23
non coding			1	61	15	77
Total	18	6	54	157	18

Highest pathogenic variant AF is 0.0000657

Variants in MECR

This is a list of pathogenic ClinVar variants found in the MECR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-29194026-A-G			Uncertain significance (Jul 13, 2022)
1-29194027-T-C		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
1-29194030-T-C		MECR-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 13, 2024)
1-29194031-G-A			Likely benign (Dec 30, 2023)
1-29194040-C-T			Likely benign (Jan 08, 2024)
1-29194043-T-C			Likely benign (Aug 09, 2023)
1-29194051-T-G			Uncertain significance (Mar 18, 2022)
1-29194064-G-A			Likely benign (Sep 12, 2023)
1-29194067-G-T			Likely benign (Jan 20, 2024)
1-29194076-G-A			Likely benign (May 02, 2023)
1-29194082-C-T			Likely benign (Oct 09, 2023)
1-29194088-G-C			Uncertain significance (Jun 07, 2022)
1-29194090-C-T		Inborn genetic diseases	Uncertain significance (Apr 20, 2024)
1-29194097-C-A			Likely benign (Nov 30, 2023)
1-29194097-C-T			Likely benign (Oct 15, 2023)
1-29194122-G-A			Uncertain significance (Dec 03, 2019)
1-29194134-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 02, 2021)
1-29194135-G-A			Likely pathogenic (Aug 28, 2023)
1-29194136-G-A			Likely benign (May 07, 2023)
1-29194138-G-A			Uncertain significance (Jun 14, 2022)
1-29194142-G-A			Likely benign (Jan 21, 2024)
1-29194142-G-T			Likely benign (Jan 28, 2024)
1-29194148-G-A			Likely benign (Aug 02, 2023)
1-29194167-TC-AA			Uncertain significance (Aug 24, 2021)
1-29194175-C-T			Likely benign (Oct 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MECR	protein_coding	protein_coding	ENST00000263702	10	38070

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000223	0.980	125703	0	45	125748	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.111	214	219	0.979	0.0000120	2386
Missense in Polyphen		39	47.757	0.81664		559
Synonymous	-0.773	98	88.7	1.10	0.00000515	778
Loss of Function	2.09	11	21.5	0.512	0.00000117	211

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000548	0.000548
Ashkenazi Jewish	0.00	0.00
East Asian	0.000116	0.000109
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000144	0.000141
Middle Eastern	0.000116	0.000109
South Asian	0.000336	0.000327
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: 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. Has a preference for short and medium chain substrates, including trans-2-hexenoyl-CoA (C6), trans-2-decenoyl-CoA (C10), and trans- 2-hexadecenoyl-CoA (C16). {ECO:0000269|PubMed:18479707, ECO:0000269|PubMed:27817865}.
• Pathway: Fatty acid elongation - Homo sapiens (human);Long-chain-3-hydroxyacyl-coa dehydrogenase deficiency (LCHAD);Fatty Acid Elongation In Mitochondria;Fatty Acid Biosynthesis;Liver steatosis AOP;Metabolism of lipids;Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA;mitochondrial fatty acid beta-oxidation of saturated fatty acids;Mitochondrial Fatty Acid Beta-Oxidation;Saturated fatty acids beta-oxidation;Metabolism;Fatty acid metabolism (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.870
• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.63

Haploinsufficiency Scores

• pHI: 0.416
• hipred: N
• hipred_score: 0.443
• ghis: 0.422

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0583

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mecr

Gene ontology

• Biological process: fatty acid metabolic process;fatty acid biosynthetic process;fatty acid beta-oxidation
• Cellular component: nucleus;mitochondrion;mitochondrial matrix
• Molecular function: trans-2-enoyl-CoA reductase (NADPH) activity