MIEF1

protein-coding

mitochondrial elongation factor 1

Gene summary

Enables identical protein binding activity; mitochondrial large ribosomal subunit binding activity; and purine ribonucleotide binding activity. Involved in several processes, including mitochondrial large ribosomal subunit assembly; mitochondrion organization; and regulation of mitochondrion organization. Located in mitochondrial matrix and mitochondrial outer membrane. Implicated in optic atrophy. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

SMCR7L

MANE transcript

NM_019008.6

Inheritance

ClinVar variants

P:2U:73B:8

Top phenotype

Optic atrophy 14

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr22:39,499,432-39,518,132

External References & Databases

Ensembl (ENSG00000100335)

UniProt (L0R8F8, Q9NQG6)

Transcript & Mutation Effects

hg38 • Region Span ~18.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

optic atrophy 14LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0957824

Submitter: PanelApp Australia

optic atrophy 14LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0957824

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Optic atrophy 14AD

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 33632269

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MIEF1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 71

not providedTotal: 7

MIEF1-related conditionTotal: 6

Retinal dystrophyTotal: 4

Optic atrophy 14Total: 2

Optic atrophyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019008.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense	2 clinvar		72 clinvar	5 clinvar	1 clinvar	80
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	2	0	73	6	2	83

Highest pathogenic variant AF is 0.000021683507

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019008.6	RefSeq	NP_061881.2	4	MANE Select
ENST00000325301.7	Ensembl	ENSP00000327124.2	4	MANE Select
NM_001304564.2	RefSeq	NP_001291493.1	5	Standard
ENST00000402881.5	Ensembl	ENSP00000385110.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

mitochondrial fission
mitochondrial fusion
positive regulation of mitochondrial fission
positive regulation of protein targeting to membrane

Molecular Function

protein binding
GDP binding
identical protein binding
ADP binding

Cellular Component

mitochondrion
mitochondrial outer membrane
peroxisome
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000325301
Coding exons: 4
Length: 18701
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125748
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.816	246	285	0.864	0.0000189	2957
Missense (PolyPhen)		101	121.09	0.83409		1315
Synonymous	1.58	97	119	0.816	0.00000735	1018
Loss of Function	2.34	6	16.2	0.371	9.82e-7	170

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the regulation of mitochondrial fission mediated by DNM1L (PubMed:29083303). May play a role in ribosome biogenesis by preventing premature association of the 28S and 39S ribosomal subunits. {ECO:0000269|PubMed:29083303, ECO:0000305|PubMed:28892042}.;

Recessive Scores

pRec: 0.0999

Intolerance Scores

RVIS EVS: 0.42
RVIS percentile EVS: 77.16

Essentials

Essential (CRISPR): N
Essential (gene trap): N

Gene Damage Prediction

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