OPA1

Chr 3ARAD

OPA1 mitochondrial dynamin like GTPase

Also known as: BERHS, MGM1, MTDPS14, MTDPS14A, MTDPS14B, NPG, NTG, largeG

The protein encoded by this gene is a nuclear-encoded mitochondrial protein with similarity to dynamin-related GTPases. The encoded protein localizes to the inner mitochondrial membrane and helps regulate mitochondrial stability and energy output. This protein also sequesters cytochrome c. Mutations in this gene have been associated with optic atrophy type 1, which is a dominantly inherited optic neuropathy resulting in progressive loss of visual acuity, leading in many cases to legal blindness. [provided by RefSeq, Aug 2017]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Mitochondrial DNA depletion syndrome 14B (cardioencephalomyopathic type)MIM #616896
AR
{Glaucoma, normal tension, susceptibility to}MIM #606657
Behr syndromeMIM #210000
AR
Mitochondrial DNA depletion syndrome 14A (encephalomyopathic type)MIM #621481
AD
Optic atrophy 1MIM #165500
AD
Optic atrophy plus syndromeMIM #125250
AD
Optic atrophy 1MIM #165500
AD

Clinical highlights

Gene-disease validity (ClinGen)
Leigh syndrome · ARModerateconsider for supplementary testing2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
502
Pubs (1 yr)
P/LP submissions
P/LP missense
0.29
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — OPA1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.29LOEUF
pLI 0.986
Z-score 6.33
OE 0.18 (0.120.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.97Z-score
OE missense 0.76 (0.700.83)
411 obs / 540.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.18 (0.120.29)
00.351.4
Missense OE?0.76 (0.700.83)
00.61.4
Synonymous OE?0.94
01.21.6
LoF obs/exp: 13 / 70.3Missense obs/exp: 411 / 540.1Syn Z: 0.57

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

OPA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.