SERAC1

Chr 6AR

serine active site containing 1

NCBI Gene: 84947ENSG00000122335UniProt: Q96JX3

The protein encoded by this gene is a phosphatidylglycerol remodeling protein found at the interface of mitochondria and endoplasmic reticula, where it mediates phospholipid exchange. The encoded protein plays a major role in mitochondrial function and intracellular cholesterol trafficking. Defects in this gene are a cause of 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL). Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Aug 2012]

Primary Disease Associations & Inheritance

3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndromeMIM #614739
AR
529
ClinVar variants
88
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SERAC1
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
88 Pathogenic / Likely Pathogenic· 171 VUS of 529 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.63LOEUF
pLI 0.000
Z-score 3.39
OE 0.41 (0.28–0.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.49Z-score
OE missense 0.78 (0.70–0.86)
278 obs / 357.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.41 (0.28–0.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.70–0.86)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 16 / 38.8Missense obs/exp: 278 / 357.3Syn Z: 1.49

ClinVar Variant Classifications

529 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic32
VUS171
Likely Benign204
Benign51
Conflicting15
56
Pathogenic
32
Likely Pathogenic
171
VUS
204
Likely Benign
51
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
1
43
0
56
Likely Pathogenic
14
6
12
0
32
VUS
5
137
25
4
171
Likely Benign
1
10
120
73
204
Benign
0
3
45
3
51
Conflicting
—15
Total3215724580529

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SERAC1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SERAC1-related 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

MIM #614739

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SERAC1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SERAC1 is a component of the mitochondrial serine transporter complex required for the maintenance of mitochondrial DNA.
Fang H et al.·Sci Transl Med
2022
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre.
Pronicka E et al.·J Transl Med
2016
[Two cases of MEGDEL syndrome due to variants of SERAC1 gene and a literature review].
Lin X et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2023Review
Mendelian non-syndromic and syndromic hearing loss genes contribute to presbycusis.
Cornejo-Sanchez DM et al.·Eur J Hum Genet
2025
Genome-wide CRISPR-Cas9 screens identify BCL family members as modulators of response to regorafenib in experimental glioma.
Haeusser LA et al.·Neuro Oncol
2025
Inborn errors of metabolism in the biosynthesis and remodelling of phospholipids.
Wortmann SB et al.·J Inherit Metab Dis
2015Review
Identification of Novel Mosaic Variants in Focal Epilepsy-Associated Patients' Brain Lesions.
Garcia CAB et al.·Genes (Basel)
2025Cohort
SERAC1 deficiency causes complicated HSP: evidence from a novel splice mutation in a large family.
Roeben B et al.·J Med Genet
2018
Hepatic histologic findings in a case of MEGDHEL syndrome due to SERAC1 deficiency.
Yuen L et al.·Am J Med Genet A
2022Case report
Hearing rehabilitation in SERAC1 related MEGD(H)EL syndrome - implications from a multi-center retrospective cohort study.
Roesch S et al.·Mol Genet Metab
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools