PRELID3A

Chr 18

PRELI domain containing 3A

Also known as: C18orf43, HFL-EDDG1, SLMO1

The PRELID3A protein transfers phosphatidic acid across the mitochondrial intermembrane space as part of a complex with TRIAP1, which is required for cardiolipin synthesis in the mitochondrial inner membrane. Mutations cause autosomal recessive mitochondrial complex IV deficiency, nuclear type 22, presenting with developmental delay, hypotonia, and metabolic acidosis. This gene shows low constraint to loss-of-function variation, consistent with recessive inheritance requiring biallelic mutations to cause disease.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
93
P/LP submissions
0%
P/LP missense
1.85
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryPRELID3A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
89 unique Pathogenic / Likely Pathogenic· 33 VUS of 130 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.85LOEUF
pLI 0.000
Z-score -0.77
OE 1.27 (0.801.85)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.46Z-score
OE missense 0.87 (0.721.04)
82 obs / 94.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.27 (0.801.85)
00.351.4
Missense OE0.87 (0.721.04)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 12 / 9.5Missense obs/exp: 82 / 94.5Syn Z: -0.41
DN
0.7229th %ile
GOF
0.78top 25%
LOF
0.3261th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

130 submitted variants in ClinVar

Classification Summary

Pathogenic86
Likely Pathogenic3
VUS33
Likely Benign1
86
Pathogenic
3
Likely Pathogenic
33
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
86
0
86
Likely Pathogenic
0
0
3
0
3
VUS
0
18
15
0
33
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total0181041123

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

View in ClinVar →

Protein Context — Lollipop Plot

PRELID3A · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found