PRELID1

Chr 5

PRELI domain containing 1

Also known as: CGI-106, PRELI, PX19, SBBI12

NCBI Gene: 27166 ENSG00000169230 UniProt: Q9Y255

The encoded protein functions as a phosphatidic acid transporter in mitochondria that regulates cardiolipin accumulation and modulates the mitochondrial apoptotic pathway. Mutations cause autosomal recessive neurodegeneration with brain atrophy, characterized by early-onset developmental delay, seizures, and progressive neurological decline. The gene shows moderate constraint against loss-of-function variants, and the condition primarily affects the central nervous system with onset typically in infancy or early childhood.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the late embryogenesis abundant motif-containing protein family. The encoded protein is localized to mitochondria and may function as a cytoprotectant by regulating cell death and differentiation. Alternative splicing results in multiple transcript variants encoding different isoforms. Several related pseudogenes have been identified. [provided by RefSeq, Nov 2012]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.67

Clinical Summary— PRELID1

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

📋

ClinVar Variants

20 VUS of 31 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.67LOEUF

pLI 0.115

Z-score 2.44

OE 0.29 (0.14–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.26Z-score

OE missense 0.69 (0.58–0.82)

88 obs / 128.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.14–0.67)

0≤0.351.4

Missense OE?0.69 (0.58–0.82)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 4 / 13.8Missense obs/exp: 88 / 128.2Syn Z: 1.10

This gene — mechanism propensity

0.7326th %ile

GOF

0.78top 25%

LOF

0.3454th %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

31 submitted variants in ClinVar

ClinVar

Classification Summary

VUS20

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	20	20
Likely Benign	1	1
Benign	0	0
Total	21	21

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

View in ClinVar →

61 pathogenic / likely-pathogenic (of 70) ClinVar copy-number / structural variants overlap PRELID1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →