CRLS1

Chr 20AR

cardiolipin synthase 1

Also known as: C20orf155, CLS, CLS1, COSPD57, GCD10, dJ967N21.6

The enzyme catalyzes the synthesis of cardiolipin, a critical phospholipid component of mitochondrial membranes essential for maintaining mitochondrial functional integrity and dynamics. Mutations cause combined oxidative phosphorylation deficiency 57, following an autosomal recessive inheritance pattern. The gene shows tolerance to loss-of-function variants (low constraint), which is consistent with the recessive disease mechanism.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 57MIM #620167
AR
0
Active trials
12
Pubs (1 yr)
33
P/LP submissions
9%
P/LP missense
0.93
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryCRLS1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 41 VUS of 91 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.93LOEUF
pLI 0.003
Z-score 1.74
OE 0.47 (0.260.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.47Z-score
OE missense 0.88 (0.741.03)
100 obs / 114.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.47 (0.260.93)
00.351.4
Missense OE0.88 (0.741.03)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 6 / 12.7Missense obs/exp: 100 / 114.2Syn Z: 0.62
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCRLS1-related mitochondrial disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.81top 10%
GOF
0.6444th %ile
LOF
0.2969th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

91 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic2
VUS41
Likely Benign6
31
Pathogenic
2
Likely Pathogenic
41
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
28
0
31
Likely Pathogenic
0
0
2
0
2
VUS
0
38
3
0
41
Likely Benign
0
2
1
3
6
Benign
0
0
0
0
0
Total04334380

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

View in ClinVar →

Protein Context — Lollipop Plot

CRLS1 · 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.

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Clinical Literature
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