CRLS1

cardiolipin synthase 1

Basic information

Region (hg38): 20:6006093-6040053

Previous symbols: [ "C20orf155" ]

Links

ENSG00000088766 ∙ NCBI:54675 ∙ OMIM:608188 ∙ HGNC:16148 ∙ Uniprot:Q9UJA2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation deficiency 57 (Limited), mode of inheritance: AR
• combined oxidative phosphorylation deficiency 57 (Strong), mode of inheritance: AR
• combined oxidative phosphorylation deficiency 57 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 57	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Neurologic; Ophthalmologic	35147173

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRLS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRLS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense			22	2		24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	22	4	0

Variants in CRLS1

This is a list of pathogenic ClinVar variants found in the CRLS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-6006250-C-A		not specified	Uncertain significance (Dec 15, 2022)
20-6006262-G-A		not specified	Uncertain significance (Nov 09, 2024)
20-6006287-T-G		not specified	Uncertain significance (Oct 22, 2021)
20-6006295-G-T		not specified	Uncertain significance (Oct 29, 2024)
20-6006300-T-G			Likely benign (May 08, 2018)
20-6006308-C-T		not specified	Uncertain significance (Aug 02, 2021)
20-6006311-G-A		not specified	Uncertain significance (Oct 27, 2022)
20-6006320-C-G		not specified	Uncertain significance (May 21, 2024)
20-6006321-G-A			Likely benign (Mar 01, 2025)
20-6006331-C-A		not specified	Uncertain significance (Apr 17, 2024)
20-6006484-G-A		not specified	Uncertain significance (Oct 07, 2022)
20-6006485-C-T		not specified	Uncertain significance (Apr 06, 2023)
20-6006503-C-T		not specified	Uncertain significance (Mar 06, 2025)
20-6006512-C-T		not specified	Uncertain significance (Feb 15, 2023)
20-6006515-C-G		not specified	Likely benign (Mar 20, 2024)
20-6006524-A-G		not specified	Likely benign (Jan 31, 2022)
20-6006538-A-T		not specified	Uncertain significance (Nov 08, 2022)
20-6009794-T-A		Combined oxidative phosphorylation deficiency 57	Pathogenic (Jan 06, 2023)
20-6009797-C-T		not specified	Uncertain significance (Feb 05, 2024)
20-6009815-C-T		not specified	Uncertain significance (Mar 08, 2025)
20-6015380-G-A		not specified	Uncertain significance (Jun 06, 2023)
20-6015431-C-A		Combined oxidative phosphorylation deficiency 57	Pathogenic (Jan 06, 2023)
20-6031336-T-C		not specified	Uncertain significance (Jan 23, 2023)
20-6031359-C-T		Combined oxidative phosphorylation deficiency 57	Pathogenic (Jan 06, 2023)
20-6032069-T-C		not specified	Uncertain significance (Dec 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRLS1	protein_coding	protein_coding	ENST00000378863	7	33964

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00311	0.951	125715	0	19	125734	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.472	100	114	0.876	0.00000553	1876
Missense in Polyphen		38	46.265	0.82136		682
Synonymous	0.616	35	40.0	0.876	0.00000195	640
Loss of Function	1.74	6	12.7	0.472	7.60e-7	177

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000131	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the synthesis of cardiolipin (CL) (diphosphatidylglycerol) by specifically transferring a phosphatidyl group from CDP-diacylglycerol to phosphatidylglycerol (PG). CL is a key phospholipid in mitochondrial membranes and plays important roles in maintaining the functional integrity and dynamics of mitochondria under both optimal and stress conditions. {ECO:0000269|PubMed:16547353, ECO:0000269|PubMed:16678169}.
• Pathway: Glycerophospholipid metabolism - Homo sapiens (human);Phospholipid Biosynthesis;Acyl chain remodelling of PG;Metabolism of lipids;cardiolipin biosynthesis;Metabolism;Synthesis of CL;Glycerophospholipid biosynthesis;Phospholipid metabolism (Consensus)

Recessive Scores

• pRec: 0.138

Haploinsufficiency Scores

• pHI: 0.125
• hipred: N
• hipred_score: 0.267
• ghis: 0.470

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Crls1
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: cardiolipin biosynthetic process;phosphatidylglycerol acyl-chain remodeling;glycerophospholipid biosynthetic process;response to thyroxine;response to phosphatidylethanolamine
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of membrane
• Molecular function: 1-acylglycerol-3-phosphate O-acyltransferase activity;cardiolipin synthase activity;CDP-diacylglycerol-phosphatidylglycerol phosphatidyltransferase activity;2-acylglycerol-3-phosphate O-acyltransferase activity