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.

not_specified (39 variants)
not_provided (3 variants)
Combined_oxidative_phosphorylation_deficiency_57 (3 variants)

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. These statistics are base on transcript: NM_000019095.6. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar		3
missense	3 clinvar		37 clinvar	2 clinvar		42
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	3	0	37	5	0

Highest pathogenic variant AF is 0.0000075787016

Loading clinvar variants...

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