TAFAZZIN

tafazzin, phospholipid-lysophospholipid transacylase

Basic information

Region (hg38): X:154411523-154421726

Previous symbols: [ "CMD3A", "EFE2", "EFE", "TAZ" ]

Links

ENSG00000102125 ∙ NCBI:6901 ∙ OMIM:300394 ∙ HGNC:11577 ∙ Uniprot:Q16635 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Barth syndrome (Definitive), mode of inheritance: XLR
• Barth syndrome (Definitive), mode of inheritance: XL
• Barth syndrome (Strong), mode of inheritance: XL
• Barth syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Barth syndrome (3-Methylglutaconic aciduria, type II)	XL	Allergy/Immunology/Infectious; Cardiovascular	Surveillance for cardiomyopathy and early medical treatment may reduce morbidity; in some individuals, early cardiac transplant may be necessary; Individuals can also have neutropenia, and prophylaxis against infections, with early and aggressive management of infections may be beneficial	Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	6142097; 2372897; 1998334; 1719174; 8434619; 8487269; 7616547; 8630491; 9332651; 9382097; 9382096; 9345098; 11238270; 11735032; 12468278; 12032589; 15098233; 7394203; 19648820; 20301486; 20812380; 22410210; 21987083

ClinVar

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

• 3-Methylglutaconic aciduria type 2 (338 variants)
• not provided (79 variants)
• Cardiovascular phenotype (54 variants)
• not specified (35 variants)
• Primary dilated cardiomyopathy (22 variants)
• Endocardial fibroelastosis (21 variants)
• Left ventricular noncompaction cardiomyopathy (13 variants)
• Cardiomyopathy (7 variants)
• 3-Methylglutaconic aciduria type 2;Primary dilated cardiomyopathy (3 variants)
• TAFAZZIN-related condition (2 variants)
• Primary familial dilated cardiomyopathy (1 variants)
• TAFAZZIN-Related Disorders (1 variants)
• Caused by mutation in the tafazzin gene (1 variants)
• Primary familial hypertrophic cardiomyopathy (1 variants)
• Left ventricular noncompaction (1 variants)
• Anemia, nonspherocytic hemolytic, due to G6PD deficiency (1 variants)
• Dilated cardiomyopathy 3B (1 variants)
• Dilated cardiomyopathy 1A (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TAFAZZIN 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		1	2	74	1	78
missense	4	19	112	7		142
nonsense	12	8	2	1		23
start loss			2			2
frameshift	14	6	3	1		24
inframe indel		1				1
splice donor/acceptor (+/-2bp)	5	13	3			21
splice region		1	16	13		30
non coding	1		9	43	7	60
Total	36	48	133	126	8

Variants in TAFAZZIN

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

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

Position	Type	Phenotype	Significance	ClinVar
X-154411725-G-G		Left ventricular noncompaction cardiomyopathy • Endocardial fibroelastosis • 3-Methylglutaconic aciduria type 2 • Dilated cardiomyopathy 3B	Benign (Jun 14, 2016)
X-154411756-G-C		Primary dilated cardiomyopathy • Left ventricular noncompaction cardiomyopathy • Endocardial fibroelastosis • 3-Methylglutaconic aciduria type 2	Benign/Likely benign (Jan 12, 2018)
X-154411792-C-T			Benign (Mar 03, 2015)
X-154411807-C-T		not specified	Likely benign (Sep 12, 2016)
X-154411825-G-C			Benign (Mar 03, 2015)
X-154411827-C-T		not specified	Likely benign (Mar 08, 2011)
X-154411840-G-A		Cardiovascular phenotype	Uncertain significance (May 31, 2022)
X-154411844-A-G		3-Methylglutaconic aciduria type 2	Uncertain significance (Aug 15, 2022)
X-154411846-G-A		3-Methylglutaconic aciduria type 2	Uncertain significance (Dec 09, 2023)
X-154411856-G-T		not specified • 3-Methylglutaconic aciduria type 2 • Cardiovascular phenotype	Uncertain significance (Jun 16, 2022)
X-154411861-G-T		3-Methylglutaconic aciduria type 2	Uncertain significance (Jul 09, 2021)
X-154411860-A-AGTGGC			Pathogenic (Nov 03, 2021)
X-154411867-G-T		3-Methylglutaconic aciduria type 2	Likely benign (Jan 17, 2024)
X-154411870-C-G		3-Methylglutaconic aciduria type 2 • Cardiovascular phenotype	Uncertain significance (Sep 06, 2022)
X-154411871-C-T		3-Methylglutaconic aciduria type 2	Uncertain significance (Nov 11, 2020)
X-154411872-C-G		Left ventricular noncompaction cardiomyopathy • 3-Methylglutaconic aciduria type 2	Uncertain significance (Aug 08, 2023)
X-154411873-C-T		3-Methylglutaconic aciduria type 2	Likely benign (May 12, 2021)
X-154411880-C-T		Cardiovascular phenotype • 3-Methylglutaconic aciduria type 2	Uncertain significance (Nov 05, 2023)
X-154411882-G-T		3-Methylglutaconic aciduria type 2	Likely benign (Sep 20, 2023)
X-154411884-C-A			Uncertain significance (Oct 27, 2022)
X-154411885-G-T		3-Methylglutaconic aciduria type 2	Likely benign (Mar 18, 2022)
X-154411888-C-T		3-Methylglutaconic aciduria type 2	Likely benign (Mar 13, 2023)
X-154411890-C-G		3-Methylglutaconic aciduria type 2	Uncertain significance (Nov 15, 2019)
X-154411891-C-G		not specified • 3-Methylglutaconic aciduria type 2 • Cardiovascular phenotype	Likely benign (Apr 19, 2023)
X-154411892-T-C		Endocardial fibroelastosis • Primary dilated cardiomyopathy • 3-Methylglutaconic aciduria type 2	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TAFAZZIN	protein_coding	protein_coding	ENST00000299328	11	10212

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.726	0.274	120450	0	1	120451	0.00000415

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.21	54	123	0.439	0.0000100	1924
Missense in Polyphen		7	38.842	0.18022		544
Synonymous	0.929	40	48.2	0.830	0.00000389	536
Loss of Function	2.82	2	13.0	0.154	8.98e-7	206

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000784	0.0000644
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Some isoforms may be involved in cardiolipin (CL) metabolism. {ECO:0000269|PubMed:12930833, ECO:0000269|PubMed:19164547}.
• Disease: DISEASE: Barth syndrome (BTHS) [MIM:302060]: An X-linked disease characterized by dilated cardiomyopathy with endocardial fibroelastosis, a predominantly proximal skeletal myopathy, growth retardation, neutropenia, and organic aciduria, particularly excess of 3-methylglutaconic acid. Additional features include hypertrophic cardiomyopathy, isolated left ventricular non- compaction, ventricular arrhythmia, motor delay, poor appetite, fatigue and exercise intolerance, hypoglycemia, lactic acidosis, hyperammonemia, and dramatic late catch-up growth after growth delay throughout childhood. {ECO:0000269|PubMed:11238270, ECO:0000269|PubMed:12032589, ECO:0000269|PubMed:9382096, ECO:0000269|PubMed:9382097}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycerophospholipid metabolism - Homo sapiens (human);Metabolism of lipids;Metabolism of proteins;Metabolism;Acyl chain remodeling of CL;Glycerophospholipid biosynthesis;Phospholipid metabolism;Mitochondrial protein import (Consensus)

Recessive Scores

• pRec: 0.193

Intolerance Scores

• loftool: 0.0874
• rvis_EVS: 0.08
• rvis_percentile_EVS: 59.76

Haploinsufficiency Scores

• pHI: 0.290
• hipred: Y
• hipred_score: 0.662
• ghis: 0.507

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.897

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Taz
• Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: taz
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: increased curvature

Gene ontology

• Biological process: muscle contraction;inner mitochondrial membrane organization;heart development;skeletal muscle tissue development;regulation of gene expression;hemopoiesis;cardiolipin biosynthetic process;mitochondrial respiratory chain complex I assembly;cardiolipin acyl-chain remodeling;cristae formation;mitochondrial ATP synthesis coupled electron transport;cardiac muscle tissue development;cardiac muscle contraction;positive regulation of cardiolipin metabolic process;positive regulation of ATP biosynthetic process
• Cellular component: nucleus;mitochondrion;mitochondrial inner membrane;cytosol;integral component of membrane
• Molecular function: 1-acylglycerol-3-phosphate O-acyltransferase activity;O-acyltransferase activity;1-acylglycerophosphocholine O-acyltransferase activity