TAFAZZIN

Chr XXLR

tafazzin, phospholipid-lysophospholipid transacylase

Also known as: BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX, TAZ, Taz1

NCBI Gene: 6901ENSG00000102125UniProt: Q16635

This gene encodes a protein that is expressed at high levels in cardiac and skeletal muscle. Mutations in this gene have been associated with a number of clinical disorders including Barth syndrome, dilated cardiomyopathy (DCM), hypertrophic DCM, endocardial fibroelastosis, and left ventricular noncompaction (LVNC). Multiple transcript variants encoding different isoforms have been described. A long form and a short form of each of these isoforms is produced; the short form lacks a hydrophobic leader sequence and may exist as a cytoplasmic protein rather than being membrane-bound. Other alternatively spliced transcripts have been described but the full-length nature of all these transcripts is not known. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Barth syndromeMIM #302060
XLR
640
ClinVar variants
191
Pathogenic / LP
0.73
pLI score
0
Active trials
Clinical Summary— TAFAZZIN
🧬
Gene-Disease Validity (ClinGen)
Barth syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.73) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
191 Pathogenic / Likely Pathogenic· 215 VUS of 640 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.48LOEUF
pLI 0.726
Z-score 2.82
OE 0.15 (0.06–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.21Z-score
OE missense 0.44 (0.35–0.55)
54 obs / 122.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.15 (0.06–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.44 (0.35–0.55)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 2 / 13.0Missense obs/exp: 54 / 122.9Syn Z: 0.93

ClinVar Variant Classifications

640 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic140
Likely Pathogenic51
VUS215
Likely Benign207
Benign9
Conflicting18
140
Pathogenic
51
Likely Pathogenic
215
VUS
207
Likely Benign
9
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
1
121
0
140
Likely Pathogenic
23
13
14
1
51
VUS
6
145
58
6
215
Likely Benign
1
1
97
108
207
Benign
0
0
9
0
9
Conflicting
—18
Total48160299115640

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

View in ClinVar →

Protein Context — Lollipop Plot

TAFAZZIN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TAFAZZIN-related Barth syndrome

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Barth syndrome

MIM #302060

Molecular basis of disorder known

X-linked recessive
📖
GeneReview available — TAFAZZIN
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RNF213 loss-of-function promotes pathological angiogenesis in moyamoya disease via the Hippo pathway.
Ye F et al.·Brain
2023
Barth syndrome.
Clarke SL et al.·Orphanet J Rare Dis
2013Review
Barth syndrome.
Jefferies JL·Am J Med Genet C Semin Med Genet
2013Review
Left ventricular noncompaction.
Ichida F·Circ J
2009Review
Barth Syndrome: TAFAZZIN Gene, Cardiologic Aspects, and Mitochondrial Studies-A Comprehensive Narrative Review.
Sergi CM·Genes (Basel)
2025Review
Eponym: Barth syndrome.
Takeda A et al.·Eur J Pediatr
2011Review
The metabolic basis of inherited neutropenias.
Oyarbide U et al.·Br J Haematol
2024Review
Anomalous peroxidase activity of cytochrome c is the primary pathogenic target in Barth syndrome.
Kagan VE et al.·Nat Metab
2023
Cardiolipin Remodeling in Cardiovascular Diseases: Implication for Mitochondrial Dysfunction.
Zhang H et al.·Acta Physiol (Oxf)
2025Review
The lipid environment modulates cardiolipin and phospholipid constitution in wild type and tafazzin-deficient cells.
Oemer G et al.·J Inherit Metab Dis
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Case Report: Deletion in the 5' untranslated region of TAFAZZIN in a boy with Barth syndrome.
Singer ES et al.·Front Cardiovasc Med
2026🔓 Open AccessCase report
Pharmacological increases in circulating ketones fail to alleviate the hypertrophic cardiomyopathy present in the Tafazzin knockdown mouse model of Barth syndrome.
Shafaati T et al.·J Pharm Pharm Sci
2025🔓 Open AccessFunctional
Defective vascular smooth muscle cell tafazzin impairs mitochondrial function and promotes atherosclerosis in preclinical models.
Dong C et al.·Nat Commun
2025🔓 Open AccessFunctional
A novel TAFAZZIN gene variant c.525_533del causing Barth syndrome and leading to heart transplantation: a case report.
Krawiec M et al.·Front Pediatr
2025🔓 Open AccessCase report
Cardiac pathology in a patient with a novel pathogenic variant c.703del (p.Ile235SerfsTer4) of the TAFAZZIN gene.
Prasanpanich M et al.·Cardiovasc Pathol
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools