HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CHCHD3
coiled-coil-helix-coiled-coil-helix domain containing 3
Chromosome 7 · 7q32.3-q33
NCBI Gene: 54927Ensembl: ENSG00000106554.13HGNC: HGNC:21906UniProt: A4D1N4
168PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingphosphatase bindingcristae formationmitochondrionneurodegenerative diseasesmoking initiationinsomniamathematical ability
✦AI Summary

CHCHD3 (coiled-coil-helix-coiled-coil-helix domain containing 3) is a peripheral protein of the mitochondrial inner membrane that faces the intermembrane space and serves as a crucial component of the MICOS (mitochondrial contact site and cristae organizing system) complex 1. The protein functions as a scaffolding protein that stabilizes protein complexes involved in maintaining crista architecture and protein import, interacting with mitofilin, OPA1, and Sam50 1. CHCHD3 is essential for maintaining crista integrity, mitochondrial fusion, and overall mitochondrial function 12. Loss of CHCHD3 results in fragmented mitochondria, reduced OPA1 protein levels, impaired mitochondrial fusion, abnormal crista morphology with reduced crista junction opening diameter, and severely restricted oxygen consumption and glycolytic rates 1. The protein undergoes myristoylation at its N-terminus and contains a CHCH domain that is essential for its import and mitochondrial localization 3. Age-related loss of MICOS complex components including CHCHD3 is associated with mitochondrial morphological changes during aging 4. CHCHD3 dysfunction has been implicated in various pathological conditions including congenital heart disease, particularly hypoplastic left heart syndrome 5, and kidney disease through mitochondrial dysfunction in podocytes 6.

Sources cited
1
CHCHD3 is a peripheral protein of the mitochondrial inner membrane, essential for maintaining crista integrity and mitochondrial function
PMID: 21081504
2
CHCHD3 undergoes myristoylation and contains a CHCH domain essential for its import and mitochondrial localization
PMID: 23019327
3
CHCHD3 is required for mitochondrial fusion and tissue growth in Drosophila development
PMID: 27317679
4
Age-related loss of MICOS complex components including CHCHD3 is associated with mitochondrial morphological changes during aging
PMID: 37960952
5
CHCHD3 dysfunction is implicated in hypoplastic left heart syndrome and cardiac contractility defects
PMID: 37404133
6
CHCHD3 deficiency leads to mitochondrial dysfunction and podocyte injury in kidney disease
PMID: 38250156
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
smoking initiationOpen Targets
0.40Weak
insomniaOpen Targets
0.39Weak
mathematical abilityOpen Targets
0.36Weak
intelligenceOpen Targets
0.29Weak
smoking cessationOpen Targets
0.28Weak
poisoningOpen Targets
0.26Weak
neuroendocrine neoplasmOpen Targets
0.26Weak
mixed connective tissue diseaseOpen Targets
0.25Weak
COVID-19Open Targets
0.24Weak
severe acute respiratory syndromeOpen Targets
0.24Weak
preeclampsiaOpen Targets
0.24Weak
ovarian dysfunctionOpen Targets
0.24Weak
cardiac transplantOpen Targets
0.18Weak
Peyronie diseaseOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
non-alcoholic steatohepatitisOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
cerebral atherosclerosisOpen Targets
0.04Suggestive
ocular hypotensionOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CHCHD2Protein interaction100%TOMM5Protein interaction100%NDUFS3Protein interaction100%CHCHD10Protein interaction99%TMEM11Protein interaction98%UQCRC2Protein interaction98%
Tissue Expression6 tissues
Heart
100%
Brain
35%
Lung
28%
Bone Marrow
25%
Ovary
18%
Liver
18%
Gene Interaction Network
Click a node to explore
CHCHD3CHCHD2TOMM5NDUFS3CHCHD10TMEM11UQCRC2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9NX63
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.87LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.56 [0.37–0.87]
RankingsWhere CHCHD3 stands among ~20K protein-coding genes
  • #2,644of 20,598
    Most Researched168 · top quartile
  • #7,648of 17,882
    Most Constrained (LOEUF)0.87
Genes detectedCHCHD3
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Loss of MTX2 causes mitochondrial dysfunction, podocyte injury, nephrotic proteinuria and glomerulopathy in mice and patients.
PMID: 38250156
Int J Biol Sci · 2024
1.00
2
3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex.
PMID: 37960952
Aging Cell · 2023
0.90
3
Cross-Talk Between Mitochondrial Fusion and the Hippo Pathway in Controlling Cell Proliferation During Drosophila Development.
PMID: 27317679
Genetics · 2016
0.80
4
Mitochondrial AR overactivation coupled with uterine decidual mitochondrial defects in PCOS-associated pregnancy loss.
PMID: 41543032
J Endocrinol · 2026
0.70
5
[Immuno-proteomic screening of human pancreatic cancer associated membrane antigens for early diagnosis].
PMID: 17403287
Zhonghua Wai Ke Za Zhi · 2007
0.68