CHCHD7

Summary

CHCHD7 (coiled-coil-helix-coiled-coil-helix domain containing 7, HGNC:28314) is a protein-coding gene on chromosome 8q12.1, encoding Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (Q9BUK0).

Predicted to be involved in mitochondrial respiratory chain complex assembly. Located in mitochondrion.

Source: NCBI Gene 79145 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 30 total — 1 likely-pathogenic
• MANE Select transcript: NM_001011671

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28314
Approved symbol	CHCHD7
Name	coiled-coil-helix-coiled-coil-helix domain containing 7
Location	8q12.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC2217, COX23
Ensembl gene	ENSG00000170791
Ensembl biotype	protein_coding
OMIM	611238
Entrez	79145

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 23 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000303759, ENST00000355315, ENST00000396723, ENST00000517636, ENST00000517933, ENST00000518169, ENST00000518801, ENST00000518944, ENST00000519367, ENST00000521524, ENST00000521831, ENST00000521982, ENST00000522166, ENST00000522366, ENST00000523061, ENST00000523532, ENST00000523667, ENST00000523975, ENST00000853105, ENST00000853106, ENST00000939671, ENST00000939672, ENST00000939673, ENST00000939674, ENST00000939675, ENST00000939676, ENST00000939677, ENST00000939678, ENST00000939679, ENST00000939680

RefSeq mRNA: 8 — MANE Select: NM_001011671 NM_001011667, NM_001011668, NM_001011669, NM_001011670, NM_001011671, NM_001317858, NM_001317859, NM_024300

CCDS: CCDS34895, CCDS34896, CCDS55232, CCDS55233, CCDS6166, CCDS83294

Canonical transcript exons

ENST00000355315 — 4 exons

Exon	Start	End
ENSE00002108253	56211789	56211837
ENSE00002121544	56217331	56218809
ENSE00003647672	56216433	56216531
ENSE00003669959	56214598	56214667

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.5429 / max 770.8726, expressed in 1815 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88932	31.5429	1815

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.72	gold quality
oocyte	CL:0000023	96.22	gold quality
monocyte	CL:0000576	95.04	gold quality
mononuclear cell	CL:0000842	94.89	gold quality
palpebral conjunctiva	UBERON:0001812	94.70	gold quality
leukocyte	CL:0000738	94.60	gold quality
calcaneal tendon	UBERON:0003701	94.25	gold quality
tendon	UBERON:0000043	94.17	gold quality
spleen	UBERON:0002106	93.73	gold quality
heart right ventricle	UBERON:0002080	93.69	gold quality
rectum	UBERON:0001052	93.36	gold quality
heart left ventricle	UBERON:0002084	93.18	gold quality
mucosa of transverse colon	UBERON:0004991	93.16	gold quality
cardiac ventricle	UBERON:0002082	93.14	gold quality
tendon of biceps brachii	UBERON:0008188	93.06	gold quality
parotid gland	UBERON:0001831	93.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.84	gold quality
lymph node	UBERON:0000029	92.72	gold quality
pituitary gland	UBERON:0000007	92.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.62	gold quality
right atrium auricular region	UBERON:0006631	92.61	gold quality
colonic epithelium	UBERON:0000397	92.53	gold quality
nucleus accumbens	UBERON:0001882	92.51	gold quality
islet of Langerhans	UBERON:0000006	92.46	gold quality
left ovary	UBERON:0002119	92.40	gold quality
adenohypophysis	UBERON:0002196	92.29	gold quality
ganglionic eminence	UBERON:0004023	92.22	gold quality
amniotic fluid	UBERON:0000173	92.20	gold quality
heart	UBERON:0000948	92.18	gold quality
body of pancreas	UBERON:0001150	92.11	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting CHCHD7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-7515	99.31	68.22	1795

Literature-anchored findings (GeneRIF, showing 2)

• CHCHD7 is a newly identified member of a ubiquitously expressed multifamily of proteins containing a conserved (coiled coil 1)-(helix 1)-(coiled coil 2)-(helix 2) domain; it has not been previously associated with neoplasia. (PMID:16736500)
• Molecular interactions guiding the protein recognition between Mia40 and the disulfide-reduced CHCHD5 and CHCHD7. (PMID:22842048)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chchd7	ENSDARG00000068156
mus_musculus	Chchd7	ENSMUSG00000042198
rattus_norvegicus	Chchd7	ENSRNOG00000031769

Protein

Protein identifiers

Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 — Q9BUK0 (reviewed: Q9BUK0)

All UniProt accessions (7): Q9BUK0, E5RFN2, E5RHM5, E5RII1, E5RJ08, E5RJ15, J3KPV1

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion intermembrane space.

Disease relevance. A chromosomal aberration involving CHCHD7 is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(6;8)(p21.3-22;q13) with PLAG1.

Similarity. Belongs to the CHCHD7 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9BUK0-1	1	yes
Q9BUK0-2	2
Q9BUK0-3	3
Q9BUK0-4	4
Q9BUK0-5	5

RefSeq proteins (8): NP_001011667, NP_001011668, NP_001011669, NP_001011670, NP_001011671, NP_001304787, NP_001304788, NP_077276 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009069	Cys_alpha_HP_mot_SF	Homologous_superfamily
IPR048280	COX6B-like	Family
IPR051040	COX23	Family

Pfam: PF02297

UniProt features (14 total): helix 3, splice variant 3, turn 2, short sequence motif 2, disulfide bond 2, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2LQT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUK0-F1	84.77	0.46

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 16–47, 26–37

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import

MSigDB gene sets: 231 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, FREAC2_01, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, HNF3ALPHA_Q6, NKX25_02, SP3_Q3, GOLDRATH_IMMUNE_MEMORY, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, AREB6_01, HNF1_Q6, FOXO4_01, FOXO1_01, FOXD3_01, NKX61_01, EVI1_05

GO Biological Process (1): mitochondrial respiratory chain complex assembly (GO:0033108)

GO Molecular Function (0):

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	1
mitochondrion organization	1
protein-containing complex assembly	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial envelope	1
organelle envelope lumen	1

Protein interactions and networks

STRING

1054 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHCHD7	PLAG1	Q6DJT9	946
CHCHD7	COA5	Q86WW8	755
CHCHD7	TCEA1	P23193	752
CHCHD7	COX17	Q14061	743
CHCHD7	COX11	Q9Y6N1	733
CHCHD7	SDR16C5	Q8N3Y7	721
CHCHD7	TMEM68	Q96MH6	686
CHCHD7	COX19	Q49B96	666
CHCHD7	TCEA3	O75764	650
CHCHD7	TCEA2	Q15560	649
CHCHD7	MTCP1	P56278	644
CHCHD7	CHCHD4	Q8N4Q1	642
CHCHD7	CELF2	O95319	631
CHCHD7	SCO1	O75880	627
CHCHD7	XKR4	Q5GH76	621

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CHCHD7	S100A6	psi-mi:“MI:0915”(physical association)	0.400
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): S100A6 (Affinity Capture-MS), CHCHD7 (Affinity Capture-RNA), RBPMS (Two-hybrid), CHCHD7 (Affinity Capture-RNA), CHCHD7 (Affinity Capture-MS), S100A6 (Affinity Capture-MS), CHCHD7 (Affinity Capture-MS), CHCHD7 (Positive Genetic), CHCHD7 (Affinity Capture-MS), CHCHD7 (Affinity Capture-RNA), CHCHD7 (Affinity Capture-RNA)

ESM2 similar proteins: A1CH57, A5DUN2, A6ZMQ6, A9ULB4, B3LM82, B5RTE0, C8ZF59, G2TRP6, P00429, P0CM70, P0CM71, P0CM86, P0CM87, P0CT19, P21976, P56277, P90789, Q02373, Q05809, Q0P451, Q0UWF1, Q17Q91, Q1DJH5, Q208S3, Q2M2S5, Q2TAP8, Q3E7A9, Q3E846, Q462Q7, Q4IAJ1, Q4R374, Q53CG4, Q5B4S6, Q6C4R1, Q6CIT9, Q6DD38, Q6FQX5, Q6INR6, Q75D94, Q7S4H6

Diamond homologs: A1CH57, P0CM70, P0CM71, P38824, Q0UWF1, Q1DJH5, Q208S3, Q28GG4, Q2TAP8, Q4IAJ1, Q5A884, Q5B4S6, Q6BKN1, Q6CF49, Q6CIT9, Q6FQX5, Q75D94, Q7S4H6, Q8K2Q5, Q8SPI2, Q9BUK0, Q17Q91

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

30 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	15
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253344	GRCh37/hg19 8q12.1(chr8:56405320-57358911)x1	Likely pathogenic

SpliceAI

816 predictions. Top by Δscore:

Variant	Effect	Δscore
8:56211835:GAGGT:G	donor_loss	1.0000
8:56211836:AGGT:A	donor_loss	1.0000
8:56211838:G:GA	donor_loss	1.0000
8:56211839:T:G	donor_loss	1.0000
8:56217312:T:G	acceptor_gain	1.0000
8:56217316:A:AG	acceptor_gain	1.0000
8:56217316:AAT:A	acceptor_gain	1.0000
8:56217317:A:G	acceptor_gain	1.0000
8:56217318:T:A	acceptor_gain	1.0000
8:56217318:T:G	acceptor_gain	1.0000
8:56211834:GGAG:G	donor_gain	0.9900
8:56211835:GAG:G	donor_gain	0.9900
8:56211835:GAGG:G	donor_gain	0.9900
8:56211838:G:GG	donor_gain	0.9900
8:56212889:GGTA:G	donor_gain	0.9900
8:56216431:A:G	acceptor_gain	0.9900
8:56217311:A:AG	acceptor_gain	0.9900
8:56217317:AT:A	acceptor_gain	0.9900
8:56217322:T:A	acceptor_gain	0.9900
8:56217325:A:AG	acceptor_gain	0.9900
8:56217328:C:G	acceptor_gain	0.9900
8:56217330:GA:G	acceptor_gain	0.9900
8:56217318:T:TA	acceptor_loss	0.9800
8:56217326:C:G	acceptor_gain	0.9800
8:56217326:CACA:C	acceptor_loss	0.9800
8:56217327:A:AG	acceptor_gain	0.9800
8:56217327:ACAG:A	acceptor_loss	0.9800
8:56217329:A:AG	acceptor_gain	0.9800
8:56217329:AGA:A	acceptor_loss	0.9800
8:56217330:G:GG	acceptor_gain	0.9800

AlphaMissense

560 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:56216531:G:C	W51C	0.989
8:56216531:G:T	W51C	0.989
8:56216529:T:A	W51R	0.988
8:56216529:T:C	W51R	0.988
8:56216454:T:A	C26S	0.975
8:56216455:G:C	C26S	0.975
8:56216530:G:C	W51S	0.975
8:56217351:A:C	R58S	0.971
8:56217351:A:T	R58S	0.971
8:56217396:A:C	R73S	0.969
8:56217396:A:T	R73S	0.969
8:56216521:G:C	R48P	0.968
8:56216526:T:C	F50L	0.967
8:56216528:C:A	F50L	0.967
8:56216528:C:G	F50L	0.967
8:56216487:T:A	C37S	0.966
8:56216488:G:C	C37S	0.966
8:56214659:T:A	C16S	0.964
8:56214660:G:C	C16S	0.964
8:56216454:T:C	C26R	0.959
8:56216517:T:A	C47S	0.956
8:56216518:G:C	C47S	0.956
8:56217350:G:C	R58T	0.956
8:56217380:C:A	P68H	0.956
8:56216519:C:G	C47W	0.954
8:56216518:G:A	C47Y	0.945
8:56216487:T:C	C37R	0.944
8:56214659:T:C	C16R	0.943
8:56216517:T:C	C47R	0.935
8:56217380:C:G	P68R	0.935

dbSNP variants (sampled 300 via entrez): RS1000404031 (8:56213827 A>T), RS1000413916 (8:56213611 T>C), RS1000876584 (8:56211873 G>T), RS1001043727 (8:56217813 G>A), RS1001392671 (8:56211090 C>A), RS1001825153 (8:56214360 C>T), RS1002426161 (8:56211486 C>T), RS1002455255 (8:56211596 C>G), RS1002586173 (8:56217948 G>C), RS1002631665 (8:56215376 A>C), RS1002805923 (8:56210214 C>T), RS1002963938 (8:56218297 A>G), RS1003164631 (8:56210542 G>A), RS1003379899 (8:56213374 G>A), RS1003534378 (8:56211565 A>G)

Disease associations

OMIM: gene MIM:611238 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000175_46	Height	7.000000e-08
GCST000176_3	Height	4.000000e-07
GCST002647_73	Height	2.000000e-41
GCST002702_59	Height	5.000000e-25
GCST008839_382	Height	1.000000e-53
GCST008839_454	Height	2.000000e-13
GCST010002_300	Refractive error	1.000000e-19
GCST010989_141	Body size at age 10	3.000000e-08
GCST90020028_302	Hip circumference adjusted for BMI	3.000000e-22

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Particulate Matter	decreases expression, decreases reaction, increases abundance, affects expression	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Arsenic	decreases expression, increases abundance, increases expression	2
Vehicle Emissions	decreases expression, decreases reaction, affects expression, increases abundance	2
Cisplatin	increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
cadmium sulfate	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	increases expression, affects cotreatment	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.