CHCHD5

Summary

CHCHD5 (coiled-coil-helix-coiled-coil-helix domain containing 5, HGNC:17840) is a protein-coding gene on chromosome 2q14.1, encoding Coiled-coil-helix-coiled-coil-helix domain-containing protein 5 (Q9BSY4).

Predicted to be involved in cellular respiration. Located in mitochondrion.

Source: NCBI Gene 84269 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_032309

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17840
Approved symbol	CHCHD5
Name	coiled-coil-helix-coiled-coil-helix domain containing 5
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC11104, MIC14, MIX14
Ensembl gene	ENSG00000125611
Ensembl biotype	protein_coding
OMIM	616978
Entrez	84269

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000324913, ENST00000409719, ENST00000454841, ENST00000469030, ENST00000489052

RefSeq mRNA: 5 — MANE Select: NM_032309 NM_001304353, NM_001304354, NM_001371322, NM_001371323, NM_032309

CCDS: CCDS2098

Canonical transcript exons

ENST00000324913 — 4 exons

Exon	Start	End
ENSE00001939261	112584609	112584649
ENSE00003499772	112588866	112589040
ENSE00003616632	112585974	112586114
ENSE00003685904	112586200	112586365

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 94.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.8223 / max 168.6955, expressed in 1812 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21988	24.9557	1805
21987	7.0345	1781
21990	0.4405	209
21991	0.3580	174
21989	0.0337	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.73	gold quality
right testis	UBERON:0004534	94.61	gold quality
body of pancreas	UBERON:0001150	93.06	gold quality
apex of heart	UBERON:0002098	92.94	gold quality
adenohypophysis	UBERON:0002196	92.09	gold quality
testis	UBERON:0000473	92.08	gold quality
right lobe of liver	UBERON:0001114	91.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.21	gold quality
right adrenal gland	UBERON:0001233	91.12	gold quality
mucosa of transverse colon	UBERON:0004991	90.79	gold quality
right uterine tube	UBERON:0001302	90.71	gold quality
left adrenal gland cortex	UBERON:0035825	90.70	gold quality
left adrenal gland	UBERON:0001234	90.69	gold quality
monocyte	CL:0000576	90.59	gold quality
leukocyte	CL:0000738	90.44	gold quality
pituitary gland	UBERON:0000007	90.40	gold quality
body of stomach	UBERON:0001161	90.40	gold quality
left lobe of thyroid gland	UBERON:0001120	90.39	gold quality
right adrenal gland cortex	UBERON:0035827	90.29	gold quality
right lobe of thyroid gland	UBERON:0001119	90.02	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.98	gold quality
granulocyte	CL:0000094	89.95	gold quality
right atrium auricular region	UBERON:0006631	89.28	gold quality
gastrocnemius	UBERON:0001388	89.19	gold quality
thyroid gland	UBERON:0002046	89.18	gold quality
stromal cell of endometrium	CL:0002255	89.09	gold quality
metanephros cortex	UBERON:0010533	89.03	gold quality
muscle of leg	UBERON:0001383	88.81	gold quality
lower esophagus mucosa	UBERON:0035834	88.64	gold quality
esophagus mucosa	UBERON:0002469	88.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting CHCHD5, 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-4797-5P	99.39	68.01	1354
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6838-3P	98.40	65.88	559

Literature-anchored findings (GeneRIF, showing 4)

• Molecular interactions guiding the protein recognition between Mia40 and the disulfide-reduced CHCHD5 and CHCHD7. (PMID:22842048)
• There was a statistically significant association between rs3748024 and systolic blood pressure (SBP) under an additive model adjusted for age, gender and body mass index (BMI) after correction for multiple testing. The SNP was also significantly associated with BMI, obesity, and triglycerides. (PMID:28893745)
• CHTM1 is a novel metabolic marker that is important for the growth of tumorigenic cells under limiting nutrient supplies and thus, links cellular metabolism and tumorigenesis. (PMID:29371680)
• Study reports a novel function of CHTM1 via which CHTM1 alters lung cancer cell survival under metabolic-stress. For example, CHTM1 interacts with AIF1 and affects stress-induced cytosol/nuclear translocation of AIF1 as well as cell death. CHTM1 appears to mediate these effects by negatively regulating the p38 kinase. Also, CHTM1 is overexpressed in lung cancer patients. (PMID:31221176)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000091754
mus_musculus	Chchd5	ENSMUSG00000037938
rattus_norvegicus	Chchd5	ENSRNOG00000018491

Paralogs (1): COX19 (ENSG00000240230)

Protein

Protein identifiers

Coiled-coil-helix-coiled-coil-helix domain-containing protein 5 — Q9BSY4 (reviewed: Q9BSY4)

All UniProt accessions (3): Q9BSY4, A0A2U9EWT9, F8WC14

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion intermembrane space.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BSY4-1	1	yes
Q9BSY4-2	2

RefSeq proteins (4): NP_001291282, NP_001358251, NP_001358252, NP_115685* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010625	CHCH	Domain
IPR031731	CX9C	Domain
IPR052848	CHCH_domain-containing_protein	Family

Pfam: PF06747, PF16860

UniProt features (20 total): helix 6, disulfide bond 4, short sequence motif 4, domain 2, chain 1, splice variant 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2LQL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSY4-F1	67.33	0.00

Functional residue map

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

Post-translational modifications (1): 1

Disulfide bonds (4): 58–89, 68–79, 12–44, 22–34

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import

MSigDB gene sets: 78 (showing top): GGGNRMNNYCAT_UNKNOWN, CGGAARNGGCNG_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, WANG_RESPONSE_TO_BEXAROTENE_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, MCCABE_HOXC6_TARGETS_CANCER_DN, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_CELLULAR_RESPIRATION

GO Biological Process (1): cellular respiration (GO:0045333)

GO Molecular Function (1): protein binding (GO:0005515)

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
energy derivation by oxidation of organic compounds	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial envelope	1
organelle envelope lumen	1

Protein interactions and networks

STRING

482 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHCHD5	MICOS13	Q5XKP0	937
CHCHD5	APOO	Q9BUR5	857
CHCHD5	CHCHD6	Q9BRQ6	830
CHCHD5	CHCHD3	Q9NX63	812
CHCHD5	APOOL	Q6UXV4	805
CHCHD5	IMMT	Q16891	695
CHCHD5	CHCHD4	Q8N4Q1	571
CHCHD5	CHCHD10	Q8WYQ3	445
CHCHD5	ZGRF1	Q86YA3	417
CHCHD5	SAMM50	Q9Y512	400
CHCHD5	CD44	P16070	399
CHCHD5	ZNG1B	Q8IUF1	397
CHCHD5	RUNDC1	Q96C34	396
CHCHD5	NT5DC4	Q86YG4	370
CHCHD5	COX19	Q49B96	366

IntAct

13 interactions, top by confidence:

A	B	Type	Score
INCA1	CHCHD5	psi-mi:“MI:0915”(physical association)	0.560
CHCHD5	HCCS	psi-mi:“MI:0915”(physical association)	0.500
CHCHD5	NS	psi-mi:“MI:0915”(physical association)	0.370
NS2	CHCHD5	psi-mi:“MI:0915”(physical association)	0.370
NS	CHCHD5	psi-mi:“MI:0915”(physical association)	0.370
FUCA1	TIPRL	psi-mi:“MI:0914”(association)	0.350
CHCHD5	SUOX	psi-mi:“MI:0914”(association)	0.350
SLC25A25	HAX1	psi-mi:“MI:0914”(association)	0.350
CHCHD5	INCA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): CHCHD5 (Affinity Capture-MS), INCA1 (Two-hybrid), CHCHD5 (Affinity Capture-RNA), CDSN (Affinity Capture-MS), CHCHD5 (Affinity Capture-MS), CHCHD2 (Affinity Capture-MS), HCCS (Affinity Capture-MS), CCDC51 (Affinity Capture-MS), SUOX (Affinity Capture-MS), GFER (Affinity Capture-MS), KPRP (Affinity Capture-MS), CHCHD4 (Affinity Capture-MS), CHCHD5 (Affinity Capture-RNA), CHCHD5 (Affinity Capture-MS)

ESM2 similar proteins: A1L188, A2AMZ4, A2XK00, A7YY73, B4FGS2, B4FTR7, B8B624, C0HAV3, C5E268, G2TRP6, O13973, O75012, O95159, O95872, Q0VDN7, Q12894, Q28H71, Q2YDD3, Q3SZA2, Q3SZW4, Q3U0S6, Q3UJV1, Q49AH0, Q4G012, Q5FVV3, Q5U509, Q5U651, Q61858, Q6ASS9, Q6P0I6, Q756Q5, Q7S4Y4, Q7XAM0, Q7XK12, Q8BGD8, Q8BGX2, Q8CC36, Q8VED2, Q96BP2, Q96C34

Diamond homologs: Q9BSY4, Q9CQP3

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	0
Uncertain significance	21
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

478 predictions. Top by Δscore:

Variant	Effect	Δscore
2:112584647:GAT:G	donor_gain	1.0000
2:112584650:G:GG	donor_gain	1.0000
2:112585969:CACA:C	acceptor_loss	1.0000
2:112585971:CAG:C	acceptor_loss	1.0000
2:112585972:A:AG	acceptor_gain	1.0000
2:112585972:AG:A	acceptor_gain	1.0000
2:112585972:AGGC:A	acceptor_loss	1.0000
2:112585973:G:GG	acceptor_gain	1.0000
2:112585973:GG:G	acceptor_gain	1.0000
2:112585973:GGC:G	acceptor_gain	1.0000
2:112585973:GGCA:G	acceptor_gain	1.0000
2:112586086:A:G	donor_gain	1.0000
2:112586115:G:GG	donor_gain	1.0000
2:112586198:A:AG	acceptor_gain	1.0000
2:112586198:AG:A	acceptor_loss	1.0000
2:112586199:G:GG	acceptor_gain	1.0000
2:112586199:G:GT	acceptor_loss	1.0000
2:112586199:GCC:G	acceptor_gain	1.0000
2:112586199:GCCC:G	acceptor_gain	1.0000
2:112586199:GCCCA:G	acceptor_gain	1.0000
2:112586362:GGAG:G	donor_gain	1.0000
2:112586363:GAG:G	donor_gain	1.0000
2:112586363:GAGG:G	donor_gain	1.0000
2:112586366:G:GG	donor_gain	1.0000
2:112586366:GTA:G	donor_loss	1.0000
2:112586367:T:A	donor_loss	1.0000
2:112584645:GAGAT:G	donor_gain	0.9900
2:112584654:GTA:G	donor_gain	0.9900
2:112586119:G:GG	donor_gain	0.9900
2:112586199:GC:G	acceptor_gain	0.9900

AlphaMissense

710 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:112586061:G:C	W30C	0.998
2:112586061:G:T	W30C	0.998
2:112586313:T:C	F86S	0.996
2:112586313:T:G	F86C	0.996
2:112586006:G:A	C12Y	0.995
2:112586071:T:A	C34S	0.995
2:112586072:G:A	C34Y	0.995
2:112586072:G:C	C34S	0.995
2:112586229:G:A	C58Y	0.995
2:112586035:T:A	C22S	0.994
2:112586036:G:C	C22S	0.994
2:112586071:T:C	C34R	0.994
2:112586072:G:T	C34F	0.994
2:112586073:T:G	C34W	0.994
2:112586101:T:A	C44S	0.994
2:112586102:G:C	C44S	0.994
2:112586027:A:G	Y19C	0.993
2:112586230:T:G	C58W	0.993
2:112586005:T:A	C12S	0.992
2:112586006:G:C	C12S	0.992
2:112586007:T:G	C12W	0.992
2:112586228:T:C	C58R	0.992
2:112586312:T:C	F86L	0.992
2:112586314:C:A	F86L	0.992
2:112586314:C:G	F86L	0.992
2:112586006:G:T	C12F	0.991
2:112586035:T:C	C22R	0.991
2:112586217:T:C	I54T	0.991
2:112586026:T:G	Y19D	0.990
2:112586228:T:A	C58S	0.990

dbSNP variants (sampled 300 via entrez): RS1001414872 (2:112587377 C>T), RS1001879160 (2:112583695 T>C), RS1002100149 (2:112589291 AT>A,ATT), RS1003026306 (2:112589105 T>C), RS1003029284 (2:112582539 G>C), RS1003316878 (2:112584161 C>A,T), RS1003369270 (2:112584391 A>G,T), RS1003491099 (2:112582742 G>A), RS1003719233 (2:112588244 T>C), RS1004406536 (2:112583771 T>C), RS1004994777 (2:112585387 G>A), RS1005049312 (2:112585701 C>G), RS1005736161 (2:112588610 G>C), RS1005788630 (2:112588308 G>A), RS1005887382 (2:112588409 G>A)

Disease associations

OMIM: gene MIM:616978 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006914_18	Sleep duration	6.000000e-17
GCST007327_59	Smoking status (ever vs never smokers)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
zinc chromate	decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Doxorubicin	decreases expression	1
Ozone	affects expression, increases abundance	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Uranium	increases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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