CHCHD1

Summary

CHCHD1 (coiled-coil-helix-coiled-coil-helix domain containing 1, HGNC:23518) is a protein-coding gene on chromosome 10q22.2, encoding Small ribosomal subunit protein mS37 (Q96BP2). It is a selective cancer dependency (DepMap: 70.9% of cell lines).

Enables RNA binding activity. Predicted to be involved in mitochondrial translation. Located in cytosol; mitochondrion; and nuclear lumen.

Source: NCBI Gene 118487 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 19 total
• Cancer dependency (DepMap): dependent in 70.9% of screened cell lines
• MANE Select transcript: NM_203298

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23518
Approved symbol	CHCHD1
Name	coiled-coil-helix-coiled-coil-helix domain containing 1
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25854, mS37
Ensembl gene	ENSG00000172586
Ensembl biotype	protein_coding
OMIM	608842
Entrez	118487

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000372833, ENST00000372837

RefSeq mRNA: 1 — MANE Select: NM_203298 NM_203298

CCDS: CCDS7334

Canonical transcript exons

ENST00000372833 — 3 exons

Exon	Start	End
ENSE00001184105	73782323	73782441
ENSE00001184112	73783074	73783652
ENSE00001184116	73782048	73782199

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 95.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.3196 / max 441.0488, expressed in 1826 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105548	59.3196	1826

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.97	gold quality
palpebral conjunctiva	UBERON:0001812	95.18	gold quality
right adrenal gland	UBERON:0001233	94.76	gold quality
right adrenal gland cortex	UBERON:0035827	94.37	gold quality
left adrenal gland	UBERON:0001234	94.33	gold quality
left adrenal gland cortex	UBERON:0035825	94.24	gold quality
oral cavity	UBERON:0000167	93.97	gold quality
ileal mucosa	UBERON:0000331	93.68	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.50	gold quality
colonic mucosa	UBERON:0000317	93.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.29	gold quality
esophagus mucosa	UBERON:0002469	93.28	gold quality
esophagus squamous epithelium	UBERON:0006920	93.18	gold quality
apex of heart	UBERON:0002098	93.16	gold quality
adult organism	UBERON:0007023	93.09	gold quality
lower esophagus mucosa	UBERON:0035834	93.00	gold quality
tibialis anterior	UBERON:0001385	92.96	gold quality
metanephros	UBERON:0000081	92.95	gold quality
biceps brachii	UBERON:0001507	92.92	gold quality
gastrocnemius	UBERON:0001388	92.85	gold quality
muscle of leg	UBERON:0001383	92.80	gold quality
gingiva	UBERON:0001828	92.74	gold quality
gingival epithelium	UBERON:0001949	92.68	gold quality
monocyte	CL:0000576	92.67	gold quality
corpus epididymis	UBERON:0004359	92.64	gold quality
leukocyte	CL:0000738	92.62	gold quality
adrenal cortex	UBERON:0001235	92.58	gold quality
parotid gland	UBERON:0001831	92.58	silver quality
heart left ventricle	UBERON:0002084	92.46	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.80
E-MTAB-7606	no	560.86
E-MTAB-6524	no	339.38
E-MTAB-7303	no	148.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting CHCHD1, 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-4533	100.00	69.48	2758
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-34C-3P	98.11	65.60	858
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-2682-3P	97.10	66.16	840
HSA-MIR-3152-5P	96.98	66.88	819
HSA-MIR-616-3P	96.82	66.99	784

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 70.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• C2360, a nuclear protein expressed in cytotrophoblasts, is a representative member of a multifamily of proteins, sharing a protein domain that is conserved in eukaryotes. (PMID:15177562)
• CHCHD1 mutations could not explain phenotype of patients with combined oxidative phosphorylation system deficiencies. (PMID:24137763)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	chchd1	ENSDARG00000029100
mus_musculus	Chchd1	ENSMUSG00000063787
rattus_norvegicus	Chchd1	ENSRNOG00000009297
drosophila_melanogaster	CG12848	FBGN0040666
caenorhabditis_elegans		WBGENE00016057

Protein

Protein identifiers

Small ribosomal subunit protein mS37 — Q96BP2 (reviewed: Q96BP2)

Alternative names: 28S ribosomal protein S37, mitochondrial, Coiled-coil-helix-coiled-coil-helix domain-containing protein 1, Nuclear protein C2360

All UniProt accessions (2): Q96BP2, A6NJX6

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Component of the mitochondrial small ribosomal subunit (mt-SSU). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins.

Subcellular location. Mitochondrion. Nucleus.

Similarity. Belongs to the mitochondrion-specific ribosomal protein mS37 family.

RefSeq proteins (1): NP_976043* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009069	Cys_alpha_HP_mot_SF	Homologous_superfamily
IPR010625	CHCH	Domain
IPR033620	Ribosomal_mS37_met	Family

Pfam: PF06747

UniProt features (10 total): helix 3, short sequence motif 2, disulfide bond 2, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

57 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7QI4	ELECTRON MICROSCOPY	2.21
7P2E	ELECTRON MICROSCOPY	2.4
8RRI	ELECTRON MICROSCOPY	2.4
9OLF	ELECTRON MICROSCOPY	2.46
9OJM	ELECTRON MICROSCOPY	2.5
6ZM6	ELECTRON MICROSCOPY	2.59
7QI5	ELECTRON MICROSCOPY	2.63
8ANY	ELECTRON MICROSCOPY	2.85
6ZM5	ELECTRON MICROSCOPY	2.89
8K2A	ELECTRON MICROSCOPY	2.9
9PGL	ELECTRON MICROSCOPY	2.9
7PO1	ELECTRON MICROSCOPY	2.92
7PO3	ELECTRON MICROSCOPY	2.92
9PGF	ELECTRON MICROSCOPY	2.93
6VMI	ELECTRON MICROSCOPY	2.96
6RW4	ELECTRON MICROSCOPY	2.97
6VLZ	ELECTRON MICROSCOPY	2.97
7QI6	ELECTRON MICROSCOPY	2.98
8QRN	ELECTRON MICROSCOPY	2.98
9PSM	ELECTRON MICROSCOPY	2.98
8OIS	ELECTRON MICROSCOPY	3
9HFM	ELECTRON MICROSCOPY	3
9UWH	ELECTRON MICROSCOPY	3
9PGI	ELECTRON MICROSCOPY	3.02
8QRM	ELECTRON MICROSCOPY	3.05
9PG8	ELECTRON MICROSCOPY	3.06
9PS7	ELECTRON MICROSCOPY	3.08
7PO2	ELECTRON MICROSCOPY	3.09
8OIR	ELECTRON MICROSCOPY	3.1
9HFO	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BP2-F1	92.51	0.81

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): 45–76, 55–66

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5368286	Mitochondrial translation initiation
R-HSA-5389840	Mitochondrial translation elongation
R-HSA-5419276	Mitochondrial translation termination
R-HSA-9937383	Mitochondrial ribosome-associated quality control

MSigDB gene sets: 95 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, WTGAAAT_UNKNOWN, GOCC_MITOCHONDRIAL_ENVELOPE, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, ACEVEDO_LIVER_CANCER_UP, GOCC_RIBOSOME, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, GOCC_SMALL_RIBOSOMAL_SUBUNIT, GOCC_ORGANELLAR_RIBOSOME, GOCC_MITOCHONDRIAL_MATRIX, GOCC_ORGANELLE_INNER_MEMBRANE

GO Biological Process (1): mitochondrial translation (GO:0032543)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (10): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial small ribosomal subunit (GO:0005763), cytosol (GO:0005829), nucleus (GO:0005634), mitochondrial ribosome (GO:0005761), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitochondrial translation	4

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
intracellular membrane-bounded organelle	2
mitochondrion	1
translation	1
mitochondrial gene expression	1
nucleic acid binding	1
binding	1
nucleolus	1
nuclear lumen	1
organelle inner membrane	1
mitochondrial membrane	1
organellar small ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1
organellar ribosome	1
mitochondrial matrix	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

2520 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHCHD1	MRPL47	Q9HD33	625
CHCHD1	PTCD3	Q96EY7	604
CHCHD1	A0A2R8YDH4	A0A2R8YDH4	580
CHCHD1	MRPL42	Q9Y6G3	525
CHCHD1	METTL17	Q9H7H0	519
CHCHD1	RTP2	Q5QGT7	491
CHCHD1	AURKAIP1	Q9NWT8	489
CHCHD1	GADD45GIP1	Q8TAE8	479
CHCHD1	TTLL1	O95922	473
CHCHD1	MTG1	Q9BT17	463
CHCHD1	ADAD1	Q96M93	458
CHCHD1	FASTKD1	Q53R41	447
CHCHD1	HTD2	P86397	446
CHCHD1	OXA1L	Q15070	442
CHCHD1	CPNE2	Q96FN4	419

IntAct

30 interactions, top by confidence:

A	B	Type	Score
CHCHD1	SDCBP2	psi-mi:“MI:0915”(physical association)	0.560
MESD	CHCHD1	psi-mi:“MI:0915”(physical association)	0.560
CHCHD1	rev	psi-mi:“MI:0915”(physical association)	0.560
CBY1	CFAP410	psi-mi:“MI:0914”(association)	0.510
rev	TMED10	psi-mi:“MI:0914”(association)	0.460
CHCHD1	RCN2	psi-mi:“MI:0914”(association)	0.350
CHCHD1	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
RBM39	RPS3A	psi-mi:“MI:0914”(association)	0.350
	GTPBP10	psi-mi:“MI:0914”(association)	0.350
	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
	SUPT5H	psi-mi:“MI:0914”(association)	0.350
	GTPBP1	psi-mi:“MI:0914”(association)	0.350
rev	MPG	psi-mi:“MI:0914”(association)	0.350
	EIF3F	psi-mi:“MI:0914”(association)	0.350
	RPS10-NUDT3	psi-mi:“MI:0914”(association)	0.350
	PHF20L1	psi-mi:“MI:0914”(association)	0.350
MRPL58		psi-mi:“MI:0914”(association)	0.350
	MRPL18	psi-mi:“MI:0915”(physical association)	0.320
CHCHD1	CBY1	psi-mi:“MI:0915”(physical association)	0.000
CHCHD1	SDCBP2	psi-mi:“MI:0915”(physical association)	0.000
CHCHD1	MESD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (248): CHCHD1 (Affinity Capture-MS), PPM1K (Affinity Capture-MS), NRD1 (Affinity Capture-MS), IDE (Affinity Capture-MS), CHCHD4 (Affinity Capture-MS), PMPCA (Affinity Capture-MS), CBY1 (Affinity Capture-MS), CHCHD1 (Affinity Capture-MS), CHCHD1 (Affinity Capture-MS), CHCHD1 (Affinity Capture-MS), CHCHD1 (Two-hybrid), CHCHD1 (Two-hybrid), AATF (Proximity Label-MS), ACAD9 (Proximity Label-MS), ACOT1 (Proximity Label-MS)

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: Q96BP2, Q9CQA6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CHCHD1	“form complex”	“28S mitochondrial small ribosomal subunit”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

274 predictions. Top by Δscore:

Variant	Effect	Δscore
10:73782218:G:GT	donor_gain	1.0000
10:73782233:G:GT	donor_gain	1.0000
10:73782195:GGGCG:G	donor_gain	0.9900
10:73782196:GGCGG:G	donor_gain	0.9900
10:73782240:GAGCA:G	donor_gain	0.9900
10:73782474:A:T	donor_gain	0.9900
10:73782197:GCG:G	donor_gain	0.9800
10:73782239:G:GT	donor_gain	0.9800
10:73782473:G:GT	donor_gain	0.9800
10:73782196:GGCG:G	donor_gain	0.9700
10:73782197:GCGG:G	donor_gain	0.9700
10:73782233:G:T	donor_gain	0.9700
10:73782197:G:T	donor_gain	0.9600
10:73782200:G:GG	donor_gain	0.9600
10:73782253:G:T	donor_gain	0.9500
10:73782321:A:AG	acceptor_gain	0.9500
10:73782322:G:C	acceptor_gain	0.9500
10:73782322:G:GG	acceptor_gain	0.9500
10:73782242:GCA:G	donor_gain	0.9400
10:73782322:GAGGC:G	acceptor_gain	0.9400
10:73782212:A:AG	donor_gain	0.9300
10:73782213:G:GG	donor_gain	0.9300
10:73782244:A:AG	donor_gain	0.9300
10:73782437:CTCAG:C	donor_loss	0.9300
10:73782438:TCAGG:T	donor_loss	0.9300
10:73782439:CAG:C	donor_loss	0.9300
10:73782440:AG:A	donor_loss	0.9300
10:73782441:GGT:G	donor_loss	0.9300
10:73782442:GTGAC:G	donor_loss	0.9300
10:73782443:T:C	donor_loss	0.9300

AlphaMissense

765 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:73782379:T:C	F61L	0.987
10:73782381:C:A	F61L	0.987
10:73782381:C:G	F61L	0.987
10:73782366:G:C	W56C	0.985
10:73782366:G:T	W56C	0.985
10:73782364:T:A	W56R	0.980
10:73782364:T:C	W56R	0.980
10:73782416:T:C	F73S	0.973
10:73782331:T:C	C45R	0.966
10:73782415:T:C	F73L	0.964
10:73782417:C:A	F73L	0.964
10:73782417:C:G	F73L	0.964
10:73782380:T:G	F61C	0.961
10:73782346:T:C	S50P	0.960
10:73782380:T:C	F61S	0.960
10:73782331:T:A	C45S	0.959
10:73782332:G:C	C45S	0.959
10:73782344:T:C	M49T	0.959
10:73782394:T:A	C66S	0.958
10:73782395:G:C	C66S	0.958
10:73782365:G:C	W56S	0.957
10:73783161:T:C	F111L	0.954
10:73783163:T:A	F111L	0.954
10:73783163:T:G	F111L	0.954
10:73782344:T:G	M49R	0.953
10:73782356:T:C	M53T	0.952
10:73782358:G:C	A54P	0.949
10:73782332:G:A	C45Y	0.948
10:73782395:G:A	C66Y	0.948
10:73782361:T:C	C55R	0.946

dbSNP variants (sampled 300 via entrez): RS1000729400 (10:73781508 A>G), RS1001097920 (10:73781165 A>G), RS1001631817 (10:73780309 TAAA>T,TA,TAA,TAAAA), RS1002900966 (10:73781832 G>A,C), RS1002922317 (10:73783478 G>A,C,T), RS1003492777 (10:73783719 G>A), RS1003715034 (10:73781865 C>A,G,T), RS1004549546 (10:73780701 C>T), RS1004582133 (10:73781020 G>A), RS1004980964 (10:73780239 G>T), RS1006148862 (10:73783823 G>T), RS1007822866 (10:73782104 T>G), RS1008158160 (10:73780741 G>C), RS1008943274 (10:73781017 C>T), RS1011029310 (10:73783610 C>T)

Disease associations

OMIM: gene MIM:608842 | 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
GCST004132_74	Crohn’s disease	2.000000e-09
GCST007656_13	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	2.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	3
bisphenol A	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nivalenol	decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
beta-Naphthoflavone	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Genistein	decreases expression, increases reaction	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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