CHCHD3

Summary

CHCHD3 (coiled-coil-helix-coiled-coil-helix domain containing 3, HGNC:21906) is a protein-coding gene on chromosome 7q32.3-q33, encoding MICOS complex subunit MIC19 (Q9NX63). Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. It is a selective cancer dependency (DepMap: 17.0% of cell lines).

The protein encoded by this gene is an inner mitochondrial membrane scaffold protein. Absence of the encoded protein affects the structural integrity of mitochondrial cristae and leads to reductions in ATP production, cell growth, and oxygen consumption. This protein is part of the mitochondrial contact site and cristae organizing system (MICOS). Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 54927 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 54 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 17.0% of screened cell lines
• MANE Select transcript: NM_017812

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21906
Approved symbol	CHCHD3
Name	coiled-coil-helix-coiled-coil-helix domain containing 3
Location	7q32.3-q33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20420, MINOS3, PPP1R22, Mic19, MICOS19
Ensembl gene	ENSG00000106554
Ensembl biotype	protein_coding
OMIM	613748
Entrez	54927

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000262570, ENST00000423635, ENST00000448878, ENST00000457942, ENST00000481152, ENST00000496427, ENST00000856659, ENST00000856660, ENST00000856661, ENST00000856662, ENST00000856663, ENST00000935578, ENST00000935579, ENST00000969750

RefSeq mRNA: 3 — MANE Select: NM_017812 NM_001317177, NM_001317178, NM_017812

CCDS: CCDS5828, CCDS87549

Canonical transcript exons

ENST00000262570 — 8 exons

Exon	Start	End
ENSE00001174753	133081857	133082090
ENSE00001261321	132784870	132785660
ENSE00003467866	133024546	133024627
ENSE00003528924	133070142	133070229
ENSE00003539285	132796442	132796577
ENSE00003586778	132975169	132975286
ENSE00003587797	132885662	132885745
ENSE00003607925	132838399	132838469

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.7013 / max 276.5269, expressed in 1824 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86300	43.5212	1824
86299	4.0342	1597
86298	0.1459	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
quadriceps femoris	UBERON:0001377	99.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.08	gold quality
gastrocnemius	UBERON:0001388	98.00	gold quality
muscle of leg	UBERON:0001383	97.99	gold quality
skeletal muscle organ	UBERON:0014892	97.99	gold quality
skeletal muscle tissue	UBERON:0001134	97.87	gold quality
heart left ventricle	UBERON:0002084	97.00	gold quality
apex of heart	UBERON:0002098	96.61	gold quality
cardiac atrium	UBERON:0002081	96.26	gold quality
right atrium auricular region	UBERON:0006631	96.26	gold quality
heart	UBERON:0000948	96.21	gold quality
muscle tissue	UBERON:0002385	96.02	gold quality
duodenum	UBERON:0002114	95.61	gold quality
ganglionic eminence	UBERON:0004023	95.53	gold quality
embryo	UBERON:0000922	95.52	gold quality
rectum	UBERON:0001052	95.34	gold quality
islet of Langerhans	UBERON:0000006	95.32	gold quality
ventricular zone	UBERON:0003053	95.24	gold quality
calcaneal tendon	UBERON:0003701	94.49	gold quality
adult mammalian kidney	UBERON:0000082	94.27	gold quality
smooth muscle tissue	UBERON:0001135	93.95	gold quality
stromal cell of endometrium	CL:0002255	93.82	gold quality
kidney	UBERON:0002113	93.64	gold quality
mucosa of transverse colon	UBERON:0004991	93.20	gold quality
cortical plate	UBERON:0005343	93.01	gold quality
placenta	UBERON:0001987	92.96	gold quality
popliteal artery	UBERON:0002250	92.94	gold quality
tibial artery	UBERON:0007610	92.94	gold quality
colon	UBERON:0001155	92.87	gold quality
corpus callosum	UBERON:0002336	92.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting CHCHD3, 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-4795-3P	100.00	74.62	4024
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-3191-5P	99.24	66.52	1722

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• mitofilin helps regulate mitochondrial morphology and at least four of the associated proteins (metaxins 1 and 2, SAM50 and CHCHD3) have been implicated in protein import (PMID:17624330)
• ChChd3 is a scaffolding protein that stabilizes protein complexes involved in maintaining crista architecture and protein import and is thus essential for maintaining mitochondrial structure and function. (PMID:21081504)
• both the myristoylation and the CHCH domain are essential for the import and mitochondrial localization of ChChd3. Once imported, ChChd3 binds to Mia40 for further folding and assembly into macromolecular complexes. (PMID:23019327)
• The findings suggest that Mic19 is a redox-dependent regulator of mitochondrial contact site and crista organizing system complex function. (PMID:26416881)
• Sub-mitochondrial localization of the genetic-tagged mitochondrial intermembrane space-bridging components Mic19, Mic60 and Sam50. (PMID:28808085)
• Sam50-Mic19-Mic60 axis determines mitochondrial cristae architecture by mediating mitochondrial outer and inner membrane contact. (PMID:31097788)
• Multicolor 3D MINFLUX nanoscopy of mitochondrial MICOS proteins. (PMID:32788360)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	chchd3a	ENSDARG00000032919
danio_rerio	chchd3b	ENSDARG00000034933
mus_musculus	Chchd3	ENSMUSG00000053768
rattus_norvegicus	Chchd3	ENSRNOG00000013211
caenorhabditis_elegans		WBGENE00010942

Paralogs (1): CHCHD6 (ENSG00000159685)

Protein

Protein identifiers

MICOS complex subunit MIC19 — Q9NX63 (reviewed: Q9NX63)

Alternative names: Coiled-coil-helix-coiled-coil-helix domain-containing protein 3

All UniProt accessions (5): Q9NX63, A0A286YEX5, A4D1N4, C9JRZ6, F8WAR4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Plays an important role in the maintenance of the MICOS complex stability and the mitochondrial cristae morphology. Has also been shown to function as a transcription factor which binds to the BAG1 promoter and represses BAG1 transcription.

Subunit / interactions. Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and MICOS13/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex. Interacts with HSPA1A/HSPA1B and OPA1, preferentially with the soluble OPA1 form. Interacts with IMMT/MIC60. (Microbial infection) Interacts with human cytomegalovirus protein UL13; this interaction alters cristae architecture.

Subcellular location. Mitochondrion inner membrane. Cytoplasm. Nucleus. Mitochondrion.

Tissue specificity. Detected at low levels in brain, placenta, lung, liver, kidney and pancreas with increased levels in heart and skeletal muscle. Higher expression in primary lung cancers than in normal lung tissue.

Similarity. Belongs to the MICOS complex subunit Mic19 family. Metazoan Mic19 subfamily.

RefSeq proteins (3): NP_001304106, NP_001304107, NP_060282* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007964	MIC19/MIC25	Family
IPR052632	MICOS_subunit_Mic19	Family

Pfam: PF05300

UniProt features (17 total): modified residue 6, disulfide bond 2, region of interest 2, short sequence motif 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NX63-F1	85.73	0.63

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 (7): 50, 56, 58, 142, 2, 29, 49

Disulfide bonds (2): 183–214, 193–204

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-8949613	Cristae formation
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-9609507	Protein localization

MSigDB gene sets: 195 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_CRISTAE_FORMATION, GNF2_RRM1, MYOD_01, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, GOCC_MITOCHONDRIAL_ENVELOPE, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, MYOD_Q6, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_MITOCHONDRIAL_FUSION, TCCAGAG_MIR518C, FISCHER_DREAM_TARGETS, RFX1_02, GOBP_MEMBRANE_ORGANIZATION

GO Biological Process (3): inner mitochondrial membrane organization (GO:0007007), mitochondrial fusion (GO:0008053), cristae formation (GO:0042407)

GO Molecular Function (3): phosphatase binding (GO:0019902), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (10): SAM complex (GO:0001401), nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial crista junction (GO:0044284), MICOS complex (GO:0061617), extracellular exosome (GO:0070062), MIB complex (GO:0140275), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Protein localization	1
Mitochondrial biogenesis	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
intracellular membrane-bounded organelle	2
inner mitochondrial membrane protein complex	2
cellular anatomical structure	2
mitochondrial membrane organization	1
mitochondrion organization	1
organelle fusion	1
inner mitochondrial membrane organization	1
enzyme binding	1
molecular_function	1
mitochondrial outer membrane translocase complex	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial inner membrane	1
organelle membrane contact site	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHCHD3	IMMT	Q16891	998
CHCHD3	MICOS10	Q5TGZ0	994
CHCHD3	APOOL	Q6UXV4	993
CHCHD3	SAMM50	Q9Y512	986
CHCHD3	APOO	Q9BUR5	985
CHCHD3	MICOS13	Q5XKP0	984
CHCHD3	CHCHD6	Q9BRQ6	983
CHCHD3	CHCHD5	Q9BSY4	812
CHCHD3	MTX1	Q13505	785
CHCHD3	DNAJC11	Q9NVH1	782
CHCHD3	MTX2	O75431	756
CHCHD3	CHCHD10	Q8WYQ3	751
CHCHD3	DNM1L	O00429	724
CHCHD3	TOMM40	O96008	624
CHCHD3	LETM1	O95202	582

IntAct

331 interactions, top by confidence:

A	B	Type	Score
SAMM50	CHCHD3	psi-mi:“MI:0915”(physical association)	0.780
CHCHD3	SAMM50	psi-mi:“MI:0915”(physical association)	0.780
BLZF1	CHCHD3	psi-mi:“MI:0915”(physical association)	0.720
FANCL	CHCHD3	psi-mi:“MI:0915”(physical association)	0.720
CHCHD3	BLZF1	psi-mi:“MI:0915”(physical association)	0.720
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
CHCHD10	IMMT	psi-mi:“MI:0915”(physical association)	0.600
IMMT	CHCHD10	psi-mi:“MI:0914”(association)	0.600
CHCHD3		psi-mi:“MI:0915”(physical association)	0.560
TRIM27	CHCHD3	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	CHCHD3	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	CHCHD3	psi-mi:“MI:0915”(physical association)	0.560
CHCHD3	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.560
PDE4DIP	CHCHD3	psi-mi:“MI:0915”(physical association)	0.560
CHCHD3	KRT40	psi-mi:“MI:0915”(physical association)	0.560
CHCHD3	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
CBY2	CHCHD3	psi-mi:“MI:0915”(physical association)	0.560
GMCL2	CHCHD3	psi-mi:“MI:0915”(physical association)	0.560
RPGRIP1	CHCHD3	psi-mi:“MI:0915”(physical association)	0.560
CHCHD3	RAB3IP	psi-mi:“MI:0915”(physical association)	0.560
SPAG5	CHCHD3	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	CHCHD3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (375): CHCHD3 (Two-hybrid), CHCHD3 (Two-hybrid), CHCHD3 (Two-hybrid), CHCHD3 (Two-hybrid), CHCHD3 (Two-hybrid), CHCHD3 (Two-hybrid), CHCHD3 (Two-hybrid), CHCHD3 (Two-hybrid), FANCL (Two-hybrid), RPGRIP1 (Two-hybrid), GMCL1P1 (Two-hybrid), CCDC33 (Two-hybrid), USHBP1 (Two-hybrid), LZTS2 (Two-hybrid), RAB3IP (Two-hybrid)

ESM2 similar proteins: B2RXB2, B5X3I1, C9JCN9, D4A7N1, D4A9E1, O75506, P58686, Q0P4J3, Q0VCF3, Q13503, Q2NKS9, Q3TY65, Q3ZC22, Q4R6N3, Q4V7L5, Q5E9D3, Q5EAU9, Q5FWT9, Q5R561, Q5R8J5, Q5RDI2, Q5RE46, Q5RGJ6, Q5ZKJ4, Q66H15, Q68EW7, Q6DF11, Q6ID77, Q6IP02, Q6P255, Q6TA25, Q7SYL1, Q7T338, Q8AVR2, Q8GW48, Q8K3X8, Q8R0H9, Q99LE1, Q9BRQ6, Q9BRV8

Diamond homologs: Q5E9D3, Q5FVV3, Q5U509, Q63ZW2, Q6AX41, Q9BRQ6, Q9CRB9, Q9NX63, D4A7N1, Q32L35, Q91VN4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKACA	unknown	CHCHD3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 132 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Cristae formation	8	36.4×	1e-08
Mitochondrial protein import	9	19.9×	9e-08
Mitochondrial biogenesis	7	15.5×	3e-05
Respiratory electron transport	6	7.5×	6e-03
Aerobic respiration and respiratory electron transport	6	7.0×	8e-03
Organelle biogenesis and maintenance	8	7.0×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
inner mitochondrial membrane organization	8	63.0×	2e-10
cristae formation	6	59.1×	2e-07
protein import into mitochondrial matrix	5	32.8×	7e-05
obsolete protein targeting to mitochondrion	5	27.1×	1e-04
endocytosis	8	7.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3776 predictions. Top by Δscore:

Variant	Effect	Δscore
7:132785657:TGCT:T	acceptor_gain	1.0000
7:132785659:CT:C	acceptor_gain	1.0000
7:132785661:C:CC	acceptor_gain	1.0000
7:132796437:CCTA:C	donor_loss	1.0000
7:132796438:CTAC:C	donor_loss	1.0000
7:132796439:TACCT:T	donor_loss	1.0000
7:132796441:C:CA	donor_loss	1.0000
7:132838392:AACTT:A	donor_loss	1.0000
7:132838393:ACTTA:A	donor_loss	1.0000
7:132838395:TTAC:T	donor_loss	1.0000
7:132838396:TACTT:T	donor_loss	1.0000
7:132838397:A:AC	donor_gain	1.0000
7:132838397:ACTTG:A	donor_loss	1.0000
7:132838398:C:CT	donor_gain	1.0000
7:132838400:TGA:T	donor_gain	1.0000
7:132841203:A:AC	donor_gain	1.0000
7:132841204:C:CC	donor_gain	1.0000
7:132885656:TCATA:T	donor_loss	1.0000
7:132885657:CATAC:C	donor_loss	1.0000
7:132885658:ATAC:A	donor_gain	1.0000
7:132885658:ATACC:A	donor_loss	1.0000
7:132885659:TACC:T	donor_loss	1.0000
7:132885660:A:T	donor_loss	1.0000
7:132885660:AC:A	donor_gain	1.0000
7:132885661:CC:C	donor_gain	1.0000
7:132885661:CCCT:C	donor_gain	1.0000
7:132885666:T:A	donor_gain	1.0000
7:132885741:CTAGC:C	acceptor_gain	1.0000
7:132885742:TAGC:T	acceptor_gain	1.0000
7:132885743:AGC:A	acceptor_gain	1.0000

AlphaMissense

1470 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:132796458:A:T	V215D	0.999
7:132796490:G:C	C204W	0.999
7:132796491:C:G	C204S	0.999
7:132796492:A:G	C204R	0.999
7:132796492:A:T	C204S	0.999
7:132796555:A:G	C183R	0.999
7:133070204:A:G	M36T	0.999
7:133070228:A:T	L28H	0.999
7:133081865:C:G	G25R	0.999
7:132796470:T:G	Y211S	0.998
7:132796471:A:C	Y211D	0.998
7:132796491:C:A	C204F	0.998
7:132796491:C:T	C204Y	0.998
7:132796524:C:G	C193S	0.998
7:132796525:A:G	C193R	0.998
7:132796525:A:T	C193S	0.998
7:132796553:A:C	C183W	0.998
7:132796554:C:G	C183S	0.998
7:132796554:C:T	C183Y	0.998
7:132796555:A:T	C183S	0.998
7:132838427:C:G	A166P	0.998
7:132838436:A:C	Y163D	0.998
7:133070228:A:G	L28P	0.998
7:133081865:C:A	G25C	0.998
7:132796470:T:C	Y211C	0.997
7:132796471:A:G	Y211H	0.997
7:132796479:G:T	A208D	0.997
7:132885672:A:G	L148P	0.997
7:133070207:C:G	R35P	0.997
7:133070216:A:T	V32E	0.997

dbSNP variants (sampled 300 via entrez): RS1000000290 (7:133006672 T>A), RS1000003611 (7:133021951 G>A,C), RS1000008546 (7:133029125 A>G), RS1000015571 (7:132958870 G>A,C), RS1000015579 (7:132833508 A>C,T), RS1000022582 (7:133019069 G>A), RS1000035899 (7:132868159 T>TA), RS1000055411 (7:132899156 C>T), RS1000066589 (7:132833894 T>C), RS1000099490 (7:132792548 G>A), RS1000107895 (7:132882038 T>C), RS1000133822 (7:132887281 T>A,C), RS1000142808 (7:132940521 G>A), RS1000151637 (7:133060060 A>G), RS1000155227 (7:132849504 G>A,C)

Disease associations

OMIM: gene MIM:613748 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004818_1	Intercellular adhesion molecule 1 (red blood cell fatty acid level interaction)	1.000000e-08
GCST006038_5	Food allergy	3.000000e-06
GCST006039_5	Peanut allergy	4.000000e-07
GCST007327_145	Smoking status (ever vs never smokers)	5.000000e-09
GCST007576_82	Chronotype	1.000000e-08
GCST008648_11	Urinary potassium excretion	7.000000e-09
GCST009391_1413	Metabolite levels	2.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004520	ICAM-1 measurement
EFO:0006809	docosapentaenoic acid measurement
EFO:0007016	food allergy measurement
EFO:0007017	peanut allergy measurement
EFO:0004318	smoking behavior
EFO:0008328	chronotype measurement
EFO:0009283	potassium measurement
EFO:0010451	aconitate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105877 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.84	Kd	14.41	nM	CHEMBL5653589
7.84	ED50	14.41	nM	CHEMBL5653589
7.57	Kd	27.14	nM	CHEMBL3752910
7.57	ED50	27.14	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 6 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148065: Binding affinity to human CHCHD3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0144	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148065: Binding affinity to human CHCHD3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0271	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, decreases expression	4
bisphenol A	decreases expression, increases expression, increases methylation	3
Benzo(a)pyrene	decreases expression	3
Valproic Acid	affects expression, increases expression	3
sodium arsenite	affects binding, increases reaction, increases abundance, increases expression	2
bisphenol S	increases expression, affects expression	2
Arsenic	increases abundance, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	increases abundance, increases expression	1
arsenite	affects binding, increases reaction	1
sodium bichromate	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Atrazine	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Tretinoin	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4012553	Binding	Binding affinity to MICOS complex subunit MIC19 in human INA-6 cells after 3 hrs by nanoLC-MS/MS method	Ugi Reaction-Derived α-Acyl Aminocarboxamides Bind to Phosphatidylinositol 3-Kinase-Related Kinases, Inhibit HSF1-Dependent Heat Shock Response, and Induce Apoptosis in Multiple Myeloma Cells. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2U9	Abcam HEK293T CHCHD3 KO	Transformed cell line	Female
CVCL_E0A4	Ubigene HeLa CHCHD3 KO	Cancer cell line	Female
CVCL_SI81	HAP1 CHCHD3 (-) 1	Cancer cell line	Male
CVCL_SI82	HAP1 CHCHD3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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