DAP3

Summary

DAP3 (death associated protein 3, HGNC:2673) is a protein-coding gene on chromosome 1q22, encoding Small ribosomal subunit protein mS29 (P51398). As a component of the mitochondrial small ribosomal subunit, it plays a role in the translation of mitochondrial mRNAs.

Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that also participates in apoptotic pathways which are initiated by tumor necrosis factor-alpha, Fas ligand, and gamma interferon. This protein potentially binds ATP/GTP and might be a functional partner of the mitoribosomal protein S27. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. Pseudogenes corresponding to this gene are found on chromosomes 1q and 2q.

Source: NCBI Gene 7818 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Strong, GenCC)
• Clinical variants (ClinVar): 134 total — 5 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes
• MANE Select transcript: NM_004632

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2673
Approved symbol	DAP3
Name	death associated protein 3
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	MRPS29, DAP-3, MRP-S29, bMRP-10, MGC126058, MGC126059, DKFZp686G12159, mS29
Ensembl gene	ENSG00000132676
Ensembl biotype	protein_coding
OMIM	602074
Entrez	7818

Gene structure

Transcript identifiers

Ensembl transcripts: 104 — 95 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000343043, ENST00000368336, ENST00000421487, ENST00000461479, ENST00000462002, ENST00000462978, ENST00000463295, ENST00000463575, ENST00000465375, ENST00000466384, ENST00000470830, ENST00000471214, ENST00000471523, ENST00000471642, ENST00000475056, ENST00000476444, ENST00000477394, ENST00000479076, ENST00000479151, ENST00000490249, ENST00000491777, ENST00000496863, ENST00000497433, ENST00000497826, ENST00000535183, ENST00000608852, ENST00000878821, ENST00000878822, ENST00000878823, ENST00000878824, ENST00000878825, ENST00000878826, ENST00000878827, ENST00000878828, ENST00000878829, ENST00000878830, ENST00000878831, ENST00000878832, ENST00000878833, ENST00000878834, ENST00000878835, ENST00000878836, ENST00000878837, ENST00000878838, ENST00000878839, ENST00000878840, ENST00000878841, ENST00000878842, ENST00000878843, ENST00000878844, ENST00000878845, ENST00000878846, ENST00000878847, ENST00000878848, ENST00000878849, ENST00000878850, ENST00000878851, ENST00000878852, ENST00000878853, ENST00000878854, ENST00000878855, ENST00000919504, ENST00000919505, ENST00000919506, ENST00000919507, ENST00000919508, ENST00000919509, ENST00000919510, ENST00000919511, ENST00000919512, ENST00000919513, ENST00000919514, ENST00000919515, ENST00000919516, ENST00000919517, ENST00000919518, ENST00000919519, ENST00000919520, ENST00000919521, ENST00000919522, ENST00000919523, ENST00000919524, ENST00000919525, ENST00000919526, ENST00000919527, ENST00000919528, ENST00000919529, ENST00000919530, ENST00000919531, ENST00000919532, ENST00000919533, ENST00000972513, ENST00000972514, ENST00000972515, ENST00000972516, ENST00000972517, ENST00000972518, ENST00000972519, ENST00000972520, ENST00000972521, ENST00000972522, ENST00000972523, ENST00000972524, ENST00000972525

RefSeq mRNA: 5 — MANE Select: NM_004632 NM_001199849, NM_001199850, NM_001199851, NM_004632, NM_033657

CCDS: CCDS1120, CCDS55646, CCDS55647

Canonical transcript exons

ENST00000368336 — 13 exons

Exon	Start	End
ENSE00001836420	155738157	155739010
ENSE00002212101	155689091	155689174
ENSE00003703253	155729042	155729122
ENSE00003703630	155725927	155726019
ENSE00003703955	155717006	155717128
ENSE00003704378	155727608	155727738
ENSE00003705309	155709773	155709824
ENSE00003706555	155731356	155731415
ENSE00003707053	155729208	155729366
ENSE00003708963	155721517	155721618
ENSE00003710235	155725382	155725490
ENSE00003711341	155736946	155737063
ENSE00003791319	155731944	155732033

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.1610 / max 390.3891, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5633	73.1904	1827
5632	0.9706	607

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	97.66	gold quality
adrenal tissue	UBERON:0018303	97.60	gold quality
colonic epithelium	UBERON:0000397	97.37	gold quality
rectum	UBERON:0001052	97.26	gold quality
lymph node	UBERON:0000029	97.12	gold quality
lower esophagus mucosa	UBERON:0035834	97.09	gold quality
islet of Langerhans	UBERON:0000006	97.07	gold quality
granulocyte	CL:0000094	96.99	gold quality
apex of heart	UBERON:0002098	96.97	gold quality
pancreas	UBERON:0001264	96.96	gold quality
monocyte	CL:0000576	96.95	gold quality
buccal mucosa cell	CL:0002336	96.95	gold quality
adenohypophysis	UBERON:0002196	96.95	gold quality
right adrenal gland	UBERON:0001233	96.87	gold quality
heart left ventricle	UBERON:0002084	96.87	gold quality
skin of abdomen	UBERON:0001416	96.84	gold quality
right adrenal gland cortex	UBERON:0035827	96.84	gold quality
left adrenal gland	UBERON:0001234	96.81	gold quality
gastrocnemius	UBERON:0001388	96.81	gold quality
body of stomach	UBERON:0001161	96.79	gold quality
cardiac ventricle	UBERON:0002082	96.79	gold quality
leukocyte	CL:0000738	96.78	gold quality
mononuclear cell	CL:0000842	96.78	gold quality
left adrenal gland cortex	UBERON:0035825	96.78	gold quality
smooth muscle tissue	UBERON:0001135	96.77	gold quality
right atrium auricular region	UBERON:0006631	96.73	gold quality
skin of leg	UBERON:0001511	96.70	gold quality
adrenal gland	UBERON:0002369	96.70	gold quality
right lobe of liver	UBERON:0001114	96.66	gold quality
mucosa of transverse colon	UBERON:0004991	96.65	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	6.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ELK1, ESRRA

miRNA regulators (miRDB)

28 targeting DAP3, 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-126-5P	100.00	72.71	3180
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-660-5P	98.16	68.27	680
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-4772-3P	98.04	65.60	1203
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-6891-3P	95.80	65.76	683
HSA-MIR-4453	95.61	65.84	436
HSA-MIR-4538	95.61	65.34	449
HSA-MIR-4707-3P	86.55	62.02	99

Literature-anchored findings (GeneRIF, showing 21)

• Functional interaction between the pro-apoptotic DAP3 and the glucocorticoid receptor (PMID:12099703)
• not involved in TRAIL-induced apoptosis (PMID:12359235)
• DAP3 has a role in the molecular pathway that culminates in fragmented mitochondria (PMID:15175341)
• DAP3 gene might be associated with the mechanisms responsible for adult bronchial asthma and contribute to airway inflammation and remodeling (PMID:15179560)
• DAP3 has a role in anoikis signaling and in apoptosis induction caused by cell detachment (PMID:15302871)
• High DAP3 expression is correlated with thymoma stage (PMID:15679048)
• B4GALT3, DAP3, RGS16, TMEM183A and UCK2–were significantly overexpressed in dup(1q)-positive ALLs compared with high hyperdiploid ALLs without dup(1q). (PMID:17613536)
• study investigated the phosphorylation status of ribosomal DAP3 and mapped the phosphorylation sites by tandem mass spectrometry (PMID:18227431)
• Complex I and DAP3, hNOA1 may play a role in mitochondrial respiration and apoptosis. (PMID:19103604)
• DAP3 may participate in mitochondrial maintenance and play a role in the balance between mitochondrial homoeostasis and tumourigenesis in thyroid oncocytic tumors. (PMID:19536094)
• show that interferon-beta promoter stimulator 1 (IPS-1) binds DAP3 and induces anoikis by caspase activation. (PMID:19644511)
• identified a novel DAP3-binding protein termed death ligand signal enhancer (DELE); results demonstrated the biological significance of DELE for apoptosis signal mediated by death receptors (PMID:20563667)
• Study demonstrates an inverse association between DAP3 mRNA levels and tumour stage and clinical outcome in breast cancer. (PMID:22287761)
• Knockdown of DAP3 expression promoted cell migration. (PMID:24300973)
• DAP3 silencing contributes to breast carcinogenesis. (PMID:25738636)
• DAP3 plays important roles in mitochondrial function and dynamics (PMID:26306039)
• The present findings indicate that DAP3 deficiency-induced chemoresistance in gastric cancer is at least partially mediated through the beta-catenin/LGR5/Bcl-2 axis. (PMID:30792218)
• Suppression of adenosine-to-inosine (A-to-I) RNA editome by death associated protein 3 (DAP3) promotes cancer progression. (PMID:32596459)
• Expression of Death Associated Proteins DAP1 and DAP3 in Human Pancreatic Cancer. (PMID:33952460)
• Death associated protein3 (DAP3) and DAP3 binding cell death enhancer1 (DELE1) in human colorectal cancer, and their impacts on clinical outcome and chemoresistance. (PMID:36382667)
• DAP3 promotes mitochondrial activity and tumour progression in hepatocellular carcinoma by regulating MT-ND5 expression. (PMID:39080251)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dap3	ENSDARG00000078500
mus_musculus	Dap3	ENSMUSG00000068921
rattus_norvegicus	Dap3	ENSRNOG00000020373
drosophila_melanogaster	mRpS29	FBGN0034727
caenorhabditis_elegans		WBGENE00000933

Protein

Protein identifiers

Small ribosomal subunit protein mS29 — P51398 (reviewed: P51398)

Alternative names: 28S ribosomal protein S29, mitochondrial, Death-associated protein 3, Ionizing radiation resistance conferring protein

All UniProt accessions (13): P51398, V9GY11, V9GYA7, V9GYC9, V9GYF7, V9GYJ3, V9GYJ9, V9GYL4, V9GYL9, V9GYR8, V9GYW1, V9GZ03, V9GZ61

UniProt curated annotations — full annotation on UniProt →

Function. As a component of the mitochondrial small ribosomal subunit, it plays a role in the translation of mitochondrial mRNAs. Involved in mediating interferon-gamma-induced cell death. Displays GTPase activity in vitro.

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. Interacts with DELE1. Interacts with NOA1.

Subcellular location. Mitochondrion.

Tissue specificity. Ubiquitous.

Disease relevance. Perrault syndrome 7 (PRLTS7) [MIM:621101] A form of Perrault syndrome, a sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile. PRLTS7 inheritance is autosomal recessive. Some affected individuals present with neurologic features. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the mitochondrion-specific ribosomal protein mS29 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P51398-1	1	yes
P51398-2	2
P51398-3	3

RefSeq proteins (5): NP_001186778, NP_001186779, NP_001186780, NP_004623, NP_387506 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008092	Ribosomal_mS29_met	Family
IPR019368	Ribosomal_mS29	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF10236

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (48 total): helix 19, strand 12, sequence variant 5, binding site 2, modified residue 2, splice variant 2, transit peptide 1, chain 1, sequence conflict 1, region of interest 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

77 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7QI4	ELECTRON MICROSCOPY	2.21
8CSS	ELECTRON MICROSCOPY	2.36
7P2E	ELECTRON MICROSCOPY	2.4
8RRI	ELECTRON MICROSCOPY	2.4
9OLF	ELECTRON MICROSCOPY	2.46
9OJM	ELECTRON MICROSCOPY	2.5
8CSQ	ELECTRON MICROSCOPY	2.54
8CSR	ELECTRON MICROSCOPY	2.54
6ZM6	ELECTRON MICROSCOPY	2.59
7QI5	ELECTRON MICROSCOPY	2.63
8CSP	ELECTRON MICROSCOPY	2.66
7PNX	ELECTRON MICROSCOPY	2.76
8ANY	ELECTRON MICROSCOPY	2.85
8CST	ELECTRON MICROSCOPY	2.85
6ZM5	ELECTRON MICROSCOPY	2.89
7PO0	ELECTRON MICROSCOPY	2.9
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
9G5C	ELECTRON MICROSCOPY	3
9G5D	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51398-F1	85.23	0.69

Functional residue map

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

Ligand- & substrate-binding residues (2): 100; 128–135

Post-translational modifications (2): 175, 207

Function

Pathways and Gene Ontology

Reactome pathways

7 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
R-HSA-392499	Metabolism of proteins
R-HSA-5368287	Mitochondrial translation
R-HSA-72766	Translation

MSigDB gene sets: 278 (showing top): CMYB_01, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, GOBP_MITOCHONDRIAL_TRANSLATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, YY1_Q6, NFKB_Q6, GOBP_TRANSLATION, NFKB_C, GOBP_APOPTOTIC_SIGNALING_PATHWAY, YY1_02, MORF_CTBP1, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, TGIF_01

GO Biological Process (4): apoptotic mitochondrial changes (GO:0008637), mitochondrial translation (GO:0032543), apoptotic signaling pathway (GO:0097190), apoptotic process (GO:0006915)

GO Molecular Function (7): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial small ribosomal subunit (GO:0005763), mitochondrial matrix (GO:0005759), mitochondrial ribosome (GO:0005761), ribosome (GO:0005840), small ribosomal subunit (GO:0015935), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mitochondrial translation	4
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	2
mitochondrion	2
mitochondrion organization	1
translation	1
mitochondrial gene expression	1
signal transduction	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nucleic acid binding	1
structural molecule activity	1
ribosome	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
organellar small ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1
intracellular organelle lumen	1
organellar ribosome	1
mitochondrial matrix	1
intracellular membraneless organelle	1
ribosomal subunit	1
protein-containing complex	1

Protein interactions and networks

STRING

2812 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAP3	MRPS30	Q9NP92	748
DAP3	MRPS18B	Q9Y676	742
DAP3	MRPL41	Q8IXM3	730
DAP3	MRPS27	Q92552	709
DAP3	MRPL12	P52815	686
DAP3	DELE1	Q14154	662
DAP3	MRPS10	P82664	625
DAP3	MRPS7	Q9Y2R9	603
DAP3	ERAL1	O75616	602
DAP3	MRPS22	P82650	597
DAP3	MRPL42	Q9Y6G3	589
DAP3	MRPL48	Q96GC5	575
DAP3	MRPL38	Q96DV4	574
DAP3	MRPL40	Q9NQ50	566
DAP3	MRPL45	Q9BRJ2	566

IntAct

240 interactions, top by confidence:

A	B	Type	Score
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
ESR1	TRIM24	psi-mi:“MI:0914”(association)	0.640
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
DAP3	MRPS35	psi-mi:“MI:0915”(physical association)	0.560
HNRNPD	HNRNPDL	psi-mi:“MI:0914”(association)	0.560
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
RPS6	IPO7	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF707	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF331	USP9Y	psi-mi:“MI:0914”(association)	0.530
ZBTB48	ZBTB24	psi-mi:“MI:0914”(association)	0.530
E4F1	ZBTB24	psi-mi:“MI:0914”(association)	0.530
MRPS15	MRPS14	psi-mi:“MI:0914”(association)	0.530
RPL6	MRPS14	psi-mi:“MI:0914”(association)	0.530
TRMT10B	MRPS14	psi-mi:“MI:0914”(association)	0.530
BHLHA15	RPLP0	psi-mi:“MI:0914”(association)	0.530
DAP3	PNMA6A	psi-mi:“MI:0914”(association)	0.530
ERAL1	DAP3	psi-mi:“MI:0403”(colocalization)	0.530
MRPS26	ERAL1	psi-mi:“MI:0914”(association)	0.530
MRPS18B	MRPS14	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530

BioGRID (452): DAP3 (Affinity Capture-Western), DAP3 (Affinity Capture-MS), DAP3 (Affinity Capture-MS), DAP3 (Affinity Capture-MS), DAP3 (Affinity Capture-MS), DAP3 (Affinity Capture-MS), DAP3 (Affinity Capture-MS), DAP3 (Affinity Capture-MS), DAP3 (Affinity Capture-MS), DAP3 (Affinity Capture-MS), DAP3 (Affinity Capture-MS), DAP3 (Affinity Capture-MS), MRPS35 (Affinity Capture-MS), MRPS10 (Affinity Capture-MS), WDFY2 (Affinity Capture-MS)

ESM2 similar proteins: A3KMX7, A5PKL6, F1MKX4, F1R2X6, F4IVI0, O94952, P35574, P42700, P51398, P97259, Q08834, Q09328, Q14997, Q2TBQ7, Q2TBU5, Q3U1V6, Q3V3E1, Q498D5, Q4R6Y8, Q5F204, Q5I0G3, Q5IH13, Q5IH14, Q5R5S1, Q5R7E8, Q5RL51, Q5SSW2, Q6IQC7, Q6NRP2, Q6NTT6, Q6P2P2, Q6YXW6, Q8BGG7, Q8C5P5, Q8CEL2, Q8N1I0, Q8NEC7, Q8NHU2, Q8R4G6, Q8TB36

Diamond homologs: P51398, P82922, Q9ER88

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKCD	up-regulates	DAP3	phosphorylation
DAP3	“form complex”	“28S mitochondrial small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 199 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
Mitochondrial translation	21	20.8×	3e-20
Mitochondrial translation initiation	22	20.1×	1e-20
Mitochondrial translation elongation	22	20.1×	1e-20
Mitochondrial ribosome-associated quality control	22	19.4×	2e-20
Mitochondrial translation termination	22	17.4×	1e-19
Translation	26	11.6×	9e-19
SARS-CoV-1 modulates host translation machinery	5	11.1×	2e-03
mRNA Polyadenylation	15	9.5×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	6	32.7×	6e-06
mitochondrial translation	23	22.0×	9e-22
RNA processing	9	10.8×	3e-05
regulation of alternative mRNA splicing, via spliceosome	8	10.7×	1e-04
translation	19	10.7×	8e-12
cytoplasmic translation	10	10.2×	1e-05
ribosomal small subunit biogenesis	7	8.8×	1e-03
negative regulation of translation	7	7.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	5
Uncertain significance	77
Likely benign	16
Benign	6

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1076776	NM_139119.3(YY1AP1):c.-151-100dup	Pathogenic
2066821	NM_139119.3(YY1AP1):c.-151-43T>A	Pathogenic
2425657	NC_000001.10:g.(?155581953)(155880552_?)del	Pathogenic
2683853	NC_000001.11:g.(155747068_155747546)_(155611487_155611965)del	Pathogenic
3571457	GRCh38/hg38 1q22(chr1:155610587-155746587)x1	Pathogenic
1723831	NM_139119.3(YY1AP1):c.-27C>T	Likely pathogenic
3065474	NM_139119.3(YY1AP1):c.-21+1G>T	Likely pathogenic
3066057	NM_004632.4(DAP3):c.1139T>G (p.Leu380Arg)	Likely pathogenic
3382939	NM_139119.3(YY1AP1):c.-151-158G>T	Likely pathogenic
3385343	NC_000001.11:g.(155641696_155642174)_(155747546_155777277)del	Likely pathogenic

SpliceAI

2242 predictions. Top by Δscore:

Variant	Effect	Δscore
1:155689241:G:GT	donor_gain	1.0000
1:155717004:A:AG	acceptor_gain	1.0000
1:155717004:AGTT:A	acceptor_gain	1.0000
1:155717005:G:GA	acceptor_gain	1.0000
1:155717005:GTTG:G	acceptor_gain	1.0000
1:155717128:GGT:G	donor_loss	1.0000
1:155717129:G:GT	donor_loss	1.0000
1:155717130:TGAG:T	donor_loss	1.0000
1:155717131:GAGT:G	donor_loss	1.0000
1:155731346:C:CA	acceptor_gain	1.0000
1:155731354:A:AG	acceptor_gain	1.0000
1:155731355:G:GG	acceptor_gain	1.0000
1:155731414:GG:G	donor_gain	1.0000
1:155731415:GG:G	donor_gain	1.0000
1:155732046:G:GT	donor_gain	1.0000
1:155732047:A:T	donor_gain	1.0000
1:155737006:G:GT	donor_gain	1.0000
1:155738150:A:AG	acceptor_gain	1.0000
1:155738155:A:AG	acceptor_gain	1.0000
1:155738156:G:GT	acceptor_gain	1.0000
1:155738156:GC:G	acceptor_gain	1.0000
1:155738156:GCT:G	acceptor_gain	1.0000
1:155738156:GCTC:G	acceptor_gain	1.0000
1:155738298:G:GG	donor_gain	1.0000
1:155738308:G:GT	donor_gain	1.0000
1:155738327:G:GT	donor_gain	1.0000
1:155689240:GGAG:G	donor_gain	0.9900
1:155709771:A:AG	acceptor_gain	0.9900
1:155709772:G:GG	acceptor_gain	0.9900
1:155717000:TTATA:T	acceptor_loss	0.9900

AlphaMissense

2629 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:155725416:G:T	R102M	0.987
1:155725417:G:C	R102S	0.986
1:155725417:G:T	R102S	0.986
1:155727698:T:C	L188P	0.986
1:155729263:T:C	L247P	0.984
1:155727694:T:A	W187R	0.982
1:155727694:T:C	W187R	0.982
1:155725416:G:C	R102T	0.981
1:155725956:A:C	S137R	0.981
1:155725958:T:A	S137R	0.981
1:155725958:T:G	S137R	0.981
1:155725960:T:C	L138P	0.980
1:155738184:T:C	L380P	0.978
1:155727685:G:C	A184P	0.976
1:155725945:G:T	G133V	0.975
1:155729208:G:C	G229R	0.975
1:155729066:T:A	W210R	0.973
1:155729066:T:C	W210R	0.973
1:155738195:A:C	S384R	0.973
1:155738197:T:A	S384R	0.973
1:155738197:T:G	S384R	0.973
1:155729115:T:A	V226D	0.971
1:155729321:T:A	N266K	0.971
1:155729321:T:G	N266K	0.971
1:155725945:G:A	G133E	0.969
1:155725980:T:C	C145R	0.969
1:155727616:T:A	W161R	0.967
1:155727616:T:C	W161R	0.967
1:155731960:T:A	V307E	0.966
1:155725446:T:C	L112P	0.965

dbSNP variants (sampled 300 via entrez): RS1000000316 (1:155733711 C>T), RS1000103489 (1:155725817 T>C,G), RS1000210721 (1:155693070 G>C), RS1000224687 (1:155689961 C>T), RS1000351271 (1:155733444 C>T), RS1000352114 (1:155695669 A>G), RS1000547312 (1:155716265 A>C,G), RS1000908400 (1:155726190 C>T), RS1000916626 (1:155703362 A>G), RS1000932437 (1:155716379 G>A), RS1000951517 (1:155723655 GT>G,GTT), RS1000967205 (1:155703590 T>C), RS1000987474 (1:155702028 C>A,G), RS1001037662 (1:155707839 G>A), RS1001097217 (1:155709539 T>C)

Disease associations

OMIM: gene MIM:602074 | disease phenotypes: MIM:602531, MIM:615355, MIM:233400, MIM:621101, MIM:617675

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial disease	Strong	Autosomal recessive

Mondo (6): grange syndrome (MONDO:0011243), Noonan syndrome 8 (MONDO:0014143), Perrault syndrome 1 (MONDO:0009300), Perrault syndrome 7 (MONDO:0976232), mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome (MONDO:0044714), mitochondrial disease (MONDO:0044970)

Orphanet (5): Grange syndrome (Orphanet:79094), Noonan syndrome (Orphanet:648), Perrault syndrome (Orphanet:2855), Perrault syndrome type 1 (Orphanet:642945), Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome (Orphanet:502423)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000479	Abnormal retinal morphology
HP:0000786	Primary amenorrhea
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001399	Hepatic failure
HP:0001943	Hypoglycemia
HP:0002240	Hepatomegaly
HP:0003128	Lactic acidosis
HP:0004322	Short stature
HP:0008209	Premature ovarian insufficiency
HP:0008232	Elevated circulating follicle stimulating hormone level
HP:0008619	Bilateral sensorineural hearing impairment
HP:0010464	Streak ovary
HP:0011463	Childhood onset
HP:0011969	Elevated circulating luteinizing hormone level
HP:0012622	Chronic kidney disease

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566529	Arterial Occlusive Disease, Progressive, with Hypertension, Heart Defects, Bone Fragility, and Brachysyndactyly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295776 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	2
sodium arsenite	increases abundance, increases expression	2
cobaltous chloride	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases reaction, decreases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
beta-lapachone	increases expression	1
2’,3’-dideoxycytidine 5’-triphosphate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
bisphenol B	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Bortezomib	increases expression	1
Rosiglitazone	decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	increases expression, increases abundance	1
Vehicle Emissions	affects expression, increases reaction	1
Hexachlorocyclohexane	increases expression	1
Benzo(a)pyrene	affects methylation	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
CHEMBL4118620	Binding	Binding affinity to DAP3 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01642056	PHASE1/PHASE2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT03384420	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD in Pediatric Patients With Pearson Syndrome
NCT06051448	PHASE1/PHASE2	COMPLETED	Promoting Resilience in Stress Management (PRISM) and Clinical-focused Narrative (CFN) Pilot in Adults With Primary Mitochondrial Disease (PMD).
NCT01252979	EARLY_PHASE1	COMPLETED	Ketones & Mitochondrial Heteroplasmy
NCT00786539	Not specified	COMPLETED	Mitochondria Inborn Errors of Metabolism and ANT Defects in Mitochondria Diseases
NCT00829270	Not specified	COMPLETED	Economic and Medical Evaluation of the Whole Mitochondrial DNA Screening by Surveyor and Mitochips Techniques
NCT00831948	Not specified	UNKNOWN	Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.
NCT01001585	Not specified	TERMINATED	Anesthetic Effects in Mitochondrial Disease
NCT01148550	Not specified	SUSPENDED	Longitudinal Study of Mitochondrial Hepatopathies