GATD3

Summary

GATD3 (glutamine amidotransferase class 1 domain containing 3, HGNC:1273) is a protein-coding gene on chromosome 21q22.3, encoding Glutamine amidotransferase-like class 1 domain-containing protein 3, mitochondrial (P0DPI2).

This gene encodes a potential mitochondrial protein that is a member of the DJ-1/PfpI gene family. This protein is overexpressed in fetal Down syndrome brain. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 8209 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 23 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_004649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1273
Approved symbol	GATD3
Name	glutamine amidotransferase class 1 domain containing 3
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KNP-Ia, GT335, ES1, HES1, D21S2048E, KNPI, KNPH, KNP-I
Ensembl gene	ENSG00000160221
Ensembl biotype	protein_coding
OMIM	601659
Entrez	8209

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000291577, ENST00000348499, ENST00000389690, ENST00000419699, ENST00000427803, ENST00000449622, ENST00000470545, ENST00000480786, ENST00000488392, ENST00000493883, ENST00000495007, ENST00000642815, ENST00000644251, ENST00000645487, ENST00000646873, ENST00000938560

RefSeq mRNA: 4 — MANE Select: NM_004649 NM_001320383, NM_001320384, NM_004649, NM_198155

CCDS: CCDS33580, CCDS33581, CCDS82680

Canonical transcript exons

ENST00000291577 — 7 exons

Exon	Start	End
ENSE00001822596	44133683	44133838
ENSE00003482790	44140250	44140342
ENSE00003570914	44136060	44136173
ENSE00003619394	44137177	44137296
ENSE00003667692	44143205	44143361
ENSE00003673943	44134102	44134154
ENSE00003847548	44144821	44145711

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 95.60.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5812 / max 10.9284, expressed in 338 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189428	2.4797	1362
209212	1.2049	803
189427	0.5812	338

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.60	gold quality
mucosa of stomach	UBERON:0001199	94.58	gold quality
stromal cell of endometrium	CL:0002255	93.93	gold quality
gastrocnemius	UBERON:0001388	90.63	gold quality
heart left ventricle	UBERON:0002084	90.49	gold quality
muscle of leg	UBERON:0001383	90.17	gold quality
endocervix	UBERON:0000458	90.01	gold quality
fundus of stomach	UBERON:0001160	89.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.35	gold quality
right ovary	UBERON:0002118	89.30	gold quality
prefrontal cortex	UBERON:0000451	89.01	gold quality
right adrenal gland	UBERON:0001233	88.99	gold quality
heart	UBERON:0000948	88.81	gold quality
cerebellum	UBERON:0002037	88.80	gold quality
cerebellar hemisphere	UBERON:0002245	88.80	gold quality
right atrium auricular region	UBERON:0006631	88.69	gold quality
cerebellar cortex	UBERON:0002129	88.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.49	gold quality
left ovary	UBERON:0002119	87.84	gold quality
cortex of kidney	UBERON:0001225	87.64	gold quality
apex of heart	UBERON:0002098	87.64	gold quality
adult mammalian kidney	UBERON:0000082	87.62	gold quality
liver	UBERON:0002107	87.57	gold quality
uterine cervix	UBERON:0000002	87.54	gold quality
ovary	UBERON:0000992	87.37	gold quality
ectocervix	UBERON:0012249	87.15	gold quality
left adrenal gland	UBERON:0001234	86.99	gold quality
kidney	UBERON:0002113	86.97	gold quality
right lobe of liver	UBERON:0001114	86.94	gold quality
frontal cortex	UBERON:0001870	86.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting GATD3, 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-4776-3P	100.00	68.73	1340
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-320E	97.49	65.96	865
HSA-MIR-6501-5P	97.41	68.24	712

Literature-anchored findings (GeneRIF, showing 1)

• ES1 protein expression was two-fold elevated (P < 0.01) in fetal Down syndrome brain compared to controls and may be a candidate protein involved in the pathogenesis of the brain deficit in DS. (PMID:15082224)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gatd3	ENSDARG00000020618
mus_musculus	Gatd3a	ENSMUSG00000053329
rattus_norvegicus	Gatd3a	ENSRNOG00000001211

Protein

Protein identifiers

Glutamine amidotransferase-like class 1 domain-containing protein 3, mitochondrial — P0DPI2 (reviewed: P0DPI2)

All UniProt accessions (9): P0DPI2, A0A096LP12, A0A140VKB0, A0A2R8Y588, A0A2R8Y6K9, A0A2R8YDR7, F2Z2Q0, H7C1F6, H7C2G3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Mitochondrion.

Similarity. Belongs to the GATD3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P0DPI2-1	1, Long	yes
P0DPI2-2	2, Short

RefSeq proteins (4): NP_001307312, NP_001307313, NP_004640, NP_937798 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029062	Class_I_gatase-like	Homologous_superfamily

UniProt features (15 total): modified residue 10, sequence variant 2, transit peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DPI2-F1	90.82	0.85

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 (10): 233, 233, 151, 157, 164, 203, 203, 219, 223, 223

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 857 (showing top): PID_FANCONI_PATHWAY, GSE45365_NK_CELL_VS_BCELL_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, AHRARNT_01, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, FXR_IR1_Q6, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, REACTOME_SIGNALING_BY_NOTCH, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION

GO Biological Process (0):

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

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

848 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GATD3	ESS2	Q96DF8	925
GATD3	NAT1	P18440	813
GATD3	NAT2	P11245	767
GATD3	CALCOCO2	Q13137	712
GATD3	RPS7	P23821	683
GATD3	RPS26	P02383	576
GATD3	PARK7	Q99497	543
GATD3	RPS28	P25112	540
GATD3	CRLF3	Q8IUI8	526
GATD3	EWSR1	Q01844	522
GATD3	H1-6	P22492	513
GATD3	SP100	P23497	497
GATD3	GEMIN4	P57678	494
GATD3	SRSF2	Q01130	490
GATD3	DDX20	Q9UHI6	490

IntAct

64 interactions, top by confidence:

A	B	Type	Score
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
PRELID1	TRIAP1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MRPL53	GATD3	psi-mi:“MI:0915”(physical association)	0.560
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
BCL2L14		psi-mi:“MI:0914”(association)	0.350
IRF2	VWA8	psi-mi:“MI:0914”(association)	0.350
NT5C3A	VWA8	psi-mi:“MI:0914”(association)	0.350
TNFRSF10A	NAP1L4	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350
GATD3	NME1	psi-mi:“MI:0914”(association)	0.350
PHYHIPL	GAPDH	psi-mi:“MI:0914”(association)	0.350
PHYHIPL	ATP5F1B	psi-mi:“MI:0914”(association)	0.350
BOLA3	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
GATD3	NDUFS2	psi-mi:“MI:0914”(association)	0.350
NIT1	PMPCB	psi-mi:“MI:0914”(association)	0.350
PHYHIPL	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
PPM1K	PMPCB	psi-mi:“MI:0914”(association)	0.350
MTRES1	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
PHYHIPL	ACOT7	psi-mi:“MI:0914”(association)	0.350
PPM1K	BCKDK	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A2TLM1, B4G0F3, B8BKI7, B9N1F9, B9SQI7, C1BJB1, C6JS30, D2XV59, E0CSI1, E9Q4Z2, F4JGR5, O00178, O00763, O04059, O08582, O19069, P0DPI2, P11029, P11497, P13086, P19356, P21343, P22907, P28492, P47968, P49247, P53597, Q13085, Q28559, Q2R483, Q3T186, Q571F8, Q58DC5, Q58DR8, Q5I0K3, Q5NAY4, Q5R8Q7, Q5SWU9, Q5XGS8, Q5ZHY5

Diamond homologs: F1QCN0, P0ABU5, P0ABU6, P0DPI2, P56571, Q90257, Q9D172, Q48464

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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 protein degradation	7	14.8×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	7
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
816172	GRCh37/hg19 21q22.3(chr21:43472147-48097372)x1	Pathogenic

SpliceAI

2559 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44137272:G:GT	donor_gain	1.0000
21:44137293:ACCT:A	donor_gain	1.0000
21:44137294:CCT:C	donor_gain	1.0000
21:44137297:G:GG	donor_gain	1.0000
21:44140341:GG:G	donor_gain	1.0000
21:44140342:GG:G	donor_gain	1.0000
21:44143200:TTCAG:T	acceptor_loss	1.0000
21:44143201:TCAGC:T	acceptor_loss	1.0000
21:44143202:CA:C	acceptor_loss	1.0000
21:44143202:CAG:C	acceptor_loss	1.0000
21:44143203:A:AC	acceptor_loss	1.0000
21:44143203:A:AG	acceptor_gain	1.0000
21:44143203:AGCTT:A	acceptor_gain	1.0000
21:44143204:G:GC	acceptor_gain	1.0000
21:44143204:GC:G	acceptor_gain	1.0000
21:44143204:GCT:G	acceptor_gain	1.0000
21:44143204:GCTT:G	acceptor_gain	1.0000
21:44143204:GCTTG:G	acceptor_gain	1.0000
21:44143353:G:GT	donor_gain	1.0000
3:194136484:GAAAG:G	donor_gain	1.0000
3:194136488:GGT:G	donor_loss	1.0000
3:194136489:GTA:G	donor_loss	1.0000
3:194136612:TGCA:T	acceptor_loss	1.0000
3:194136614:CA:C	acceptor_loss	1.0000
3:194136615:A:AG	acceptor_gain	1.0000
3:194136616:G:GT	acceptor_gain	1.0000
3:194136616:GT:G	acceptor_gain	1.0000
3:194136616:GTC:G	acceptor_gain	1.0000
3:194136616:GTCAT:G	acceptor_gain	1.0000
3:194136708:AAGAT:A	donor_gain	1.0000

AlphaMissense

1733 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:44134129:G:T	G57W	0.999
21:44134112:G:A	G51E	0.998
21:44134130:G:A	G57E	0.998
21:44134146:G:C	E62D	0.998
21:44134146:G:T	E62D	0.998
21:44136173:G:T	R103M	0.998
21:44137277:T:C	F137L	0.998
21:44137279:T:A	F137L	0.998
21:44137279:T:G	F137L	0.998
21:44137281:G:A	G138E	0.998
21:44137291:A:C	K141N	0.998
21:44137291:A:T	K141N	0.998
21:44143211:C:G	C176W	0.998
21:44144866:T:C	F242L	0.998
21:44144868:C:A	F242L	0.998
21:44144868:C:G	F242L	0.998
21:44134126:G:C	D56H	0.997
21:44134127:A:T	D56V	0.997
21:44134130:G:T	G57V	0.997
21:44134136:A:T	E59V	0.997
21:44137200:G:C	R111T	0.997
21:44137200:G:T	R111M	0.997
21:44137201:G:C	R111S	0.997
21:44137201:G:T	R111S	0.997
21:44137272:G:A	G135E	0.997
21:44140251:A:C	S144R	0.997
21:44140253:C:A	S144R	0.997
21:44140253:C:G	S144R	0.997
21:44140257:T:C	F146L	0.997
21:44140259:T:A	F146L	0.997

dbSNP variants (sampled 300 via entrez): RS1000154936 (21:44146111 A>G), RS1000691184 (21:44133742 A>G), RS1001011303 (21:44142496 G>A), RS1001508312 (21:44144641 A>G), RS1002237794 (21:44137695 T>C), RS1002331551 (21:44132890 T>G), RS1002403461 (21:44132699 C>T), RS1002886970 (21:44138043 C>T), RS1002970605 (21:44139932 C>T), RS1003400912 (21:44139802 G>A), RS1003465920 (21:44143886 C>T), RS1004075239 (21:44138081 T>G), RS1004136343 (21:44141982 C>T), RS1004532782 (21:44134399 C>T), RS1004988914 (21:44134135 G>C)

Disease associations

OMIM: gene MIM:601659 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006904_6	Cerebral amyloid deposition (PET imaging)	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007707	cerebral amyloid deposition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169114 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
methylselenic acid	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
perfluorooctanoic acid	increases expression	1
periodate-oxidized adenosine	affects expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
celastrol	decreases expression	1
gedunin	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Aminoglutethimide	increases expression	1
Arsenic	decreases expression, increases abundance	1
Aspirin	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	increases oxidation, increases abundance, affects cotreatment	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5108433	Binding	Binding affinity to GATD3A in human HEK293 cells assessed as fold change at 130 nM incubated for 3 to 6 hrs by LFQ-chemical proteomics analysis	Activity-based protein profiling reveals deubiquitinase and aldehyde dehydrogenase targets of a cyanopyrrolidine probe. — RSC Med Chem

Clinical trials (associated diseases)

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