GATD1

Summary

GATD1 (glutamine amidotransferase class 1 domain containing 1, HGNC:26616) is a protein-coding gene on chromosome 11p15.5, encoding Glutamine amidotransferase-like class 1 domain-containing protein 1 (Q8NB37). Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary).

Predicted to enable glyoxalase III activity. Predicted to be involved in methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione. Located in extracellular exosome.

Source: NCBI Gene 347862 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 60 total — 1 pathogenic
• MANE Select transcript: NM_182612

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26616
Approved symbol	GATD1
Name	glutamine amidotransferase class 1 domain containing 1
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34283, Fy-5, FERRY5
Ensembl gene	ENSG00000177225
Ensembl biotype	protein_coding
OMIM	621361
Entrez	347862

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 7 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000319863, ENST00000354286, ENST00000397472, ENST00000465313, ENST00000524550, ENST00000526325, ENST00000526650, ENST00000528309, ENST00000528602, ENST00000529362, ENST00000529966, ENST00000530209, ENST00000532320, ENST00000532839, ENST00000533960, ENST00000534603

RefSeq mRNA: 8 — MANE Select: NM_182612 NM_001318818, NM_001318820, NM_001318821, NM_001318822, NM_001318823, NM_001318824, NM_001410955, NM_182612

CCDS: CCDS7713, CCDS81530, CCDS91400

Canonical transcript exons

ENST00000319863 — 8 exons

Exon	Start	End
ENSE00001410658	767222	770903
ENSE00003512199	777399	777487
ENSE00003535055	773522	773629
ENSE00003570249	775066	775142
ENSE00003594159	774008	774113
ENSE00003616612	772427	772521
ENSE00003651263	770993	771104
ENSE00003671960	771333	771426

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 95.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.2994 / max 183.3407, expressed in 1814 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117816	35.0416	1814
117815	0.2156	98
117814	0.0422	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	95.90	gold quality
kidney epithelium	UBERON:0004819	95.45	gold quality
tendon of biceps brachii	UBERON:0008188	94.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.36	gold quality
upper arm skin	UBERON:0004263	94.25	gold quality
cerebellar hemisphere	UBERON:0002245	94.24	gold quality
cerebellar cortex	UBERON:0002129	94.23	gold quality
cerebellum	UBERON:0002037	93.92	gold quality
ventricular zone	UBERON:0003053	93.90	gold quality
left adrenal gland cortex	UBERON:0035825	93.66	gold quality
left adrenal gland	UBERON:0001234	93.63	gold quality
adrenal cortex	UBERON:0001235	93.55	gold quality
anterior cingulate cortex	UBERON:0009835	93.52	gold quality
right adrenal gland	UBERON:0001233	93.36	gold quality
right adrenal gland cortex	UBERON:0035827	93.26	gold quality
adenohypophysis	UBERON:0002196	93.23	gold quality
right frontal lobe	UBERON:0002810	93.22	gold quality
hypothalamus	UBERON:0001898	93.18	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.07	gold quality
amygdala	UBERON:0001876	92.83	gold quality
pituitary gland	UBERON:0000007	92.75	gold quality
adrenal gland	UBERON:0002369	92.63	gold quality
caudate nucleus	UBERON:0001873	92.47	gold quality
nucleus accumbens	UBERON:0001882	92.44	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.33	gold quality
putamen	UBERON:0001874	92.31	gold quality
prefrontal cortex	UBERON:0000451	92.18	gold quality
substantia nigra	UBERON:0002038	92.18	gold quality
pancreatic ductal cell	CL:0002079	92.15	silver quality
spinal cord	UBERON:0002240	92.13	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.27
E-ENAD-27	no	3.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting GATD1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-378A-5P	99.65	66.33	1311

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gatd1	ENSMUSG00000051007
rattus_norvegicus	Gatd1	ENSRNOG00000045795

Protein

Protein identifiers

Glutamine amidotransferase-like class 1 domain-containing protein 1 — Q8NB37 (reviewed: Q8NB37)

Alternative names: Ferry endosomal RAB5 effector complex subunit 5, Parkinson disease 7 domain-containing protein 1

All UniProt accessions (6): Q8NB37, E9PLI5, E9PQD8, H0YE25, H0YER3, H0YF25

UniProt curated annotations — full annotation on UniProt →

Function. Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary). The FERRY complex directly interacts with mRNAs and RAB5A, and functions as a RAB5A effector involved in the localization and the distribution of specific mRNAs most likely by mediating their endosomal transport. The complex recruits mRNAs and ribosomes to early endosomes through direct mRNA-interaction.

Subunit / interactions. Homotetramer. Component of the FERRY complex composed of five subunits, TBCK, PPP1R21, FERRY3, CRYZL1 and GATD1 with a ratio of 1:2:1:2:4, respectively.

Subcellular location. Secreted. Early endosome.

Similarity. Belongs to the peptidase C56 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8NB37-1	1	yes
Q8NB37-2	2
Q8NB37-3	3
Q8NB37-4	4

RefSeq proteins (8): NP_001305747, NP_001305749, NP_001305750, NP_001305751, NP_001305752, NP_001305753, NP_001397884, NP_872418* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029062	Class_I_gatase-like	Homologous_superfamily
IPR050325	Prot/Nucl_acid_deglycase	Family

UniProt features (28 total): helix 12, strand 7, splice variant 3, turn 2, signal peptide 1, chain 1, glycosylation site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8A3P	X-RAY DIFFRACTION	2.7
7ND2	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NB37-F1	94.70	0.92

Functional residue map

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

Glycosylation sites (1): 201

Mutagenesis-validated functional residues (1):

Position	Phenotype
166	does not affect ferry complex assembly. does not affect ferry complex binding to mrna.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 66 (showing top): GOBP_ALDEHYDE_CATABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_KETONE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_RESPONSE_TO_KETONE, GOBP_DETOXIFICATION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_MONOCARBOXYLIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOBP_ALDEHYDE_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_KETONE

GO Biological Process (2): obsolete methylglyoxal catabolic process to pyruvate via (R)-S-lactoyl-glutathione (GO:0019243), lactate biosynthetic process (GO:0019249)

GO Molecular Function (1): glyoxalase III activity (GO:0019172)

GO Cellular Component (5): cytoplasm (GO:0005737), early endosome (GO:0005769), extracellular exosome (GO:0070062), extracellular region (GO:0005576), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
lactate metabolic process	1
monocarboxylic acid biosynthetic process	1
hydro-lyase activity	1
methylglyoxal catabolic process	1
intracellular anatomical structure	1
endosome	1
extracellular vesicle	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GATD1	PARK7	Q99497	548
GATD1	TRIB3	Q96RU7	466
GATD1	DPYSL5	Q9BPU6	458
GATD1	ATP6V1A	P38606	457
GATD1	PDHA1	P08559	443
GATD1	HYPK	Q9NX55	437
GATD1	PDHB	P11177	434
GATD1	DPYSL2	Q16555	425
GATD1	DRD4	P21917	405
GATD1	DLAT	P10515	405
GATD1	KANK4	Q5T7N3	401
GATD1	CCDC125	Q86Z20	390
GATD1	LYRM7	Q5U5X0	380
GATD1	TLCD2	A6NGC4	379
GATD1	TXNDC15	Q96J42	372

IntAct

27 interactions, top by confidence:

A	B	Type	Score
FERRY3	CRYZL1	psi-mi:“MI:0915”(physical association)	0.690
TRIB3	STK40	psi-mi:“MI:0914”(association)	0.640
GATD1	CRYZL1	psi-mi:“MI:0915”(physical association)	0.570
GATD1		psi-mi:“MI:0915”(physical association)	0.400
Tbck	FAM20B	psi-mi:“MI:0914”(association)	0.350
PPP1R21		psi-mi:“MI:0914”(association)	0.350
HTRA2	VWA8	psi-mi:“MI:0914”(association)	0.350
IMMP1L	EIF1AY	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
RAB5A	CRYZL1	psi-mi:“MI:0914”(association)	0.350
CCDC85A	CIBAR1	psi-mi:“MI:0914”(association)	0.350
TAFA3	FUOM	psi-mi:“MI:0914”(association)	0.350
UBA52	FUOM	psi-mi:“MI:0914”(association)	0.350
GATD1	MYO9A	psi-mi:“MI:0914”(association)	0.350
KHDRBS2	SUPT5H	psi-mi:“MI:0914”(association)	0.350
CARTPT	MEIS1	psi-mi:“MI:0914”(association)	0.350
FERRY3	GAPDHS	psi-mi:“MI:0914”(association)	0.350
IL6R	MID1	psi-mi:“MI:0914”(association)	0.350
PLA2G2D	ZZEF1	psi-mi:“MI:0914”(association)	0.350
TCP10L	RNF40	psi-mi:“MI:0914”(association)	0.350
PHF1	DNAJC13	psi-mi:“MI:0914”(association)	0.350
PRSS23	GATD1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (99): PDDC1 (Affinity Capture-MS), PDDC1 (Affinity Capture-MS), PDDC1 (Affinity Capture-MS), PDDC1 (Affinity Capture-MS), PREPL (Affinity Capture-MS), HPS5 (Affinity Capture-MS), PDDC1 (Affinity Capture-MS), RTEL1 (Affinity Capture-MS), FMN2 (Affinity Capture-MS), ITSN1 (Affinity Capture-MS), PER1 (Affinity Capture-MS), LSS (Affinity Capture-MS), TRIM65 (Affinity Capture-MS), USP54 (Affinity Capture-MS), PRAME (Affinity Capture-MS)

ESM2 similar proteins: A2A825, A2VE14, A9CQL8, D3ZVR7, P28801, P47802, Q0VCJ8, Q0VD18, Q0VD27, Q27HK4, Q29RZ1, Q2TBS1, Q3SZB3, Q3U129, Q4R3I0, Q58CY6, Q5H8A4, Q5I0D5, Q5NVN7, Q5R7S9, Q5R8R5, Q5RAJ8, Q5VYX0, Q5ZIL9, Q5ZJB7, Q5ZMH6, Q67FW5, Q6AXQ0, Q6GV29, Q7RTV5, Q86XA0, Q86XW9, Q8BGB7, Q8N8L6, Q8NB37, Q8TBF2, Q91YQ7, Q96G75, Q96MZ0, Q9BU20

Diamond homologs: Q29RZ1, Q32NG4, Q3B7H1, Q8BFQ8, Q8NB37

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	50
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57258	GRCh38/hg38 11p15.5-15.4(chr11:196966-4435344)x3	Pathogenic

SpliceAI

1669 predictions. Top by Δscore:

Variant	Effect	Δscore
11:771332:CCA:C	donor_gain	1.0000
11:772419:ACACT:A	donor_loss	1.0000
11:772420:CACT:C	donor_loss	1.0000
11:772421:ACTCA:A	donor_loss	1.0000
11:772422:CTCA:C	donor_loss	1.0000
11:772423:TCAC:T	donor_loss	1.0000
11:772424:C:CG	donor_loss	1.0000
11:772425:A:AC	donor_gain	1.0000
11:772425:A:C	donor_loss	1.0000
11:772425:AC:A	donor_gain	1.0000
11:772425:ACC:A	donor_gain	1.0000
11:772426:C:CC	donor_gain	1.0000
11:772426:CC:C	donor_gain	1.0000
11:772426:CCC:C	donor_gain	1.0000
11:772518:GGTTC:G	acceptor_loss	1.0000
11:772519:GTTC:G	acceptor_loss	1.0000
11:772520:TT:T	acceptor_gain	1.0000
11:772520:TTCTG:T	acceptor_loss	1.0000
11:772521:TCTG:T	acceptor_loss	1.0000
11:772522:C:CC	acceptor_gain	1.0000
11:772522:C:CG	acceptor_loss	1.0000
11:772523:T:A	acceptor_loss	1.0000
11:773520:A:AC	donor_gain	1.0000
11:773521:C:CC	donor_gain	1.0000
11:773521:CTG:C	donor_gain	1.0000
11:773521:CTGCT:C	donor_gain	1.0000
11:774003:CCTA:C	donor_loss	1.0000
11:774004:CTA:C	donor_loss	1.0000
11:774006:A:AC	donor_gain	1.0000
11:774007:C:CC	donor_gain	1.0000

AlphaMissense

1437 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:771014:A:G	L212P	0.998
11:771056:G:T	T198K	0.998
11:771059:A:T	V197D	0.998
11:772513:A:G	C122R	0.998
11:773611:A:T	L89H	0.998
11:774022:A:T	L78H	0.998
11:775076:G:T	A44D	0.998
11:771038:G:A	S204F	0.997
11:771053:C:T	G199D	0.997
11:771062:A:G	L196P	0.997
11:771080:A:T	V190D	0.997
11:772509:G:T	A123D	0.997
11:772511:G:C	C122W	0.997
11:773611:A:G	L89P	0.997
11:773621:A:C	Y86D	0.997
11:777425:A:G	L13P	0.997
11:771026:G:T	A208D	0.996
11:773545:A:G	L111P	0.996
11:773602:G:C	P92R	0.996
11:773608:A:G	L90P	0.996
11:771038:G:T	S204Y	0.995
11:771056:G:C	T198R	0.995
11:772428:C:T	G150E	0.995
11:772429:C:G	G150R	0.995
11:772429:C:T	G150R	0.995
11:772431:G:T	T149K	0.995
11:772488:G:T	A130D	0.995
11:772503:C:A	G125V	0.995
11:773602:G:T	P92H	0.995
11:773611:A:C	L89R	0.995

dbSNP variants (sampled 300 via entrez): RS1000167206 (11:776293 T>C), RS1000352175 (11:776331 T>A,C), RS1000424456 (11:776108 G>A,C), RS1000456980 (11:775836 A>C,G), RS1000603710 (11:777109 G>A,C), RS1000657218 (11:771647 G>T), RS1000672022 (11:776040 T>C), RS1000912777 (11:769169 C>T), RS1000951522 (11:777333 C>T), RS1001020499 (11:768849 C>T), RS1001257493 (11:772627 T>C), RS1001368236 (11:769004 G>C), RS1001413834 (11:768742 G>A), RS1001429715 (11:777065 G>C), RS1001462162 (11:776899 C>G,T)

Disease associations

OMIM: gene MIM:621361 | 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
GCST90013442_17	Keratoconus	1.000000e-26

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
aristolochic acid I	decreases expression	1
bisphenol A	decreases methylation	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	decreases methylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	decreases expression	1
monomethylarsonous acid	decreases expression	1
dimethylarsinous acid	decreases expression	1
jinfukang	increases expression	1
MT19c compound	decreases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Arsenic	increases abundance, decreases expression	1
Atrazine	decreases expression	1
Cadmium	increases expression, increases abundance	1
Cisplatin	decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Gasoline	increases abundance, increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Methapyrilene	decreases methylation	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Aflatoxin B1	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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