GADL1

Summary

GADL1 (GAD like acidic amino acid decarboxylase 1, HGNC:27949) is a protein-coding gene on chromosome 3p24.1-p23, encoding Acidic amino acid decarboxylase GADL1 (Q6ZQY3). May catalyze the decarboxylation of L-aspartate, 3-sulfino-L-alanine (cysteine sulfinic acid), and L-cysteate to beta-alanine, hypotaurine and taurine, respectively.

Predicted to enable carboxy-lyase activity. Predicted to be involved in carboxylic acid metabolic process. Predicted to be located in cytosol. Predicted to be active in cytoplasm.

Source: NCBI Gene 339896 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 99 total — 1 pathogenic
• MANE Select transcript: NM_207359

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27949
Approved symbol	GADL1
Name	GAD like acidic amino acid decarboxylase 1
Location	3p24.1-p23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000144644
Ensembl biotype	protein_coding
OMIM	615601
Entrez	339896

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000282538, ENST00000454381, ENST00000498387, ENST00000944949, ENST00000944950

RefSeq mRNA: 1 — MANE Select: NM_207359 NM_207359

CCDS: CCDS2649

Canonical transcript exons

ENST00000282538 — 15 exons

Exon	Start	End
ENSE00000966273	30838997	30839113
ENSE00001075593	30844210	30844264
ENSE00001075646	30844387	30844466
ENSE00001298416	30833853	30833934
ENSE00001303491	30800889	30801088
ENSE00001306754	30726197	30728415
ENSE00001316904	30834217	30834281
ENSE00001327777	30786355	30786406
ENSE00001635885	30861593	30861765
ENSE00001673941	30850835	30850941
ENSE00001678138	30849996	30850111
ENSE00001740758	30854699	30854789
ENSE00001805856	30857015	30857141
ENSE00002306035	30894578	30894661
ENSE00003672594	30778179	30778268

Expression profiles

Bgee: expression breadth broad, 79 present calls, max score 96.43.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0509 / max 6.6996, expressed in 22 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41569	0.0509	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.43	gold quality
germinal epithelium of ovary	UBERON:0001304	86.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.92	gold quality
deltoid	UBERON:0001476	74.32	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.61	silver quality
skeletal muscle tissue	UBERON:0001134	70.57	gold quality
muscle of leg	UBERON:0001383	70.29	gold quality
gastrocnemius	UBERON:0001388	68.19	gold quality
cortical plate	UBERON:0005343	68.08	gold quality
muscle tissue	UBERON:0002385	67.51	gold quality
tendon of biceps brachii	UBERON:0008188	66.17	gold quality
mucosa of stomach	UBERON:0001199	65.83	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	65.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	63.66	gold quality
vastus lateralis	UBERON:0001379	62.00	silver quality
quadriceps femoris	UBERON:0001377	61.86	silver quality
biceps brachii	UBERON:0001507	61.25	silver quality
lower esophagus muscularis layer	UBERON:0035833	60.97	gold quality
lower esophagus	UBERON:0013473	60.82	gold quality
descending thoracic aorta	UBERON:0002345	55.17	gold quality
sural nerve	UBERON:0015488	54.09	silver quality
tendon	UBERON:0000043	52.35	silver quality
colonic epithelium	UBERON:0000397	51.69	gold quality
thoracic aorta	UBERON:0001515	51.64	gold quality
ascending aorta	UBERON:0001496	51.32	gold quality
parietal pleura	UBERON:0002400	51.26	silver quality
lower lobe of lung	UBERON:0008949	49.73	silver quality
smooth muscle tissue	UBERON:0001135	47.73	gold quality
stromal cell of endometrium	CL:0002255	47.68	gold quality
middle temporal gyrus	UBERON:0002771	46.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

102 targeting GADL1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942

Literature-anchored findings (GeneRIF, showing 5)

• Genetic variations in GADL1 are associated with the response to lithium maintenance treatment for bipolar I disorder in patients of Han Chinese descent. (PMID:24369049)
• The study did not identify a major relationship between the GADL1 polymorphisms and lithium response in an Indian population. (PMID:25415457)
• taurine biosynthesis in vertebrates involves two structurally related PLP-dependent decarboxylases (cysteine sulfinic acid decarboxylase and glutamic acid decarboxylase like 1) (PMID:26327310)
• No difference in GADL1 expression was observed among lymphoblastoid cells from excellent-responders, non-responders or controls. Furthermore, lithium did not induce significant changes in GADL1 expression levels after 4 or 8 days. These results did not support an association of GADL1 expression in the determination of a lithium response in BD patients. (PMID:28214779)
• Effects of GADL1 overexpression on cell migration and the associated morphological changes. (PMID:30923325)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gadl1	ENSMUSG00000056880
rattus_norvegicus	Gadl1	ENSRNOG00000067908
drosophila_melanogaster	Tdc2	FBGN0050446
caenorhabditis_elegans		WBGENE00006562

Paralogs (7): GAD1 (ENSG00000128683), DDC (ENSG00000132437), GAD2 (ENSG00000136750), CSAD (ENSG00000139631), HDC (ENSG00000140287), SGPL1 (ENSG00000166224), PDXDC1 (ENSG00000179889)

Protein

Protein identifiers

Acidic amino acid decarboxylase GADL1 — Q6ZQY3 (reviewed: Q6ZQY3)

Alternative names: Aspartate 1-decarboxylase, Cysteine sulfinic acid decarboxylase, Glutamate decarboxylase-like protein 1

All UniProt accessions (1): Q6ZQY3

UniProt curated annotations — full annotation on UniProt →

Function. May catalyze the decarboxylation of L-aspartate, 3-sulfino-L-alanine (cysteine sulfinic acid), and L-cysteate to beta-alanine, hypotaurine and taurine, respectively. Does not exhibit any decarboxylation activity toward glutamate.

Subunit / interactions. Homodimer.

Tissue specificity. Expressed very weakly in neurons and not detected in astrocytes, brain or liver.

Similarity. Belongs to the group II decarboxylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZQY3-1	1	yes
Q6ZQY3-3	2

RefSeq proteins (1): NP_997242* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002129	PyrdxlP-dep_de-COase	Domain
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR021115	Pyridoxal-P_BS	Binding_site

Pfam: PF00282

Catalyzed reactions (Rhea), 3 shown:

• 3-sulfino-L-alanine + H(+) = hypotaurine + CO2 (RHEA:16877)
• L-aspartate + H(+) = beta-alanine + CO2 (RHEA:19497)
• L-cysteate + H(+) = taurine + CO2 (RHEA:25221)

UniProt features (4 total): chain 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZQY3-F1	94.77	0.91

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 (1): 333

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1614558	Degradation of cysteine and homocysteine
R-HSA-8963693	Aspartate and asparagine metabolism

MSigDB gene sets: 75 (showing top): AAGTCCA_MIR422B_MIR422A, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, IRF1_Q6, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, NKX3A_01, TGGAAA_NFAT_Q4_01, GOMF_CARBOXY_LYASE_ACTIVITY, GOMF_CARBON_CARBON_LYASE_ACTIVITY, GOMF_VITAMIN_BINDING, GOMF_VITAMIN_B6_BINDING, REACTOME_DEGRADATION_OF_CYSTEINE_AND_HOMOCYSTEINE, REACTOME_ASPARTATE_AND_ASPARAGINE_METABOLISM, TFEB_TARGET_GENES, MIR8485, MIR3662

GO Biological Process (1): carboxylic acid metabolic process (GO:0019752)

GO Molecular Function (6): aspartate 1-decarboxylase activity (GO:0004068), sulfinoalanine decarboxylase activity (GO:0004782), carboxy-lyase activity (GO:0016831), pyridoxal phosphate binding (GO:0030170), lyase activity (GO:0016829), carbon-carbon lyase activity (GO:0016830)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Sulfur amino acid metabolism	1
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
carboxy-lyase activity	2
cellular anatomical structure	2
oxoacid metabolic process	1
carbon-carbon lyase activity	1
anion binding	1
vitamin B6 binding	1
catalytic activity	1
lyase activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1877 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GADL1	CDO1	P78513	743
GADL1	SLC6A6	P31641	533
GADL1	ADO	Q96SZ5	503
GADL1	MEOX1	P50221	492
GADL1	ARHGEF15	O94989	487
GADL1	NRG2	O14511	465
GADL1	POU6F1	Q14863	460
GADL1	BHMT	Q93088	440
GADL1	SEMA3G	Q9NS98	421
GADL1	OPALIN	Q96PE5	421
GADL1	NME8	Q8N427	418
GADL1	SCARF1	Q14162	412
GADL1	CTH	P32929	412
GADL1	MYBL1	P10243	407
GADL1	P0DN79	P0DN79	395

IntAct

4 interactions, top by confidence:

A	B	Type	Score
OR7A5	UBE4B	psi-mi:“MI:0914”(association)	0.350
OR10A4	LRRC73	psi-mi:“MI:0914”(association)	0.350
GADL1	HSPA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): GADL1 (Proximity Label-MS), ANKMY2 (Affinity Capture-MS), PPP5C (Affinity Capture-MS), HSPA2 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), GADL1 (Affinity Capture-MS), RBM14-RBM4 (Affinity Capture-MS), GADL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2H5AIY0, A0A2H5AIY2, A0A2I6B3P0, A0AA51Z3J4, A6QM00, A8XKT0, O82415, O88533, O96567, O96569, O96571, P05031, P14173, P17770, P18486, P20228, P20711, P22781, P27718, P48320, P48321, P48861, P54768, P54769, P54770, P54771, P80041, P81893, P93082, P93083, Q05329, Q05683, Q06085, Q06086, Q06087, Q06088, Q0VCA1, Q0ZQX0, Q0ZS27, Q16S21

Diamond homologs: A0PA85, A2STQ3, A6QM00, E9FCP7, P14748, P18088, P20228, P48318, P48319, P48320, P48321, Q05329, Q05683, Q0VCA1, Q28D99, Q2FSD2, Q4PRC2, Q5IS68, Q5R7S7, Q64611, Q6ZQY3, Q80WP8, Q99259, Q9DBE0, Q9Y600, Q9Z3R1, A0A481NV25, I1RV23, O96571, P71362, Q0W498, Q43908, A0A0A2IDH4, Q8TV92, Q05733, A7B1V0, A0B9M9, A4G060, A6VIC0, A7IAB9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GADL1	“down-regulates quantity”	L-aspartate(1-)	“chemical modification”
GADL1	“up-regulates quantity”	“beta-alanine zwitterion”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	91
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
984746	GRCh37/hg19 3p24.1-23(chr3:30863773-31433693)x1	Pathogenic

SpliceAI

2782 predictions. Top by Δscore:

Variant	Effect	Δscore
3:30728411:GCCAC:G	acceptor_gain	1.0000
3:30728412:CCAC:C	acceptor_gain	1.0000
3:30728412:CCACC:C	acceptor_gain	1.0000
3:30728413:CAC:C	acceptor_gain	1.0000
3:30728413:CACC:C	acceptor_gain	1.0000
3:30728414:ACCT:A	acceptor_loss	1.0000
3:30728415:CC:C	acceptor_loss	1.0000
3:30728415:CCTG:C	acceptor_gain	1.0000
3:30728416:C:CA	acceptor_loss	1.0000
3:30778173:ACTT:A	donor_loss	1.0000
3:30778175:TTACC:T	donor_loss	1.0000
3:30778176:TACC:T	donor_loss	1.0000
3:30778177:A:T	donor_loss	1.0000
3:30778178:C:CA	donor_loss	1.0000
3:30778276:T:C	acceptor_gain	1.0000
3:30778276:T:TC	acceptor_gain	1.0000
3:30786353:A:AC	donor_gain	1.0000
3:30786353:ACTT:A	donor_gain	1.0000
3:30786354:C:CC	donor_gain	1.0000
3:30786354:CTTC:C	donor_gain	1.0000
3:30786356:T:TA	donor_gain	1.0000
3:30800940:AGGG:A	donor_gain	1.0000
3:30800947:T:TA	donor_gain	1.0000
3:30833851:A:AC	donor_gain	1.0000
3:30833852:C:CC	donor_gain	1.0000
3:30833934:CCTAT:C	acceptor_gain	1.0000
3:30838995:A:AC	donor_gain	1.0000
3:30838996:C:CC	donor_gain	1.0000
3:30838996:CAT:C	donor_gain	1.0000
3:30850942:C:CC	acceptor_gain	1.0000

AlphaMissense

3467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:30728328:G:T	R494S	0.998
3:30800981:T:A	R386S	0.998
3:30800981:T:G	R386S	0.998
3:30800982:C:G	R386T	0.998
3:30800984:G:C	S385R	0.998
3:30800984:G:T	S385R	0.998
3:30800986:T:G	S385R	0.998
3:30801044:G:C	F365L	0.998
3:30801044:G:T	F365L	0.998
3:30801046:A:G	F365L	0.998
3:30833918:A:G	W329R	0.998
3:30833918:A:T	W329R	0.998
3:30854701:A:C	S142R	0.998
3:30854701:A:T	S142R	0.998
3:30854703:T:G	S142R	0.998
3:30854776:A:C	F117L	0.998
3:30854776:A:T	F117L	0.998
3:30854778:A:G	F117L	0.998
3:30728327:C:G	R494P	0.997
3:30800950:A:G	W397R	0.997
3:30800950:A:T	W397R	0.997
3:30800959:A:G	W394R	0.997
3:30800959:A:T	W394R	0.997
3:30801048:A:G	L364P	0.997
3:30833880:G:C	C341W	0.997
3:30833904:C:A	K333N	0.997
3:30833904:C:G	K333N	0.997
3:30833905:T:A	K333M	0.997
3:30833905:T:G	K333T	0.997
3:30834275:A:G	W304R	0.997

dbSNP variants (sampled 300 via entrez): RS1000015897 (3:30847163 G>C,T), RS1000018580 (3:30799721 G>A,C), RS1000041830 (3:30845701 A>G), RS1000050516 (3:30775054 G>C), RS1000052838 (3:30777737 C>T), RS1000062573 (3:30765576 G>A), RS1000070448 (3:30836176 G>A), RS1000078061 (3:30761481 TTTA>T), RS1000081436 (3:30809575 A>G), RS1000106377 (3:30777891 C>A,G), RS1000117128 (3:30733599 T>C), RS1000142312 (3:30778493 T>C), RS1000144576 (3:30845921 T>C), RS1000171439 (3:30815411 G>A,T), RS1000200748 (3:30752514 G>A)

Disease associations

OMIM: gene MIM:615601 | disease phenotypes: MIM:615485

GenCC curated gene-disease

Mondo (2): primary amenorrhea (MONDO:1060208), severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome (MONDO:0014205)

Orphanet (1): Bainbridge-Ropers syndrome (Orphanet:352577)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001959_10	Eating disorders (purging via substances)	8.000000e-06
GCST003542_42	Night sleep phenotypes	5.000000e-06
GCST012020_92	Serum metabolite levels	4.000000e-18
GCST012174_1	Diabetic retinopathy in type 2 diabetes	7.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17026688	GADL1		0.00	0

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
titanium dioxide	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Lipopolysaccharides	affects response to substance, increases expression	1
Rotenone	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07164248	Not specified	COMPLETED	Evaluation of Bone Mineral Density Indications and Outcomes in Female Adolescents: Implications for Early Detection of Osteopenia/Osteoporosis and Gynecologic Practice
NCT07197268	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for A Single Participant With ASXL3 Gene Mutation
NCT03303716	Not specified	RECRUITING	ASXL-Related Disorders Natural History Study