AASDHPPT

Summary

AASDHPPT (aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase, HGNC:14235) is a protein-coding gene on chromosome 11q22.3, encoding L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (Q9NRN7). Catalyzes the post-translational modification of target proteins by phosphopantetheine. It is a selective cancer dependency (DepMap: 29.9% of cell lines).

The protein encoded by this gene is similar to Saccharomyces cerevisiae LYS5, which is required for the activation of the alpha-aminoadipate dehydrogenase in the biosynthetic pathway of lysine. Yeast alpha-aminoadipate dehydrogenase converts alpha-biosynthetic-aminoadipate semialdehyde to alpha-aminoadipate. It has been suggested that defects in the human gene result in pipecolic acidemia.

Source: NCBI Gene 60496 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 59 total — 7 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 29.9% of screened cell lines
• MANE Select transcript: NM_015423

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14235
Approved symbol	AASDHPPT
Name	aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase
Location	11q22.3
Locus type	gene with protein product
Status	Approved
Aliases	LYS5, CGI-80, AASD-PPT, ACPS
Ensembl gene	ENSG00000149313
Ensembl biotype	protein_coding
OMIM	607756
Entrez	60496

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000278618, ENST00000524411, ENST00000525660, ENST00000533423, ENST00000534152, ENST00000878108, ENST00000926644, ENST00000926645

RefSeq mRNA: 1 — MANE Select: NM_015423 NM_015423

CCDS: CCDS31664

Canonical transcript exons

ENST00000278618 — 6 exons

Exon	Start	End
ENSE00001251591	106090557	106090678
ENSE00001290916	106077662	106077893
ENSE00002154468	106096743	106098695
ENSE00003563255	106091316	106091477
ENSE00003645123	106079467	106079692
ENSE00003788948	106094583	106094654

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 98.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.2194 / max 387.5476, expressed in 1821 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116492	36.8758	1820
116493	2.9219	1273
116494	0.2359	94
116491	0.1859	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.37	gold quality
sperm	CL:0000019	97.80	gold quality
choroid plexus epithelium	UBERON:0003911	97.68	gold quality
frontal pole	UBERON:0002795	97.49	gold quality
postcentral gyrus	UBERON:0002581	97.29	gold quality
parietal lobe	UBERON:0001872	97.26	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.22	gold quality
superior frontal gyrus	UBERON:0002661	97.03	gold quality
superior vestibular nucleus	UBERON:0007227	96.99	gold quality
adrenal tissue	UBERON:0018303	96.92	gold quality
pons	UBERON:0000988	96.87	gold quality
cerebellar vermis	UBERON:0004720	96.81	gold quality
orbitofrontal cortex	UBERON:0004167	96.69	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.68	gold quality
middle frontal gyrus	UBERON:0002702	96.67	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.48	gold quality
ganglionic eminence	UBERON:0004023	96.39	gold quality
male germ cell	CL:0000015	96.28	gold quality
entorhinal cortex	UBERON:0002728	96.28	gold quality
secondary oocyte	CL:0000655	96.19	gold quality
CA1 field of hippocampus	UBERON:0003881	96.17	gold quality
paraflocculus	UBERON:0005351	95.88	gold quality
occipital lobe	UBERON:0002021	95.83	gold quality
primary visual cortex	UBERON:0002436	95.72	gold quality
prefrontal cortex	UBERON:0000451	95.64	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.52	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.39	gold quality
ventral tegmental area	UBERON:0002691	95.35	gold quality
embryo	UBERON:0000922	95.34	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)

102 targeting AASDHPPT, 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-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-126-5P	100.00	72.71	3180
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 29.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• humans appear to utilize a single, broad specificity enzyme, 4’-phosphopantetheine transferase, for all posttranslational 4’-phosphopantetheinylation reactions (PMID:12815048)
• Our study identifies human PPT as the FDH-modifying enzyme and supports the hypothesis that mammals utilize a single enzyme for all phosphopantetheinylation reactions. (PMID:19933275)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	aasdhppt	ENSDARG00000037501
mus_musculus	Aasdhppt	ENSMUSG00000025894
rattus_norvegicus	Aasdhppt	ENSRNOG00000005795
drosophila_melanogaster	CG32099	FBGN0052099
caenorhabditis_elegans		WBGENE00012142
caenorhabditis_elegans		WBGENE00020215

Protein

Protein identifiers

L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase — Q9NRN7 (reviewed: Q9NRN7)

Alternative names: 4’-phosphopantetheinyl transferase, Alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase, LYS5 ortholog

All UniProt accessions (3): Q9NRN7, E9PLW6, E9PNF3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the post-translational modification of target proteins by phosphopantetheine. Can transfer the 4’-phosphopantetheine moiety from coenzyme A, regardless of whether the CoA is presented in the free thiol form or as an acetyl thioester, to a serine residue of a broad range of acceptors including the acyl carrier domain of FASN.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Detected in heart, skeletal muscle, placenta, testis, brain, pancreas, liver and kidney.

Cofactor. Binds 1 Mg(2+) ion.

Similarity. Belongs to the P-Pant transferase superfamily. AcpS family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRN7-1	1	yes
Q9NRN7-2	2

RefSeq proteins (1): NP_056238* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008278	4-PPantetheinyl_Trfase_dom	Domain
IPR037143	4-PPantetheinyl_Trfase_dom_sf	Homologous_superfamily
IPR050559	P-Pant_transferase_sf	Family
IPR055066	AASDHPPT_N	Domain

Pfam: PF01648, PF22624

Enzyme classification (BRENDA):

• EC 2.7.8.7 — holo-[acyl-carrier-protein] synthase (BRENDA: 51 organisms, 153 substrates, 34 inhibitors, 152 Km, 104 kcat entries)

Substrate kinetics (BRENDA)

37 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
APO-ACYL-CARRIER PROTEIN	0.0002–0.072	22
ACETYL-COA	0.0077–0.399	13
APO-[ACYL-CARRIER PROTEIN]	0.0008–0.215	13
MG2+	0.44–104.1	10
COA	0.0011–0.15	9
APO-ACP	0.017–0.068	5
APO-PEPTIDYL CARRIER PROTEIN	0.0044–0.026	4
ACETOACETYL-COA	0.0088–0.051	3
APO-[BPSA PROTEIN]	0.0033–0.0086	3
BUTYRYL-COA	0.007–0.035	3
COA-[4’-PHOSPHOPANTETHEINE]	0.0006–0.011	3
MALONYL-COA	0.0071–0.094	3
APO-PEPTIDE(1–>74)	0.002	2
APO-[PEPTIDYL CARRIER PROTEIN]	0.0031–0.0039	2
CROTONYL-COA	0.0052–0.018	2

Catalyzed reactions (Rhea), 2 shown:

• apo-[ACP] + CoA = holo-[ACP] + adenosine 3’,5’-bisphosphate + H(+) (RHEA:12068)
• apo-[ACP] + acetyl-CoA = acetyl-[ACP] + adenosine 3’,5’-bisphosphate + H(+) (RHEA:46564)

UniProt features (50 total): strand 14, helix 14, mutagenesis site 8, binding site 6, sequence conflict 2, turn 2, splice variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2C43	X-RAY DIFFRACTION	1.93
2BYD	X-RAY DIFFRACTION	2
2CG5	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRN7-F1	90.61	0.84

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 (6): 47; 86–91; 108–111; 129; 181–185; 181

Post-translational modifications (1): 258

Mutagenesis-validated functional residues (8):

Position	Phenotype
47	reduces affinity for magnesium by 7-fold, and holo-[acyl-carrier-protein] synthase activity by 2-fold.
86	reduces affinity for magnesium and coenzyme a, and reduces holo-[acyl-carrier-protein] synthase activity by 7-fold.
111	reduces affinity for magnesium by 75-fold, and holo-[acyl-carrier-protein] synthase activity by 150-fold.
112	reduces affinity for magnesium by 200-fold and abolishes holo-[acyl-carrier-protein] synthase activity; when associated
129	reduces affinity for magnesium by 10-fold, and holo-[acyl-carrier-protein] synthase activity by 30000-fold.
181	reduces affinity for magnesium by 40-fold, and holo-[acyl-carrier-protein] synthase activity by 32000-fold.
181	reduces affinity for magnesium by 20-fold, and holo-[acyl-carrier-protein] synthase activity by 6500-fold.
185	reduces holo-[acyl-carrier-protein] synthase activity by 2000-fold, with only minor change in the affinity for magnesium

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-199220	Vitamin B5 (pantothenate) metabolism
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 126 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, chr11q22, GOBP_MODIFIED_AMINO_ACID_CATABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GGGTGGRR_PAX4_03, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_PROTEIN_MATURATION, GOBP_PTERIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_TETRAHYDROFOLATE_METABOLIC_PROCESS, KEGG_LYSINE_DEGRADATION, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN

GO Biological Process (4): 10-formyltetrahydrofolate catabolic process (GO:0009258), pantothenate metabolic process (GO:0015939), obsolete L-lysine biosynthetic process via aminoadipic acid (GO:0019878), protein maturation (GO:0051604)

GO Molecular Function (5): magnesium ion binding (GO:0000287), holo-[acyl-carrier-protein] synthase activity (GO:0008897), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
10-formyltetrahydrofolate metabolic process	1
folic acid-containing compound catabolic process	1
dicarboxylic acid catabolic process	1
modified amino acid metabolic process	1
monocarboxylic acid metabolic process	1
gene expression	1
protein metabolic process	1
metal ion binding	1
phosphotransferase activity, for other substituted phosphate groups	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AASDHPPT	HAT1	O14929	872
AASDHPPT	AASDH	Q4L235	827
AASDHPPT	TMEM126B	Q8IUX1	825
AASDHPPT	TMEM126A	Q9H061	815
AASDHPPT	DLD	P09622	814
AASDHPPT	H4C7	Q99525	801
AASDHPPT	H4C16	P02304	799
AASDHPPT	NDUFAB1	O14561	714
AASDHPPT	POLDIP3	Q9BY77	694
AASDHPPT	ATP5F1B	P06576	688
AASDHPPT	BRDT	Q58F21	682
AASDHPPT	BACE1	P56817	673
AASDHPPT	MCAT	Q8IVS2	647
AASDHPPT	RBBP7	Q16576	613
AASDHPPT	TACR2	P21452	574

IntAct

86 interactions, top by confidence:

A	B	Type	Score
AASDHPPT	TRAF2	psi-mi:“MI:0915”(physical association)	0.780
TRAF2	AASDHPPT	psi-mi:“MI:0915”(physical association)	0.780
AASDHPPT	USP22	psi-mi:“MI:0915”(physical association)	0.740
USP22	AASDHPPT	psi-mi:“MI:0915”(physical association)	0.740
TSEN15	TSEN54	psi-mi:“MI:0914”(association)	0.740
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AASDHPPT	USP22	psi-mi:“MI:0915”(physical association)	0.670
AASDHPPT	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
SIAH1	AASDHPPT	psi-mi:“MI:0915”(physical association)	0.560
EFHC2	AASDHPPT	psi-mi:“MI:0915”(physical association)	0.560
CRX	AASDHPPT	psi-mi:“MI:0915”(physical association)	0.560
ANGPTL4	NMT2	psi-mi:“MI:0914”(association)	0.530
PPP1R3C	STBD1	psi-mi:“MI:0914”(association)	0.530
AASDHPPT	POTEI	psi-mi:“MI:0914”(association)	0.530
rep	NKRF	psi-mi:“MI:0914”(association)	0.500

BioGRID (110): AASDHPPT (Two-hybrid), AASDHPPT (Two-hybrid), AASDHPPT (Two-hybrid), AASDHPPT (Affinity Capture-RNA), AASDHPPT (Affinity Capture-RNA), STIL (Affinity Capture-MS), POTEI (Affinity Capture-MS), USP22 (Affinity Capture-MS), AASDHPPT (Two-hybrid), AASDHPPT (Two-hybrid), AASDHPPT (Co-fractionation), AASDHPPT (Co-fractionation), AASDHPPT (Co-fractionation), AASDHPPT (Co-fractionation), AASDHPPT (Co-fractionation)

ESM2 similar proteins: A6NDL7, A7X672, B0K012, D3ZV31, E1BGQ2, F1N9S8, O08848, P0C0T1, P42694, P50747, Q05B63, Q0V8R7, Q13572, Q3U2J5, Q4R528, Q5BJZ6, Q5F480, Q5NVE1, Q5R962, Q5ZIA0, Q6DC64, Q6DFV5, Q6DJF8, Q6GQ33, Q6GR37, Q6NYU2, Q6P4H8, Q6YJI5, Q7SY78, Q7TNK6, Q7Z4G4, Q7Z624, Q80YV4, Q8BKW4, Q8BYN3, Q8C436, Q8CDZ2, Q8N4J0, Q8R1C6, Q8VDG3

Diamond homologs: A0A0S1RVB0, A0A1B3PEJ0, B2RYJ4, P37695, P39144, P55810, Q10474, Q5NVE1, Q6DJH2, Q74Z24, Q9CQF6, Q9F4F7, Q9NRN7, P39135, P40683, P37623, P43954, P50113, Q55185, Q8X5U4, Q8Z259, Q8ZLE2, A0A1L7T8M0, A0A223GB52

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	47
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1075501	NC_000011.9:g.(?94153285)(111965700_?)del	Pathogenic
1807688	GRCh37/hg19 11q22.1-22.3(chr11:101371503-109306519)x1	Pathogenic
441837	GRCh37/hg19 11q14.2-22.3(chr11:88152458-109414650)x1	Pathogenic
4682792	GRCh37/hg19 11q22.1-22.3(chr11:101504957-108516865)x1	Pathogenic
58918	GRCh38/hg38 11q14.1-22.3(chr11:78232836-106779420)x1	Pathogenic
688050	GRCh37/hg19 11q22.3-23.3(chr11:104101411-116680918)x1	Pathogenic
815462	GRCh37/hg19 11q22.3-23.2(chr11:103320065-114349787)x1	Pathogenic
563877	GRCh37/hg19 11q22.2-22.3(chr11:102578709-107230611)x1	Likely pathogenic

SpliceAI

1189 predictions. Top by Δscore:

Variant	Effect	Δscore
11:106079465:A:AG	acceptor_gain	1.0000
11:106079465:A:C	acceptor_loss	1.0000
11:106079465:AG:A	acceptor_gain	1.0000
11:106079465:AGGCT:A	acceptor_gain	1.0000
11:106079466:G:GA	acceptor_gain	1.0000
11:106079466:GG:G	acceptor_gain	1.0000
11:106079466:GGCT:G	acceptor_gain	1.0000
11:106079466:GGCTG:G	acceptor_gain	1.0000
11:106079688:TCCAG:T	donor_loss	1.0000
11:106079689:CCAGG:C	donor_loss	1.0000
11:106079690:CAG:C	donor_loss	1.0000
11:106079691:AGGT:A	donor_loss	1.0000
11:106079692:GGT:G	donor_loss	1.0000
11:106079693:GTAA:G	donor_loss	1.0000
11:106079694:T:G	donor_loss	1.0000
11:106090640:GA:G	donor_gain	1.0000
11:106090641:A:G	donor_gain	1.0000
11:106090658:GA:G	donor_gain	1.0000
11:106090659:A:G	donor_gain	1.0000
11:106090672:G:GT	donor_gain	1.0000
11:106091311:CTTA:C	acceptor_loss	1.0000
11:106091312:TTA:T	acceptor_loss	1.0000
11:106091314:A:AG	acceptor_gain	1.0000
11:106091314:AGG:A	acceptor_loss	1.0000
11:106091315:G:GG	acceptor_gain	1.0000
11:106091474:TGAGG:T	donor_loss	1.0000
11:106091475:GAG:G	donor_gain	1.0000
11:106091475:GAGGT:G	donor_loss	1.0000
11:106091476:AGGTA:A	donor_loss	1.0000
11:106091477:GGT:G	donor_loss	1.0000

AlphaMissense

2053 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:106079669:A:C	D129A	0.998
11:106090676:T:A	W177R	0.998
11:106090676:T:C	W177R	0.998
11:106091324:G:C	K180N	0.998
11:106091324:G:T	K180N	0.998
11:106091328:A:C	S182R	0.998
11:106091330:C:A	S182R	0.998
11:106091330:C:G	S182R	0.998
11:106091338:A:T	K185I	0.998
11:106091339:A:C	K185N	0.998
11:106091339:A:T	K185N	0.998
11:106091340:G:C	A186P	0.998
11:106091466:T:A	W228R	0.998
11:106091466:T:C	W228R	0.998
11:106079487:G:C	R68S	0.997
11:106079487:G:T	R68S	0.997
11:106079633:T:A	V117E	0.997
11:106079639:C:A	A119D	0.997
11:106079662:G:A	G127R	0.997
11:106079662:G:C	G127R	0.997
11:106079663:G:A	G127E	0.997
11:106079607:C:A	N108K	0.996
11:106079607:C:G	N108K	0.996
11:106079612:C:T	S110F	0.996
11:106079636:T:C	L118P	0.996
11:106079669:A:T	D129V	0.996
11:106079670:T:A	D129E	0.996
11:106079670:T:G	D129E	0.996
11:106091320:T:C	L179P	0.996
11:106091326:A:T	E181V	0.996

dbSNP variants (sampled 300 via entrez): RS1000110129 (11:106080711 A>G), RS1000556668 (11:106082725 C>T), RS1000623423 (11:106076359 G>A), RS1000646334 (11:106085137 T>C,G), RS1000652680 (11:106097993 G>A), RS1000722954 (11:106098182 C>T), RS1000736127 (11:106088697 G>C), RS1000793449 (11:106082480 A>T), RS1001344542 (11:106092505 T>C), RS1001446730 (11:106085364 G>A), RS1001693312 (11:106079404 A>G), RS1001705616 (11:106088517 A>C,G), RS1001819875 (11:106094960 T>C), RS1002086424 (11:106081749 T>G), RS1002327339 (11:106086626 C>T)

Disease associations

OMIM: gene MIM:607756 | disease phenotypes: MIM:208900

GenCC curated gene-disease

Mondo (1): ataxia telangiectasia (MONDO:0008840)

Orphanet (1): Ataxia-telangiectasia (Orphanet:100)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006107_9	Upper eyelid morphology	6.000000e-06
GCST011116_5	Coronary artery disease in type 1 diabetes	8.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001260	Ataxia Telangiectasia	C10.228.140.252.190.530.060; C10.562.100; C10.597.350.090.500.530.060; C14.907.823.213; C16.320.080; C16.320.798.250; C18.452.284.060; C20.673.795.250

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3137295 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.26	Kd	5496	nM	CHEMBL5653589
5.26	ED50	5496	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 5 total; 1 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	2147766: Binding affinity to human AASDHPPT incubated for 45 mins by Kinobead based pull down assay	kd	5.4964	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
sodium arsenate	increases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric chloride	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
torcetrapib	increases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Cadmium	increases abundance, increases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Ivermectin	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Rotenone	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Uranium	affects expression	1
Valproic Acid	decreases 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
CHEMBL3130424	Binding	Inhibition of human PPTase up to 125 uM by gel-based fluorescence assay	4-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), a potent inhibitor of bacterial phosphopantetheinyl transferase that attenuates secondary metabolism and thwarts bacterial growth. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01052623	PHASE4	UNKNOWN	Status of Growth Hormone/ Insulin-like Growth Factor-1 (GH/IGF-1) Axis and Growth Failure in Ataxia Telangiectasia (AT)
NCT02733679	PHASE4	COMPLETED	Response of Individuals With Ataxia-Telangiectasia to Metformin and Pioglitazone
NCT00656409	PHASE3	COMPLETED	Conjugate Pneumococcal Vaccine in Ataxia Telangiectasia (AT)
NCT03563053	PHASE3	TERMINATED	Extension Treatment Using EryDex System in Patients With AT Who Participated in the ATTeST-IEDAT-02-2015 Study
NCT06193200	PHASE3	COMPLETED	Evaluate the Neurological Effects of EryDex on Subjects With A-T
NCT06664853	PHASE3	TERMINATED	Open-Label Extension of EryDex Study IEDAT-04-2022
NCT06673056	PHASE3	ACTIVE_NOT_RECRUITING	A Pivotal Study of N-Acetyl-L-Leucine on Ataxia-Telangiectasia (A-T)
NCT03759678	PHASE2	TERMINATED	N-Acetyl-L-Leucine for Ataxia-Telangiectasia (A-T)
NCT03962114	PHASE2	COMPLETED	Effects of Vitamin B3 in Patients With Ataxia Telangiectasia
NCT04513002	PHASE2	COMPLETED	Ataxia-telangiectasia: Treating Mitochondrial Dysfunction With a Novel Form of Anaplerosis
NCT04870866	PHASE2	ACTIVE_NOT_RECRUITING	NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia
NCT04887311	PHASE2	UNKNOWN	MBM-01 (Tempol) for the Treatment of Ataxia Telangiectasia
NCT05531890	PHASE1	UNKNOWN	Comparative Bioavailability of Betamethasone Oral Solution Metered Spray (GTX-102) in Healthy Subjects
NCT07215416	PHASE1/PHASE2	RECRUITING	Safety and Efficacy of Mutation-targeted Precision Genetic Therapy for Ataxia-Telangiectasia (A-T)
NCT00640003	EARLY_PHASE1	COMPLETED	Baclofen Treatment of Ataxia Telangiectasia
NCT00187057	Not specified	COMPLETED	Study for Treatment of Cancer in Children With Ataxia-telangiectasia
NCT00951886	Not specified	UNKNOWN	The Validity of Forced Expiratory Maneuvers in Ataxia Telangiectasia Studied Longitudinally
NCT01075438	Not specified	UNKNOWN	Immunogenicity of Pneumococcal Vaccines in Ataxia-telangiectasia Patients
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01942850	Not specified	COMPLETED	International Ataxia Rating Scale in Younger Patients
NCT02285348	Not specified	COMPLETED	Oxidative Stress, Low Grade Inflammation, Tissue Breakdown and Biomarkers in Cerebrospinal Fluid of A-T
NCT02309632	Not specified	WITHDRAWN	Pancreatic Cancer Screening of High-Risk Individuals in Arkansas
NCT02345135	Not specified	COMPLETED	Susceptibility to Infections in Ataxia Telangiectasia
NCT02345200	Not specified	COMPLETED	Body Composition and Hormonal Status in Ataxia Telangiectasia
NCT03357978	Not specified	UNKNOWN	Susceptibility to Infections, Tumor Risk and Liver Disease in Patients With Ataxia Telangiectasia
NCT04037189	Not specified	UNKNOWN	Treatment of Leukemia and Lymphoma in Children With Ataxia Telangiectasia
NCT04605523	Not specified	UNKNOWN	Neurofilament Light- Chain in Ataxia Telangiectasia
NCT04991701	Not specified	UNKNOWN	A National Retrospective Population Based Cohort Study of the Natural History of Ataxia Telangiectasia
NCT05252819	Not specified	COMPLETED	Whole Body MRI for Cancer Surveillance in A-T
NCT05471310	Not specified	COMPLETED	Videoocular Assessment of Eye Movement Activity in an Ataxia Telangiectasia
NCT05692596	Not specified	ACTIVE_NOT_RECRUITING	The Pancreas Interception Center (PIC) for Early Detection, Prevention, and Novel Therapeutics
NCT05692622	Not specified	UNKNOWN	Home-based Complex Intervention for Children With Ataxia Telangiectasia
NCT06324877	Not specified	UNKNOWN	Ataxia-telangiectasia: Treating Mitochondrial Dysfunction With Nicotinamide Riboside