PDS5A

Summary

PDS5A (PDS5 cohesin associated factor A, HGNC:29088) is a protein-coding gene on chromosome 4p14, encoding Sister chromatid cohesion protein PDS5 homolog A (Q29RF7). Probable regulator of sister chromatid cohesion in mitosis which may stabilize cohesin complex association with chromatin. It is a selective cancer dependency (DepMap: 26.5% of cell lines).

The protein encoded by this gene binds to the cohesin complex and associates with chromatin through most of the cell cycle. The encoded protein may play a role in regulating sister chromatid cohesion during mitosis. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 23244 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 145 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 26.5% of screened cell lines
• MANE Select transcript: NM_001100399

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29088
Approved symbol	PDS5A
Name	PDS5 cohesin associated factor A
Location	4p14
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0648, PIG54, SCC-112
Ensembl gene	ENSG00000121892
Ensembl biotype	protein_coding
OMIM	613200
Entrez	23244

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 29 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay

ENST00000303538, ENST00000503396, ENST00000503696, ENST00000503867, ENST00000506262, ENST00000507020, ENST00000507766, ENST00000508625, ENST00000512643, ENST00000513798, ENST00000852888, ENST00000852889, ENST00000852890, ENST00000852891, ENST00000852892, ENST00000852893, ENST00000852894, ENST00000852895, ENST00000928551, ENST00000928552, ENST00000928553, ENST00000928554, ENST00000928555, ENST00000928556, ENST00000928557, ENST00000928558, ENST00000928559, ENST00000928560, ENST00000928561, ENST00000971060, ENST00000971061, ENST00000971062, ENST00000971063, ENST00000971064, ENST00000971065, ENST00000971066

RefSeq mRNA: 2 — MANE Select: NM_001100399 NM_001100399, NM_001100400

CCDS: CCDS47045, CCDS54759

Canonical transcript exons

ENST00000303538 — 33 exons

Exon	Start	End
ENSE00000361648	39866861	39866997
ENSE00000361660	39876993	39877153
ENSE00000826518	39872986	39873144
ENSE00000826525	39910244	39910338
ENSE00000969623	39920319	39920399
ENSE00001077338	39869394	39869462
ENSE00001232528	39862219	39862333
ENSE00001232536	39862869	39863073
ENSE00001232660	39927961	39928164
ENSE00001271474	39874289	39874412
ENSE00001271493	39879728	39879833
ENSE00001271499	39890249	39890364
ENSE00001271514	39898777	39898825
ENSE00001271572	39913611	39913726
ENSE00001271582	39917048	39917188
ENSE00001271594	39922622	39922748
ENSE00001271695	39976440	39976617
ENSE00001297736	39837856	39838208
ENSE00001309059	39848851	39848970
ENSE00001315570	39898389	39898528
ENSE00001329789	39845818	39845880
ENSE00001330852	39849520	39849652
ENSE00001593976	39925836	39925933
ENSE00001677029	39926775	39926861
ENSE00001960136	39822863	39825488
ENSE00003478945	39908395	39908540
ENSE00003479517	39841948	39842056
ENSE00003520627	39902347	39902460
ENSE00003548473	39844656	39844801
ENSE00003648361	39904040	39904191
ENSE00003655208	39863336	39863459
ENSE00003790195	39900426	39900507
ENSE00003847218	39977457	39977911

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 96.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.0176 / max 670.5165, expressed in 1826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51873	25.4930	1817
51871	9.8301	1759
51872	6.6162	1704
51868	0.7970	331
51874	0.2813	132

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	96.63	gold quality
epithelium of nasopharynx	UBERON:0001951	96.16	gold quality
nasopharynx	UBERON:0001728	96.14	gold quality
calcaneal tendon	UBERON:0003701	95.16	gold quality
tonsil	UBERON:0002372	95.01	gold quality
gingival epithelium	UBERON:0001949	94.91	gold quality
colonic epithelium	UBERON:0000397	94.75	gold quality
squamous epithelium	UBERON:0006914	94.40	gold quality
esophagus squamous epithelium	UBERON:0006920	94.28	gold quality
gingiva	UBERON:0001828	94.02	gold quality
choroid plexus epithelium	UBERON:0003911	94.01	gold quality
cervix squamous epithelium	UBERON:0006922	93.97	gold quality
cartilage tissue	UBERON:0002418	93.79	gold quality
seminal vesicle	UBERON:0000998	93.51	gold quality
bone marrow cell	CL:0002092	93.45	gold quality
tendon	UBERON:0000043	93.40	gold quality
visceral pleura	UBERON:0002401	93.37	gold quality
upper leg skin	UBERON:0004262	93.34	gold quality
ventricular zone	UBERON:0003053	93.13	gold quality
palpebral conjunctiva	UBERON:0001812	93.10	gold quality
islet of Langerhans	UBERON:0000006	92.85	gold quality
parotid gland	UBERON:0001831	92.81	gold quality
pleura	UBERON:0000977	92.78	gold quality
skin of hip	UBERON:0001554	92.73	gold quality
nephron tubule	UBERON:0001231	92.59	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.59	gold quality
parietal pleura	UBERON:0002400	92.52	gold quality
adrenal tissue	UBERON:0018303	92.52	gold quality
epithelium of esophagus	UBERON:0001976	92.44	gold quality
tibia	UBERON:0000979	92.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	296.74
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• Findings suggest that the SCC-112 gene expression is likely to be associated with normal cell growth and proliferation. (PMID:15019998)
• SCC-112 improve cell proliferation and contributes to tumorigenesis by interacting with p63 and promoting cell cycling. (PMID:17846787)
• Data show that the siRNA-mediated knockdown of Pds5A affects sister chromatid cohesion but does not influence mitotic checkpoint function or the proliferation and survival of glioblastoma multiforme cells. (PMID:21069257)
• The data show a downregulation of proliferation-associated host gene PDS5A and suggest a role of PDS5A in HIV-1-induced cellular pathogenesis but not viral replication. (PMID:21865657)
• By interacting with a unique domain of Esco1, Pds5 recruits Esco1 to chromatin-bound cohesin complexes to form cohesion. (PMID:26051894)
• These results provide the first evidence indicating a tumor suppressor role of SA1 in early colon carcinogenesis (PMID:27549371)
• The results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL. (PMID:29217591)
• depletion of Rad21 in a Pds5-deficient background rescues the phenotype observed upon Pds5 depletion alone. These findings support a model where loss of either component of the cohesin releasin complex perturbs cohesin dynamics on replication forks, hindering fork progression and promoting MRE11-dependent fork slowing (PMID:29917110)
• PDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection. (PMID:31757807)
• PDS5A and PDS5B in Cohesin Function and Human Disease. (PMID:34070827)
• Knockdown of CDCA5 suppresses malignant progression of breast cancer cells by regulating PDS5A. (PMID:35506437)
• The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism. (PMID:35710836)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pds5a	ENSDARG00000055022
mus_musculus	Pds5a	ENSMUSG00000029202
rattus_norvegicus	Pds5a	ENSRNOG00000002541
drosophila_melanogaster	pds5	FBGN0260012
caenorhabditis_elegans		WBGENE00001352

Paralogs (1): PDS5B (ENSG00000083642)

Protein

Protein identifiers

Sister chromatid cohesion protein PDS5 homolog A — Q29RF7 (reviewed: Q29RF7)

Alternative names: Cell proliferation-inducing gene 54 protein, Sister chromatid cohesion protein 112

All UniProt accessions (5): Q29RF7, G1UI16, H0Y9L6, H0Y9L9, H0Y9X6

UniProt curated annotations — full annotation on UniProt →

Function. Probable regulator of sister chromatid cohesion in mitosis which may stabilize cohesin complex association with chromatin. May couple sister chromatid cohesion during mitosis to DNA replication. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair.

Subunit / interactions. Interacts with the cohesin complex. Interacts with WAPL (via FGF motifs) or CDCA5 (via the FGF motif); the interaction is direct, cohesin-dependent and competitive. Interacts with SMC3. Interacts with TP63.

Subcellular location. Nucleus.

Tissue specificity. Highest level in colon. Low levels in lung, ovary, breast and kidney. Reduced level in renal tumor tissue. Isoform 2 is expressed in kidney.

Miscellaneous. HeLa cells with a reduced level of PDS5A show a mild defect in sister chromatid cohesion. HeLa cells with a reduced level of RAD21 show reduced association of PDS5A with chromatin.

Similarity. Belongs to the PDS5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q29RF7-1	1	yes
Q29RF7-3	2

RefSeq proteins (2): NP_001093869, NP_001093870 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR039776	Pds5	Family

Pfam: PF20168

UniProt features (19 total): modified residue 8, compositionally biased region 3, splice variant 2, sequence conflict 2, chain 1, repeat 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q29RF7-F1	82.61	0.66

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 (8): 1208, 1211, 1290, 1305, 1, 1097, 1146, 1195

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2468052	Establishment of Sister Chromatid Cohesion
R-HSA-2470946	Cohesin Loading onto Chromatin
R-HSA-2500257	Resolution of Sister Chromatid Cohesion

MSigDB gene sets: 242 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, CTATGCA_MIR153, ATGTTAA_MIR302C, PUJANA_CHEK2_PCC_NETWORK, MARTINEZ_RB1_TARGETS_UP, YGACNNYACAR_UNKNOWN, ONKEN_UVEAL_MELANOMA_UP, E2F_Q3, GOBP_SISTER_CHROMATID_COHESION, WTGAAAT_UNKNOWN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, ATTCTTT_MIR186, AACTTT_UNKNOWN

GO Biological Process (3): mitotic sister chromatid cohesion (GO:0007064), negative regulation of DNA replication (GO:0008156), cell division (GO:0051301)

GO Molecular Function (2): cohesin unloader activity (GO:0140670), protein binding (GO:0005515)

GO Cellular Component (7): chromosome, centromeric region (GO:0000775), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytosol (GO:0005829), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Mitotic Anaphase	1
S Phase	1
Mitotic Telophase/Cytokinesis	1
Mitotic Prometaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
sister chromatid cohesion	1
DNA replication	1
regulation of DNA replication	1
negative regulation of DNA metabolic process	1
cellular process	1
catalytic activity, acting on DNA	1
binding	1
chromosomal region	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2899 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDS5A	WAPL	Q7Z5K2	999
PDS5A	STAG1	Q8WVM7	999
PDS5A	SMC3	Q9UQE7	999
PDS5A	RAD21	O60216	998
PDS5A	CDCA5	Q96FF9	994
PDS5A	NIPBL	Q6KC79	991
PDS5A	ESCO1	Q5FWF5	981
PDS5A	STAG2	Q8N3U4	978
PDS5A	MAU2	Q9Y6X3	975
PDS5A	ESCO2	Q56NI9	959
PDS5A	SMC1A	Q14683	953
PDS5A	CHTF18	Q8WVB6	940
PDS5A	REC8	O95072	936
PDS5A	HASPIN	Q8TF76	910
PDS5A	ESPL1	Q14674	898

IntAct

230 interactions, top by confidence:

A	B	Type	Score
STAG2	RAD21	psi-mi:“MI:0914”(association)	0.970
SMC3	RAD21	psi-mi:“MI:0914”(association)	0.960
SMC3	RAD21	psi-mi:“MI:0915”(physical association)	0.960
STAG1	RAD21	psi-mi:“MI:0914”(association)	0.930
SMC1A	RAD21	psi-mi:“MI:0914”(association)	0.930
RAD21	SMC1A	psi-mi:“MI:0914”(association)	0.930
SMC1A	RAD21	psi-mi:“MI:0915”(physical association)	0.930
WAPL	RAD21	psi-mi:“MI:0914”(association)	0.910
WAPL	RAD21	psi-mi:“MI:0915”(physical association)	0.910
BCL2L1	BCL2L11	psi-mi:“MI:0914”(association)	0.870
PDS5A	RAD21	psi-mi:“MI:0914”(association)	0.860
PDS5A	RAD21	psi-mi:“MI:0915”(physical association)	0.860
PDS5A	WAPL	psi-mi:“MI:0914”(association)	0.810
TIRAP	TLR4	psi-mi:“MI:0914”(association)	0.810
PDS5A	STAG2	psi-mi:“MI:0915”(physical association)	0.800
SMC1A	PDS5A	psi-mi:“MI:0914”(association)	0.800
SGO1	RAD21	psi-mi:“MI:0914”(association)	0.740
HRAS	MTHFD2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710

BioGRID (392): PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-MS), PDS5A (Affinity Capture-Western), PDS5A (Co-fractionation), PDS5A (Co-fractionation)

ESM2 similar proteins: A0A0R4ITC5, A1L1F4, A4L9P7, E9Q8I9, F1MKX4, F1QFR9, F1R2X6, F8VPU6, O94915, P21359, P42345, P42346, P51593, P97526, Q04690, Q14997, Q29RF7, Q2HJG5, Q498H0, Q4KLU7, Q4QXM3, Q4VA53, Q5F3U9, Q5F3V3, Q5R6J0, Q5SSW2, Q5TBA9, Q5U241, Q5VYK3, Q6A026, Q6DDM4, Q6GP04, Q6NRP2, Q6P4S8, Q6PDI5, Q6TRW4, Q7PX35, Q7TMY8, Q7Z3U7, Q7Z6Z7

Diamond homologs: A1L1F4, A4L9P7, A8MRD9, Q29RF7, Q498H0, Q4KLU7, Q4QXM3, Q4VA53, Q5F3U9, Q5F3V3, Q5U241, Q6A026, Q6TRW4, Q9NTI5, B6EUB3, O04716, Q6K431, Q8GUP3, Q9S9P0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 203 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
Resolution of Sister Chromatid Cohesion	13	8.4×	1e-06
S Phase	6	8.1×	6e-03
ESR-mediated signaling	7	6.7×	6e-03
Mitotic Metaphase and Anaphase	9	6.5×	1e-03
Mitotic Anaphase	9	6.5×	1e-03
Separation of Sister Chromatids	14	6.3×	9e-06
Mitotic Prometaphase	11	5.7×	5e-04
Estrogen-dependent gene expression	9	5.1×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
sister chromatid cohesion	5	22.1×	2e-03
mitotic spindle assembly	6	11.9×	3e-03
positive regulation of interleukin-6 production	8	7.7×	3e-03
positive regulation of ERK1 and ERK2 cascade	10	4.9×	6e-03
cell division	14	3.7×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

6249 predictions. Top by Δscore:

Variant	Effect	Δscore
4:39841943:TTTA:T	donor_loss	1.0000
4:39841944:TTA:T	donor_loss	1.0000
4:39841945:TAC:T	donor_loss	1.0000
4:39841946:ACCTT:A	donor_loss	1.0000
4:39841947:CC:C	donor_loss	1.0000
4:39842056:CCTG:C	acceptor_gain	1.0000
4:39845821:T:A	donor_gain	1.0000
4:39849514:T:C	donor_gain	1.0000
4:39849518:A:AC	donor_gain	1.0000
4:39849518:ACT:A	donor_loss	1.0000
4:39849518:ACTT:A	donor_gain	1.0000
4:39849519:C:CA	donor_gain	1.0000
4:39849519:CTT:C	donor_gain	1.0000
4:39849519:CTTC:C	donor_gain	1.0000
4:39849519:CTTCA:C	donor_gain	1.0000
4:39849521:T:TA	donor_gain	1.0000
4:39849651:ACCTA:A	acceptor_loss	1.0000
4:39862217:A:AC	donor_gain	1.0000
4:39862218:C:CC	donor_gain	1.0000
4:39862218:CT:C	donor_gain	1.0000
4:39863070:CATC:C	acceptor_gain	1.0000
4:39863072:TC:T	acceptor_gain	1.0000
4:39863073:CC:C	acceptor_gain	1.0000
4:39863436:C:CT	acceptor_gain	1.0000
4:39863455:ATTTA:A	acceptor_gain	1.0000
4:39863456:TTTA:T	acceptor_gain	1.0000
4:39863457:TTA:T	acceptor_gain	1.0000
4:39863458:TA:T	acceptor_gain	1.0000
4:39863460:C:CC	acceptor_gain	1.0000
4:39863460:CTATA:C	acceptor_loss	1.0000

AlphaMissense

8854 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:39849647:A:G	L1031P	1.000
4:39862282:A:G	L1008P	1.000
4:39862312:G:C	P998R	1.000
4:39862312:G:T	P998H	1.000
4:39862900:C:A	R980S	1.000
4:39862900:C:G	R980S	1.000
4:39862904:C:G	R979P	1.000
4:39862905:G:T	R979S	1.000
4:39862934:C:G	R969P	1.000
4:39862964:T:C	D959G	1.000
4:39862965:C:G	D959H	1.000
4:39862970:G:T	A957D	1.000
4:39863033:A:G	L936P	1.000
4:39863053:C:A	R929S	1.000
4:39863053:C:G	R929S	1.000
4:39863054:C:A	R929M	1.000
4:39863054:C:G	R929T	1.000
4:39863055:T:A	R929W	1.000
4:39863067:A:G	C925R	1.000
4:39863072:T:A	D923V	1.000
4:39863072:T:G	D923A	1.000
4:39863073:C:A	D923Y	1.000
4:39863073:C:G	D923H	1.000
4:39863406:A:G	L899P	1.000
4:39863406:A:T	L899H	1.000
4:39863419:C:G	A895P	1.000
4:39863424:C:T	G893D	1.000
4:39863425:C:G	G893R	1.000
4:39863427:G:T	A892D	1.000
4:39863428:C:G	A892P	1.000

dbSNP variants (sampled 300 via entrez): RS1000003182 (4:39937591 T>G), RS1000025569 (4:39965285 T>C), RS1000056665 (4:39965030 C>T), RS1000078721 (4:39886644 T>C,G), RS1000123937 (4:39882244 C>G), RS1000136106 (4:39933631 C>G), RS1000144311 (4:39955414 C>G,T), RS10001599 (4:39917016 A>T), RS1000190258 (4:39933400 C>T), RS1000195195 (4:39886383 A>G), RS1000204414 (4:39901727 T>C), RS1000210431 (4:39827607 T>C,G), RS1000210515 (4:39960919 A>C), RS1000238225 (4:39842383 C>G), RS1000276335 (4:39830484 G>C)

Disease associations

OMIM: gene MIM:613200 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006804_136	Red cell distribution width	5.000000e-10
GCST90002401_143	Platelet distribution width	3.000000e-10
GCST90002404_77	Red cell distribution width	7.000000e-20

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725176 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.01	Kd	977.8	nM	CHEMBL3752910
6.01	ED50	977.8	nM	CHEMBL3752910
5.55	Kd	2817	nM	CHEMBL5653589
5.55	ED50	2817	nM	CHEMBL5653589
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148970: Binding affinity to human PDS5A incubated for 45 mins by Kinobead based pull down assay	kd	0.9778	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148970: Binding affinity to human PDS5A incubated for 45 mins by Kinobead based pull down assay	kd	2.8174	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179064: Inhibition of PDS5A (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	6
trichostatin A	affects cotreatment, decreases expression, affects expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
tetrahydropalmatine	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
eprenetapopt	increases expression, affects reaction	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Progesterone	increases expression	1
Ribonucleotides	affects binding	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652012	Binding	Binding affinity to human PDS5A incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder