PRDM6

Summary

PRDM6 (PR/SET domain 6, HGNC:9350) is a protein-coding gene on chromosome 5q23.2, encoding Putative histone-lysine N-methyltransferase PRDM6 (Q9NQX0). Putative histone methyltransferase that acts as a transcriptional repressor of smooth muscle gene expression.

The protein encoded by this gene is a transcriptional repressor and a member of the PRDM family. Family members contain a PR domain and multiple zinc-finger domains. The encoded protein is involved in regulation of vascular smooth muscle cells (VSMC) contractile proteins. Mutations in this gene result in patent ductus arteriosus 3 (PDA3).

Source: NCBI Gene 93166 — RefSeq curated summary.

At a glance

• Gene–disease (curated): patent ductus arteriosus 3 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 35
• Clinical variants (ClinVar): 150 total — 3 pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001136239

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9350
Approved symbol	PRDM6
Name	PR/SET domain 6
Location	5q23.2
Locus type	gene with protein product
Status	Approved
Aliases	PRISM, KMT8C
Ensembl gene	ENSG00000061455
Ensembl biotype	protein_coding
OMIM	616982
Entrez	93166

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000407847, ENST00000427739, ENST00000434521, ENST00000464424, ENST00000890813

RefSeq mRNA: 1 — MANE Select: NM_001136239 NM_001136239

CCDS: CCDS47259

Canonical transcript exons

ENST00000407847 — 8 exons

Exon	Start	End
ENSE00000761373	123099654	123099961
ENSE00001088412	123159514	123159638
ENSE00001326378	123180147	123180323
ENSE00001557451	123089241	123089519
ENSE00001558416	123090000	123090606
ENSE00001560452	123187087	123194266
ENSE00003530919	123170766	123171108
ENSE00003617536	123155884	123156011

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 90.29.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7619 / max 91.3304, expressed in 270 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58223	0.4280	187
58224	0.2777	114
58228	0.0261	12
58225	0.0226	6
203673	0.0076	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	90.29	gold quality
thoracic aorta	UBERON:0001515	86.97	gold quality
ascending aorta	UBERON:0001496	86.64	gold quality
aorta	UBERON:0000947	83.88	gold quality
urinary bladder	UBERON:0001255	82.83	gold quality
popliteal artery	UBERON:0002250	81.57	gold quality
tibial artery	UBERON:0007610	81.46	gold quality
visceral pleura	UBERON:0002401	80.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.38	gold quality
right coronary artery	UBERON:0001625	79.31	gold quality
left coronary artery	UBERON:0001626	78.59	gold quality
coronary artery	UBERON:0001621	78.32	gold quality
urethra	UBERON:0000057	78.24	gold quality
placenta	UBERON:0001987	76.29	gold quality
lower lobe of lung	UBERON:0008949	76.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.15	gold quality
gall bladder	UBERON:0002110	75.66	gold quality
muscle layer of sigmoid colon	UBERON:0035805	75.41	gold quality
right lung	UBERON:0002167	74.20	gold quality
lung	UBERON:0002048	73.92	gold quality
mucosa of stomach	UBERON:0001199	73.68	gold quality
tibia	UBERON:0000979	71.70	gold quality
upper lobe of lung	UBERON:0008948	71.53	gold quality
upper lobe of left lung	UBERON:0008952	71.24	gold quality
sural nerve	UBERON:0015488	70.05	gold quality
pancreatic ductal cell	CL:0002079	69.42	silver quality
parietal pleura	UBERON:0002400	69.31	gold quality
epithelial cell of pancreas	CL:0000083	68.53	silver quality
colonic epithelium	UBERON:0000397	68.17	silver quality
left ovary	UBERON:0002119	68.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting PRDM6, 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-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1976	99.74	65.48	1127

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 5)

• Three novel loci were identified in East Asians with cardiac arrhythmias: rs2483280 (PRDM16 locus) and rs335206 (PRDM6 locus) were associated with QRS duration; and rs17026156 (SLC8A1 locus) correlated with PR interval. (PMID:25035420)
• Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus. (PMID:27181681)
• we detected a novel obesity and BMI-associated locus at PKHD1 and novel variants driving associations at previously established signals (e.g. rs205262 at the SNRPC/C6orf106 locus and rs112446794 at the PRDM6-CEP120 locus). (PMID:30677029)
• Patent ductus arteriosus and coarctation of the aorta in association with PRDM6 variants. (PMID:38071433)
• PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression. (PMID:38992221)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prdm6	ENSMUSG00000069378
rattus_norvegicus	Prdm6	ENSRNOG00000030486

Paralogs (36): ZBTB32 (ENSG00000011590), SNAI2 (ENSG00000019549), PRDM1 (ENSG00000057657), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), SNAI1 (ENSG00000124216), ZNF384 (ENSG00000126746), ZBTB1 (ENSG00000126804), VEZF1 (ENSG00000136451), PRDM14 (ENSG00000147596), ZNF276 (ENSG00000158805), ZNF362 (ENSG00000160094), ZNF653 (ENSG00000161914), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), ZNF143 (ENSG00000166478), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF296 (ENSG00000170684), ZNF692 (ENSG00000171163), ZNF575 (ENSG00000176472), HIC1 (ENSG00000177374), ZBTB18 (ENSG00000179456), ZBTB42 (ENSG00000179627), ZBTB20 (ENSG00000181722), ZBTB7C (ENSG00000184828), SNAI3 (ENSG00000185669), ZFP91 (ENSG00000186660), MTF1 (ENSG00000188786), SCRT2 (ENSG00000215397), SCRT1 (ENSG00000261678)

Protein

Protein identifiers

Putative histone-lysine N-methyltransferase PRDM6 — Q9NQX0 (reviewed: Q9NQX0)

Alternative names: PR domain zinc finger protein 6, PR domain-containing protein 6

All UniProt accessions (2): Q9NQX0, H7BZR2

UniProt curated annotations — full annotation on UniProt →

Function. Putative histone methyltransferase that acts as a transcriptional repressor of smooth muscle gene expression. Promotes the transition from differentiated to proliferative smooth muscle by suppressing differentiation and maintaining the proliferative potential of vascular smooth muscle cells. Also plays a role in endothelial cells by inhibiting endothelial cell proliferation, survival and differentiation. It is unclear whether it has histone methyltransferase activity in vivo. According to some authors, it does not act as a histone methyltransferase by itself and represses transcription by recruiting EHMT2/G9a. According to others, it possesses histone methyltransferase activity when associated with other proteins and specifically methylates ‘Lys-20’ of histone H4 in vitro. ‘Lys-20’ methylation represents a specific tag for epigenetic transcriptional repression.

Subunit / interactions. Interacts with HDAC1, HDAC2, HDAC3, CBX1 and EP300.

Subcellular location. Nucleus.

Disease relevance. Patent ductus arteriosus 3 (PDA3) [MIM:617039] A congenital heart defect characterized by the persistent opening of fetal ductus arteriosus that fails to close after birth. Fetal ductus arteriosus connects the pulmonary artery to the descending aorta, allowing unoxygenated blood to bypass the lung and flow to the placenta. Normally, the ductus occludes shortly after birth. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NQX0-3	1	yes
Q9NQX0-2	2, B
Q9NQX0-1	3, A

RefSeq proteins (1): NP_001129711* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR044416	PRDM6_PR-SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF21549

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine + H(+) (RHEA:60344)

UniProt features (15 total): zinc finger region 4, sequence variant 3, compositionally biased region 3, splice variant 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQX0-F1	57.72	0.04

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEUROGENESIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_CHROMATIN_REMODELING, GOBP_METHYLATION, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_UP, GOBP_MUSCLE_CELL_DIFFERENTIATION, GOMF_N_METHYLTRANSFERASE_ACTIVITY, GOMF_PROTEIN_METHYLTRANSFERASE_ACTIVITY, GOMF_S_ADENOSYLMETHIONINE_DEPENDENT_METHYLTRANSFERASE_ACTIVITY, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of gene expression (GO:0010468), neurogenesis (GO:0022008), methylation (GO:0032259), negative regulation of smooth muscle cell differentiation (GO:0051151), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (8): zinc ion binding (GO:0008270), identical protein binding (GO:0042802), histone H4K20 monomethyltransferase activity (GO:0140944), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), histone methyltransferase activity (GO:0042054), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
gene expression	1
regulation of macromolecule biosynthetic process	1
nervous system development	1
cell differentiation	1
metabolic process	1
smooth muscle cell differentiation	1
negative regulation of muscle cell differentiation	1
regulation of smooth muscle cell differentiation	1
cellular component organization	1
chromatin organization	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transition metal ion binding	1
protein binding	1
histone H4K20 methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
protein methyltransferase activity	1
histone modifying activity	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

524 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDM6	IBSP	P21815	682
PRDM6	BMPR1B	P78366	635
PRDM6	KBTBD4	Q9NVX7	622
PRDM6	PRDM8	Q9NQV8	618
PRDM6	MSX2	P35548	605
PRDM6	ALX4	Q9H161	593
PRDM6	HNMT	P50135	558
PRDM6	F12	P00748	548
PRDM6	KMT5C	Q86Y97	542
PRDM6	TMEM184B	Q9Y519	506
PRDM6	PRDM14	Q9GZV8	474
PRDM6	SMYD2	Q9NRG4	459
PRDM6	EP300	Q09472	456
PRDM6	SNCAIP	Q9Y6H5	448
PRDM6	SMYD5	Q6GMV2	447

IntAct

220 interactions, top by confidence:

A	B	Type	Score
QARS1	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
PRDM6	ABI2	psi-mi:“MI:0915”(physical association)	0.560
GADD45GIP1	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
CBFA2T2	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
ELOA	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
KCTD9	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
GEM	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
PRKAA2	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
ANKS1A	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
PRDM6	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
COX5B	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
PRDM6	FOXD4L1	psi-mi:“MI:0915”(physical association)	0.560
GPANK1	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
BAG3	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
NCK2	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
ATOSB	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
STK16	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
KANK2	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
TRMT12	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
TSGA10IP	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
FRS3	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
USP54	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
NEK6	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
PATZ1	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
PRDM6	SAMD4A	psi-mi:“MI:0915”(physical association)	0.560
KAT5	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
CSTF2	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
BANF2	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
ROPN1	PRDM6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (103): PRDM6 (Affinity Capture-Western), CBX1 (Affinity Capture-Western), HDAC1 (Affinity Capture-Western), HDAC2 (Affinity Capture-Western), HDAC3 (Affinity Capture-Western), EP300 (Affinity Capture-Western), PRDM6 (Affinity Capture-Western), HIST1H3A (Affinity Capture-Western), PRDM6 (Affinity Capture-MS), PRDM6 (Affinity Capture-MS), PRDM6 (Affinity Capture-MS), PRDM6 (Affinity Capture-MS), PRDM6 (Affinity Capture-MS), PRDM6 (Two-hybrid), PRDM6 (Two-hybrid)

ESM2 similar proteins: A0A140LI67, A0JN76, A1L2U9, A2A5N8, A2AJ77, A6QPM3, B1WAZ8, B8A5Y1, D3ZWK4, E9Q3T6, E9Q8T2, O15060, O88866, O94966, P0C2N6, P57058, Q05516, Q0IH98, Q0IJ29, Q3B725, Q3TES0, Q3UZD5, Q4R739, Q60760, Q68UT7, Q6NZK8, Q6P2A1, Q6P4K6, Q6Q783, Q6S5L9, Q6YND2, Q76M68, Q7ZWZ4, Q80X44, Q8BXX2, Q8N680, Q8NE63, Q96CK0, Q99592, Q9GZV8

Diamond homologs: A0A163UT06, A2AGX3, A6QPM3, B8A5Y1, E9Q3T6, E9Q8T2, O75626, P0C6Y7, P14404, P57071, Q3UZD5, Q5R5M1, Q60636, Q6P2A1, Q80V63, Q96EQ9, Q9GZV8, Q9NQV5, Q9NQV7, Q9NQW5, Q9NQX0, Q9QZP2, Q9UKN5, A2AJ77, Q13029, Q63755, Q8BZ97, Q9CXE0, Q9H4Q4, Q9NQV8, Q9NQX1, E9PZZ1, Q9H4Q3, A2ANX9, A7Y7X5, B0X9H6, J9VE33, O35615, O75362, O77459

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	121
Likely benign	16
Benign	7

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
243049	NM_001136239.4(PRDM6):c.1646G>A (p.Arg549Gln)	Pathogenic
243050	NM_001136239.4(PRDM6):c.788G>C (p.Cys263Ser)	Pathogenic
243051	NM_001136239.4(PRDM6):c.1385A>G (p.Gln462Arg)	Pathogenic

SpliceAI

2301 predictions. Top by Δscore:

Variant	Effect	Δscore
5:123090607:G:GG	donor_gain	1.0000
5:123099648:CCGCA:C	acceptor_loss	1.0000
5:123099649:CGCAG:C	acceptor_loss	1.0000
5:123099650:GCAGG:G	acceptor_loss	1.0000
5:123099651:CA:C	acceptor_loss	1.0000
5:123099652:A:G	acceptor_loss	1.0000
5:123099653:G:A	acceptor_loss	1.0000
5:123159639:G:GG	donor_gain	1.0000
5:123180145:A:AG	acceptor_gain	1.0000
5:123180146:G:GG	acceptor_gain	1.0000
5:123180321:CAAGT:C	donor_loss	1.0000
5:123180322:AAGT:A	donor_loss	1.0000
5:123180323:AG:A	donor_loss	1.0000
5:123180324:G:GG	donor_gain	1.0000
5:123180325:T:A	donor_loss	1.0000
5:123187232:G:GT	donor_gain	1.0000
5:123187233:A:T	donor_gain	1.0000
5:123099642:T:TA	acceptor_gain	0.9900
5:123099652:A:AG	acceptor_gain	0.9900
5:123099653:G:GA	acceptor_gain	0.9900
5:123099653:GGTT:G	acceptor_gain	0.9900
5:123099961:GGTA:G	donor_loss	0.9900
5:123099962:GT:G	donor_loss	0.9900
5:123119840:C:CG	donor_gain	0.9900
5:123119840:C:G	donor_gain	0.9900
5:123159629:G:GT	donor_gain	0.9900
5:123159635:AACT:A	donor_gain	0.9900
5:123159637:CT:C	donor_gain	0.9900
5:123170764:A:AG	acceptor_gain	0.9900
5:123170765:G:GG	acceptor_gain	0.9900

AlphaMissense

3868 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:123099665:T:A	C202S	1.000
5:123099666:G:C	C202S	1.000
5:123099689:T:A	C210S	1.000
5:123099689:T:C	C210R	1.000
5:123099690:G:C	C210S	1.000
5:123180157:T:C	C503R	1.000
5:123180166:T:C	C506R	1.000
5:123180168:C:G	C506W	1.000
5:123180178:T:C	F510L	1.000
5:123180180:T:A	F510L	1.000
5:123180180:T:G	F510L	1.000
5:123180205:C:G	H519D	1.000
5:123180207:C:A	H519Q	1.000
5:123180207:C:G	H519Q	1.000
5:123180235:T:C	F529L	1.000
5:123180237:C:A	F529L	1.000
5:123180237:C:G	F529L	1.000
5:123180241:T:A	C531S	1.000
5:123180241:T:C	C531R	1.000
5:123180242:G:C	C531S	1.000
5:123180243:C:G	C531W	1.000
5:123180250:T:A	C534S	1.000
5:123180250:T:C	C534R	1.000
5:123180251:G:A	C534Y	1.000
5:123180251:G:C	C534S	1.000
5:123180252:T:G	C534W	1.000
5:123180262:T:A	F538I	1.000
5:123180262:T:C	F538L	1.000
5:123180263:T:C	F538S	1.000
5:123180263:T:G	F538C	1.000

dbSNP variants (sampled 300 via entrez): RS1000043147 (5:123109397 G>A,T), RS1000053908 (5:123123733 T>C), RS1000098407 (5:123186420 T>C), RS1000116313 (5:123093147 C>T), RS1000128069 (5:123189089 A>G), RS1000148562 (5:123095379 A>G), RS1000152573 (5:123104790 A>G), RS1000182432 (5:123168197 A>C), RS1000228555 (5:123121295 T>C), RS1000230552 (5:123180231 G>A,T), RS1000235731 (5:123166454 T>A), RS1000268200 (5:123099105 T>A), RS1000295140 (5:123088204 G>A,C), RS1000313152 (5:123166815 A>G), RS1000328373 (5:123098620 T>A)

Disease associations

OMIM: gene MIM:616982 | disease phenotypes: MIM:617039, MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
patent ductus arteriosus 3	Strong	Autosomal dominant
familial patent arterial duct	Supportive	Autosomal dominant

Mondo (4): patent ductus arteriosus 3 (MONDO:0024266), congenital heart disease (MONDO:0005453), congenital anomaly of kidney and urinary tract (MONDO:0019719), (MONDO:0018758)

Orphanet (2): Familial patent arterial duct (Orphanet:466729), Renal or urinary tract malformation (Orphanet:93545)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001643	Patent ductus arteriosus

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST002533_2	QRS duration	3.000000e-10
GCST002667_3	Mammographic density (dense area)	3.000000e-07
GCST002669_1	Percent mammographic density	3.000000e-09
GCST003272_14	Systolic blood pressure	9.000000e-16
GCST004904_259	Body mass index	5.000000e-09
GCST004904_53	Body mass index	1.000000e-08
GCST005194_256	Coronary artery disease	7.000000e-07
GCST005845_3	Heart rate increase in response to exercise	2.000000e-15
GCST005848_12	Heart rate response to recovery post exercise (50 sec)	1.000000e-09
GCST005848_13	Heart rate response to recovery post exercise (50 sec)	2.000000e-10
GCST005849_12	Heart rate response to recovery post exercise (40 sec)	2.000000e-09
GCST006020_8	Diastolic blood pressure	7.000000e-06
GCST006021_43	Systolic blood pressure	3.000000e-09
GCST006022_6	Pulse pressure	9.000000e-06
GCST006661_166	Male-pattern baldness	5.000000e-11
GCST007094_92	Diastolic blood pressure	2.000000e-10
GCST007095_75	Systolic blood pressure	4.000000e-06
GCST007096_143	Pulse pressure	5.000000e-06
GCST007099_249	Systolic blood pressure	2.000000e-12
GCST007267_205	Systolic blood pressure	8.000000e-10
GCST007929_35	Medication use (calcium channel blockers)	1.000000e-10
GCST007930_166	Medication use (agents acting on the renin-angiotensin system)	1.000000e-09
GCST010796_1582	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-12
GCST010796_1583	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-12
GCST010796_1584	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-13
GCST010796_1585	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-14
GCST010796_1586	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-13
GCST010796_1587	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-14
GCST010796_1588	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-13
GCST010796_1589	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-13

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0005941	mammographic density measurement
EFO:0006503	dense area measurement
EFO:0006502	mammographic density percentage
EFO:0006335	systolic blood pressure
EFO:0004340	body mass index
EFO:0009184	heart rate response to exercise
EFO:0009185	heart rate response to recovery post exercise
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004327	electrocardiography
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
C566906	Cakut (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5214858 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects expression, affects methylation, decreases methylation, increases abundance	3
Valproic Acid	affects expression, decreases expression, increases methylation	3
GSK-J4	increases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, affects methylation, decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	increases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	decreases methylation	1
Smoke	increases expression	1
Zinc	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Metals, Heavy	decreases methylation, increases abundance	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5214671	Binding	Selectivity interaction (Methyltransferase panel (DSF assay)) EUB0000234b PRDM6	Selectivity Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XV75	HEK293 eGFP-PRDM6	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE