PRDM4

Summary

PRDM4 (PR/SET domain 4, HGNC:9348) is a protein-coding gene on chromosome 12q23.3, encoding PR domain zinc finger protein 4 (Q9UKN5). May function as a transcription factor involved in cell differentiation.

The protein encoded by this gene is a transcription factor of the PR-domain protein family. It contains a PR-domain and multiple zinc finger motifs. Transcription factors of the PR-domain family are known to be involved in cell differentiation and tumorigenesis. An elevated expression level of this gene has been observed in PC12 cells treated with nerve growth factor, beta polypeptide (NGF). This gene is located in a chromosomal region that is thought to contain tumor suppressor genes.

Source: NCBI Gene 11108 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 119 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 36 tissues, sQTL in 8 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.73 (unconstrained)
• MANE Select transcript: NM_012406
• Notable: 119 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9348
Approved symbol	PRDM4
Name	PR/SET domain 4
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	PFM1
Ensembl gene	ENSG00000110851
Ensembl biotype	protein_coding
OMIM	605780
Entrez	11108

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 15 protein_coding, 8 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000228437

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 2, TSL 5: 1

ENST00000228437, ENST00000547188, ENST00000547268, ENST00000549416, ENST00000550376, ENST00000550659, ENST00000861823, ENST00000861824, ENST00000861825, ENST00000861826, ENST00000861827, ENST00000861828, ENST00000861829, ENST00000917533, ENST00000917534, ENST00000978541, ENST00000978542, ENST00000978544, ENST00000978545, ENST00000978546, ENST00000978547, ENST00001069789, ENST00001069790, ENST00001113499, ENST00001143438

RefSeq mRNA: 1 — MANE Select: NM_012406 NM_012406

CCDS: CCDS9115

Canonical transcript exons

ENST00000228437 — 12 exons

Exon	Start	End
ENSE00000818376	107751415	107752209
ENSE00000818377	107753924	107754109
ENSE00001366540	107760957	107761137
ENSE00002250300	107732871	107734522
ENSE00003475988	107739383	107739551
ENSE00003555392	107744543	107744661
ENSE00003562610	107740946	107741260
ENSE00003565425	107742221	107742348
ENSE00003577287	107756832	107756965
ENSE00003618573	107760505	107760771
ENSE00003659252	107743197	107743282
ENSE00003671644	107746275	107746424

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 95.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4637 / max 83.8338, expressed in 1786 samples.

Highest expression (Bgee): oocyte, secondary oocyte, endothelial cell, metanephric glomerulus, renal glomerulus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRDM4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 36 tissues and its splicing (sQTL) in 8 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 44 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	1.7e-31	-1.10	12:107707352:T:G
Nerve Tibial	eqtl	3.1e-31	+0.33	12:107704193:G:A
Testis	eqtl	2.5e-17	+0.37	12:107752695:A:G
Skin Not Sun Exposed Suprapubic	eqtl	4.8e-16	+0.29	12:107738224:C:T
Whole Blood	eqtl	3.9e-15	+0.26	12:107711200:G:T
Pancreas	eqtl	4.9e-12	+0.31	12:107761331:G:A
Adipose Subcutaneous	eqtl	8.4e-12	+0.23	12:107750324:T:C
Adipose Visceral Omentum	eqtl	8.0e-11	+0.28	12:107768653:C:G
Thyroid	eqtl	1.0e-10	+0.19	12:107761331:G:A
Skin Sun Exposed Lower leg	eqtl	4.6e-10	+0.17	12:107704262:T:C
Breast Mammary Tissue	eqtl	1.6e-09	+0.18	12:107756981:C:A
Skin Sun Exposed Lower leg	sqtl	5.3e-09	+0.44	12:107750324:T:C
Brain Hypothalamus	eqtl	7.2e-08	+0.30	12:107696741:A:G
Adipose Subcutaneous	sqtl	2.2e-07	+0.43	12:107756981:C:A
Brain Cerebellar Hemisphere	eqtl	4.1e-07	+0.26	12:107700897:T:TC
Brain Cerebellum	eqtl	2.8e-06	+0.22	12:107704262:T:C
Skin Not Sun Exposed Suprapubic	sqtl	2.9e-05	+0.37	12:107750324:T:C
Stomach	eqtl	3.1e-05	-0.84	12:107573974:C:T
Pituitary	eqtl	3.5e-05	+0.27	12:107761331:G:A
Esophagus Mucosa	eqtl	3.6e-05	+0.14	12:107761331:G:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
133100	6.5729	1758
133101	1.4948	1016
133099	0.2033	71
133098	0.1927	74

Top tissues by expression

showing 100 of 289 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.47	gold quality
secondary oocyte	CL:0000655	94.91	gold quality
endothelial cell	CL:0000115	94.49	gold quality
metanephric glomerulus	UBERON:0004736	92.23	gold quality
renal glomerulus	UBERON:0000074	91.74	gold quality
amniotic fluid	UBERON:0000173	91.67	gold quality
cervix epithelium	UBERON:0004801	91.60	gold quality
tongue squamous epithelium	UBERON:0006919	91.46	gold quality
islet of Langerhans	UBERON:0000006	91.42	gold quality
pancreatic ductal cell	CL:0002079	91.37	gold quality
kidney epithelium	UBERON:0004819	91.33	gold quality
cerebellar vermis	UBERON:0004720	90.74	gold quality
cervix squamous epithelium	UBERON:0006922	90.73	gold quality
nephron tubule	UBERON:0001231	90.70	gold quality
epithelium of esophagus	UBERON:0001976	90.69	gold quality
diaphragm	UBERON:0001103	90.49	gold quality
esophagus squamous epithelium	UBERON:0006920	90.30	gold quality
upper arm skin	UBERON:0004263	89.83	gold quality
squamous epithelium	UBERON:0006914	89.83	gold quality
metanephros	UBERON:0000081	89.82	gold quality
hair follicle	UBERON:0002073	89.71	gold quality
middle temporal gyrus	UBERON:0002771	89.35	gold quality
type B pancreatic cell	CL:0000169	89.18	silver quality
cardia of stomach	UBERON:0001162	89.15	gold quality
cortex of kidney	UBERON:0001225	89.13	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.06	gold quality
renal medulla	UBERON:0000362	88.99	gold quality
pons	UBERON:0000988	88.97	gold quality
epithelium of nasopharynx	UBERON:0001951	88.95	gold quality
lower esophagus mucosa	UBERON:0035834	88.94	gold quality
olfactory bulb	UBERON:0002264	88.86	silver quality
vena cava	UBERON:0004087	88.75	gold quality
mucosa of urinary bladder	UBERON:0001259	88.71	gold quality
kidney	UBERON:0002113	88.56	gold quality
dorsal plus ventral thalamus	UBERON:0001897	88.35	gold quality
parotid gland	UBERON:0001831	88.31	gold quality
endometrium	UBERON:0001295	88.30	gold quality
rectum	UBERON:0001052	88.26	gold quality
substantia nigra pars compacta	UBERON:0001965	88.26	gold quality
trigeminal ganglion	UBERON:0001675	88.22	gold quality
layer of synovial tissue	UBERON:0007616	88.22	gold quality
epithelial cell of pancreas	CL:0000083	88.18	silver quality
male germ cell	CL:0000015	87.97	gold quality
subthalamic nucleus	UBERON:0001906	87.94	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.91	gold quality
dorsal root ganglion	UBERON:0000044	87.89	gold quality
sperm	CL:0000019	87.80	gold quality
adult mammalian kidney	UBERON:0000082	87.66	gold quality
oviduct epithelium	UBERON:0004804	87.51	gold quality
body of tongue	UBERON:0011876	87.48	gold quality
tongue	UBERON:0001723	87.43	gold quality
orbitofrontal cortex	UBERON:0004167	87.41	gold quality
ventral tegmental area	UBERON:0002691	87.37	gold quality
uterine cervix	UBERON:0000002	87.36	gold quality
pharyngeal mucosa	UBERON:0000355	87.34	gold quality
smooth muscle tissue	UBERON:0001135	87.30	gold quality
superior vestibular nucleus	UBERON:0007227	87.17	gold quality
nipple	UBERON:0002030	87.15	gold quality
trachea	UBERON:0003126	87.12	gold quality
lateral globus pallidus	UBERON:0002476	87.00	gold quality
thymus	UBERON:0002370	86.99	gold quality
synovial joint	UBERON:0002217	86.96	gold quality
superior surface of tongue	UBERON:0007371	86.90	gold quality
granulocyte	CL:0000094	86.88	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.87	gold quality
Brodmann (1909) area 46	UBERON:0006483	86.84	gold quality
colonic mucosa	UBERON:0000317	86.80	gold quality
pericardium	UBERON:0002407	86.75	gold quality
choroid plexus epithelium	UBERON:0003911	86.73	gold quality
cortical plate	UBERON:0005343	86.70	gold quality
uterus	UBERON:0000995	86.67	gold quality
mucosa of stomach	UBERON:0001199	86.57	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.55	gold quality
pylorus	UBERON:0001166	86.52	gold quality
gingival epithelium	UBERON:0001949	86.52	gold quality
duodenum	UBERON:0002114	86.49	gold quality
inferior vagus X ganglion	UBERON:0005363	86.36	gold quality
embryo	UBERON:0000922	86.35	gold quality
ventricular zone	UBERON:0003053	86.33	gold quality
superficial temporal artery	UBERON:0001614	86.26	gold quality
nasal cavity epithelium	UBERON:0005384	86.26	gold quality
gingiva	UBERON:0001828	86.24	gold quality
pancreas	UBERON:0001264	86.21	gold quality
fallopian tube	UBERON:0003889	86.13	gold quality
buccal mucosa cell	CL:0002336	86.07	gold quality
medulla oblongata	UBERON:0001896	86.04	gold quality
vastus lateralis	UBERON:0001379	86.02	gold quality
adrenal tissue	UBERON:0018303	85.99	gold quality
CA1 field of hippocampus	UBERON:0003881	85.90	gold quality
stromal cell of endometrium	CL:0002255	85.88	gold quality
penis	UBERON:0000989	85.86	gold quality
saphenous vein	UBERON:0007318	85.81	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.76	gold quality
mammalian vulva	UBERON:0000997	85.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.61	gold quality
esophagus mucosa	UBERON:0002469	85.54	gold quality
small intestine	UBERON:0002108	85.53	gold quality
quadriceps femoris	UBERON:0001377	85.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.45	gold quality
lymph node	UBERON:0000029	85.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.87
E-GEOD-99795	no	100.94

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Parathyroid gland	tissue	41.8	low
Choroid plexus	tissue	24.3
Locus coeruleus	tissue	23.3
Postcentral gyrus	tissue	21.7
Nucleus accumbens	tissue	20.9
Kidney	tissue	19.6	medium
Retina	tissue	19.4
Hippocampus	tissue	19.3	not detected
Bone marrow	tissue	15.9	not detected
Caudate putamen	tissue	15.6
Rectum	tissue	15.4	medium
Frontal cortex	tissue	14.8
Esophagus	tissue	14.7	low
Endometrium 1	tissue	14.2	low
Colon	tissue	14.0	medium
Tonsil	tissue	13.2	low
Thalamus	tissue	13.1
Smooth muscle	tissue	13.0	not detected
Superior colliculi	tissue	13.0
Pons	tissue	12.8
Cerebellum	tissue	12.8	not detected
Ovary	tissue	12.7	low
Vagina	tissue	12.7	low
Hypothalamus	tissue	12.7
Epididymis	tissue	12.6	medium
Small intestine	tissue	12.5	medium
Duodenum	tissue	12.5	medium
Lung	tissue	12.2	medium
Stomach 1	tissue	12.0	medium
Midbrain	tissue	12.0
Tongue	tissue	11.9
Thyroid gland	tissue	11.8	medium
Cerebral cortex	tissue	11.7	low
Placenta	tissue	11.7	medium
Somatosensory cortex	tissue	11.7
Lymph node	tissue	11.6	low
Spleen	tissue	11.6	not detected
Periaqueductal gray	tissue	11.6
Occipital cortex	tissue	11.6
Medulla oblongata	tissue	11.5
Seminal vesicle	tissue	11.4	medium
Cervix	tissue	11.3	low
Substantia nigra	tissue	11.2
Spinal cord	tissue	11.2
Appendix	tissue	11.2	medium
Fallopian tube	tissue	11.1	low
Breast	tissue	11.0	low
Prefrontal cortex	tissue	10.9
Adipose tissue	tissue	10.9	not detected
Testis	tissue	10.8	high
Salivary gland	tissue	10.8	medium
Urinary bladder	tissue	10.8	medium
Motor cortex	tissue	10.8
Prostate	tissue	10.8	low
Thymus	tissue	10.6
Gallbladder	tissue	10.5	medium
Hippocampal formation	tissue	10.4
Entorhinal cortex	tissue	10.4
Retrosplenial and cingulate cortex	tissue	10.4
Skin 1	tissue	10.3	not detected

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral posteromedial thalamic nucleus (27.6), Cerebellar cortex (26.8), Ventral posterolateral thalamic nucleus (26.7), Posterior thalamic nucleus (26.2), Somatosensory cortex, postcentral gyrus, ventral (white matter) (25.9).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets:

Target	Regulation
BMP4	Activation
C6
ESRRB	Activation
GATA6	Activation
KLF5	Activation
PRDM14	Activation
TBX3	Activation
TET2
TET3

JASPAR motifs

Motif	Name	Family
MA1647.1	PRDM4	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:23918801

miRNA regulators (miRDB)

Targeting PRDM4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 99 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-511-3P	99.99	68.85	1467
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-3617-3P	99.98	67.86	918
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778

Functional genomics

gnomAD constraint: pLI 2.23e-06, LOEUF 0.734, missense Z 2.18 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000228437 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
12:107,734,213–107,744,584	355 / 432.6	0.82	no
12:107,744,585–107,744,629	4 / 17.8	0.23	yes (p 1.1e-03)
12:107,744,630–107,760,515	499 / 546.7	0.91	no

Literature-anchored findings (GeneRIF, showing 3)

• PRDM4 zinc knuckle by NMR spectroscopy. (PMID:21604305)
• Both Prdm 4 and Prdm 5 are expressed in human corneal endothelium, primary hCECs and in HCECs-12 cells, characterised by expression of the Na(+)/K(+)-ATPase. (PMID:28228349)
• results demonstrate that YAP promotes cell invasion by inducing leukocyte-specific integrin expression, and identify PRDM4 as a novel transcription factor for YAP targets. (PMID:29669796)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prdm4	ENSDARG00000017366
mus_musculus	Prdm4	ENSMUSG00000035529
rattus_norvegicus	Prdm4	ENSRNOG00000004962

Paralogs (51): WIZ (ENSG00000011451), ZNF416 (ENSG00000083817), MYNN (ENSG00000085274), PRDM2 (ENSG00000116731), ZBTB17 (ENSG00000116809), ZNF644 (ENSG00000122482), GZF1 (ENSG00000125812), ZNF426 (ENSG00000130818), ZNF287 (ENSG00000141040), ZNF697 (ENSG00000143067), ZNF687 (ENSG00000143373), ZNF214 (ENSG00000149050), ZNF547 (ENSG00000152433), ZNF776 (ENSG00000152443), ZNF230 (ENSG00000159882), ZNF222 (ENSG00000159885), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF646 (ENSG00000167395), ZNF507 (ENSG00000168813), ZNF768 (ENSG00000169957), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF223 (ENSG00000178386), ZNF852 (ENSG00000178917), ZNF784 (ENSG00000179922), ZNF572 (ENSG00000180938), ZNF707 (ENSG00000181135), ZNF746 (ENSG00000181220), ZNF467 (ENSG00000181444), ZNF530 (ENSG00000183647), ZNF17 (ENSG00000186272), ZNF527 (ENSG00000189164), ZKSCAN7 (ENSG00000196345), ZNF34 (ENSG00000196378), ZNF774 (ENSG00000196391), ZNF777 (ENSG00000196453), ZNF136 (ENSG00000196646), ZNF398 (ENSG00000197024), ZNF587 (ENSG00000198466), ZNF627 (ENSG00000198551), ZFP57 (ENSG00000204644), ZNF155 (ENSG00000204920), ZNF407 (ENSG00000215421), ZNF625 (ENSG00000257591), ZNF285 (ENSG00000267508), ZNF670 (ENSG00000277462), (ENSG00000284691)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1920093) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 14 distinct phenotype terms.

Mouse phenotype (MP)	Records
absent spleen	1
microphthalmia	1
abnormal cornea morphology	1
abnormal iris morphology	1
abnormal gait	1
short tibia	1
thick ventricular wall	1
abnormal heart left ventricle morphology	1
increased lean body mass	1
impaired glucose tolerance	1
increased cardiac muscle contractility	1
increased circulating amylase level	1
decreased total body fat amount	1
enlarged urinary bladder	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R5M1	99.5%	Diamond
Xenopus tropicalis	B4F6U4	71.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PRDM4-AS1	ncRNA	101929162
PWP1	protein-coding	11137
ASCL4	protein-coding	121549
ABTB3	protein-coding	121551

Protein

Protein identifiers

PR domain zinc finger protein 4 — Q9UKN5 (reviewed: Q9UKN5)

Alternative names: PR domain-containing protein 4

All UniProt accessions (4): F8VRG2, F8VZQ2, H0YIF6, Q9UKN5

UniProt curated annotations — full annotation on UniProt →

Function. May function as a transcription factor involved in cell differentiation.

Subcellular location. Nucleus.

Tissue specificity. Expressed in many tissues. Highly expressed in ovary, testis, pancreas, brain, heart and prostate.

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

RefSeq proteins (1): NP_036538* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR013087	Zf-C2H2_type	Domain
IPR017124	PRDM4	Family
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR041493	PRDM4_Znf	Domain
IPR044404	PRDM4_PR/SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF18445, PF21549

UniProt features (32 total): strand 10, zinc finger region 6, helix 5, sequence conflict 4, turn 3, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
3DB5	Crystal structure of methyltransferase domain of human PR domain-containing protein 4	X-RAY DIFFRACTION	2.15
2L9Z	Zinc knuckle in PRDM4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKN5-F1	44.77	0.00

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Zinc-coordinating DNA-binding domains

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-73887	Death Receptor Signaling	—
R-HSA-162582	Signal Transduction	—
R-HSA-193704	p75 NTR receptor-mediated signalling	—
R-HSA-193670	p75NTR negatively regulates cell cycle via SC1	electronic

MSigDB gene sets: 169 (showing top): GCM_GSPT1, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, CTAGGAA_MIR384, USF_01, GCM_NUMA1, CYTAGCAAY_UNKNOWN, USF_02, GCM_NF2, PID_P75_NTR_PATHWAY, GOBP_METHYLATION, PODAR_RESPONSE_TO_ADAPHOSTIN_UP, KEGG_NEUROTROPHIN_SIGNALING_PATHWAY, GOCC_TRANSFERASE_COMPLEX, GOCC_HISTONE_METHYLTRANSFERASE_COMPLEX

GO Biological Process (4): transcription by RNA polymerase II (GO:0006366), regulation of gene expression (GO:0010468), methylation (GO:0032259), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (11): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), methyltransferase activity (GO:0008168), zinc ion binding (GO:0008270), histone methyltransferase binding (GO:1990226), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), histone methyltransferase complex (GO:0035097)

Reactome top-level categories

3 top-level categories:

Category	Pathways
p75 NTR receptor-mediated signalling	1
Death Receptor Signaling	1
Signal Transduction	1

GO top-level categories

29 GO namespaces:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
DNA-templated transcription	1
gene expression	1
regulation of macromolecule biosynthetic process	1
metabolic process	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transferase activity, transferring one-carbon groups	1
transition metal ion binding	1
enzyme binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
methyltransferase complex	1
nuclear protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
nucleoplasm	CC	direct assay
sequence-specific double-stranded DNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 488 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDM4	SETD4	Q9NVD3	493
PRDM4	NGF	P01138	467
PRDM4	SMYD5	Q6GMV2	462
PRDM4	TCP11L2	Q8N4U5	458
PRDM4	TMEM263	Q8WUH6	456
PRDM4	SMYD4	Q8IYR2	453
PRDM4	PRMT5	O14744	451
PRDM4	VIPAS39	Q9H9C1	427
PRDM4	PRDM8	Q9NQV8	415
PRDM4	SETD3	Q86TU7	414
PRDM4	PRDM2	Q13029	412
PRDM4	ASH1L	Q9NR48	382
PRDM4	DYTN	A2CJ06	374
PRDM4	RBFOX3	A6NFN3	370
PRDM4	WIZ	O95785	370
PRDM4	TTC28	Q96AY4	370

IntAct

Human interaction partners of PRDM4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
CTNNBL1	physical association	0.560	3
MSRB3	physical association	0.560	3
NCS1	physical association	0.560	3
CFTR	physical association	0.370	1
EIF4E	physical association	0.370	1
EMX1	physical association	0.370	1
SERTAD1	physical association	0.370	1
SMAD3	physical association	0.370	1
DBT	association	0.350	1
DYRK1A	physical association	0.000	1
FMR1	physical association	0.000	1
RCAN1	physical association	0.000	1
RUNX1	physical association	0.000	1

BioGRID (24 interactions; top human partners by supporting records): APEX1 (Affinity Capture-RNA), CFTR (PCA), CTNNBL1 (Two-hybrid), DBT (Affinity Capture-MS), DYRK1A (Two-hybrid), EIF4E (Two-hybrid), EMX1 (Two-hybrid), ERH (Affinity Capture-MS), HDAC1 (Affinity Capture-Western), HDAC2 (Affinity Capture-Western), HDAC3 (Affinity Capture-Western), LGALS7 (Affinity Capture-MS), MSRB3 (Two-hybrid), NCS1 (Two-hybrid), NT5C2 (Affinity Capture-MS)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
YAP-PRDM4 transcription factor complex	2	PRDM4, YAP1

Disease & clinical

Genetic variants

Variant evidence for PRDM4: 119 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	5
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 814):

Position(s)	Effect	Δscore	Sites
12:107742361–107742363	acceptor_gain	1.0000	2
12:107743283–107743284	acceptor_loss	1.0000	6
12:107744541–107744542	donor_loss	1.0000	5
12:107744545	donor_gain	1.0000
12:107756830–107756831	donor_loss	1.0000	5
12:107756966–107756967	acceptor_loss	1.0000	4
12:107734523–107734524	acceptor_loss	0.9900	6
12:107742289	acceptor_gain	0.9900
12:107742349–107742350	acceptor_loss	0.9900	2
12:107742354	acceptor_gain	0.9900

AlphaMissense

1,871 missense substitutions predicted likely pathogenic (of 5,324 scored), across 450 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H636	8	0.999	1.000
H640	8	0.999	1.000
H664	8	0.999	1.000
H720	8	0.998	1.000
H668	8	0.997	0.999
H692	8	0.997	0.999
H608	8	0.996	0.999
H748	8	0.996	0.999
H696	8	0.993	0.998
H612	8	0.992	0.998
H724	8	0.992	0.997
F627	8	0.990	1.000
D688	8	0.990	0.998
D629	8	0.987	0.999
F655	8	0.987	1.000
H660	8	0.985	0.997
F683	8	0.980	0.999
H391	8	0.979	0.994
F711	8	0.978	0.999
F599	8	0.973	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	2.1e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.5e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000499

Disease associations

OMIM: gene MIM:605780 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST011494_4	Daytime nap	1e-14
GCST007561_70	Sleep duration	3e-8
GCST002481_2	Acne (severe)	5e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
bisphenol F	decreases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
geraniol	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	decreases expression	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
N-Nitrosopyrrolidine	increases expression	1
Piroxicam	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	decreases expression, affects cotreatment	1
Paclitaxel	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases expression, increases abundance	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5Q5	SEES3-1V human PRDM4, clone1	Embryonic stem cell	Male
CVCL_A5Q6	SEES3-1V human PRDM4, clone2	Embryonic stem cell	Male
CVCL_A5Q7	SEES3-1V human PRDM4, clone3	Embryonic stem cell	Male
CVCL_XV74	HEK293 eGFP-PRDM4	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.