PRDM8

Summary

PRDM8 (PR/SET domain 8, HGNC:13993) is a protein-coding gene on chromosome 4q21.21, encoding PR domain zinc finger protein 8 (Q9NQV8). Probable histone methyltransferase, preferentially acting on ‘Lys-9’ of histone H3.

This gene encodes a protein that belongs to a conserved family of histone methyltransferases that predominantly act as negative regulators of transcription. The encoded protein contains an N-terminal Su(var)3-9, Enhancer-of-zeste, and Trithorax (SET) domain and a double zinc-finger domain. Knockout of this gene in mouse results in mistargeting by neurons of the dorsal telencephalon, abnormal itch-like behavior, and impaired differentiation of rod bipolar cells. In humans, the protein has been shown to interact with the phosphatase laforin and the ubiquitin ligase malin, which regulate glycogen construction in the cytoplasm. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 56978 — RefSeq curated summary.

At a glance

• Gene–disease (curated): early-onset Lafora body disease (Strong, GenCC)
• GWAS associations: 52 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 416 total — 1 pathogenic (top 8% of genes corpus-wide)
• GTEx eGene: eQTL in 31 tissues, sQTL in 6 (q < 0.05)
• Phenotypes (HPO): 25
• Constraint (gnomAD): pLI 0.98 (loss-of-function intolerant), LOEUF 0.50 (moderately constrained)
• MANE Select transcript: NM_001099403

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13993
Approved symbol	PRDM8
Name	PR/SET domain 8
Location	4q21.21
Locus type	gene with protein product
Status	Approved
Aliases	KMT8D
Ensembl gene	ENSG00000152784
Ensembl biotype	protein_coding
OMIM	616639
Entrez	56978

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 13 protein_coding, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000415738

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 3: 4, TSL 5: 3

ENST00000415738, ENST00000339711, ENST00000504452, ENST00000506547, ENST00000507025, ENST00000508061, ENST00000508965, ENST00000509375, ENST00000511825, ENST00000515013, ENST00000861821, ENST00000861822, ENST00000952373, ENST00000952374, ENST00000952375, ENST00000952376, ENST00001095807, ENST00001127750, ENST00001127751, ENST00001140375

RefSeq mRNA: 2 — MANE Select: NM_001099403 NM_001099403, NM_020226

CCDS: CCDS43243

Canonical transcript exons

ENST00000415738 — 4 exons

Exon	Start	End
ENSE00001007102	80201290	80201521
ENSE00001007107	80200079	80200299
ENSE00001792844	80197503	80197763
ENSE00002075265	80201914	80204329

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 96.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5828 / max 616.5629, expressed in 1064 samples.

Highest expression (Bgee): cortical plate, ganglionic eminence, mucosa of stomach, esophagogastric junction muscularis propria, Brodmann (1909) area 9.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRDM8 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 37 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	3.3e-29	+0.51	4:80181123:T:G
Thyroid	eqtl	2.7e-17	+0.43	4:80181123:T:G
Pancreas	eqtl	2.8e-13	+0.53	4:80209654:A:G
Adipose Visceral Omentum	eqtl	4.7e-12	+0.39	4:80183489:G:A
Muscle Skeletal	eqtl	8.7e-11	+0.34	4:80183489:G:A
Esophagus Muscularis	sqtl	5.7e-10	-0.46	4:80206511:T:A
Brain Putamen basal ganglia	eqtl	6.5e-10	+0.45	4:80183870:GCGGCCC:G
Brain Cortex	eqtl	3.7e-09	+0.27	4:80206891:T:G
Cells Cultured fibroblasts	eqtl	1.3e-08	+0.19	4:80168337:T:C
Brain Frontal Cortex BA9	eqtl	5.7e-08	+0.28	4:80188497:T:C
Cells Cultured fibroblasts	sqtl	5.2e-07	-0.39	4:80191461:C:CTATAT
Heart Left Ventricle	eqtl	4.4e-06	-0.21	4:79852307:C:T
Adipose Subcutaneous	eqtl	9.1e-06	+0.23	4:80181123:T:G
Brain Cerebellum	eqtl	6.9e-05	+0.21	4:80198529:A:C
Testis	eqtl	1.4e-04	-0.31	4:80183490:T:C
Esophagus Muscularis	eqtl	5.5e-04	-0.14	4:79800610:C:G
Brain Anterior cingulate cortex BA24	eqtl	2.0e-03	+0.16	4:80192990:T:A
Artery Aorta	eqtl	2.7e-03	-0.21	4:79614887:A:G
Stomach	eqtl	2.9e-03	-0.15	4:80013516:C:G
Brain Cortex	sqtl	3.3e-03	-0.51	4:80206511:T:A

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
48522	7.4075	556
48516	1.4346	488
48519	0.7135	315
48518	0.6530	332
48515	0.4987	226
48517	0.4418	223
48520	0.2236	81
48521	0.2101	74

Top tissues by expression

showing 100 of 246 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.91	gold quality
ganglionic eminence	UBERON:0004023	94.58	gold quality
mucosa of stomach	UBERON:0001199	88.92	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.32	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.93	gold quality
lower esophagus	UBERON:0013473	87.84	gold quality
right frontal lobe	UBERON:0002810	87.00	gold quality
prefrontal cortex	UBERON:0000451	85.90	gold quality
anterior cingulate cortex	UBERON:0009835	85.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.83	gold quality
body of uterus	UBERON:0009853	83.48	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.95	gold quality
stromal cell of endometrium	CL:0002255	82.17	gold quality
endocervix	UBERON:0000458	82.13	gold quality
neocortex	UBERON:0001950	81.62	gold quality
frontal cortex	UBERON:0001870	80.90	gold quality
ectocervix	UBERON:0012249	80.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.15	gold quality
granulocyte	CL:0000094	79.03	gold quality
amygdala	UBERON:0001876	78.96	gold quality
prostate gland	UBERON:0002367	78.78	gold quality
cerebral cortex	UBERON:0000956	78.53	gold quality
left uterine tube	UBERON:0001303	78.26	gold quality
right ovary	UBERON:0002118	78.07	gold quality
left ovary	UBERON:0002119	77.13	gold quality
calcaneal tendon	UBERON:0003701	76.76	gold quality
esophagus	UBERON:0001043	76.58	gold quality
spinal cord	UBERON:0002240	76.56	gold quality
vermiform appendix	UBERON:0001154	76.42	gold quality
smooth muscle tissue	UBERON:0001135	75.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.49	gold quality
tibial nerve	UBERON:0001323	75.25	gold quality
popliteal artery	UBERON:0002250	74.97	gold quality
tibial artery	UBERON:0007610	74.97	gold quality
uterine cervix	UBERON:0000002	73.67	gold quality
colon	UBERON:0001155	73.66	gold quality
hypothalamus	UBERON:0001898	73.63	gold quality
primary visual cortex	UBERON:0002436	73.36	gold quality
vagina	UBERON:0000996	73.34	gold quality
Ammon’s horn	UBERON:0001954	73.18	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.08	gold quality
transverse colon	UBERON:0001157	73.00	gold quality
sural nerve	UBERON:0015488	72.87	gold quality
ventricular zone	UBERON:0003053	72.72	gold quality
left coronary artery	UBERON:0001626	72.59	gold quality
forebrain	UBERON:0001890	72.51	gold quality
large intestine	UBERON:0000059	72.48	gold quality
omental fat pad	UBERON:0010414	72.36	gold quality
small intestine	UBERON:0002108	72.32	gold quality
aorta	UBERON:0000947	72.30	gold quality
peritoneum	UBERON:0002358	72.28	gold quality
right coronary artery	UBERON:0001625	72.25	gold quality
intestine	UBERON:0000160	72.15	gold quality
muscle of leg	UBERON:0001383	72.08	gold quality
gastrocnemius	UBERON:0001388	72.00	gold quality
blood	UBERON:0000178	71.85	gold quality
lymph node	UBERON:0000029	71.41	gold quality
body of stomach	UBERON:0001161	71.41	gold quality
brain	UBERON:0000955	71.23	gold quality
descending thoracic aorta	UBERON:0002345	71.13	gold quality
apex of heart	UBERON:0002098	70.93	gold quality
ovary	UBERON:0000992	70.85	gold quality
coronary artery	UBERON:0001621	70.81	gold quality
skin of leg	UBERON:0001511	70.68	gold quality
adipose tissue of abdominal region	UBERON:0007808	70.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	70.38	gold quality
parotid gland	UBERON:0001831	70.14	gold quality
urinary bladder	UBERON:0001255	70.06	gold quality
temporal lobe	UBERON:0001871	69.77	gold quality
stomach	UBERON:0000945	69.70	gold quality
fundus of stomach	UBERON:0001160	69.52	gold quality
adenohypophysis	UBERON:0002196	69.45	gold quality
skin of abdomen	UBERON:0001416	69.32	gold quality
thoracic aorta	UBERON:0001515	69.14	gold quality
ascending aorta	UBERON:0001496	68.87	gold quality
substantia nigra	UBERON:0002038	68.82	gold quality
colonic epithelium	UBERON:0000397	68.69	silver quality
hindlimb stylopod muscle	UBERON:0004252	68.68	gold quality
caecum	UBERON:0001153	68.66	gold quality
anatomical system	UBERON:0000467	68.33	gold quality
cerebellar cortex	UBERON:0002129	68.14	gold quality
cerebellar hemisphere	UBERON:0002245	68.03	gold quality
multicellular organism	UBERON:0000468	67.82	gold quality
material anatomical entity	UBERON:0000465	67.79	gold quality
gall bladder	UBERON:0002110	67.77	gold quality
right atrium auricular region	UBERON:0006631	67.72	gold quality
right uterine tube	UBERON:0001302	67.64	gold quality
myometrium	UBERON:0001296	67.39	gold quality
zone of skin	UBERON:0000014	67.38	gold quality
esophagus mucosa	UBERON:0002469	67.31	gold quality
pituitary gland	UBERON:0000007	67.18	gold quality
cardiac atrium	UBERON:0002081	67.02	gold quality
cerebellum	UBERON:0002037	67.01	gold quality
rectum	UBERON:0001052	67.00	gold quality
female reproductive system	UBERON:0000474	66.85	gold quality
minor salivary gland	UBERON:0001830	66.75	gold quality
nasal cavity epithelium	UBERON:0005384	66.75	gold quality
heart left ventricle	UBERON:0002084	66.67	gold quality
heart	UBERON:0000948	66.39	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	1055.89
E-GEOD-137537	yes	625.20
E-GEOD-75140	yes	166.42
E-MTAB-7316	yes	30.67
E-CURD-11	no	31.63
E-ANND-3	no	2.75

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Postcentral gyrus	tissue	59.0
Hippocampus	tissue	42.4
Hippocampal formation	tissue	29.9
Cerebral cortex	tissue	28.6
Somatosensory cortex	tissue	28.6
Occipital cortex	tissue	28.1
Entorhinal cortex	tissue	27.1
Temporal cortex	tissue	26.6
Seminal vesicle	tissue	25.6
Prostate	tissue	23.6
Prefrontal cortex	tissue	22.6
Retina	tissue	22.4
Insular cortex	tissue	21.3
Motor cortex	tissue	17.4
Amygdala	tissue	17.3
Retrosplenial and cingulate cortex	tissue	16.8
Retrosplenial cortex	tissue	14.6
Frontal cortex	tissue	10.3
Spinal cord	tissue	9.7
Vagina	tissue	9.1
Locus coeruleus	tissue	8.4
Nucleus accumbens	tissue	6.6
Endometrium 1	tissue	5.9
Cerebellum	tissue	5.3
Pituitary gland	tissue	5.1
Medulla oblongata	tissue	5.1
Lymph node	tissue	4.8
Midbrain	tissue	4.7
Appendix	tissue	4.7
Corpus callosum	tissue	4.3
Placenta	tissue	4.1
Pons	tissue	4.0
Substantia nigra	tissue	4.0
Bone marrow	tissue	3.8
Smooth muscle	tissue	3.5
Hypothalamus	tissue	3.4
Cervix	tissue	3.0
Superior colliculi	tissue	2.9
Thalamus	tissue	2.7
Periaqueductal gray	tissue	2.7
Choroid plexus	tissue	2.6
Ovary	tissue	2.5
Urinary bladder	tissue	2.5
Tonsil	tissue	2.3
Ventral forebrain	tissue	2.2
Septum	tissue	2.2
Skeletal muscle	tissue	2.1
Adrenal gland	tissue	2.1
Fallopian tube	tissue	2.1
Epididymis	tissue	1.8
Adipose tissue	tissue	1.6
Esophagus	tissue	1.6
Spleen	tissue	1.6
Gallbladder	tissue	1.6
Small intestine	tissue	1.5
Olfactory bulb	tissue	1.5
Breast	tissue	1.4
Rectum	tissue	1.4
Colon	tissue	1.4
Stomach 1	tissue	1.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Dentate gyrus (53.1), Posterior cingulate cortex (50.7), Posterior insular cortex (47.7), Parieto-insular cortex (47.0), Claustrum (45.8).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
CYP17A1	Repression

Upstream regulators (CollecTRI, top): GLI1, MYC

miRNA regulators (miRDB)

Targeting PRDM8 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 85 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-2110	99.96	66.68	1930
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
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-556-3P	99.74	68.75	1203

Functional genomics

gnomAD constraint: pLI 0.983, LOEUF 0.498, missense Z -1.4 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000415738 — one region, missense o/e 1.04.

Literature-anchored findings (GeneRIF, showing 4)

• Aberrant hypermethylation is particularly observed in PRDM8 and this may support identification and classification of bone marrow failure syndromes (PMID:26909595)
• alteration of hydroxymethylation and methylation of PRDM8 correlates with changes in its expression in the peripheral blood of children with DS. Given the proposed function of PRDM8 in cognitive disability in DS (PMID:27278638)
• Through regulating NAP1L1, PRDM8 inhibits PI3K/AKT/mTOR signaling in hepatocellular carcinoma. (PMID:29572888)
• PRDM8 reveals aberrant DNA methylation in aging syndromes and is relevant for hematopoietic and neuronal differentiation. (PMID:32819411)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	prdm8b	ENSDARG00000054683
mus_musculus	Prdm8	ENSMUSG00000035456
rattus_norvegicus	Prdm8	ENSRNOG00000002004
drosophila_melanogaster	CG13287	FBGN0035643

Paralogs (1): ZNF488 (ENSG00000265763)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1924880) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 31 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart morphology	1
abnormal spleen morphology	1
small spleen	1
abnormal thymus morphology	1
enlarged thymus	1
abnormal uterus morphology	1
skin lesions	1
decreased body weight	1
abnormal retina morphology	1
increased anxiety-related response	1
hyperactivity	1
decreased locomotor activity	1
excessive scratching	1
abnormal motor coordination/balance	1
abnormal seminal vesicle morphology	1
abnormal skin morphology	1
abnormal tooth morphology	1
small heart	1
absent corpus callosum	1
abnormal inspiratory capacity	1
increased heart rate	1
abnormal heart left ventricle morphology	1
enlarged uterus	1
impaired glucose tolerance	1
increased circulating sodium level	1

+6 more (showing top 25).

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
Caenorhabditis elegans	A0A163UT06	42.2%	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
PRDM8-AS1	ncRNA	105377303
FGF5	protein-coding	2250
ANTXR2	protein-coding	118429
CFAP299	protein-coding	255119

Protein

Protein identifiers

PR domain zinc finger protein 8 — Q9NQV8 (reviewed: Q9NQV8)

Alternative names: PR domain-containing protein 8

All UniProt accessions (2): Q9NQV8, E9PEH0

UniProt curated annotations — full annotation on UniProt →

Function. Probable histone methyltransferase, preferentially acting on ‘Lys-9’ of histone H3. Involved in the control of steroidogenesis through transcriptional repression of steroidogenesis marker genes such as CYP17A1 and LHCGR. Forms with BHLHE22 a transcriptional repressor complex controlling genes involved in neural development and neuronal differentiation. In the retina, it is required for rod bipolar and type 2 OFF-cone bipolar cell survival.

Subunit / interactions. Interacts with EPM2A and NHLRC1. This interaction sequesters EPM2A and NHLRC1 to the nucleus. Interacts with BHLHE22.

Subcellular location. Nucleus.

Tissue specificity. Expressed in brain, heart, skeletal muscle, testes, prostate.

Disease relevance. Epilepsy, progressive myoclonic 10 (EPM10) [MIM:616640] A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM10 is an autosomal recessive form characterized by progressive dysarthria, myoclonus, ataxia, cognitive decline, psychosis, dementia and spasticity, with onset in childhood. There is variability between patients. 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 (2)

UniProt ID	Names	Canonical?
Q9NQV8-1	1	yes
Q9NQV8-2	2

RefSeq proteins (2): NP_001092873, NP_064611 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR013087	Zf-C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR044402	PRDM8-like_PR/SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR052296	TR-Histone_Methyltrans	Family

Pfam: PF13894, PF21549

UniProt features (20 total): compositionally biased region 6, sequence conflict 3, zinc finger region 3, splice variant 2, region of interest 2, chain 1, domain 1, binding site 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQV8-F1	55.64	0.15

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Zinc-coordinating DNA-binding domains, Disease related genes, Human disease related genes, Epilepsy

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear bodies; nucleoplasm

Antibody reliability (HPA): IF supported

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 (1)

Position	Role
130	S-adenosyl-L-methionine

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-418990	Adherens junctions interactions	—
R-HSA-446728	Cell junction organization	—
R-HSA-1500931	Cell-Cell communication	—
R-HSA-421270	Cell-cell junction organization	—
R-HSA-9759475	Regulation of CDH11 Expression and Function	—
R-HSA-9762293	Regulation of CDH11 gene transcription	electronic
R-HSA-9764260	Regulation of Expression and Function of Type II Classical Cadherins	—
R-HSA-9759476	Regulation of Homotypic Cell-Cell Adhesion	—

MSigDB gene sets: 216 (showing top): TAATAAT_MIR126, MODULE_255, SP3_Q3, GOBP_GLIAL_CELL_DEVELOPMENT, MODULE_317, GOBP_NEUROGENESIS, CAGCTG_AP4_Q5, GOBP_FOREBRAIN_DEVELOPMENT, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, GOBP_CENTRAL_NERVOUS_SYSTEM_PROJECTION_NEURON_AXONOGENESIS, GATA1_03, GOBP_HEAD_DEVELOPMENT, NKX25_01, DOUGLAS_BMI1_TARGETS_UP

GO Biological Process (7): DNA-templated transcription (GO:0006351), regulation of DNA-templated transcription (GO:0006355), oligodendrocyte development (GO:0014003), methylation (GO:0032259), chromatin remodeling (GO:0006338), nervous system development (GO:0007399), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (10): DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), histone H3K9 methyltransferase activity (GO:0046974), 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 (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604)

Reactome top-level categories

7 top-level categories:

Category	Pathways
Regulation of CDH11 Expression and Function	1
Cell-cell junction organization	1
Cell junction organization	1
Cell-Cell communication	1
Regulation of Expression and Function of Type II Classical Cadherins	1
Adherens junctions interactions	1
Regulation of Homotypic Cell-Cell Adhesion	1

GO top-level categories

30 GO namespaces:

Category	Terms
DNA-templated transcription	2
binding	2
gene expression	1
RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
glial cell development	1
oligodendrocyte differentiation	1
metabolic process	1
chromatin organization	1
system development	1
animal gross anatomical part developmental process	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
nucleic acid binding	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
transition metal ion binding	1
protein-lysine N-methyltransferase activity	1
histone H3 methyltransferase activity	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
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
nuclear body	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 606 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDM8	BHLHE22	Q8NFJ8	660
PRDM8	PRDM6	Q9NQX0	601
PRDM8	PRDM5	Q9NQX1	599
PRDM8	PRDM15	P57071	582
PRDM8	PRDM2	Q13029	577
PRDM8	PRDM10	Q9NQV6	563
PRDM8	NHLRC1	Q6VVB1	539
PRDM8	PRDM11	Q9NQV5	529
PRDM8	ANTXR2	P58335	495
PRDM8	PRDM16	Q9HAZ2	488
PRDM8	VSX1	Q9NZR4	486
PRDM8	BHLHE23	Q8NDY6	466
PRDM8	MECOM	Q03112	448
PRDM8	TMEM215	Q68D42	437
PRDM8	EPM2A	O95278	418

IntAct

BioGRID (7 interactions; top human partners by supporting records): NHLRC1 (Affinity Capture-Western; 2 records), DDX39A (Affinity Capture-RNA), MCM2 (Affinity Capture-MS), NUDT21 (Affinity Capture-RNA), PARP10 (Proximity Label-MS), TOP1 (Cross-Linking-MS (XL-MS))

Disease & clinical

Genetic variants

Variant evidence for PRDM8: 416 ClinVar records (1 pathogenic / likely pathogenic); 52 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	249
Likely benign	148
Benign	10

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
217865	NM_001099403.2(PRDM8):c.781T>C (p.Phe261Leu)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PRDM8’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 328):

Position(s)	Effect	Δscore	Sites
4:80197764–80197765	donor_loss	1.0000	3
4:80200062	acceptor_gain	1.0000
4:80200072	acceptor_gain	1.0000
4:80200077–80200078	acceptor_loss	1.0000	5
4:80200300–80200301	donor_loss	1.0000	5
4:80197764–80197765	donor_loss	0.9900	2
4:80200078	acceptor_loss	0.9900
4:80201464	donor_gain	0.9900
4:80201931	acceptor_gain	0.9900
4:80201288–80201289	acceptor_loss	0.9800	6

AlphaMissense

1,777 missense substitutions predicted likely pathogenic (of 4,443 scored), across 377 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
M685	9	0.990	1.000
M644	9	0.988	1.000
M636	9	0.982	1.000
H684	8	1.000	1.000
D639	8	0.999	1.000
H643	8	0.999	1.000
F675	8	0.999	1.000
H679	8	0.999	1.000
H680	8	0.999	1.000
H688	8	0.999	1.000
F634	8	0.998	1.000
H648	8	0.998	1.000
N625	8	0.996	1.000
H173	8	0.992	0.999
F41	8	0.989	0.999
F501	8	0.989	0.999
F386	8	0.988	0.999
D75	8	0.986	0.997
D53	8	0.984	0.998
N102	8	0.983	0.999

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Prostate Adenocarcinoma)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.000445

Disease associations

OMIM: gene MIM:616639 | disease phenotypes: MIM:616640

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
early-onset Lafora body disease	Strong	Autosomal recessive	3

Mondo (1): early-onset Lafora body disease (MONDO:0014717)

Orphanet (1): PRDM8-related progressive myoclonus epilepsy (Orphanet:324290)

HPO phenotypes

25 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000726	Dementia
HP:0000738	Hallucinations
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001285	Spastic tetraparesis
HP:0001289	Confusion
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0002073	Progressive cerebellar ataxia
HP:0002123	Generalized myoclonic seizure
HP:0002300	Mutism
HP:0002497	Spastic ataxia
HP:0002510	Spastic tetraplegia
HP:0003676	Progressive
HP:0003828	Variable expressivity
HP:0011999	Paranoia
HP:0100318	Lafora bodies
HP:0100543	Cognitive impairment

GWAS associations

showing 30 of 52 associations:

Study	Trait	p-value
GCST010002_134	Refractive error	2e-65
GCST007094_55	Diastolic blood pressure	1e-59
GCST007099_20	Systolic blood pressure	2e-53
GCST007706_115	Mean arterial pressure	1e-44
GCST007706_114	Mean arterial pressure	8e-33
GCST007707_97	Hypertension	3e-29
GCST007706_6	Mean arterial pressure	8e-28
GCST006010_24	Mean arterial pressure	2e-27
GCST007706_5	Mean arterial pressure	4e-27
GCST005979_11	Systolic blood pressure	1e-25
GCST005116_48	Male-pattern baldness	5e-25
GCST007098_96	Diastolic blood pressure	9e-24
GCST007707_95	Hypertension	2e-23
GCST005978_9	Diastolic blood pressure	2e-22
GCST000394_1	Diastolic blood pressure	1e-21
GCST006031_7	Potassium levels	1e-21
GCST007707_65	Hypertension	2e-21
GCST007706_3	Mean arterial pressure	1e-20
GCST007707_62	Hypertension	2e-20
GCST007706_121	Mean arterial pressure	8e-20
GCST007095_76	Systolic blood pressure	4e-19
GCST010866_100	Coronary artery disease	6e-19
GCST007098_22	Diastolic blood pressure	2e-17
GCST005985_66	Creatinine levels	2e-16
GCST007344_47	Estimated glomerular filtration rate	5e-16
GCST007096_39	Pulse pressure	1e-15
GCST007707_56	Hypertension	3e-15
GCST005984_12	Glomerular filtration rate	2e-14
GCST007707_104	Hypertension	4e-14
GCST007705_48	Pulse pressure	5e-13

EFO canonical traits (from GWAS)

10 canonical traits:

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0007700	exploratory eye movement measurement
EFO:0004761	uric acid measurement
EFO:0004305	erythrocyte count
EFO:0006340	mean arterial pressure
EFO:0009283	potassium measurement
EFO:0007820	cognitive behavioural therapy
EFO:0004918	age at diagnosis

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5214864 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Tretinoin	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
butyraldehyde	increases expression	1
beta-methylcholine	affects expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Amiodarone	increases expression	1
Cytarabine	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Phthalic Acids	increases abundance, increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases 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
CHEMBL5214665	Binding	Selectivity interaction (Methyltransferase panel (DSF assay)) EUB0000234b PRDM8	Selectivity Literature for EUbOPEN Chemogenomics Library wave 3

Clinical trials (associated diseases)

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