PRDM8

PR/SET domain 8, the group of PR/SET domain family|Lysine methyltransferases

Basic information

Region (hg38): 4:80183878-80204329

Links

ENSG00000152784 ∙ NCBI:56978 ∙ OMIM:616639 ∙ HGNC:13993 ∙ Uniprot:Q9NQV8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• early-onset Lafora body disease (Supportive), mode of inheritance: AR
• early-onset Lafora body disease (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, progressive myoclonic, 10	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	22961547
As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRDM8 gene.

• Early-onset Lafora body disease (387 variants)
• Inborn genetic diseases (28 variants)
• not provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRDM8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				125	12	137
missense			222	1	3	226
nonsense			2			2
start loss						0
frameshift			1			1
inframe indel			26	1	1	28
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				8		8
Total	0	0	251	135	16

Variants in PRDM8

This is a list of pathogenic ClinVar variants found in the PRDM8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-80200090-A-G		Early-onset Lafora body disease	Uncertain significance (Sep 06, 2022)
4-80200094-G-A		Early-onset Lafora body disease	Uncertain significance (Oct 13, 2022)
4-80200097-T-A		Early-onset Lafora body disease	Uncertain significance (Sep 01, 2021)
4-80200103-G-A		not specified	Uncertain significance (Jan 04, 2022)
4-80200106-G-A		Early-onset Lafora body disease	Uncertain significance (Oct 13, 2022)
4-80200114-G-A		Early-onset Lafora body disease	Uncertain significance (Jan 06, 2020)
4-80200114-G-T		not specified	Uncertain significance (Nov 03, 2022)
4-80200116-T-G		Early-onset Lafora body disease • not specified	Uncertain significance (Dec 16, 2023)
4-80200120-G-A		Early-onset Lafora body disease	Uncertain significance (Oct 05, 2021)
4-80200137-A-G		Early-onset Lafora body disease	Likely benign (Aug 28, 2023)
4-80200138-C-A		Early-onset Lafora body disease	Uncertain significance (Jan 28, 2021)
4-80200148-C-A		Early-onset Lafora body disease	Uncertain significance (Jul 19, 2022)
4-80200161-C-T		Early-onset Lafora body disease	Likely benign (Dec 15, 2022)
4-80200165-G-A		Early-onset Lafora body disease	Uncertain significance (May 25, 2022)
4-80200170-C-T		Early-onset Lafora body disease	Likely benign (Oct 18, 2023)
4-80200197-T-C		Early-onset Lafora body disease	Benign (Aug 23, 2023)
4-80200198-A-G		Early-onset Lafora body disease	Uncertain significance (Aug 16, 2022)
4-80200201-T-G		Early-onset Lafora body disease	Uncertain significance (Dec 11, 2023)
4-80200207-C-T		Early-onset Lafora body disease	Uncertain significance (Jul 14, 2020)
4-80200226-C-A		Early-onset Lafora body disease • not specified	Uncertain significance (Dec 09, 2023)
4-80200239-C-T		Early-onset Lafora body disease	Likely benign (Jun 14, 2019)
4-80200243-A-G		Early-onset Lafora body disease	Uncertain significance (Jan 15, 2021)
4-80200244-T-A		Early-onset Lafora body disease	Uncertain significance (Jul 14, 2022)
4-80200252-A-G		Early-onset Lafora body disease	Uncertain significance (Mar 18, 2022)
4-80200272-C-A		Early-onset Lafora body disease	Uncertain significance (Feb 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRDM8	protein_coding	protein_coding	ENST00000339711	3	20451

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.776	0.224	124788	0	6	124794	0.0000240

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0172	331	332	0.997	0.0000159	4368
Missense in Polyphen		84	109.25	0.76886		1387
Synonymous	-1.30	168	148	1.14	0.00000751	1478
Loss of Function	3.29	3	18.1	0.166	7.79e-7	227

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000182	0.0000177
Middle Eastern	0.0000556	0.0000556
South Asian	0.0000654	0.0000654
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable histone methyltransferase, preferentially acting on 'Lys-9' of histone H3 (By similarity). Involved in the control of steroidogenesis through transcriptional repression of steroidogenesis marker genes such as CYP17A1 and LHCGR (By similarity). Forms with BHLHE22 a transcriptional repressor complex controlling genes involved in neural development and neuronal differentiation (By similarity). In the retina, it is required for rod bipolar and type 2 OFF-cone bipolar cell survival (By similarity). {ECO:0000250|UniProtKB:Q8BZ97}.

Recessive Scores

• pRec: 0.105

Haploinsufficiency Scores

• pHI: 0.278
• ghis: 0.578

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.139

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Prdm8
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;oligodendrocyte development;methylation
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;protein binding;methyltransferase activity;metal ion binding