PRDM5

PR/SET domain 5, the group of Zinc fingers C2H2-type|PR/SET domain family

Basic information

Region (hg38): 4:120684919-120922870

Links

ENSG00000138738 ∙ NCBI:11107 ∙ OMIM:614161 ∙ HGNC:9349 ∙ Uniprot:Q9NQX1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• brittle cornea syndrome 2 (Strong), mode of inheritance: AR
• brittle cornea syndrome 2 (Strong), mode of inheritance: AR
• brittle cornea syndrome 2 (Moderate), mode of inheritance: AR
• brittle cornea syndrome (Supportive), mode of inheritance: AR
• brittle cornea syndrome 2 (Definitive), mode of inheritance: AR
• brittle cornea syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Brittle cornea syndrome 2	AR	Ophthalmologic	Individuals are prone to ophthalmologic injury (such as corneal rupture) with minimal trauma, and protective measures may be beneficial	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic	21664999; 22122778; 26395458
Manifestations can occur in heterozygote

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRDM5 gene.

• not provided (15 variants)
• Brittle cornea syndrome 2 (4 variants)
• Ehlers-Danlos syndrome (1 variants)
• Cardiovascular phenotype (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRDM5 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			1	151	6	158
missense		1	147	12	2	162
nonsense	11	3		2		16
start loss			1			1
frameshift	5	6				11
inframe indel						0
splice donor/acceptor (+/-2bp)	1	9				10
splice region			6	23	3	32
non coding			11	149	46	206
Total	17	19	160	314	54

Highest pathogenic variant AF is 0.00000658

Variants in PRDM5

This is a list of pathogenic ClinVar variants found in the PRDM5 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-120694935-A-G		Brittle cornea syndrome 1	Uncertain significance (Jun 14, 2016)
4-120694957-T-A		Brittle cornea syndrome 1	Uncertain significance (Jun 14, 2016)
4-120694970-A-G		Brittle cornea syndrome 1	Uncertain significance (Jun 14, 2016)
4-120694991-A-G		Brittle cornea syndrome 1	Conflicting classifications of pathogenicity (Jun 26, 2018)
4-120695107-C-T			Likely benign (Jul 19, 2019)
4-120695114-G-A			Likely benign (Nov 24, 2022)
4-120695117-G-A		Brittle cornea syndrome 1	Uncertain significance (Jun 14, 2016)
4-120695130-T-C		Cardiovascular phenotype	Uncertain significance (Feb 20, 2023)
4-120695132-G-T		PRDM5-related disorder	Likely benign (Aug 26, 2022)
4-120695142-A-G		Cardiovascular phenotype	Uncertain significance (Feb 09, 2023)
4-120695143-T-C		Cardiovascular phenotype	Uncertain significance (Apr 12, 2024)
4-120695145-TG-T		Brittle cornea syndrome 2	Likely pathogenic (Aug 01, 2020)
4-120695153-G-A		Ehlers-Danlos syndrome • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jan 04, 2024)
4-120695156-G-A			Likely benign (Jul 11, 2023)
4-120695157-T-C		Cardiovascular phenotype	Uncertain significance (May 30, 2024)
4-120695171-A-G		Cardiovascular phenotype	Likely benign (Mar 26, 2021)
4-120695195-T-C		Cardiovascular phenotype	Likely benign (Aug 29, 2023)
4-120695199-G-C			Uncertain significance (Jan 03, 2022)
4-120695200-C-T		Cardiovascular phenotype	Uncertain significance (Sep 16, 2020)
4-120695209-G-A		Ehlers-Danlos syndrome • Cardiovascular phenotype	Uncertain significance (Nov 29, 2023)
4-120695211-T-C			Uncertain significance (Apr 01, 2022)
4-120695213-G-A		Cardiovascular phenotype	Likely benign (Aug 02, 2023)
4-120695217-TTA-T		Brittle cornea syndrome 2	Likely pathogenic (Apr 20, 2022)
4-120695234-T-G		Cardiovascular phenotype	Likely benign (Sep 21, 2019)
4-120695236-G-A		Brittle cornea syndrome 2	Pathogenic (Mar 01, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRDM5	protein_coding	protein_coding	ENST00000264808	16	237952

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.60e-10	0.982	125704	0	43	125747	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.698	305	341	0.894	0.0000180	4238
Missense in Polyphen		112	134.48	0.83282		1577
Synonymous	-1.29	136	118	1.15	0.00000628	1054
Loss of Function	2.32	21	36.1	0.582	0.00000185	467

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000478	0.000478
Ashkenazi Jewish	0.00	0.00
East Asian	0.000274	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000203	0.000202
Middle Eastern	0.000274	0.000272
South Asian	0.0000982	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sequence-specific DNA-binding transcription factor. Represses transcription at least in part by recruitment of the histone methyltransferase EHMT2/G9A and histone deacetylases such as HDAC1. Regulates hematopoiesis-associated protein-coding and microRNA (miRNA) genes. May regulate the expression of proteins involved in extracellular matrix development and maintenance, including fibrillar collagens, such as COL4A1 and COL11A1, connective tissue components, such as HAPLN1, and molecules regulating cell migration and adhesion, including EDIL3 and TGFB2. May caused G2/M arrest and apoptosis in cancer cells. {ECO:0000269|PubMed:15077163, ECO:0000269|PubMed:17636019, ECO:0000269|PubMed:21664999}.

Recessive Scores

• pRec: 0.0981

Intolerance Scores

• loftool: 0.411
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.36

Haploinsufficiency Scores

• pHI: 0.436
• hipred: N
• hipred_score: 0.492
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.967

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prdm5
• Phenotype: skeleton phenotype

Zebrafish Information Network

• Gene name: prdm5
• Affected structure: anterior neural plate
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;mitotic cell cycle;histone deacetylation;negative regulation of transcription, DNA-templated;histone H3-K9 methylation;cellular response to leukemia inhibitory factor
• Cellular component: nucleus;nucleolus;nuclear body
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;methyltransferase activity;chromatin DNA binding;sequence-specific DNA binding;transcription regulatory region DNA binding;metal ion binding;repressing transcription factor binding