GeneBe

PRDM5

protein-coding

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

Gene summary

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_018699.4

Inheritance

AR, AD

ClinVar variants

P:67U:289B:243

Top phenotype

Brittle cornea syndrome 2

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr4:120,684,919-120,922,870

External References & Databases

Ensembl (ENSG00000138738)NCBI Gene (11107)OMIM (614161)HGNC:9349GenCCUniProt (Q9NQX1)AlphaFoldClinVar (PRDM5)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~238.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

brittle cornea syndrome 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013605

Submitter: G2P

brittle cornea syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009242

Submitter: Orphanet

brittle cornea syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013605

Submitter: Genomics England PanelApp

aortic disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005561

Submitter: Ambry Genetics

brittle cornea syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013605

Submitter: PanelApp Australia

Axenfeld-Rieger syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019187

Submitter: G2P

brittle cornea syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013605

Submitter: Labcorp Genetics (formerly Invitae)

brittle cornea syndrome 2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013605

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Brittle cornea syndrome 2AR

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic

Intervention: Ophthalmologic

Rationale: Individuals are prone to ophthalmologic injury (such as corneal rupture) with minimal trauma, and protective measures may be beneficial

Comments: Manifestations can occur in heterozygote

Refs: 21664999; 22122778; 26395458Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRDM5 variants in ClinVar

8 Conditions Cataloged
not providedTotal: 538
Cardiovascular phenotypeTotal: 402
not specifiedTotal: 96
Brittle cornea syndrome 2Total: 58
Ehlers-Danlos syndromeTotal: 28
PRDM5-related disorderTotal: 22
Axenfeld-Rieger syndrome type 1Total: 1
Connective tissue disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018699.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
211
clinvar
1
clinvar
 214
missense
5
clinvar
281
clinvar
31
clinvar
 317
nonsense
14
clinvar
9
clinvar
1
clinvar
 24
start loss
1
clinvar
 1
frameshift
11
clinvar
10
clinvar
 21
splice donor/acceptor (+/-2bp)
3
clinvar
15
clinvar
4
clinvar
 22
Total28392892421599

Highest pathogenic variant AF is 0.000027311924

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_018699.4RefSeqNP_061169.216MANE Select
ENST00000264808.8EnsemblENSP00000264808.316MANE Select
NM_001300823.2RefSeqNP_001287752.115Standard
NM_001300824.2RefSeqNP_001287753.113Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
prdm5Danio rerio

Structure: anterior neural plate

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

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

Cellular Component

  • nucleus
  • nucleolus
  • nuclear body

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000264808
Coding exons
16
Length
237952
Individuals with no LoFs
125704
Homozygous LoFs
0
Heterozygous LoFs
43
Defined
125747
p
0.000171
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.6983053410.8940.00001804238
Missense (PolyPhen)112134.480.832821577
Synonymous-1.291361181.150.000006281054
Loss of Function2.322136.10.5820.00000185467

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000230.00023rare
Ashkenazi Jewish00.0absent
East Asian0.000270.00027rare
Finnish00.0absent
European (Non-Finnish)0.000200.00020rare
South Asian0.0000980.000098rare
Other00.0absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.967

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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