PRDM10

protein-coding

PR/SET domain 10, the group of Zinc fingers C2H2-type|PR/SET domain family

Gene summary

The protein encoded by this gene is a transcription factor that contains C2H2-type zinc-fingers. It also contains a positive regulatory domain, which has been found in several other zinc-finger transcription factors including those involved in B cell differentiation and tumor suppression. Studies of the mouse counterpart suggest that this protein may be involved in the development of the central nerve system (CNS), as well as in the pathogenesis of neuronal storage disease. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

MANE transcript

NM_199437.2

Inheritance

ClinVar variants

U:126B:9

Top phenotype

Birt-Hogg-Dube syndrome

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr11:129,899,706-130,002,835

External References & Databases

Ensembl (ENSG00000170325)

Transcript & Mutation Effects

hg38 • Region Span ~103.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Birt-Hogg-Dube syndrome 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0800455

Submitter: Ambry Genetics

Birt-Hogg-Dube syndrome 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0800455

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Birt-Hogg-Dube syndrome AD

Manifestation: Dermatologic; Oncologic

Intervention: Oncologic

Rationale: The condtiion involve an increased risk of a variety of neoplasms, and awareness may allow early detection and management of oncologic sequelae

Refs: 36440963

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRDM10 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 117

not providedTotal: 12

Birt-Hogg-Dube syndrome 2Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_199437.2. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar	3 clinvar	6
missense			118 clinvar	2 clinvar	2 clinvar	122
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	126	4	5	135

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_199437.2	RefSeq	NP_955469.1	20	MANE Select
ENST00000360871.8	Ensembl	ENSP00000354118.3	20	MANE Select
NM_001367890.1	RefSeq	NP_001354819.1	19	Standard
NM_001367891.1	RefSeq	NP_001354820.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
regulation of gene expression
methylation

Molecular Function

RNA polymerase II core promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
protein binding
methyltransferase activity

Cellular Component

nucleus
histone methyltransferase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358825
Coding exons: 21
Length: 103130
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.28	465	711	0.654	0.0000439	7621
Missense (PolyPhen)		195	362.29	0.53825		3716
Synonymous	0.0254	287	288	0.998	0.0000189	2235
Loss of Function	5.61	15	63.1	0.238	0.00000354	656

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000061	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000065	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in transcriptional regulation. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.185
RVIS EVS: -0.01
RVIS percentile EVS: 52.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.834

Gene Damage Prediction

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