BDP1

protein-coding

B double prime 1, subunit of RNA polymerase III transcription initiation factor IIIB, the group of Myb/SANT domain containing|General transcription factor IIIB complex subunits

Gene summary

The product of this gene is a subunit of the TFIIIB transcription initiation complex, which recruits RNA polymerase III to target promoters in order to initiate transcription. The encoded protein localizes to concentrated aggregates in the nucleus, and is required for transcription from all three types of polymerase III promoters. It is phosphorylated by casein kinase II during mitosis, resulting in its release from chromatin and suppression of polymerase III transcription. [provided by RefSeq, Jul 2008]

Previous symbols:

TFNR
TAF3B1

MANE transcript

NM_018429.3

Inheritance

ClinVar variants

P:3U:368B:139

Top phenotype

Deafness, autosomal recessive 112

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr5:71,455,651-71,567,820

External References & Databases

Ensembl (ENSG00000145734)

Transcript & Mutation Effects

hg38 • Region Span ~112.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nonsyndromic genetic hearing lossLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019497

Submitter: ClinGen

The BDP1 gene has been associated with autosomal recessive nonsyndromic hearing loss using the ClinGen Clinical Validity Framework as of 11/15/2016. This association was made using case-level data only. At least 1 variant occurring at the stop codon has been reported in humans. BDP1 was first associated with this disease in humans as early as 2013 (Girotto et al.). Association is seen in at least 1 probands in 1 publications (24312468). Variants in this gene segregated with disease in 3 additional family members. This gene-disease association is supported by an expression study. In summary, there is limited evidence to support this gene-disease association. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease association. This classification was originally evaluated by the ClinGen Hearing Loss Gene Curation Expert Panel on 9/11/2017. It was reevaluated on 3/26/2021. As a result of this reevaluation, the classification did not change.

hearing loss, autosomal recessiveSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: Orphanet

nonsyndromic genetic hearing lossMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0019497

Submitter: LiferaOmics

ClinGen AR non syndromic hearing loss classification: Limited (03/26/2021) with total score = 3.0 points: genetic = 2.5 (0.5 variant + 2 segregation) and experimental = 0.5 (inner-ear expression), based on the original consanguineous family with homozygous stop-loss variant c.7873T>G (PMID:24312468) Additional published genetic evidence not included in original ClinGen scoring: PMID:36597107 reports four independent AR NSHL probands (three compound heterozygous c.282A>T/c.7189T>G; one compound heterozygous c.7873T>G/c.2005G>A) - case-level scoring = 1.4. PMID:39504961 reports one independent proband homozygous for c.282A>T - case-level = 0.1 Our current case: 1 proband with hearing impairment, consanguineous parents; homozygous frameshift NM_018429.3:c.7542_7549dup;p.(Leu2517Ter); no segregation data; conservative case-level (biallelic variant,consanguinity) = 1.0 Recalculated totals: genetic = 2.5 (ClinGen baseline; PMID:24312468) + 1.4 (PMID:36597107) + 0.1 (PMID:39504961) + 1.0 (current case) = 8.5 / 12 Experimental Evidence: Expression = 2 (PMID:24312468) Overall score = 7.0 points

hearing loss, autosomal recessive 112LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032639

Submitter: PanelApp Australia

hearing loss, autosomal recessive 112LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032639

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 112AR

Manifestation: Audiologic/Otolaryngologic

Intervention: General

Rationale: 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

Comments: Hearing loss has been described as postlingual

Refs: 24312468

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BDP1 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 423

not providedTotal: 190

BDP1-related disorderTotal: 95

Hearing loss, autosomal recessive 112Total: 11

DeafnessTotal: 1

Hearing impairmentTotal: 1

Waardenburg syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018429.3. 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			5 clinvar	61 clinvar	5 clinvar	71
missense		1 clinvar	347 clinvar	66 clinvar	7 clinvar	421
nonsense		1 clinvar	3 clinvar			4
start loss						0
frameshift		1 clinvar	2 clinvar			3
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	3	368	127	12	510

Highest pathogenic variant AF is 0.0000013736452

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018429.3	RefSeq	NP_060899.2	39	MANE Select
ENST00000358731.9	Ensembl	ENSP00000351575.4	39	MANE Select
ENST00000514903.7	Ensembl	ENSP00000421910.3	11	Standard
ENST00000525844.1	Ensembl	ENSP00000432404.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
rna polymerase iii transcription
RNA Polymerase III Abortive And Retractive Initiation
RNA Polymerase III Transcription Initiation From Type 1 Promoter
RNA Polymerase III Transcription Initiation From Type 2 Promoter

Biological Process

RNA polymerase III preinitiation complex assembly

Molecular Function

RNA polymerase III general transcription initiation factor activity
TFIIIC-class transcription factor complex binding
DNA binding

Cellular Component

transcription factor TFIIIB complex
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358731
Coding exons: 39
Length: 112208
Individuals with no LoFs: 124706
Homozygous LoFs: 0
Heterozygous LoFs: 88
Defined: 124794
p: 0.000353

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.124	1314	1.30e+3	1.01	0.0000624	17220
Missense (PolyPhen)		324	365.95	0.88536		5029
Synonymous	-1.25	482	448	1.08	0.0000225	4917
Loss of Function	5.22	55	116	0.476	0.00000601	1614

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00041	0.00039	rare
Latino/Admixed American	0.00068	0.00064	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00038	0.00037	rare
South Asian	0.00027	0.00026	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: General activator of RNA polymerase III transcription. Requires for transcription from all three types of polymerase III promoters. Requires for transcription of genes with internal promoter elements and with promoter elements upstream of the initiation site. {ECO:0000269|PubMed:11040218}.;

Recessive Scores

pRec: 0.0695

Intolerance Scores

LoFtool: 0.904
RVIS EVS: 2.39
RVIS percentile EVS: 98.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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