BRDT

protein-coding

bromodomain testis associated, the group of Bromodomain containing|Bromodomain and extra-terminal domain family

Gene summary

BRDT is similar to the RING3 protein family. It possesses 2 bromodomain motifs and a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation. The bromodomain is found in proteins that regulate transcription. Several transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

MANE transcript

NM_207189.4

Inheritance

ClinVar variants

P:2U:110B:9

Top phenotype

Spermatogenic failure 21

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr1:91,949,343-92,014,426

External References & Databases

Ensembl (ENSG00000137948)

Transcript & Mutation Effects

hg38 • Region Span ~65.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 21LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0054725

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spermatogenic failure 21AR

Manifestation: Genitourinary

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

Refs: 28199965

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BRDT variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 115

BRDT-related disorderTotal: 3

Spermatogenic failure 21Total: 2

not providedTotal: 1

Premature ovarian failureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_207189.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense			108 clinvar	7 clinvar		115
nonsense		1 clinvar	1 clinvar			2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	1	110	8	1	121

Highest pathogenic variant AF is 0.0000013682361

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_207189.4	RefSeq	NP_997072.2	18	MANE Select
ENST00000399546.7	Ensembl	ENSP00000387822.3	18	MANE Select
NM_001242805.2	RefSeq	NP_001229734.2	18	Standard
NM_001242806.2	RefSeq	NP_001229735.2	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Chemical Compounds to monitor Proteins

Biological Process

histone displacement
chromatin remodeling
regulation of transcription, DNA-templated
mRNA processing
male meiotic nuclear division

Molecular Function

transcription coactivator activity
histone binding
lysine-acetylated histone binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000362005
Coding exons: 18
Length: 65056
Individuals with no LoFs: 125686
Homozygous LoFs: 0
Heterozygous LoFs: 58
Defined: 125744
p: 0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.457	437	465	0.940	0.0000230	6268
Missense (PolyPhen)		87	109.53	0.7943		1509
Synonymous	-0.367	167	161	1.04	0.00000829	1668
Loss of Function	3.46	22	47.8	0.460	0.00000239	649

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00051	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00061	0.00060	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00013	rare
South Asian	0.00037	0.00036	rare
Other	0.00055	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Testis-specific chromatin protein that specifically binds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) and plays a key role in spermatogenesis (PubMed:22464331, PubMed:22901802). Required in late pachytene spermatocytes: plays a role in meiotic and post-meiotic cells by binding to acetylated histones at the promoter of specific meiotic and post-meiotic genes, facilitating their activation at the appropriate time (PubMed:22901802). In the post-meiotic phase of spermatogenesis, binds to hyperacetylated histones and participates in their general removal from DNA (PubMed:22901802). Also recognizes and binds a subset of butyrylated histones: able to bind histone H4 butyrylated at 'Lys-8' (H4K8ac), while it is not able to bind H4 butyrylated at 'Lys-5' (H4K5ac) (By similarity). Also acts as a component of the splicing machinery in pachytene spermatocytes and round spermatids and participates in 3'-UTR truncation of specific mRNAs in post-meiotic spermatids (By similarity). Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin. {ECO:0000250|UniProtKB:Q91Y44, ECO:0000269|PubMed:15647849, ECO:0000269|PubMed:22464331, ECO:0000269|PubMed:22901802, ECO:0000269|PubMed:9367677}.;
Disease: DISEASE: Spermatogenic failure 21 (SPGF21) [MIM:617644]: An infertility disorder caused by spermatogenesis defects and characterized by acephalic spermatozoa in the semen of affected individuals. SPGF21 inheritance is autosomal recessive. {ECO:0000269|PubMed:28199965}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.305

Intolerance Scores

LoFtool: 0.932
RVIS EVS: 0.78
RVIS percentile EVS: 87.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0431

Gene Damage Prediction

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