HSF2BP

protein-coding

heat shock transcription factor 2 binding protein, the group of Armadillo like helical domain containing|MicroRNA protein coding host genes

Gene summary

HSF2 binding protein (HSF2BP) associates with HSF2. The interaction occurs between the trimerization domain of HSF2 and the amino terminal hydrophilic region of HSF2BP that comprises two leucine zipper motifs. HSF2BP may therefore be involved in modulating HSF2 activation. [provided by RefSeq, Jul 2008]

MANE transcript

NM_007031.2

Inheritance

ClinVar variants

P:2U:48B:7

Top phenotype

Premature ovarian failure 19

gnomAD constraint

pLI —, LoF o/e 1.31

Max pathogenic AF

—

Genomic locus

chr21:43,529,186-43,659,488

External References & Databases

Ensembl (ENSG00000160207)

Transcript & Mutation Effects

hg38 • Region Span ~130.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

premature ovarian failure 19LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030985

Submitter: Labcorp Genetics (formerly Invitae)

premature ovarian failure 19STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030985

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Premature ovarian failure 19AR

Manifestation: Obstetric

Intervention: Obstetric

Rationale: The condition can involve infertility, and fertility treatment has been described as successful in some indviduals

Refs: 32845237

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HSF2BP variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 6

Premature ovarian failure 19Total: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007031.2. 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			2 clinvar	2 clinvar		4
missense		2 clinvar	45 clinvar	5 clinvar		52
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	2	48	7	0	57

Highest pathogenic variant AF is 0.00000867408

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007031.2	RefSeq	NP_008962.1	8	MANE Select
ENST00000291560.7	Ensembl	ENSP00000291560.2	8	MANE Select
ENST00000443485.1	Ensembl	ENSP00000409585.1	6	Standard
ENST00000869315.1	Ensembl	ENSP00000539374.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

transcription by RNA polymerase II
spermatogenesis

Molecular Function

protein binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000291560
Coding exons: 8
Length: 130303
Individuals with no LoFs: 125672
Homozygous LoFs: 0
Heterozygous LoFs: 76
Defined: 125748
p: 0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.172	197	190	1.03	0.0000112	2178
Missense (PolyPhen)		95	102.59	0.92603		1203
Synonymous	0.274	71	74.0	0.960	0.00000440	644
Loss of Function	-1.14	21	16.1	1.31	7.38e-7	207

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0016	0.0016	notable
Latino/Admixed American	0.00039	0.00038	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00033	0.00033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in modulating HSF2 activation in testis (PubMed:9651507). Inhibits BNC1 transcriptional activity during spermatogenesis, probably by sequestering it in the cytoplasm (By similarity). {ECO:0000250|UniProtKB:Q9D4G2, ECO:0000269|PubMed:9651507}.;

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.516
RVIS EVS: -0.36
RVIS percentile EVS: 29.16

Essentials

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

Gene Damage Prediction

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