POF1B

protein-coding

POF1B actin binding protein

Gene summary

Premature ovarian failure (POF) is characterized by primary or secondary amenorrhea in women less than 40 years old. Two POF susceptibility regions called "POF1" and "POF2" have been identified by breakpoint mapping of X-autosome translocations. POF1 extends from Xq21-qter while POF2 extends from Xq13.3 to Xq21.1. This gene, POF1B, resides in the POF2 region. This gene is expressed at trace levels in mouse prenatal ovary and is barely detectable or absent from adult ovary, in human and in the mouse respectively. This gene's expression is restricted to epithelia with its highest expression in the epidermis, and oro-pharyngeal and gastro-intestinal tracts. The protein encoded by this gene binds non-muscle actin filaments. The role this gene may play in the etiology of premature ovarian failure remains to be determined. [provided by RefSeq, Jan 2010]

MANE transcript

NM_024921.4

Inheritance

ClinVar variants

U:126B:24

Top phenotype

Premature ovarian failure 2B

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chrX:85,277,396-85,379,717

External References & Databases

Ensembl (ENSG00000124429)

Transcript & Mutation Effects

hg38 • Region Span ~102.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

premature ovarian failure 2BLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0010373

Submitter: Ambry Genetics

premature ovarian failure 2BMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010373

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Premature ovarian failure 2BXL

Manifestation: Endocrine; Obstetric

Intervention: Obstetric

Rationale: Genetic knowledge may allow fertility preservation such as by storing eggs

Refs: 16773570

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POF1B variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 22

Premature ovarian failure 2BTotal: 20

POF1B-related disorderTotal: 9

Premature ovarian insufficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024921.4. 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			10 clinvar	10 clinvar	4 clinvar	24
missense			90 clinvar	6 clinvar	4 clinvar	100
nonsense			6 clinvar			6
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			20 clinvar			20
Total	0	0	126	16	8	150

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024921.4	RefSeq	NP_079197.3	16	MANE Select
ENST00000262753.9	Ensembl	ENSP00000262753.4	16	MANE Select
NM_001307940.2	RefSeq	NP_001294869.1	15	Standard
ENST00000373145.3	Ensembl	ENSP00000362238.3	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

epithelial cell morphogenesis
actin filament organization
actin cytoskeleton organization
bicellular tight junction assembly

Molecular Function

actin filament binding

Cellular Component

actin filament
adherens junction
bicellular tight junction
desmosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262753
Coding exons: 16
Length: 102347
Individuals with no LoFs: 125699
Homozygous LoFs: 6
Heterozygous LoFs: 30
Defined: 125735
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.780	163	194	0.842	0.0000139	3883
Missense (PolyPhen)		54	74.778	0.72214		1621
Synonymous	-0.209	72	69.8	1.03	0.00000495	1032
Loss of Function	1.03	19	24.5	0.776	0.00000175	464

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00025	rare
Latino/Admixed American	0.00020	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00025	0.00016	rare
Finnish	0.000063	0.000046	rare
European (Non-Finnish)	0.00024	0.00017	rare
South Asian	0.00018	0.000098	rare
Other	0.00026	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a key role in the organization of epithelial monolayers by regulating the actin cytoskeleton. May be involved in ovary development. {ECO:0000269|PubMed:16773570, ECO:0000269|PubMed:21940798}.;
Disease: DISEASE: Premature ovarian failure 2B (POF2B) [MIM:300604]: An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. {ECO:0000269|PubMed:16773570, ECO:0000269|PubMed:21940798}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.414

Intolerance Scores

LoFtool: 0.580
RVIS EVS: 0.93
RVIS percentile EVS: 89.79

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.157

Gene Damage Prediction

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