FST

protein-coding

follistatin

Gene summary

Follistatin is a single-chain gonadal protein that specifically inhibits follicle-stimulating hormone release. The single FST gene encodes two isoforms, FST317 and FST344 containing 317 and 344 amino acids respectively, resulting from alternative splicing of the precursor mRNA. In a study in which 37 candidate genes were tested for linkage and association with polycystic ovary syndrome (PCOS) or hyperandrogenemia in 150 families, evidence was found for linkage between PCOS and follistatin. [provided by RefSeq, Jul 2008]

MANE transcript

NM_013409.3

Inheritance

ClinVar variants

P:1U:30B:4

Top phenotype

Orofacial cleft

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr5:53,480,626-53,487,134

External References & Databases

Ensembl (ENSG00000134363)

Transcript & Mutation Effects

hg38 • Region Span ~6.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cleft lip/palateLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0016044

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FST variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 28

not providedTotal: 7

Orofacial cleftTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013409.3. 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			1 clinvar	1 clinvar		2
missense		1 clinvar	28 clinvar		3 clinvar	32
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	30	1	3	35

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013409.3	RefSeq	NP_037541.1	6	MANE Select
ENST00000256759.8	Ensembl	ENSP00000256759.3	6	MANE Select
NM_006350.5	RefSeq	NP_006341.1	6	Standard
ENST00000396947.7	Ensembl	ENSP00000380151.2	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fsta	Danio rerio	Structure: ceratobranchial cartilage Quality: hyperplastic abnormal

Gene / Model

Organism

Observed Phenotype

fsta

Danio rerio

Structure: ceratobranchial cartilage

Quality: hyperplastic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TGF-beta signaling pathway - Homo sapiens (human)
Hair Follicle Development- Induction (Part 1 of 3)
Differentiation Pathway
TGF-beta Receptor Signaling
Signal Transduction

Biological Process

negative regulation of transcription by RNA polymerase II
hematopoietic progenitor cell differentiation
negative regulation of activin receptor signaling pathway
positive regulation of hair follicle development

Molecular Function

protein binding
activin receptor antagonist activity
heparan sulfate proteoglycan binding
activin binding

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000256759
Coding exons: 6
Length: 6726
Individuals with no LoFs: 125746
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125748
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.33	101	192	0.527	0.00000995	2257
Missense (PolyPhen)		29	80.938	0.3583		862
Synonymous	0.676	70	77.6	0.902	0.00000439	640
Loss of Function	3.52	1	16.4	0.0610	7.76e-7	211

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds directly to activin and functions as an activin antagonist. Specific inhibitor of the biosynthesis and secretion of pituitary follicle stimulating hormone (FSH).;

Recessive Scores

pRec: 0.486

Intolerance Scores

RVIS EVS: 0.59
RVIS percentile EVS: 82.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.978

Gene Damage Prediction

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