BFSP2

protein-coding

beaded filament structural protein 2, the group of Beaded filament structural proteins

Gene summary

More than 99% of the vertebrate ocular lens is comprised of terminally differentiated lens fiber cells. Two lens-specific intermediate filament-like proteins, the protein product of this gene (phakinin), and filensin, are expressed only after fiber cell differentiation has begun. Both proteins are found in a structurally unique cytoskeletal element that is referred to as the beaded filament (BF). Mutations in this gene have been associated with juvenile-onset, progressive cataracts and Dowling-Meara epidermolysis bullosa simplex. [provided by RefSeq, Jun 2009]

MANE transcript

NM_003571.4

Inheritance

AD, AR

ClinVar variants

P:3U:84B:37

Top phenotype

Cataract 12, multiple types

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr3:133,400,056-133,475,222

External References & Databases

Ensembl (ENSG00000170819)

Transcript & Mutation Effects

hg38 • Region Span ~75.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataract 12 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012701

Submitter: PanelApp Australia

early-onset lamellar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018611

Submitter: Orphanet

cataract 12 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012701

Submitter: Labcorp Genetics (formerly Invitae)

cataract 12 multiple typesDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0012701

Submitter: G2P

cataract 12 multiple typesDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012701

Submitter: G2P

cataract 12 multiple typesMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0012701

Submitter: Ambry Genetics

early-onset non-syndromic cataractMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0011060

Submitter: Ambry Genetics

pulverulent cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011430

Submitter: Orphanet

early-onset sutural cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020372

Submitter: Orphanet

Clinical Genomic Database (CGD)

Cataract 12, multiple typesAD/AR

Manifestation: Ophthalmologic

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: 10729115; 10739768; 10634598; 15570218; 17982427; 18958306; 21836522

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BFSP2 variants in ClinVar

12 Conditions Cataloged

not specifiedTotal: 73

Cataract 12 multiple typesTotal: 62

not providedTotal: 24

BFSP2-related disorderTotal: 12

Developmental cataractTotal: 2

CataractTotal: 1

StrabismusTotal: 1

NystagmusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003571.4. 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			3 clinvar	15 clinvar	6 clinvar	24
missense			78 clinvar	13 clinvar	3 clinvar	94
nonsense	1 clinvar	1 clinvar	2 clinvar			4
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	2	1	84	28	9	124

Highest pathogenic variant AF is 0.0000041072876

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003571.4	RefSeq	NP_003562.1	7	MANE Select
ENST00000302334.3	Ensembl	ENSP00000304987.2	7	MANE Select
XM_017007315.2	RefSeq	XP_016862804.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

visual perception
intermediate filament cytoskeleton organization
cell maturation
response to stimulus
lens fiber cell development

Molecular Function

structural constituent of cytoskeleton
structural constituent of eye lens
protein binding

Cellular Component

intermediate filament
plasma membrane
cell cortex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000302334
Coding exons: 7
Length: 75228
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125748
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.292	239	252	0.948	0.0000161	2683
Missense (PolyPhen)		64	63.914	1.0013		770
Synonymous	0.917	88	99.6	0.883	0.00000613	855
Loss of Function	1.42	15	22.3	0.674	0.00000138	218

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00027	0.00027	rare
Finnish	0.00031	0.00028	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00026	0.00026	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in stabilization of lens fiber cell cytoskeleton. {ECO:0000250|UniProtKB:Q6NVD9}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.218
RVIS EVS: -0.38
RVIS percentile EVS: 27.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0918

Gene Damage Prediction

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