BFSP2

Chr 3AD

beaded filament structural protein 2

Also known as: CP47, CP49, CTRCT12, LIFL-L, PHAKOSIN

NCBI Gene: 8419 ENSG00000170819 UniProt: Q13515 OMIM: 603212

BFSP2 encodes phakinin, a lens-specific intermediate filament protein required for correct formation of lens intermediate filaments and maintenance of lens optical clarity. Mutations cause autosomal dominant Cataract 12, which presents with juvenile-onset, progressive cataracts. The gene is highly intolerant to loss-of-function mutations (pLI near 0), indicating it is essential for normal lens function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cataract 12, multiple typesMIM #611597

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Cataract 12, multiple types; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.04

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.000

Z-score 1.42

OE 0.67 (0.45–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.29Z-score

OE missense 0.95 (0.85–1.06)

239 obs / 252.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.45–1.04)

0≤0.351.4

Missense OE?0.95 (0.85–1.06)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 15 / 22.3Missense obs/exp: 239 / 252.0Syn Z: 0.92

Background carrier burden — how many people carry a rare variant somewhere in BFSP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 92

552 rare PASS variants

Rare truncating (LoF)

1 in 1,900

86 rare PASS variants

Rare synonymous (reference)

1 in 290

210 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BFSP2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 1,900
South Asian	~43k	1 in 80	1 in 2,200
Remaining (unassigned)	~30k	1 in 88	1 in 2,500
European (Finnish)	~27k	1 in 590	1 in 2,600
Admixed American	~22k	1 in 110	1 in 2,300
African / African American	~21k	1 in 93	1 in 3,500
East Asian	~20k	1 in 97	1 in 1,700
Ashkenazi Jewish	~13k	≈ 1 in 3,300	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 110	≈ 1 in 710

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓