RFLNB

Chr 17

refilin B

Also known as: CFM1, FAM101B

NCBI Gene: 359845 ENSG00000183688 UniProt: Q8N5W9 OMIM: 615928

The RFLNB protein regulates the perinuclear actin network and nuclear shape through filamin binding and plays an essential role in cartilaginous skeletal element formation. Mutations cause autosomal recessive spondylocarpotarsal synostosis syndrome, characterized by vertebral fusions and joint abnormalities affecting the skeletal system. The gene shows moderate tolerance to loss-of-function variants based on population genetics data.

OMIM ResearchSummary from RefSeq, UniProt

Enables filamin binding activity. Predicted to be involved in several processes, including actin filament bundle organization; negative regulation of bone mineralization involved in bone maturation; and negative regulation of chondrocyte development. Predicted to act upstream of or within actin cytoskeleton organization and epithelial to mesenchymal transition. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.27

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.270

Z-score 1.28

OE 0.28 (0.10–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.12Z-score

OE missense 1.03 (0.88–1.23)

95 obs / 91.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.28 (0.10–1.27)

0≤0.351.4

Missense OE?1.03 (0.88–1.23)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 1 / 3.6Missense obs/exp: 95 / 91.9Syn Z: -0.90

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

208 rare PASS variants

Rare truncating (LoF)

1 in 11,000

29 rare PASS variants

Rare synonymous (reference)

1 in 280

105 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RFLNB. 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 290	1 in 12,000
South Asian	~43k	1 in 310	≈ 1 in 12,000
Remaining (unassigned)	~30k	1 in 120	≈ 1 in 9,300
European (Finnish)	~27k	1 in 730	none seen
Admixed American	~22k	1 in 140	≈ 1 in 7,200
African / African American	~21k	1 in 96	≈ 1 in 6,600
East Asian	~20k	1 in 370	1 in 1,800
Ashkenazi Jewish	~13k	1 in 760	1 in 2,300
Middle Eastern	~2,884	1 in 200	none seen

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): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓