RFLNB

Chr 17

refilin B

Also known as: CFM1, FAM101B

NCBI Gene: 359845 ENSG00000183688 UniProt: Q8N5W9

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.

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. Predicted to be located in actin cytoskeleton and cytoplasm. Predicted to be active in actin filament bundle. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.27

Clinical Summary— RFLNB

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

2 total variants — no pathogenic classifications of 2 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

This gene — mechanism propensity

0.5673th %ile

GOF

0.74top 25%

LOF

0.4332th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

2 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Benign2

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	0	0
Likely Benign	2	2
Benign	0	0
Total	2	2

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

59 pathogenic / likely-pathogenic (of 109) ClinVar copy-number / structural variants overlap RFLNB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →