RFTN2

Chr 2

raftlin family member 2

ENSG00000162944 UniProt: Q52LD8 OMIM: 618215

The protein mediates clathrin-dependent internalization of TLR4 upon bacterial stimulation in dendritic cells and may regulate B-cell antigen receptor signaling. Mutations in RFTN2 cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and brain malformations. This gene shows tolerance to loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Upon bacterial lipopolysaccharide stimulation, mediates clathrin-dependent internalization of TLR4 in dendritic cells, resulting in activation of TICAM1-mediated signaling and subsequent IFNB1 production. May regulate B-cell antigen receptor-mediated signaling

OMIM ResearchGenerating clinical summary…

LOEUF 0.84

Clinical Summary— RFTN2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

70 VUS of 82 total submissions

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Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.000

Z-score 2.14

OE 0.52 (0.33–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.33Z-score

OE missense 0.94 (0.85–1.05)

256 obs / 271.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.33–0.84)

0≤0.351.4

Missense OE?0.94 (0.85–1.05)

0≤0.61.4

Synonymous OE?0.72

0≤1.21.6

LoF obs/exp: 12 / 23.1Missense obs/exp: 256 / 271.3Syn Z: 2.28

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

VUS70

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	70	70
Likely Benign	3	3
Benign	0	0
Total	73	73

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

View in ClinVar →

36 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap RFTN2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →