RFTN1

Chr 3

raftlin, lipid raft linker 1

Also known as: MIG2, PIB10, PIG9, RAFTLIN

RFTN1 encodes a protein involved in endosomal trafficking and immune receptor signaling, mediating internalization of toll-like receptors and regulating T-cell and B-cell receptor pathways through interactions with clathrin and the AP2 complex. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene shows very low constraint against loss-of-function variants (pLI near 0), consistent with recessive inheritance requiring biallelic mutations.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.97
Clinical SummaryRFTN1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 76 VUS of 115 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.97LOEUF
pLI 0.000
Z-score 1.68
OE 0.60 (0.380.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.40Z-score
OE missense 0.94 (0.851.03)
312 obs / 332.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.380.97)
00.351.4
Missense OE0.94 (0.851.03)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 12 / 20.1Missense obs/exp: 312 / 332.3Syn Z: 0.11

ClinVar Variant Classifications

115 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS76
Likely Benign10
22
Pathogenic
1
Likely Pathogenic
76
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
1
0
1
VUS
0
73
3
0
76
Likely Benign
0
6
1
3
10
Benign
0
0
0
0
0
Total079273109

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

View in ClinVar →

Protein Context — Lollipop Plot

RFTN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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