RELCH

Chr 18

RAB11 binding and LisH domain, coiled-coil and HEAT repeat containing

Also known as: HsT3308, HsT885, KIAA1468

The RELCH protein regulates intracellular cholesterol distribution by facilitating cholesterol transfer from recycling endosomes to the trans-Golgi network through interactions with RAB11 and OSBP. Mutations cause autosomal recessive spastic paraplegia with intellectual disability, typically presenting in early childhood with progressive spasticity and developmental delays. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
91
P/LP submissions
0%
P/LP missense
0.23
LOEUF· LoF intol.
Mechanism
Clinical SummaryRELCH
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
88 unique Pathogenic / Likely Pathogenic· 122 VUS of 248 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.23LOEUF
pLI 1.000
Z-score 6.57
OE 0.13 (0.080.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.87Z-score
OE missense 0.57 (0.520.62)
361 obs / 635.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.13 (0.080.23)
00.351.4
Missense OE0.57 (0.520.62)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 9 / 67.0Missense obs/exp: 361 / 635.8Syn Z: 1.82

ClinVar Variant Classifications

248 submitted variants in ClinVar

Classification Summary

Pathogenic82
Likely Pathogenic6
VUS122
Likely Benign3
Benign2
82
Pathogenic
6
Likely Pathogenic
122
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
82
0
82
Likely Pathogenic
0
0
6
0
6
VUS
0
118
4
0
122
Likely Benign
0
1
0
2
3
Benign
0
1
0
1
2
Total0120923215

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

View in ClinVar →

Protein Context — Lollipop Plot

RELCH · 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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