RASSF8

Chr 12

Ras association domain family member 8

Also known as: C12orf2, HOJ1

This gene encodes a tumor suppressor protein that maintains adherens junction function in epithelial cells and regulates epithelial cell migration. Chromosomal translocations involving RASSF8 cause complex synpolydactyly, a limb malformation disorder characterized by fusion of digits. The gene shows autosomal dominant inheritance and is highly constrained against loss-of-function variants.

Summary from RefSeq
Research Assistant →
0
Active trials
7
Pubs (1 yr)
36
P/LP submissions
0%
P/LP missense
0.35
LOEUF· LoF intol.
Mechanism
Clinical SummaryRASSF8
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 58 VUS of 102 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.35LOEUF
pLI 0.942
Z-score 3.78
OE 0.14 (0.060.35)
Highly constrained

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

Missense Constraint
1.10Z-score
OE missense 0.79 (0.700.90)
175 obs / 221.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.060.35)
00.351.4
Missense OE0.79 (0.700.90)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 3 / 22.2Missense obs/exp: 175 / 221.2Syn Z: 0.67

ClinVar Variant Classifications

102 submitted variants in ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic1
VUS58
Likely Benign3
Benign1
35
Pathogenic
1
Likely Pathogenic
58
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
1
0
1
VUS
0
58
0
0
58
Likely Benign
0
3
0
0
3
Benign
0
1
0
0
1
Total06236098

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

View in ClinVar →

Protein Context — Lollipop Plot

RASSF8 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →