RASSF6

Chr 4

Ras association domain family member 6

NCBI Gene: 166824 ENSG00000169435 UniProt: Q6ZTQ3 OMIM: 612620

The protein is involved in apoptosis induction and functions as a Ras effector protein that may suppress NF-kappa-B signaling. Mutations cause neurodevelopmental disorder with epilepsy, spasticity, and brain abnormalities, following autosomal recessive inheritance. This gene is not highly constrained against loss-of-function variants, indicating tolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the Ras-association domain family (RASSF). Members of this family form the core of a highly conserved tumor suppressor network, the Salvador-Warts-Hippo (SWH) pathway. The protein encoded by this gene is a Ras effector protein that induces apoptosis. A genomic region containing this gene has been linked to susceptibility to viral bronchiolitis. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.93

Clinical Summary— RASSF6

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

64 VUS of 79 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.93LOEUF

pLI 0.000

Z-score -2.46

OE 1.59 (1.19–1.93)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.19Z-score

OE missense 1.25 (1.12–1.40)

225 obs / 180.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.59 (1.19–1.93)

0≤0.351.4

Missense OE?1.25 (1.12–1.40)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 32 / 20.1Missense obs/exp: 225 / 180.0Syn Z: -1.28

This gene — mechanism propensity

0.6161th %ile

GOF

0.4972th %ile

LOF

0.4430th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

79 submitted variants in ClinVar

ClinVar

Classification Summary

VUS64

Likely Benign4

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	64	0	64
Likely Benign	4	0	4
Benign	0	1	1
Total	68	1	69

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap RASSF6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →