RASSF6

protein-coding

Ras association domain family member 6, the group of Ras association domain family

Gene summary

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]

MANE transcript

NM_177532.5

Inheritance

—

ClinVar variants

U:59B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.59

Max pathogenic AF

—

Genomic locus

chr4:73,571,550-73,620,631

External References & Databases

Ensembl (ENSG00000169435)

Transcript & Mutation Effects

hg38 • Region Span ~49.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RASSF6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_177532.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		1 clinvar	2
missense			55 clinvar	3 clinvar		58
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	59	3	1	63

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_177532.5	RefSeq	NP_803876.1	10	MANE Select
ENST00000307439.10	Ensembl	ENSP00000303877.5	10	MANE Select
NM_001270391.2	RefSeq	NP_001257320.1	9	Standard
NM_001270392.1	RefSeq	NP_001257321.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Hippo signaling pathway - Homo sapiens (human)
Hippo signaling pathway - multiple species - Homo sapiens (human)

Biological Process

apoptotic process
signal transduction
regulation of apoptotic process

Molecular Function

protein binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342081
Coding exons: 11
Length: 49082
Individuals with no LoFs: 125304
Homozygous LoFs: 1
Heterozygous LoFs: 436
Defined: 125741
p: 0.00174

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.19	225	180	1.25	0.00000857	2440
Missense (PolyPhen)		69	50.147	1.376		701
Synonymous	-1.28	72	59.4	1.21	0.00000296	630
Loss of Function	-2.46	32	20.1	1.59	9.55e-7	265

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.00098	notable
Latino/Admixed American	0.0043	0.0023	notable
Ashkenazi Jewish	0.00070	0.00069	rare
East Asian	0.014	0.014	notable
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.00048	0.00046	rare
South Asian	0.00095	0.00091	rare
Other	0.00035	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the induction of apoptosis, through both caspase-dependent and caspase-independent pathways. May act as a Ras effector protein. May suppress the serum-induced basal levels of NF-kappa-B (By similarity). {ECO:0000250, ECO:0000269|PubMed:17367779}.;

Recessive Scores

pRec: 0.0974

Intolerance Scores

LoFtool: 0.990
RVIS EVS: 1.33
RVIS percentile EVS: 94.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.129

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium