RASSF1

protein-coding

Ras association domain family member 1, the group of Ras association domain family

Gene summary

This gene encodes a protein similar to the RAS effector proteins. Loss or altered expression of this gene has been associated with the pathogenesis of a variety of cancers, which suggests the tumor suppressor function of this gene. The inactivation of this gene was found to be correlated with the hypermethylation of its CpG-island promoter region. The encoded protein was found to interact with DNA repair protein XPA. The protein was also shown to inhibit the accumulation of cyclin D1, and thus induce cell cycle arrest. Several alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, May 2011]

MANE transcript

NM_007182.5

Inheritance

—

ClinVar variants

U:56B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr3:50,329,782-50,340,980

External References & Databases

Ensembl (ENSG00000068028)

Transcript & Mutation Effects

hg38 • Region Span ~11.2 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 RASSF1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 52

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007182.5. 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					2 clinvar	2
missense			53 clinvar			53
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	56	0	2	58

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007182.5	RefSeq	NP_009113.3	6	MANE Select
ENST00000359365.9	Ensembl	ENSP00000352323.4	6	MANE Select
NM_001206957.2	RefSeq	NP_001193886.1	4	Standard
NM_170712.3	RefSeq	NP_733830.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Non-small cell lung cancer - Homo sapiens (human)
Bladder cancer - Homo sapiens (human)
Hippo signaling pathway - Homo sapiens (human)
Hippo signaling pathway - multiple species - Homo sapiens (human)
Ras signaling pathway - Homo sapiens (human)

Biological Process

cell cycle arrest
Ras protein signal transduction
regulation of microtubule cytoskeleton organization

Molecular Function

protein binding
zinc ion binding

Cellular Component

spindle pole
nucleus
cytoplasm
microtubule organizing center
microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357043
Coding exons: 6
Length: 11193
Individuals with no LoFs: 125714
Homozygous LoFs: 1
Heterozygous LoFs: 30
Defined: 125745
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.338	187	200	0.933	0.0000124	2166
Missense (PolyPhen)		68	72.71	0.93522		857
Synonymous	0.252	76	78.8	0.964	0.00000394	719
Loss of Function	1.00	10	14.1	0.711	7.79e-7	154

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.000081	0.000079	rare
South Asian	0.00033	0.00029	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Potential tumor suppressor. Required for death receptor- dependent apoptosis. Mediates activation of STK3/MST2 and STK4/MST1 during Fas-induced apoptosis by preventing their dephosphorylation. When associated with MOAP1, promotes BAX conformational change and translocation to mitochondrial membranes in response to TNF and TNFSF10 stimulation. Isoform A interacts with CDC20, an activator of the anaphase-promoting complex, APC, resulting in the inhibition of APC activity and mitotic progression. Inhibits proliferation by negatively regulating cell cycle progression at the level of G1/S-phase transition by regulating accumulation of cyclin D1 protein. Isoform C has been shown not to perform these roles, no function has been identified for this isoform. Isoform A disrupts interactions among MDM2, DAXX and USP7, thus contributing to the efficient activation of TP53 by promoting MDM2 self-ubiquitination in cell-cycle checkpoint control in response to DNA damage. {ECO:0000269|PubMed:10888881, ECO:0000269|PubMed:11333291, ECO:0000269|PubMed:12024041, ECO:0000269|PubMed:14743218, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:15949439, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:21199877}.;

Recessive Scores

pRec: 0.424

Intolerance Scores

LoFtool: 0.858
RVIS EVS: 0.66
RVIS percentile EVS: 84.55

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.747

Gene Damage Prediction

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