MCF2

protein-coding

MCF.2 cell line derived transforming sequence, the group of Dbl family Rho GEFs

Gene summary

The oncogenic protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that exerts control over some members of the Rho family of small GTPases. Several transcript variants encoding different isoforms have been found for this gene. These isoforms exhibit different expression patterns and varying levels of GEF activity.[provided by RefSeq, Jan 2010]

MANE transcript

NM_001171876.2

Inheritance

ClinVar variants

U:158B:10

Top phenotype

Hypotonia

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chrX:139,581,770-139,708,216

External References & Databases

Ensembl (ENSG00000101977)

Transcript & Mutation Effects

hg38 • Region Span ~126.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

polymicrogyria, bilateral perisylvian, X-linkedLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0010314

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MCF2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 81

not providedTotal: 15

HypotoniaTotal: 1

Failure to thriveTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001171876.2. 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			12 clinvar	2 clinvar	1 clinvar	15
missense			119 clinvar	4 clinvar	3 clinvar	126
nonsense			8 clinvar			8
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			17 clinvar			17
Total	0	0	158	6	4	168

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001171876.2	RefSeq	NP_001165347.1	28	MANE Select
ENST00000519895.6	Ensembl	ENSP00000430276.1	28	MANE Select
NM_001099855.2	RefSeq	NP_001093325.1	27	Standard
NM_001171877.2	RefSeq	NP_001165348.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases
Integrin

Biological Process

G protein-coupled receptor signaling pathway
dendrite development
regulation of Rho protein signal transduction
intracellular signal transduction
positive regulation of apoptotic process

Molecular Function

guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
protein binding

Cellular Component

cytosol
cytoskeleton
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000519895
Coding exons: 28
Length: 126458
Individuals with no LoFs: 125696
Homozygous LoFs: 5
Heterozygous LoFs: 5
Defined: 125706
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	278	335	0.831	0.0000242	6637
Missense (PolyPhen)		80	117.12	0.68304		2381
Synonymous	0.125	113	115	0.985	0.00000830	1732
Loss of Function	4.99	7	41.9	0.167	0.00000305	794

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00017	0.00012	rare
Latino/Admixed American	0.000039	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000079	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000049	0.000035	rare
South Asian	0.000054	0.000033	rare
Other	0.00022	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor (GEF) that modulates the Rho family of GTPases. Promotes the conversion of some member of the Rho family GTPase from the GDP-bound to the GTP-bound form. Isoform 1 exhibits no activity toward RHOA, RAC1 or CDC42. Isoform 2 exhibits decreased GEF activity toward CDC42. Isoform 3 exhibits a weak but significant activity toward RAC1 and CDC42. Isoform 4 exhibits significant activity toward RHOA and CDC42. The truncated DBL oncogene is active toward RHOA, RAC1 and CDC42.;
Disease: DISEASE: Note=MCF2 and DBL represent two activated versions of the same proto-oncogene. {ECO:0000305}.;

Recessive Scores

pRec: 0.414

Intolerance Scores

LoFtool: 0.700
RVIS EVS: 0.87
RVIS percentile EVS: 88.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.562

Gene Damage Prediction

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