MCF2L

protein-coding

MCF.2 cell line derived transforming sequence like, the group of Dbl family Rho GEFs|Pleckstrin homology domain containing

Gene summary

This gene encodes a guanine nucleotide exchange factor that interacts specifically with the GTP-bound Rac1 and plays a role in the Rho/Rac signaling pathways. A variant in this gene was associated with osteoarthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

MANE transcript

NM_001112732.3

Inheritance

ClinVar variants

U:152B:42

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr13:112,894,378-113,099,742

External References & Databases

Ensembl (ENSG00000126217)

Transcript & Mutation Effects

hg38 • Region Span ~205.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

vascular malformationLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0024291

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MCF2L variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 161

not providedTotal: 36

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001112732.3. 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			3 clinvar	15 clinvar	3 clinvar	21
missense			145 clinvar	22 clinvar	2 clinvar	169
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	152	37	5	194

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001112732.3	RefSeq	NP_001106203.2	30	MANE Select
ENST00000535094.7	Ensembl	ENSP00000440374.2	30	MANE Select
NM_001320815.2	RefSeq	NP_001307744.1	31	Standard
NM_001320816.2	RefSeq	NP_001307745.1	30	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
NRAGE signals death through JNK

Biological Process

G protein-coupled receptor signaling pathway
regulation of Rho protein signal transduction
intracellular signal transduction
positive regulation of apoptotic process
regulation of small GTPase mediated signal transduction

Molecular Function

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

Cellular Component

extracellular space
cytosol
plasma membrane
endomembrane system

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000535094
Coding exons: 30
Length: 205362
Individuals with no LoFs: 125697
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 125748
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.85	564	702	0.804	0.0000461	7331
Missense (PolyPhen)		105	195.88	0.53606		2113
Synonymous	0.290	310	317	0.979	0.0000239	2129
Loss of Function	4.86	24	67.0	0.358	0.00000331	750

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00022	0.00018	rare
Latino/Admixed American	0.00018	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00032	0.00030	rare
South Asian	0.00014	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor that catalyzes guanine nucleotide exchange on RHOA and CDC42, and thereby contributes to the regulation of RHOA and CDC42 signaling pathways (By similarity). Seems to lack activity with RAC1. Becomes activated and highly tumorigenic by truncation of the N-terminus (By similarity). Isoform 5 activates CDC42 (PubMed:15157669). {ECO:0000250|UniProtKB:Q63406, ECO:0000269|PubMed:15157669}.;

Intolerance Scores

LoFtool: 0.715
RVIS EVS: -1.58
RVIS percentile EVS: 3.14

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.588

Gene Damage Prediction

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