MCF2L

Chr 13

MCF.2 cell line derived transforming sequence like

Also known as: ARHGEF14, DBS, OST

The protein is a guanine nucleotide exchange factor that catalyzes nucleotide exchange on RHOA and CDC42, regulating these critical cellular signaling pathways. MCF2L is highly constrained against loss-of-function variants, but specific neurogenetic disorders caused by mutations in this gene have not been well-established in the medical literature. The gene shows strong evolutionary conservation suggesting biological importance, but clear genotype-phenotype correlations require further clinical documentation.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.50
Clinical SummaryMCF2L
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.50LOEUF
pLI 0.000
Z-score 4.86
OE 0.36 (0.260.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.85Z-score
OE missense 0.80 (0.750.86)
564 obs / 701.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.260.50)
00.351.4
Missense OE0.80 (0.750.86)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 24 / 67.0Missense obs/exp: 564 / 701.9Syn Z: 0.29
DN
0.6743th %ile
GOF
0.73top 25%
LOF
0.3066th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MCF2L · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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