MACF1

Chr 1AD

microtubule actin crosslinking factor 1

Also known as: ABP620, ACF7, KIAA0754, LIS9, Lnc-PMIF, MACF, OFC4

NCBI Gene: 23499 ENSG00000127603 UniProt: Q9UPN3 OMIM: 608271

This protein cross-links actin filaments to microtubules and other cytoskeletal elements, playing essential roles in cytoskeletal organization, focal adhesion dynamics, and neurite development during brain formation. Mutations cause lissencephaly 9 with complex brainstem malformation, a severe early-onset brain malformation syndrome. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants (pLI = 1.0), reflecting its critical role in normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. The encoded protein is a member of a family of proteins that form bridges between different cytoskeletal elements. This protein facilitates actin-microtubule interactions at the cell periphery and couples the microtubule network to cellular junctions. Alternative splicing results in multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, May 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Lissencephaly 9 with complex brainstem malformationMIM #618325

Clinical highlights

Gene-disease validity (ClinGen)

lissencephaly spectrum disorder with complex brainstem malformation · ADModerateconsider for supplementary testing

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.08

LOEUF· LoF intol.

—

Mechanism

📖

GeneReview available — MACF1