MACF1

Chr 1AD

microtubule actin crosslinking factor 1

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ADLOEUF 0.081 OMIM phenotype
Clinical SummaryMACF1
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Gene-Disease Validity (ClinGen)
lissencephaly spectrum disorder with complex brainstem malformation · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📖
GeneReview available — MACF1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 15.61
OE 0.06 (0.040.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.43Z-score
OE missense 0.82 (0.790.85)
2325 obs / 2840.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.06 (0.040.08)
00.351.4
Missense OE0.82 (0.790.85)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 18 / 318.8Missense obs/exp: 2325 / 2840.0Syn Z: -0.63

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MACF1 · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC