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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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ACTL7A
actin like 7A
Chromosome 9 Β· 9q31.3
NCBI Gene: 10881Ensembl: ENSG00000187003.7HGNC: HGNC:161UniProt: A0A140VK03
24PubMed Papers
21Diseases
0Drugs
7Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingprotein-containing complexnucleusperinuclear thecaspermatogenic failure 86hidradenitis suppurativaAbnormality of the skeletal systemlobe attachment
✦AI Summary

ACTL7A (actin-like 7A) is essential for male fertility and normal spermatogenesis 1. The protein functions primarily in acrosome biogenesis and sperm head morphology, where it anchors and stabilizes acrosomal adherence to the acroplaxome by facilitating F-actin in the subacrosomal space 2. ACTL7A also plays a critical role in formation and fusion of Golgi-derived vesicles during acrosome development 2. Loss of ACTL7A causes small head sperm through defective formation of the acrosome-acroplaxome-manchette complex, with mechanistic studies revealing that ACTL7A deletion impairs autophagy inhibition via the PI3K/AKT/mTOR signaling pathway, leading to PDLIM1 accumulation and manchette developmental failure 1. ACTL7A mutations are associated with Spermatogenic failure 86 and cause total fertilization failure (TFF) in 14.81% of male patients with low fertilization after ICSI 3. The protein complexes with zona pellucida binding protein (ZPBP) and regulates phospholipase C zeta 1 (PLCZ1) localization and expression, critical for calcium oscillations during oocyte activation 45. Intracytoplasmic sperm injection combined with artificial oocyte activation (ICSI-AOA) significantly rescues fertility defects caused by ACTL7A mutations, increasing fertilization rates from ~11% to ~62% 31.

Sources cited
1
ACTL7A is essential for acrosome formation and causes small head sperm when defective; its loss impairs acrosome-acroplaxome-manchette complex formation via autophagy inhibition through PI3K/AKT/mTOR pathway
PMID: 37667331
2
ACTL7A mutations cause sperm acrosomal ultrastructural defects, reduced PLCΞΆ expression/localization, and early embryonic arrest; AOA rescues fertilization failure
PMID: 32923619
3
ACTL7A variants occur in 14.81% of fertilization failure cases after ICSI; ICSI-AOA treatment increases fertilization rate from 11.24% to 61.80% in patients with ACTL7A mutations
PMID: 39411542
4
Actl7a deficiency leads to malformed sperm acrosomes, altered ZPBP localization, abnormal PLCZ1 expression, and reduced sperm-zona pellucida binding ability
PMID: 35921706
5
ACTL7A mutations in the actin domain cause absent protein expression, reduced PLCΞΆ expression, and acrosome dysfunction; ICSI-AOA improves fertilization rates
PMID: 37991128
6
ACTL7A mutations are classified among genes causing deformed acrosome formation and sperm morphological abnormalities
PMID: 39417902
7
Novel ACTL7A variants associated with total fertilization failure show acrosome detachment and increased perinuclear matrix thickness; ICSI-AOA partly rescues TFF
PMID: 36593593
8
ACTL7A is identified as a gene where mutations cause fertilization failure; ICSI-AOA is recommended as therapeutic approach for ACTL7A-associated male infertility
PMID: 37758324
Disease Associationsβ“˜21
spermatogenic failure 86Open Targets
0.51Moderate
hidradenitis suppurativaOpen Targets
0.29Weak
Abnormality of the skeletal systemOpen Targets
0.28Weak
lobe attachmentOpen Targets
0.21Weak
keratoconusOpen Targets
0.21Weak
bronchopneumoniaOpen Targets
0.20Weak
Lung AbscessOpen Targets
0.20Weak
ulcer of lower limbOpen Targets
0.19Weak
Abnormality of the gastrointestinal tractOpen Targets
0.15Weak
diabetes mellitusOpen Targets
0.15Weak
cardiomyopathyOpen Targets
0.14Weak
androgenetic alopeciaOpen Targets
0.12Weak
disorder of pilosebaceous unitOpen Targets
0.11Weak
azoospermiaOpen Targets
0.11Weak
VertigoOpen Targets
0.11Weak
adolescent idiopathic scoliosisOpen Targets
0.11Weak
idiopathic pulmonary fibrosisOpen Targets
0.09Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
aortic diseaseOpen Targets
0.07Suggestive
spermatogenic failure 20Open Targets
0.07Suggestive
Spermatogenic failure 86UniProt
Pathogenic Variants7
NM_006687.4(ACTL7A):c.1204G>A (p.Gly402Ser)Likely pathogenic
Spermatogenic failure 86
β˜…β˜†β˜†β˜†β†’ Residue 402
NM_006687.4(ACTL7A):c.737G>C (p.Gly246Ala)Pathogenic
Spermatogenic failure 86
β˜†β˜†β˜†β˜†2023β†’ Residue 246
NM_006687.4(ACTL7A):c.733G>A (p.Ala245Thr)Pathogenic
Spermatogenic failure 86
β˜†β˜†β˜†β˜†2023β†’ Residue 245
NM_006687.4(ACTL7A):c.463C>T (p.Arg155Ter)Pathogenic
Spermatogenic failure 86
β˜†β˜†β˜†β˜†2023β†’ Residue 155
NM_006687.4(ACTL7A):c.1084G>A (p.Gly362Arg)Pathogenic
Spermatogenic failure 86
β˜†β˜†β˜†β˜†2023β†’ Residue 362
NM_006687.4(ACTL7A):c.146C>G (p.Ser49Ter)Pathogenic
Spermatogenic failure 86
β˜†β˜†β˜†β˜†2023β†’ Residue 49
NM_006687.4(ACTL7A):c.149_150del (p.Glu50fs)Pathogenic
Male infertility with normal semen parameters
β˜†β˜†β˜†β˜†β†’ Residue 50
View on ClinVar β†—
Related Genes
CTNNAL1Protein interaction95%TESProtein interaction95%ENAHProtein interaction90%ACRBPShared pathway75%DCTN2Protein interaction74%ACTR10Protein interaction74%
Tissue Expression6 tissues
Brain
100%
Liver
100%
Bone Marrow
40%
Ovary
40%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
ACTL7ACTNNAL1TESENAHACRBPDCTN2ACTR10
PROTEIN STRUCTURE
Preparing viewer…
PDB2XQN Β· 2.62 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.18LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.86 [0.63–1.18]
RankingsWhere ACTL7A stands among ~20K protein-coding genes
  • #13,131of 20,598
    Most Researched24
  • #3,262of 5,498
    Most Pathogenic Variants7
  • #12,402of 17,882
    Most Constrained (LOEUF)1.18
Genes detectedACTL7A
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetic mechanisms of fertilization failure and early embryonic arrest: a comprehensive review.
PMID: 37758324
Hum Reprod Update Β· 2024
1.00
2
Genetic etiological spectrum of sperm morphological abnormalities.
PMID: 39417902
J Assist Reprod Genet Β· 2024
0.90
3
Loss of ACTL7A causes small head sperm by defective acrosome-acroplaxome-manchette complex.
PMID: 37667331
Reprod Biol Endocrinol Β· 2023
0.80
4
Disruption in
PMID: 32923619
Sci Adv Β· 2020
0.70
5
High rate of detected variants in male
PMID: 39411542
Hum Reprod Open Β· 2024
0.60