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ACTL9

gene
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Also known as MGC33407

Summary

ACTL9 (actin like 9, HGNC:28494) is a protein-coding gene on chromosome 19p13.2, encoding Actin-like protein 9 (Q8TC94). Testis-specic protein that plays an important role in fusion of proacrosomal vesicles and perinuclear theca formation.

Involved in acrosome assembly and fertilization. Located in acrosomal vesicle; perinuclear theca; and sperm head. Implicated in spermatogenic failure 53.

Source: NCBI Gene 284382 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): spermatogenic failure 53 (Strong, GenCC) — +1 more curated relationship
  • GWAS associations: 23
  • Clinical variants (ClinVar): 75 total — 3 pathogenic
  • Phenotypes (HPO): 3
  • MANE Select transcript: NM_178525

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:28494
Approved symbolACTL9
Nameactin like 9
Location19p13.2
Locus typegene with protein product
StatusApproved
AliasesMGC33407
Ensembl geneENSG00000181786
Ensembl biotypeprotein_coding
OMIM619251
Entrez284382

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000324436

RefSeq mRNA: 1 — MANE Select: NM_178525 NM_178525

CCDS: CCDS12207

Canonical transcript exons

ENST00000324436 — 1 exons

ExonStartEnd
ENSE0000122736286974008698795

Expression profiles

Bgee: expression breadth broad, 28 present calls, max score 96.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1494 / max 146.6026, expressed in 3 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
1789730.09143
1789720.05113
1789710.00683

Top tissues by expression

215 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047396.80gold quality
spermCL:000001996.51gold quality
left testisUBERON:000453394.88gold quality
right testisUBERON:000453494.84gold quality
testisUBERON:000047391.73gold quality
adult organismUBERON:000702390.98gold quality
quadriceps femorisUBERON:000137760.42gold quality
vastus lateralisUBERON:000137960.41gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450258.52gold quality
biceps brachiiUBERON:000150757.22gold quality
cardiac muscle of right atriumUBERON:000337954.34gold quality
left ventricle myocardiumUBERON:000656654.23gold quality
kidney epitheliumUBERON:000481953.93gold quality
upper arm skinUBERON:000426353.52gold quality
epithelial cell of pancreasCL:000008353.37gold quality
deltoidUBERON:000147653.18gold quality
tibialis anteriorUBERON:000138553.12silver quality
ileal mucosaUBERON:000033152.70silver quality
myocardiumUBERON:000234950.25gold quality
amniotic fluidUBERON:000017349.55silver quality
pancreatic ductal cellCL:000207949.44silver quality
skeletal muscle tissueUBERON:000113447.83gold quality
nasal cavity epitheliumUBERON:000538447.03gold quality
muscle tissueUBERON:000238546.66gold quality
jejunumUBERON:000211545.69gold quality
cauda epididymisUBERON:000436045.59silver quality
layer of synovial tissueUBERON:000761643.55gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451143.37gold quality
epithelium of nasopharynxUBERON:000195142.73gold quality
secondary oocyteCL:000065542.57gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no0.20

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

  • Association of KIF3A, but not OVOL1 and ACTL9, with atopic eczema in Italian patients (PMID:23278845)
  • KIF3A and OVOL1, but not ACTL9, are involved in the development of Atopic dermatitis in the Chinese pediatric population. (PMID:26127003)
  • Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice. (PMID:33626338)
  • Identification of a new mutation in the ACTL9 gene in men with unexplained infertility. (PMID:38769899)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
mus_musculusActl9ENSMUSG00000092519
rattus_norvegicusActl9bENSRNOG00000026033
rattus_norvegicusActl9ENSRNOG00000049571

Paralogs (26): ACTR6 (ENSG00000075089), ACTB (ENSG00000075624), ACTL6B (ENSG00000077080), ACTR5 (ENSG00000101442), ACTR3C (ENSG00000106526), ACTA2 (ENSG00000107796), ACTR8 (ENSG00000113812), ACTR1B (ENSG00000115073), ACTR3 (ENSG00000115091), ACTL8 (ENSG00000117148), ACTRT1 (ENSG00000123165), ACTR10 (ENSG00000131966), ACTR3B (ENSG00000133627), ACTL6A (ENSG00000136518), ACTR2 (ENSG00000138071), ACTR1A (ENSG00000138107), ACTA1 (ENSG00000143632), ACTL7B (ENSG00000148156), ACTC1 (ENSG00000159251), ACTG2 (ENSG00000163017), ACTBL2 (ENSG00000169067), ACTRT2 (ENSG00000169717), ACTG1 (ENSG00000184009), ACTRT3 (ENSG00000184378), ACTL7A (ENSG00000187003), ACTL10 (ENSG00000288649)

Protein

Protein identifiers

Actin-like protein 9 — Q8TC94 (reviewed: Q8TC94)

All UniProt accessions (1): Q8TC94

UniProt curated annotations — full annotation on UniProt →

Function. Testis-specic protein that plays an important role in fusion of proacrosomal vesicles and perinuclear theca formation.

Subunit / interactions. Interacts with ACTL7A.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Cytoplasm. Cytoskeleton. Perinuclear theca.

Tissue specificity. Testis-specific.

Disease relevance. Spermatogenic failure 53 (SPGF53) [MIM:619258] An autosomal recessive infertility disorder characterized by impaired oocyte fertilization due to oocyte activation failure, in association with structural anomalies in sperm heads. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the actin family.

RefSeq proteins (1): NP_848620* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR004000ActinFamily
IPR043129ATPase_NBDHomologous_superfamily

Pfam: PF00022

UniProt features (11 total): sequence variant 8, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q8TC94-F187.560.74

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 54 (showing top): GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_ACROSOME_ASSEMBLY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_FERTILIZATION, GOCC_SECRETORY_VESICLE, GOCC_ACROSOMAL_VESICLE, chr19p13

GO Biological Process (3): acrosome assembly (GO:0001675), single fertilization (GO:0007338), fertilization (GO:0009566)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): acrosomal vesicle (GO:0001669), actin cytoskeleton (GO:0015629), perinuclear theca (GO:0033011), sperm head (GO:0061827), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cytoskeleton2
cellular anatomical structure2
developmental process involved in reproduction1
spermatid development1
cellular component assembly involved in morphogenesis1
cellular process involved in reproduction in multicellular organism1
secretory granule organization1
organelle assembly1
fertilization1
sexual reproduction1
reproductive process1
binding1
secretory granule1
perinuclear region of cytoplasm1
intracellular anatomical structure1
intracellular membraneless organelle1
cytoplasm1
intracellular vesicle1

Protein interactions and networks

STRING

1922 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
ACTL9OVOL1O14753620
ACTL9OR2Z1Q8NG97582
ACTL9OR10A3P58181573
ACTL9TMEM232C9JQI7495
ACTL9EMSYQ7Z589479
ACTL9ACTRT2Q8TDY3478
ACTL9KIF3AQ9Y496447
ACTL9SCP2D1Q9UJQ7419
ACTL9SPATA46Q5T0L3405
ACTL9ZNF442Q9H7R0381
ACTL9SLC25A46Q96AG3371
ACTL9PRR5LQ6MZQ0370
ACTL9ZGPATQ8N5A5370
ACTL9MTNR1BP49286359
ACTL9FLGP20930354

IntAct

2 interactions, top by confidence:

ABTypeScore
KLHL22TRAV18psi-mi:“MI:0914”(association)0.350

BioGRID (2): QRICH1 (Two-hybrid), ACTL9 (Affinity Capture-MS)

ESM2 similar proteins: A0JNU3, A2AKE7, A6H603, A6QQ74, D3ZBP4, F1MH07, O43542, Q149M9, Q2T9W4, Q2TA43, Q2V057, Q32KZ2, Q32L91, Q3ZBE0, Q49HH9, Q49KI5, Q4QR76, Q4R317, Q4R6Q3, Q4R821, Q5JWF8, Q5REQ1, Q5XIK1, Q641W9, Q643R3, Q68FW7, Q6AY16, Q6NVG1, Q76HM9, Q86U10, Q8CG27, Q8K4F6, Q8TC94, Q8TDG2, Q8TDY3, Q8TDZ2, Q8VCZ9, Q8VDP3, Q8VEI3, Q95JK8

Diamond homologs: O94241, P0CM04, P0CM05, Q12509, Q17GZ9, Q4W9M3, Q5AP59, Q6BML9, Q6C982, Q6CJF4, Q6FKE7, Q74ZV8, Q7S6X6, Q8TC94, Q9Y7X8, A2BDB0, O17320, O18499, O18840, O42161, O93400, P02578, P04829, P07836, P07837, P0DM41, P0DM42, P10984, P10986, P10990, P11426, P12716, P12717, P17126, P17304, P27131, P30162, P30163, P45885, P48465

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

75 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic3
Likely pathogenic0
Uncertain significance67
Likely benign5
Benign0

Top pathogenic / likely-pathogenic (3)

Variant IDHGVSClassification
1048625NM_178525.5(ACTL9):c.1034C>T (p.Ser345Leu)Pathogenic
1048626NM_178525.5(ACTL9):c.1138G>T (p.Val380Leu)Pathogenic
1048627NM_178525.5(ACTL9):c.1209C>G (p.Tyr403Ter)Pathogenic

SpliceAI

135 predictions. Top by Δscore:

VariantEffectΔscore
19:8698177:CATGG:Cdonor_gain0.8300
19:8698134:G:GTdonor_gain0.7000
19:8698176:A:ACdonor_gain0.6600
19:8698177:C:CCdonor_gain0.6600
19:8698090:G:GTacceptor_gain0.5500
19:8698091:T:TTacceptor_gain0.5500
19:8698154:A:ACdonor_gain0.5100
19:8698178:A:Cdonor_gain0.5100
19:8698353:CG:Cacceptor_gain0.5100
19:8698352:CCG:Cacceptor_gain0.4800
19:8698353:CGC:Cacceptor_gain0.4800
19:8698080:C:CAacceptor_gain0.4700
19:8698206:C:CTdonor_gain0.4700
19:8698207:C:CTdonor_gain0.4600
19:8698355:C:CCacceptor_gain0.4600
19:8698211:T:TAdonor_gain0.4400
19:8698083:G:GAacceptor_gain0.4100
19:8698354:G:GCacceptor_gain0.4100
19:8698133:C:CTdonor_gain0.4000
19:8698174:G:Tdonor_gain0.4000
19:8698070:CC:Cacceptor_gain0.3900
19:8698071:CC:Cacceptor_gain0.3900
19:8698089:TG:Tacceptor_gain0.3700
19:8698072:C:CCacceptor_gain0.3600
19:8698082:G:GAacceptor_gain0.3600
19:8697714:T:Cdonor_gain0.3400
19:8698068:AGCC:Aacceptor_loss0.3400
19:8698071:CCT:Cacceptor_loss0.3400
19:8698072:C:CGacceptor_loss0.3400
19:8698073:T:Aacceptor_loss0.3400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000979064 (19:8699063 C>G,T), RS1000983990 (19:8699430 A>G), RS1003583455 (19:8697887 G>A,T), RS1004547213 (19:8698798 G>A,C), RS1005171339 (19:8699013 T>C), RS1009837151 (19:8699490 G>C), RS1010134450 (19:8699703 T>C), RS1013308039 (19:8699050 G>A), RS1014308608 (19:8700569 A>G), RS1015127960 (19:8698810 G>A,T), RS1017904303 (19:8697292 T>A,C,G), RS1019858575 (19:8699497 T>C), RS1019910953 (19:8699740 T>C), RS1023323457 (19:8699053 T>C), RS1024323234 (19:8700586 T>C)

Disease associations

OMIM: gene MIM:619251 | disease phenotypes: MIM:619258

GenCC curated gene-disease

DiseaseClassificationInheritance
spermatogenic failure 53StrongAutosomal recessive
non-syndromic male infertility due to sperm motility disorderSupportiveAutosomal recessive

Mondo (3): spermatogenic failure 53 (MONDO:0030989), breast ductal adenocarcinoma (MONDO:0005590), (MONDO:0017173)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0003251Male infertility
HP:0032562Tapered sperm head

GWAS associations

23 associations (top):

StudyTraitp-value
GCST001363_2Atopic dermatitis7.000000e-09
GCST003184_26Atopic dermatitis2.000000e-11
GCST003184_36Atopic dermatitis5.000000e-12
GCST003995_23Tonsillectomy1.000000e-09
GCST004523_10Resting metabolic rate9.000000e-06
GCST004861_23Itch intensity from mosquito bite4.000000e-15
GCST004862_161Itch intensity from mosquito bite adjusted by bite size8.000000e-12
GCST004862_207Itch intensity from mosquito bite adjusted by bite size5.000000e-09
GCST004865_20Itch intensity from mosquito bite adjusted by bite size1.000000e-09
GCST005014_21Tonsillectomy1.000000e-09
GCST005146_46Birth weight2.000000e-08
GCST007798_108Asthma9.000000e-07
GCST007800_61Asthma (childhood onset)5.000000e-10
GCST008362_29Birth weight1.000000e-08
GCST008362_66Birth weight1.000000e-08
GCST008363_129Offspring birth weight6.000000e-25
GCST008363_8Offspring birth weight2.000000e-25
GCST010984_45Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)5.000000e-11
GCST010985_20Allergic disease (asthma, hay fever and/or eczema) (age of onset)5.000000e-11
GCST90007320_1circulating leptin levels adjusted for BMI9.000000e-07
GCST90007323_1circulating leptin levels adjusted for BMI4.000000e-07
GCST90007326_2circulating leptin levels adjusted for BMI7.000000e-07
GCST90007329_1circulating leptin levels adjusted for BMI2.000000e-07

EFO canonical traits (8, from GWAS)

EFO IDTrait name
EFO:0007924tonsillectomy risk measurement
EFO:0008004resting metabolic rate measurement
EFO:0008377mosquito bite reaction itch intensity measurement
EFO:0008378mosquito bite reaction size measurement
EFO:0004344birth weight
EFO:0005939parental genotype effect measurement
EFO:0004847age at onset
EFO:0007793BMI-adjusted leptin measurement

MeSH disease descriptors (1)

DescriptorNameTree numbers
D018270Carcinoma, Ductal, BreastC04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

ChemicalActions (top 5)PubMed papers
terbufosincreases methylation1
Resveratrolaffects cotreatment, decreases expression1
Benzo(a)pyreneaffects methylation, increases methylation1
Fonofosincreases methylation1
Parathionincreases methylation1
Plant Extractsaffects cotreatment, decreases expression1
Valproic Acidincreases methylation1

Clinical trials (associated diseases)

11 trials via MONDO — disease-level, not drug-specific.

TrialPhaseStatusTitle
NCT03414970PHASE3ACTIVE_NOT_RECRUITINGHypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344PHASE2TERMINATEDDocetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999PHASE2NOT_YET_RECRUITINGRandomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364PHASE1/PHASE2SUSPENDEDHigh Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855PHASE1/PHASE2COMPLETEDTalimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908EARLY_PHASE1COMPLETEDBroccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041EARLY_PHASE1COMPLETEDIntraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974Not specifiedACTIVE_NOT_RECRUITINGNipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198Not specifiedTERMINATEDOncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397Not specifiedUNKNOWNMRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532Not specifiedCOMPLETEDLiving Well After Breast Surgery

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot