ACTL9

protein-coding

actin like 9, the group of Actin related proteins

Gene summary

Predicted to be a structural constituent of cytoskeleton. Involved in acrosome assembly and fertilization. Located in acrosomal vesicle; perinuclear theca; and sperm head. Implicated in spermatogenic failure 53. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_178525.5

Inheritance

ClinVar variants

P:3U:64B:6

Top phenotype

Spermatogenic failure 53

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr19:8,697,400-8,698,795

External References & Databases

Ensembl (ENSG00000181786)

Transcript & Mutation Effects

hg38 • Region Span ~1.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

non-syndromic male infertility due to sperm motility disorderSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017173

Submitter: Orphanet

spermatogenic failure 53STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030989

Submitter: Labcorp Genetics (formerly Invitae)

spermatogenic failure 53STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030989

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spermatogenic failure 53AR

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 33626338

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACTL9 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 66

Spermatogenic failure 53Total: 4

not providedTotal: 2

ACTL9-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178525.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense	2 clinvar		63 clinvar	4 clinvar		69
nonsense	1 clinvar					1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	3	0	64	6	0	73

Highest pathogenic variant AF is 0.0000013691372

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178525.5	RefSeq	NP_848620.3	1	MANE Select
ENST00000324436.5	Ensembl	ENSP00000316674.3	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

cytoplasm
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000324436
Coding exons: 1
Length: 1422
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.131	279	285	0.978	0.0000196	2623
Missense (PolyPhen)		104	122.32	0.85023		1127
Synonymous	0.814	133	145	0.914	0.0000112	958
Loss of Function	1.29	5	9.24	0.541	4.00e-7	97

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.135
RVIS EVS: 0.33
RVIS percentile EVS: 73.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium