ACTL7A

protein-coding

actin like 7A, the group of Actin related proteins

Gene summary

The protein encoded by this gene is a member of a family of actin-related proteins (ARPs) which share significant amino acid sequence identity to conventional actins. Both actins and ARPs have an actin fold, which is an ATP-binding cleft, as a common feature. The ARPs are involved in diverse cellular processes, including vesicular transport, spindle orientation, nuclear migration and chromatin remodeling. This gene (ACTL7A), and related gene, ACTL7B, are intronless, and are located approximately 4 kb apart in a head-to-head orientation within the familial dysautonomia candidate region on 9q31. Based on mutational analysis of the ACTL7A gene in patients with this disorder, it was concluded that it is unlikely to be involved in the pathogenesis of dysautonomia. The ACTL7A gene is expressed in a wide variety of adult tissues, however, its exact function is not known. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006687.4

Inheritance

ClinVar variants

P:8U:73B:4

Top phenotype

Spermatogenic failure 86

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr9:108,862,266-108,863,756

External References & Databases

Ensembl (ENSG00000187003)

Transcript & Mutation Effects

hg38 • Region Span ~1.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

male infertilityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005372

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Spermatogenic failure 86AR

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: 32923619; 34727571; 36593593

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACTL7A variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 77

Spermatogenic failure 86Total: 7

Male infertility with normal semen parametersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006687.4. 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				1 clinvar		1
missense	3 clinvar	2 clinvar	73 clinvar	3 clinvar		81
nonsense	2 clinvar					2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	6	2	73	4	0	85

Highest pathogenic variant AF is 0.000025403167

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_006687.4	RefSeq	NP_006678.1	1	MANE Select
ENST00000333999.5	Ensembl	ENSP00000334300.3	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cytoskeleton organization

Molecular Function

structural constituent of cytoskeleton
protein binding

Cellular Component

male germ cell nucleus
nucleus
cytoplasm
Golgi apparatus
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000333999
Coding exons: 1
Length: 1433
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	0.180	268	276	0.970	0.0000170	2836
Missense (PolyPhen)		118	127.08	0.92852		1332
Synonymous	-0.872	139	127	1.10	0.00000897	897
Loss of Function	0.663	11	13.6	0.806	7.50e-7	144

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

Recessive Scores

pRec: 0.108

Intolerance Scores

RVIS EVS: -0.13
RVIS percentile EVS: 43.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.695

Gene Damage Prediction

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