ACTRT1

protein-coding

actin related protein T1, the group of Actin related proteins

Gene summary

This gene encodes a protein related to the cytoskeletal protein beta-actin. This protein is a major component of the calyx in the perinuclear theca of mammalian sperm heads, and it therefore likely functions in spermatid formation. This gene is intronless and is similar to a related gene located on chromosome 1. A related pseudogene has also been identified approximately 75 kb downstream of this gene on chromosome X. [provided by RefSeq, May 2010]

MANE transcript

NM_138289.4

Inheritance

—

ClinVar variants

P:1U:55B:10

Top phenotype

ACTRT1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chrX:128,050,962-128,052,403

External References & Databases

Ensembl (ENSG00000123165)

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

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACTRT1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 9

ACTRT1-related disorderTotal: 7

Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138289.4. 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				2 clinvar		2
missense			55 clinvar	5 clinvar	3 clinvar	63
nonsense						0
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)						0
Total	0	1	55	7	3	66

Highest pathogenic variant AF is 0.002566134

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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_138289.4	RefSeq	NP_612146.1	1	MANE Select
ENST00000371124.5	Ensembl	ENSP00000360165.3	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of smoothened signaling pathway
negative regulation of transcription, DNA-templated

Molecular Function

chromatin binding

Cellular Component

nucleus
cytoplasm
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371124
Coding exons: 1
Length: 1440
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	-1.24	189	147	1.29	0.0000112	2465
Missense (PolyPhen)		67	52.542	1.2752		903
Synonymous	-0.344	63	59.6	1.06	0.00000470	771
Loss of Function	0.555	4	5.39	0.742	3.80e-7	115

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

Function: FUNCTION: Negatively regulates the Hedgehog (SHH) signaling. Binds to the promoter of the SHH signaling mediator, GLI1, and inhibits its expression. {ECO:0000269|PubMed:28869610}.;

Intolerance Scores

LoFtool: 0.312
RVIS EVS: 0.37
RVIS percentile EVS: 75.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.123

Gene Damage Prediction

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