MOV10L1

protein-coding

Mov10 like RISC complex RNA helicase 1, the group of UPF1 like RNA helicases

Gene summary

This gene is similar to a mouse gene that encodes a putative RNA helicase and shows testis-specific expression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

MANE transcript

NM_018995.3

Inheritance

ClinVar variants

P:4U:182B:17

Top phenotype

Spermatogenic failure 73

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr22:50,090,006-50,161,690

External References & Databases

Ensembl (ENSG00000073146)

Transcript & Mutation Effects

hg38 • Region Span ~71.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 73MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030818

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spermatogenic failure 73AR

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: 35476666

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MOV10L1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 188

not providedTotal: 6

Spermatogenic failure 73Total: 6

Male infertilityTotal: 4

Non-obstructive azoospermiaTotal: 3

AzoospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018995.3. 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		1 clinvar	179 clinvar	14 clinvar	1 clinvar	195
nonsense			2 clinvar			2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)		2 clinvar	1 clinvar			3
Total	1	3	182	16	1	203

Highest pathogenic variant AF is 0.000013013797

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018995.3	RefSeq	NP_061868.1	27	MANE Select
ENST00000262794.10	Ensembl	ENSP00000262794.5	27	MANE Select
NM_001164104.2	RefSeq	NP_001157576.1	26	Standard
NM_001164105.2	RefSeq	NP_001157577.1	26	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
PIWI-interacting RNA (piRNA) biogenesis
Gene Silencing by RNA

Biological Process

male meiosis I
multicellular organism development
germ cell development
spermatogenesis
piRNA metabolic process

Molecular Function

magnesium ion binding
RNA binding
ATP-dependent RNA helicase activity
ATP binding

Cellular Component

cytosol
P granule
pi-body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262794
Coding exons: 27
Length: 71812
Individuals with no LoFs: 125636
Homozygous LoFs: 0
Heterozygous LoFs: 112
Defined: 125748
p: 0.000445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.18	602	689	0.874	0.0000401	7872
Missense (PolyPhen)		125	200.17	0.62447		2292
Synonymous	-0.240	284	279	1.02	0.0000184	2333
Loss of Function	3.07	38	64.6	0.588	0.00000340	766

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00058	0.00058	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00058	0.00057	rare
South Asian	0.00030	0.00029	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: ATP-dependent RNA helicase required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Involved in the primary piRNA metabolic process. Specifically binds to piRNA precursors and promotes the generation of intermediate piRNA processing fragments that are subsequently loaded to Piwi proteins. Acts via its ATP-dependent RNA helicase activity: displays 5'-3' RNA unwinding activity and probably mediates unwinding and funneling of single-stranded piRNA precursor transcripts to the endonuclease that catalyzes the first cleavage step of piRNA processing to generate piRNA intermediate fragments that are subsequently loaded to Piwi proteins. {ECO:0000250|UniProtKB:Q99MV5}.;

Recessive Scores

pRec: 0.126

Intolerance Scores

LoFtool: 0.0247
RVIS EVS: -0.69
RVIS percentile EVS: 14.84

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.216

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High