MOV10L1

Chr 22AR

Mov10 like RNA helicase 1

Also known as: CHAMP, DJ402G11.8, SPGF73

NCBI Gene: 54456 ENSG00000073146 UniProt: Q9BXT6 OMIM: 605794

MOV10L1 encodes an ATP-dependent RNA helicase that represses transposable elements during spermatogenesis through the piRNA pathway, which is essential for maintaining germline integrity. Biallelic mutations cause autosomal recessive spermatogenic failure, leading to male infertility. This gene shows very low constraint against loss-of-function variants and has testis-specific expression.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.771 OMIM phenotype

Clinical Summary— MOV10L1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 176 VUS of 218 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.000

Z-score 3.07

OE 0.59 (0.45–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.18Z-score

OE missense 0.87 (0.82–0.93)

602 obs / 689.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.45–0.77)

0≤0.351.4

Missense OE?0.87 (0.82–0.93)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 38 / 64.6Missense obs/exp: 602 / 689.1Syn Z: -0.24

This gene — mechanism propensity

0.6646th %ile

GOF

0.6540th %ile

LOF

0.2777th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

218 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic4

VUS176

Likely Benign17

Benign5

Pathogenic

Likely Pathogenic

176

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	1	0	2
Likely Pathogenic	2	1	1	0	4
VUS	1	174	1	0	176
Likely Benign	0	15	1	1	17
Benign	0	3	0	2	5
Total	4	193	4	3	204

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

141 pathogenic / likely-pathogenic (of 154) ClinVar copy-number / structural variants overlap MOV10L1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →