Mutations of the NR5A1 gene were found in a small percentage of infertile men, reports the American Journal of Human Genetics.
Scientists from the Pasteur Institute in France and University College London said it could help doctors investigating men with the condition.
A UK expert said he hoped that further gene defects could be found.
In the majority of cases, doctors can find no cause for male infertility, despite it accounting for up to half of cases in which couples have difficulty conceiving.
Male infertility appears to be more common within certain families, and this leads scientists to believe that there may be a genetic root for some cases, but only a handful of gene mutations which might be responsible have actually been found.
The latest research looks at a gene already known to be involved in sexual development in both men and women - defects in NR5A1 have been linked to physical defects in the development of the testicles or ovaries.
Their findings suggest that, even where there is no physical evidence of a problem, defects in the gene may be hampering the ability to make sperm.
They looked at the gene in 315 apparently healthy men who had an unexplained inability to produce sperm.
From this group, they found mutations in the gene in just seven, and closer examination revealed the men had altered levels of sex hormones and, in one case, mild abnormalities in the cellular structure of the testicles.
The research authors, from the UCL Institute of Child Health in London and the Institut Pasteur in Paris, said: "We conclude that approximately 4% of men with otherwise unexplained failure to produce sperm carry mutations in the NR5A1 gene."
Although the find would affect only a small proportion of infertile men, other specialists believe that other similar discoveries could help build up a clearer picture of the origins of the condition.
Dr Allan Pacey, a senior lecturer in andrology at the University of Sheffield, said that there was still "embarrassingly little" known about the genetics behind male infertility.
"Given the complexity of the sperm production process it is likely that many genes are involved and therefore that may gene defects linked to infertility may be found.
"Although this gene defect affects only a small number of men, we need more studies like this so that we can fill in the gaps in our knowledge and possibly one day build a robust diagnostic test for male fertility based on genetics."

A further 70 people are reported to have been injured in the blaze at an industrial complex in Tongi, north of the capital Dhaka.
Police said about 100 people were in the four-storey building at the time, including machine operators and guards.
The blast was caused by an explosion in the boiler room, at the start of the working day, officials say.
Firefighters are struggling to bring the blaze under control.
Local fire and civil defence chief Anis Ahamed said there were now 20 fire trucks working to extinguish the fire.
"We have removed eight bodies to the hospital and are trying to retrieve a further two. Once the fire is out we will be able to enter the damaged structure to see if there are more bodies," he said.
Relatives have been gathering outside the local hospital for news.
One man, Wridoy Barua, said he was looking for his brother. "I haven't heard from him since this morning. There is no news of him."
Low-cost manufacturing is a mainstay of Bangladesh's economy, but a series of industrial disasters in recent years have raised concerns about safety standards, the BBC's South Asia Editor Jill McGivering reports.
Tighter controls have been introduced, but dozens of workers still die every year, she notes.
Bangladesh factories: 'About 40% have major safety issues'
Can Bangladesh safety accord bring change?
At least 13 people  died in a fire at a plastics factory Dhaka last year.
In 2012, 112 workers died in a fire at a factory just outside the capital.
The country suffered an even greater tragedy in 2013 when the Rana Plaza garment complex collapsed on the outskirts of Dhaka, killing 1,135 people.
A faulty gene could help explain some cases of unexplained male infertility, according to research.
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At least 20 people have been killed in a huge fire that broke out at a packaging factory in Bangladesh.