Male infertility with azoospermia or oligozoospermia due to single gene mutation: genes and variants

Genes linked to Male infertility with azoospermia or oligozoospermia due to single gene mutation

• PTPN11: Tyrosine-protein phosphatase non-receptor type 11

  Its SHP2 phosphatase activity promotes RAS-MAPK signaling downstream of many receptor tyrosine kinases and cytokine receptors. Germline dysregulating variants cause Noonan-spectrum disorders, while somatic activating variants drive juvenile myelomonocytic leukemia and other cancers.

  3 disease-causing and 0 uncertain variants in PTPN11 are linked to Male infertility with azoospermia or oligozoospermia due to single gene mutation.

• AR: Androgen receptor

  Androgen binding redirects its transcriptional program to control male sexual differentiation, reproductive physiology, muscle and bone biology, and other androgen-responsive processes. Loss-of-function variants cause androgen insensitivity, CAG expansion causes spinal and bulbar muscular atrophy, and persistent signaling drives prostate cancer.

  1 disease-causing and 1 uncertain variants in AR are linked to Male infertility with azoospermia or oligozoospermia due to single gene mutation.

• MAP2K1: Dual specificity mitogen-activated protein kinase kinase 1

  It phosphorylates ERK1 and ERK2 downstream of RAF and thereby propagates RAS-MAPK growth and developmental signals. Activating somatic variants occur in several cancers, while germline activating variants can cause cardio-facio-cutaneous syndrome and related RASopathies.

  1 disease-causing and 0 uncertain variants in MAP2K1 are linked to Male infertility with azoospermia or oligozoospermia due to single gene mutation.

• SOS1: Son of sevenless homolog 1

  It activates RAS by exchanging GDP for GTP downstream of receptor tyrosine kinases. Germline activating variants are a common cause of Noonan syndrome, while excessive SOS1-RAS signaling can contribute to cancer.

  1 disease-causing and 0 uncertain variants in SOS1 are linked to Male infertility with azoospermia or oligozoospermia due to single gene mutation.

• TUBB3: Tubulin beta-3 chain

  It forms neuronal microtubules required for axon growth, guidance, and intracellular transport. Heterozygous pathogenic variants can cause congenital fibrosis of the extraocular muscles type 3 and broader tubulinopathy phenotypes with brain and cranial-nerve abnormalities.

  1 disease-causing and 0 uncertain variants in TUBB3 are linked to Male infertility with azoospermia or oligozoospermia due to single gene mutation.

Weakly linked (only a few uncertain records): GATA4 and NF1.

Known disease-causing variants in Male infertility with azoospermia or oligozoospermia due to single gene mutation

Same protein, different disease

• RASopathy is also caused by PTPN11 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (51 disease-causing).
• Noonan syndrome is also caused by PTPN11 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (44 disease-causing).
• Noonan syndrome and Noonan-related syndrome is also caused by PTPN11 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (29 disease-causing).
• LEOPARD syndrome 1 is also caused by PTPN11 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (16 disease-causing).
• Metachondromatosis is also caused by PTPN11 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (11 disease-causing).
• Androgen resistance syndrome is also caused by AR variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (85 disease-causing).
• Kennedy disease is also caused by AR variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (46 disease-causing).
• Differences in sex development is also caused by AR variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (9 disease-causing).
• Male infertility is also caused by AR variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (7 disease-causing).
• Partial androgen insensitivity syndrome is also caused by AR variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (7 disease-causing).
• RASopathy is also caused by MAP2K1 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (14 disease-causing).
• Cardiofaciocutaneous syndrome is also caused by MAP2K1 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (14 disease-causing).
• Cardio-facio-cutaneous syndrome is also caused by MAP2K1 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (6 disease-causing).
• Noonan syndrome is also caused by SOS1 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (30 disease-causing).
• RASopathy is also caused by SOS1 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (22 disease-causing).
• Noonan syndrome and Noonan-related syndrome is also caused by SOS1 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (9 disease-causing).
• Fibromatosis, gingival, 1 is also caused by SOS1 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (4 disease-causing).
• Complex cortical dysplasia with other brain malformations 7 is also caused by TUBB3 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (23 disease-causing).
• Fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement is also caused by TUBB3 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (6 disease-causing).
• TUBB3-related tubulinopathy is also caused by TUBB3 variants; they fall mostly in different places as the Male infertility with azoospermia or oligozoospermia due to single gene mutation variants (5 disease-causing).

Diseases related to Male infertility with azoospermia or oligozoospermia due to single gene mutation

• RASopathy, also linked to MAP2K1, PTPN11 and SOS1
• Noonan syndrome, also linked to MAP2K1, PTPN11 and SOS1
• Noonan syndrome and Noonan-related syndrome, also linked to MAP2K1, PTPN11 and SOS1
• Ovarian cancer, also linked to AR and TUBB3
• Non-small cell lung carcinoma, also linked to MAP2K1 and TUBB3
• Monogenic short statue, also linked to PTPN11 and SOS1
• Prostate cancer, also linked to AR and TUBB3
• Noonan syndrome with multiple lentigines, also linked to MAP2K1 and PTPN11
• Hypertrophic cardiomyopathy, also linked to MAP2K1
• Androgen resistance syndrome, also linked to AR
• Neurofibromatosis, also linked to MAP2K1
• Cardiofaciocutaneous syndrome, also linked to MAP2K1

Frequently asked questions

Which genes are linked to Male infertility with azoospermia or oligozoospermia due to single gene mutation?

In CATVariant, Male infertility with azoospermia or oligozoospermia due to single gene mutation is linked to 5 analyzed proteins: PTPN11 (Tyrosine-protein phosphatase non-receptor type 11), AR (Androgen receptor), MAP2K1 (Dual specificity mitogen-activated protein kinase kinase 1), SOS1 (Son of sevenless homolog 1) and TUBB3 (Tubulin beta-3 chain).

How many genetic variants are linked to Male infertility with azoospermia or oligozoospermia due to single gene mutation?

12 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 5 are of uncertain significance or have conflicting reports.

Which uncertain variants in Male infertility with azoospermia or oligozoospermia due to single gene mutation look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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