Microcephaly: genes and variants

Genes linked to Microcephaly

• STXBP1: Syntaxin-binding protein 1

  It controls SNARE-complex assembly and synaptic-vesicle fusion, making it essential for rapid neurotransmitter release. Haploinsufficiency causes STXBP1-related neurodevelopmental disorder with developmental impairment, epilepsy, movement abnormalities, and intellectual disability.

  1 disease-causing and 0 uncertain variants in STXBP1 are linked to Microcephaly.

• ABL1: Tyrosine-protein kinase ABL1

  It coordinates cytoskeletal remodeling, adhesion, DNA-damage responses, and growth signaling through tightly regulated tyrosine phosphorylation. Fusion with BCR removes normal control and creates the constitutively active kinase that drives chronic myeloid leukemia and subsets of acute lymphoblastic leukemia.

  1 disease-causing and 0 uncertain variants in ABL1 are linked to Microcephaly.

• FOXG1: Forkhead box protein G1

  It controls forebrain progenitor proliferation, neuronal differentiation, and cortical patterning during embryonic development. Haploinsufficiency or dysregulating variants cause FOXG1 syndrome, characterized by severe developmental impairment, absent or limited speech, abnormal movements, and frequent epilepsy.

  1 disease-causing and 0 uncertain variants in FOXG1 are linked to Microcephaly.

• MAPK1: Mitogen-activated protein kinase 1

  It converts upstream RAS-RAF-MEK signaling into phosphorylation of cytoplasmic and nuclear targets controlling proliferation, differentiation, and development. Germline dysregulating variants can cause neurodevelopmental RASopathy phenotypes, while pathway hyperactivation is common in cancer.

  1 disease-causing and 0 uncertain variants in MAPK1 are linked to Microcephaly.

• 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.

  1 disease-causing and 0 uncertain variants in PTPN11 are linked to Microcephaly.

• DYRK1A: Dual specificity tyrosine-phosphorylation-regulated kinase 1A

  It phosphorylates numerous transcriptional, synaptic, and cell-cycle targets during brain development and is highly dosage sensitive. Haploinsufficiency causes DYRK1A syndrome, typically with microcephaly, developmental delay, intellectual disability, and frequent seizures or autism-related features.

  0 disease-causing and 0 uncertain variants in DYRK1A are linked to Microcephaly.

• KCNJ10: ATP-sensitive inward rectifier potassium channel 10

  1 disease-causing and 0 uncertain variants in KCNJ10 are linked to Microcephaly.

Weakly linked (only a few uncertain records): ADNP, KMT2C, ARID1A, BCOR, CHD2, CHD7, EP300, F8 and 9 more.

Known disease-causing variants in Microcephaly

Same protein, different disease

• Early-infantile DEE is also caused by STXBP1 variants; they fall mostly in different places as the Microcephaly variants (45 disease-causing).
• Noonan syndrome is also caused by MAPK1 variants; they fall mostly in different places as the Microcephaly variants (4 disease-causing).
• Congenital heart defects and skeletal malformations syndrome is also caused by ABL1 variants; they fall mostly in different places as the Microcephaly variants (14 disease-causing).
• Leukemia, Philadelphia chromosome-positive, resistant to imatinib is also caused by ABL1 variants; they fall mostly in different places as the Microcephaly variants (5 disease-causing).
• Chronic myeloid leukemia is also caused by ABL1 variants; they fall mostly in different places as the Microcephaly variants (3 disease-causing).
• FOXG1 disorder is also caused by FOXG1 variants; they fall mostly in different places as the Microcephaly variants (70 disease-causing).
• Rett syndrome is also caused by FOXG1 variants; they fall mostly in different places as the Microcephaly variants (5 disease-causing).
• RASopathy is also caused by PTPN11 variants; they fall mostly in different places as the Microcephaly variants (51 disease-causing).
• Noonan syndrome is also caused by PTPN11 variants; they fall mostly in different places as the Microcephaly variants (44 disease-causing).
• Noonan syndrome and Noonan-related syndrome is also caused by PTPN11 variants; they fall mostly in different places as the Microcephaly variants (29 disease-causing).
• LEOPARD syndrome 1 is also caused by PTPN11 variants; they fall mostly in different places as the Microcephaly variants (16 disease-causing).
• Metachondromatosis is also caused by PTPN11 variants; they fall mostly in different places as the Microcephaly variants (11 disease-causing).
• EAST syndrome is also caused by KCNJ10 variants; they fall mostly in different places as the Microcephaly variants (12 disease-causing).
• Autosomal recessive nonsyndromic hearing loss 4 is also caused by KCNJ10 variants; they fall mostly in different places as the Microcephaly variants (3 disease-causing).

Diseases related to Microcephaly

• Noonan syndrome, also linked to MAPK1 and PTPN11
• Early-infantile DEE, also linked to STXBP1
• Hypertrophic cardiomyopathy, also linked to MAPK1
• RASopathy, also linked to PTPN11
• Autosomal recessive nonsyndromic hearing loss 4, also linked to KCNJ10
• Pendred syndrome, also linked to KCNJ10
• Gastrointestinal stromal tumor, also linked to ABL1
• Rett syndrome, also linked to FOXG1
• Noonan syndrome and Noonan-related syndrome, also linked to PTPN11
• FOXG1 disorder, also linked to FOXG1
• Complex neurodevelopmental disorder, also linked to DYRK1A
• Acute myeloid leukemia, also linked to PTPN11

Frequently asked questions

Which genes are linked to Microcephaly?

In CATVariant, Microcephaly is linked to 7 analyzed proteins: STXBP1 (Syntaxin-binding protein 1), ABL1 (Tyrosine-protein kinase ABL1), FOXG1 (Forkhead box protein G1), MAPK1 (Mitogen-activated protein kinase 1), PTPN11 (Tyrosine-protein phosphatase non-receptor type 11), DYRK1A (Dual specificity tyrosine-phosphorylation-regulated kinase 1A) and 1 more.

How many genetic variants are linked to Microcephaly?

29 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 18 are of uncertain significance or have conflicting reports.

Which uncertain variants in Microcephaly 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.

Download every variant as CSV · Browse all diseases · Methods · About the Center