Table 1 Summary table of genes identified in patients displaying a MMAF phenotype
From: Genetic causes of male infertility: snapshot on morphological abnormalities of the sperm flagellum
Mutant models | |||||||
|---|---|---|---|---|---|---|---|
Gene | Mutation Frequency | Protein features | Protein localisation | Mouse model | Chlamydomonas | Tetrahymena | Trypanosoma |
DNAH1 | 7.69% | Dynein Heavy chain | - Inner Dynein Arm [14] | MDHC7 mutant: Reduced ciliary beating and asthenozoospermia (no MMAF-like phenotype) [14] | dhc1b/dhc2 mutant: short flagella [13] | - | - |
CFAP43 | 12.8% | WD repeat domains | - cilia associated and component of the (T/TH) complex connected to inner dynein arm [18,19,20] (Tetrahymena, Chlamydomonas), - flagellar protein located between doublet microtubules 5 and 6 and paraflagellar rod [6] (Trypanosoma) | Asthenozoospermia (MMAF-like phenotype) [6] | – | Fap43 gene deletion: Altered waveform, beat stroke and reduced swimming speed [18] | TbCfap43 (Tb.927.4.5380) RNAi mutant: Cell growth defects, Abnormal flagellum beating (axonemal disorganization), normal flagellum length [6] |
CFAP44 | 7.7% | WD repeat domains | - cilia associated and component of the (T/TH) complex connected to inner dynein arm [18,19,20] (Tetrahymena, Chlamydomonas), - flagellar protein located between doublet microtubules 5 and 6 and paraflagellar rod [6] (Trypanosoma) | Asthenozoospermia (no MMAF like phenotype) [6] | – | Fap44 gene deletion: Altered waveform, beat stroke and reduced swimming speed [18] | TbCfap44 (Tb.927.7.3560) RNAi mutant: Cell growth defects, Abnormal flagellum beating (axonemal disorganization), normal flagellum length [6] |
CFAP69 | 2.6% | Armadillo-type α-helical repeats | - cilia from olfactory sensory neurons [23], sperm flagellum midpiece (mammals) [17], | Olfactory defects [23] and Asthenozoospermia (MMAF-like phenotype) [17] | – | – | – |
FSIP2 | 5.1% | AKAP4 Interacting domain | - sperm flagellum fibrous sheath (mammals) [24] | – | – | – | – |
WDR66 (CFAP251) | 9% | calcium regulating EF-hand domain | - sperm flagellum (mammals) [16], - flagella (Trypanosoma) [16], - radial spoke component (Chlamydomonas, Tetrahymena) [25, 26], | – | – | Fap251 mutant: Reduced cell swimming, Impaired ciliary beating coordination, normal length [26] | Tbwdr66 (Tb927.3.1670) deletion: Abnormal motility (axonemal disorganization), growth defects, normal flagellum length [16] |
AK7 | 1.28% | ADK domain, coiled-coil domain, DPY30 domain | – | – | – | ||