| Study/date and URL/DOI | Cohort | SPEF2 variants | Core phenotype/quantitative findings | Respiratory/PCD findings | ART outcome |
|---|---|---|---|---|---|
| **Liu et al., May 2019**, *J Med Genet*; [doi:10.1136/jmedgenet-2018-105952](https://doi.org/10.1136/jmedgenet-2018-105952) | **2 SPEF2-positive men among 42** infertile Han Chinese men with MMAF; 10 fertile controls | P1: **c.12delC** and **c.1745-2A>G**; P2: **c.4102G>T** and **c.4323dupA**; reported as rare, potentially deleterious loss-of-function alleles | Severe asthenozoospermia with absent, short, bent, coiled, and/or irregular-calibre flagella; TEM showed disrupted axonemes and mitochondrial-sheath defects; sperm SPEF2 was significantly reduced by immunofluorescence and western blot (pqac-00000002, pqac-00000004) | No reported bronchitis, sinusitis, pneumonia, or other PCD-related symptoms; genital examination and bilateral testes were normal (pqac-00000002) | P1: two blastocysts after ICSI and one embryo transferred, but **no pregnancy**; maternal age was noted as a possible contributor (pqac-00000004) |
| **Liu et al., May 2020**, *J Med Genet*; [doi:10.1136/jmedgenet-2019-106011](https://doi.org/10.1136/jmedgenet-2019-106011) | **3 affected men** from unrelated consanguineous families: two Han Chinese and one Iranian | Homozygous **c.910C>T (p.Arg304\*)**, **c.3400delA (p.Ile1134Serfs\*13)**, and **c.3240delT (p.Phe1080Leufs\*2)**. gnomAD frequencies: **8×10⁻⁶, 4×10⁻⁶, and 0**, respectively (pqac-00000000, pqac-00000006) | Semen volume **2.9–4.0 mL**; concentration **9.3–21.0×10⁶/mL**; total motility **0–0.6%**; progressive motility **0%**. Normal flagella occurred in only **13.5–35%**; short flagella in **25–48%**. TEM showed central-pair loss and a **9+0** rather than 9+2 axoneme; SPEF2 and CFAP69 staining was absent or markedly reduced (pqac-00000005, pqac-00000006, pqac-00000007) | No obvious PCD-like manifestations documented; one subject had normal chest radiography and olfactory testing, without evident pulmonary or cardiac abnormality (pqac-00000007) | Not reported in the available evidence |
| **Li et al., online Nov 2021 / vol. 24, 2022**, *Asian J Androl*; [doi:10.4103/aja202154](https://doi.org/10.4103/aja202154) | Sperm proteomics from **3 SPEF2-mutant patients** | Previously identified pathogenic SPEF2 genotypes; individual variant notation was not restated in the extracted evidence | **1,262 differentially expressed proteins:** **486 upregulated** and **776 downregulated**. Reduced proteins included SPAG6, RSPH1/RSPH4A, DYNLT1, MNS1 and TOM20; IFT20 and other IFT proteins increased. SPEF2–IFT20 and SPEF2–RSPH9 interactions were experimentally supported, implicating central-pair, radial-spoke, mitochondrial-sheath, and cargo-transport defects (pqac-00000009, pqac-00000010, pqac-00000015) | Not evaluated or not reported in the extracted proteomic evidence | Not reported |
| **Aprea et al., 3 Feb 2023**, *Front Genet*; [doi:10.3389/fgene.2023.1117821](https://doi.org/10.3389/fgene.2023.1117821) | **2 SPEF2 cases within a 10-man cohort** carrying defects in six axonemal genes; overall cohort comprised eight men diagnosed with PCD and two with MMAF-associated infertility | Pathogenic SPEF2 variants were reported, but exact patient-level nomenclature and allele frequencies were not available in the extracted evidence | Andrological assessment plus sperm high-speed video, immunofluorescence, and TEM demonstrated abnormal flagellar composition; SPEF2 was absent or severely reduced in SPEF2-mutant sperm. The study positioned SPEF2 in the central-pair **C1b projection** and supported sperm immunofluorescence as a variant-classification aid (pqac-00000017) | Respiratory-cilia work-up was performed, but SPEF2-specific respiratory findings and definitive patient-level PCD classifications were not available in the extracted evidence | Not reported |
| **Lu et al., online 3 Apr 2024**, *J Assist Reprod Genet*; [doi:10.1007/s10815-024-03106-9](https://doi.org/10.1007/s10815-024-03106-9) | **3 affected men from 3 unrelated Han Chinese families** | F1: homozygous **c.4447+1G>A**; F2: compound heterozygous **c.1339C>T (p.Arg447\*)** and **c.1645G>T (p.Glu549\*)**; F3: homozygous **c.2524G>A (p.Asp842Asn)**, transcript **NM_024867.4**. All four were novel/very rare and experimentally supported as deleterious; exact database frequencies and formal ACMG classes were not available in the extracted evidence (pqac-00000001, pqac-00000016) | Male infertility with MMAF; mutant sperm had abnormal flagella and loss of the axonemal central-pair complex. Reported ICSI fertilization rates were **100%, 90%, and 82%** (pqac-00000003, pqac-00000016) | Chronic wet cough, chronic sinusitis, and/or nasal congestion supported **likely PCD/PCD-like disease**, although respiratory-cilium ultrastructure was reportedly unaffected; definitive PCD status therefore remains cautious (pqac-00000001, pqac-00000016) | Each couple underwent one ICSI cycle; **all three achieved healthy live births** (pqac-00000001, pqac-00000003) |


*Table: Compact study-level evidence for biallelic SPEF2-associated SPGF43, spanning initial human discovery through 2024 clinical expansion. It highlights cohort sizes, variants, quantitative sperm findings, respiratory involvement, and reported ICSI outcomes while preserving uncertainty.*