Table 1:
Selected male infertility phenotypes and associated genes. The human phenotype ontology (HPO) defines the recently improved terms for male infertility [28].
|
Phenotype |
HPO-ID |
Sperm count [concentration] |
Associated genes (Mode of inheritance) |
|
Decreased male fertility |
HP:0012041 |
|
|
|
Mild oligozoospermia |
HP:0034816 |
30–39 million [10–15 million/mL] |
to be determined |
|
Moderate oligozoospermia |
HP:0034817 |
10–29 million [5–10 million/mL] |
to be determined |
|
Severe oligozoospermia |
HP:0034818 |
2–9 million [1–5 million/mL] |
to be determined |
|
Extreme oligozoospermia |
HP:0034815 |
0–2 million [0–1 million/mL] |
to be determined |
|
Cryptozoospermia |
HP:0030974 |
few sperm after centrifugation |
Validated crypto-/azoospermia panel [23] ADAD2 (AR), AR (XL), C14orf39 (AR), DDX3Y (YL), DMC1 (AR), DMRT1 (AD), FANCM (AR), FKBP6 (AR), GCNA (XL), HFM1 (AR), KASH5 (AR), KCTD19 (AR), M1AP (AR), MCM8 (AR), MCM9 (AR), MCMDC2 (AR), MEI1 (AR), MEIOB (AR), MLH3 (AR), MSH4 (AR), MSH5 (AR), NR5A1 (AD), PNLDC1 (AR), RAD21L1 (AR), SHOC1 (AR), SPO11 (AR), STAG3 (AR), STRA8 (AR), SYCE1 (AR), TDRD9 (AR), TERB1 (AR), TERB2 (AR), TEX11 (XL), TEX14 (AR), TEX15 (AR), ZMYND15 (AR), ZSWIM7 (AR) |
|
Azoospermia |
HP:0000027 |
no sperm |
|
|
Non-obstructive azoospermia |
HP:0011961 |
no sperm |
Validated crypto-/azoospermia panel [23] ADAD2 (AR), AR (XL), C14orf39 (AR), DDX3Y (YL), DMC1 (AR), DMRT1 (AD), FANCM (AR), FKBP6 (AR), GCNA (XL), HFM1 (AR), KASH5 (AR), KCTD19 (AR), M1AP (AR), MCM8 (AR), MCM9 (AR), MCMDC2 (AR), MEI1 (AR), MEIOB (AR), MLH3 (AR), MSH4 (AR), MSH5 (AR), NR5A1 (AD), PNLDC1 (AR), RAD21L1 (AR), SHOC1 (AR), SPO11 (AR), STAG3 (AR), STRA8 (AR), SYCE1 (AR), TDRD9 (AR), TERB1 (AR), TERB2 (AR), TEX11 (XL), TEX14 (AR), TEX15 (AR), ZMYND15 (AR), ZSWIM7 (AR) |
|
Spermiation failure |
HP:0034812 |
no sperm |
|
|
Hypospermatogenesis |
HP:0034813 |
no sperm |
to be determined |
|
Germ cell arrest |
HP:0031038 |
no sperm |
to be determined |
|
Spermatogonial arrest |
HP:4000187 |
no sperm |
to be determined |
|
Spermatocyte arrest |
HP:0031039 |
no sperm |
many meiotic genes from crypto-/azoospermia panel |
|
Round spermatid arrest |
HP:0031040 |
no sperm |
to be determined |
|
Sertoli cell-only |
HP:0034299 |
no sperm |
to be determined |
|
Tubular shadows |
HP:0034945 |
no sperm |
|
|
Obstructive azoospermia |
HP:0011962 |
no sperm |
ADGRG2 (XL), CFTR (AR) [23, 29] |
|
Congenital bilateral aplasia of the vas deferens |
HP:0012873 |
no sperm |
ADGRG2 (XL), CFTR (AR) [23, 29] |
|
Asthenozoospermia |
HP:0012207 |
reduced |
SSX1 (XL) [23] |
|
Teratozoospermia |
HP:0012864 |
reduced |
|
|
Sperm head anomaly |
HP:0012865 |
reduced |
CFAP61 (AR) [23] |
|
Globozoospermia |
HP:0012205 |
reduced |
DPY19L2 (AR) [23] |
|
Acephalic sperm |
HP:0012869 |
reduced |
DNAH6 (AR), PMFBP1 (AR), SUN5 (AR), TSGA10 (AR) [23] |
|
Macrozoospermia |
HP:0025437 |
reduced |
AURKC (AR) [23] |
|
Sperm tail anomaly |
HP:0012868, HP:0033393 |
reduced |
Validated Multiple Morphological Abnormalities of the sperm Flagella (MMAF) panel [23] ARMC2 (AR), CFAP251 (AR), CFAP43 (AR), CFAP44 (AR), CFAP58 (AR), CFAP61 (AR), CFAP65 (AR), CFAP69 (AR), CFAP70 (AR), CFAP91 (AR), DNAH1 (AR), DNAH6 (AR), DNAH1 (AR), DNAH17 (AR), DNAH2 (AR), DNAH8 (AR), DNHD1 (AR), DRC1 (AR), FSIP2 (AR), QRICH2 (AR), SPEF2 (AR), TTC29 (AR) |
|
Short |
HP:0032559 |
reduced |
|
|
Bent |
HP:0034811 |
reduced |
|
|
Coiled |
HP:0032560 |
reduced |
|
|
Hypogonadotrophic hypogonadism |
HP:0000044 |
reduced |
Proposed Congenital Hypogonadotrophic Hypogonadism (CHH) panel [3, 30] ANOS1 (XL), CHD7 (AD, AR, olig), DMXL2 (AD), DUSP6 (olig), FGF8 (olig), FGF17 (olig), FGFR1 (AD, AR, olig), FLRT3 (olig), GNRH1 (AR, olig), GNRHR (AR, olig), HESX1 (AD, AR), IL17RD (olig), KISS1 (AR), KISS1R (AR), KLB (AD), NSMF (AR, olig), PNPLA6 (AR), POLR3A (AR), POLR3B (AR), PROK2 (AD, AR, olig), PROKR2 (AD, AR, olig), SEMA3A (AD, olig), SEMA7A (olig), SOX2 (AR), SOX10 (AD), SPRY4 (olig), TAC3 (AR), TACR3 (AR, olig) |
Abbreviations: AD: autosomal dominant, AR: autosomal recessive, XL: X-linked, YL: Y-linked, olig: oligogenic