Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Deficiency in DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice.
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Six biallelic DNAH12 variants co-segregate with recessive male infertility in six families. Dnah12-/- and knock-in mice reproduce the phenotype, with IDA loss and central-pair loss in sperm, preserved mouse tracheal beating and morphology, and comparable knockout tracheal ultrastructure and oviductal/tracheal DNALI1/DNAH1 measurements. Patients reported no PCD symptoms. DNAH12 binds DNALI1 and DNAH1 and is required to recruit them, and ICSI rescues fertility in mice.
"we unveiled six biallelic mutations in DNAH12 that co-segregate recessively with male infertility in the studied families"
Further evidence from DNAH12 supports favorable fertility outcomes of infertile males with dynein axonemal heavy chain gene family variants.
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An independent cohort of three Chinese men with biallelic DNAH12 variants, plus a separate Dnah12 knockout mouse, confirms the association with asthenozoospermia and flagellar defects (3/1532 infertile men). In patient AY0749 DNAH12 and SPAG6 were lost but DNAH1 and DNAI2 were retained. After ICSI, one couple had a live birth, one a clinical pregnancy, and one was awaiting embryo transfer.
"Semen analysis revealed severe asthenozoospermia, abnormal morphology, and structure of sperm flagella."
Biallelic loss-of-function variants in DNAH12 cause inner dynein arm defects and sperm head abnormalities leading to male infertility.
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Two further homozygous loss-of-function variants. Patient sperm lose DNAH1, DNALI1, RSPH9 and SPAG6 and show sperm head abnormalities. DNAH12 is expressed from secondary spermatocytes to round spermatids.
"Single-cell analyses showed stage-specific DNAH12 expression from secondary spermatocytes to round spermatids"
Genotype-based management of fertilization and cleavage failure: case-series evidence from DNAH10, DNAH12, CFAP47 , and PLCZ1.
Exome sequencing reveals variants in known and novel candidate genes for severe sperm motility disorders.
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The first candidate report: two DNAH12 missense variants in one MMAF patient, possibly on the same allele, so the authors left causality open.
"It remains unclear whether variants in DNAH12 cause DFS-MMAF in this patient."
Whole exome sequencing analysis of 167 men with primary infertility.
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DNAH12 was listed as a candidate gene, with expression mainly in spermatocytes and early spermatids.
"DNAH12 and GALNT3 are found primarily in spermatocytes and early spermatids."
Axonemal dynein gene dysfunction as a cause of male infertility: insights from DNAH family mutations.
DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath.
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IP-MS from human sperm recovers DNAH12 with DNALI1. DNAH12 remains in DNALI1-mutant sperm that lack DNAH1, so DNAH12 localization does not need DNALI1.
"DNAH1 was completely absent in the DNALI1663_666del sperm, while no significant DNAH12 deficiency was observed"
IQUB mutation induces radial spoke 1 deficiency causing asthenozoospermia with normal sperm morphology in humans and mice.
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Loss of IQUB (radial spoke 1) depletes DNAH12 and DNAH7 from human and mouse sperm, which places DNAH12 near RS1.
"DNAH7 and DNAH12, the components of IDA, were significantly reduced both in the spermatozoa of IQUB842del patient and Iqub−/− mice"
Falcon deep research report for DNAH12
UniProt entry Q6ZR08 (DNAH12)