Alt. symbols: DFNA1 | hDIA1 | LFHL1

Approved name: diaphanous related formin 1
Alt. names: diaphanous (Drosophila, homolog) 1, diaphanous homolog 1 (Drosophila)

Location: 5q31.3: 141515016 - 141619055 (-)
Gene type: protein_coding, 15 transcripts.

Scores: LoFtool: 0.270000 | pLI: 0.26710967 | LOEUF: 0.320

HGNC: 2876

NCBI: 1729, RefSeq: NG_011594.2

Ensembl: ENSG00000131504.18

LRG_1117 | Status: public

OMIM: 602121

Expression | ProteinAtlas

DIAPH1 encodes Diaphanous-related formin 1, a protein involved in the organization of the cytoskeleton and regulation of cell morphology during adhesion, migration and division in immune cells and neuroepithelial cells. Diaph1 binds to the rough ends of actin filaments and enables the assembly of linear actin filaments by administrating the process of actin polymerization. It is speculated that the biologic role of Diaph1 in hearing is the regulation of actin polymerization in hair cells of the inner ear. This theory is supported by Lynch et al. (1997), showing the expression of DIAPH1 in the cochlea by RT-PCR of cochlear RNA and by Neuhaus et al. (2017), showing the expression of Diaph1 in the organ of Corti in the inner ear of mice. In the latter study, Diaph1 was specifically expressed in hair cells as well as in neuronal cells in the ear, including spiral ganglion neurons and the cochlear nerve. Another study showed that Diaph1 is found in cells of the developing mouse and human forebrain (Ercan-Sencicek et al., 2015).

Mutations in DIAPH1 have been linked to autosomal dominant progressive non-syndromic hearing loss (DFNA1), as well as autosomal recessive cortical blindness and microcephaly syndrome. In a large Costa Rican family with various cases of DFNA1, a splice site mutation (c.3661+1G>T) in DIAPH1 was detected in affected family members leading to partial loss of function of the gene (Lynch et al., 1997). In two unrelated families with DFNA1 and thrombocytopenia, two heterozygous mutations in DIAPH1 were found leading to truncation of the protein; a frameshift mutation p.Ala1210Serfs*31, present in all five affected members of the first family, and a nonsense mutation p.Arg1213*, present in two of the affected members of the second family (Neuhaus et al., 2017). The nonsense mutation p.Arg1213* was also found in affected individuals of three additional unrelated families with DFNA1 and thrombocytopenia and segregated with disease in all three families (Stritt et al., 2016; Ganaha et al., 2017). In-vivo functional studies performed by Stritt et al. showed defective maturation and pro-platelet formation in megakaryocytes derived from one of the patients in comparison to control cells. Mutant platelets also presented with altered cytoskeleton including disorganized F-actin. Moreover, biallelic mutations in DIAPH1 (p.Gln778*, p.Phe923Leufs*4 and p.Arg1049*) have been associated with the development of cortical blindness, seizures and microcephaly syndrome [MIM:616632] in affected members of three unrelated families (Ercan-Sencicek et al., 2015; Al-Maawali et al., 2016). [Load More]