Human Molecular Genetics Journal Impact Factor & Information

Publisher: Oxford University Press (OUP)

Journal description

Human Molecular Genetics concentrates on full-length research papers covering a wide range of topics in all aspects of human molecular genetics. These include: the molecular basis of human genetic disease developmental genetics neurogenetics chromosome structure and function molecular aspects of cancer genetics gene therapy biochemical genetics major advances in gene mapping understanding of genome organisation In addition the journal also publishes research on other model systems for the analysis of genes especially when there is an obvious relevance to human genetics. Key features of the journal include: Articles - comprehensive reports and definitive research findings of interest to a broad audience of human molecular geneticists. We encourage inclusion of full experimental details with as many display items (figures and tables) as required to tell the complete story. Reports - descriptions of novel results of biological and genetic importance in the field. Commentaries - these discuss recent papers in the journal or review areas of particular interest in the field. Now in its eighth year of publication Human Molecular Genetics has clearly become one of the leading journals in this exciting frontier of scientific research. With the enthusiastic support of the executive editors and editorial board we intend to ensure that the journal's reputation for quality is reinforced in the years to come.

Current impact factor: 6.68

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 6.677
2012 Impact Factor 7.692
2011 Impact Factor 7.636
2010 Impact Factor 8.058
2009 Impact Factor 7.386
2008 Impact Factor 7.249
2007 Impact Factor 7.806
2006 Impact Factor 8.099
2005 Impact Factor 7.764
2004 Impact Factor 7.801
2003 Impact Factor 8.597
2002 Impact Factor 8.726
2001 Impact Factor 9.318
2000 Impact Factor 9.048
1999 Impact Factor 9.359
1998 Impact Factor 9.307
1997 Impact Factor 8.505
1996 Impact Factor 6.512
1995 Impact Factor 5.273
1994 Impact Factor 4.528
1993 Impact Factor 3.783

Impact factor over time

Impact factor

Additional details

5-year impact 7.54
Cited half-life 6.60
Immediacy index 1.55
Eigenfactor 0.11
Article influence 3.08
Website Human Molecular Genetics website
Other titles Human molecular genetics
ISSN 0964-6906
OCLC 25594670
Material type Periodical, Internet resource
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details

Oxford University Press (OUP)

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • Pre-print can only be posted prior to acceptance
    • Pre-print must be accompanied by set statement (see link)
    • Pre-print must not be replaced with post-print, instead a link to published version with amended set statement should be made
    • Pre-print on author's personal website, employer website, free public server or pre-prints in subject area
    • Post-print in Institutional repositories or Central repositories
    • Publisher's version/PDF cannot be used
    • Published source must be acknowledged
    • Must link to publisher version
    • Set phrase to accompany archived copy (see policy)
    • Eligible authors may deposit in OpenDepot
    • The publisher will deposit in PubMed Central on behalf of NIH authors
    • Publisher last contacted on 19/02/2015
    • This policy is an exception to the default policies of 'Oxford University Press (OUP)'
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: CRISPR/Cas9 has been used to genetically modify genomes in a variety of species, including non-human primates. Unfortunately, this new technology does cause mosaic mutations, and we do not yet know whether such mutations can functionally disrupt the targeted gene, or cause the pathology seen in human disease. Addressing these issues is necessary if we are to generate large animal models of human diseases using CRISPR/Cas9. Here we used CRISPR/Cas9 to target the monkey dystrophin gene to create mutations that lead to Duchenne muscular dystrophy (DMD), a recessive X-linked form of muscular dystrophy. Examination of the relative targeting rate revealed that Crispr/Cas9 targeting could lead to mosaic mutations in up to 87% of the dystrophin alleles in monkey muscle. Moreover, CRISPR/Cas9 induced mutations in both male and female monkeys, with the markedly depleted dystrophin and muscle degeneration seen in early DMD. Our findings indicate that CRISPR/Cas9 can efficiently generate monkey models of human diseases, regardless of inheritance patterns. The presence of degenerated muscle cells in newborn Cas9-targeted monkeys suggests that therapeutic interventions at the early disease stage may be effective at alleviating the myopathy.
    Human Molecular Genetics 07/2015; DOI:10.1093/hmg/ddv120
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    ABSTRACT: Spinocerebellar Ataxia Type 6 (SCA6) belongs to the family of CAG/polyglutamine (polyQ)-dependent neurodegenerative disorders. SCA6 is caused by abnormal expansion in a CAG trinucleotide repeat within exon 47 of CACNA1A, a bicistronic gene that encodes α1A, a P/Q-type calcium channel subunit, and a C-terminal protein, termed α1ACT. Expansion of the CAG/polyQ region of CACNA1A occurs within α1ACT and leads to ataxia. There are few animal models of SCA6. Here, we describe the generation and characterization of the first Drosophila melanogaster models of SCA6, which express the entire human α1ACT protein with a normal or expanded polyQ. The polyQ-expanded version of α1ACT recapitulates the progressively degenerative nature of SCA6 when expressed in various fly tissues and the presence of densely staining aggregates. Additional studies identify the co-chaperone DnaJ-1 as a potential therapeutic target for SCA6. Expression of DnaJ-1 potently suppresses α1ACT-dependent degeneration and lethality, concomitant with decreased aggregation and reduced nuclear localization of the pathogenic protein. Mutating the nuclear importer karyopherin α-3 also leads to reduced toxicity from pathogenic α1ACT. Little is known about the steps leading to degeneration in SCA6 and the means to protect neurons in this disease are lacking. Invertebrate animal models of SCA6 can expand our understanding of molecular sequelae related to degeneration in this disorder and lead to the rapid identification of cellular components that can be targeted to treat it. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email:
    Human Molecular Genetics 05/2015; DOI:10.1093/hmg/ddv174
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by loss of motor neuron-like cells. Mutations in the RNA- and DNA-binding proteins, fused in sarcoma (FUS) and transactive response DNA-binding protein 43kda (TDP-43) are responsible for 5-10% of familial and 1% of sporadic ALS cases. Importantly, aggregation of misfolded FUS or TDP-43 is also characteristic of several neurodegenerative disorders in addition to ALS, including frontotemporal lobar degeneration (FTLD). Moreover, splicing deregulation of FUS and TDP-43 target genes as well as mitochondrial abnormalities are both associated with disease-causing FUS and TDP-43 mutants. While progress has been made to understand the functions of these proteins, the exact mechanisms by which FUS and TDP-43 cause ALS remain unknown. Recently we discovered that, in addition to being up-regulated in spinal cords of ALS patients, the novel protein oxidative resistance 1 (Oxr1) protects neurons from oxidative stress-induced apoptosis. To further understand the function of Oxr1, we present here the first interaction study of the protein. We show that Oxr1 binds to Fus and Tdp-43 and that certain ALS-associated mutations in Fus and Tdp-43 affect their Oxr1 binding properties. We further demonstrate that increasing Oxr1 levels in cells expressing specific Fus and Tdp-43 mutants improves the three main cellular features associated with ALS: cytoplasmic mis-localisation and aggregation, splicing changes of a mitochondrial gene, and mitochondrial defects. Taken together, these findings suggest that OXR1 may have therapeutic benefits for the treatment of ALS and related neurodegenerative disorders with TDP-43 pathology.
    Human Molecular Genetics 03/2015; 24(12). DOI:10.1093/hmg/ddv104
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    ABSTRACT: Temporal lobe epilepsy (TLE) is a common epilepsy syndrome with a complex etiology. Despite evidence for the participation of genetic factors, the genetic basis of TLE remains largely unknown. A role for the galanin neuropeptide in the regulation of epileptic seizures has been established in animal models more than two decades ago. However, until now there was no report of pathogenic mutations in GAL, the galanin-encoding gene, and therefore its role in human epilepsy was not established. Here, we studied a family with a pair of monozygotic twins affected by TLE and two unaffected siblings born to healthy parents. Exome sequencing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene. Functional analysis revealed that the p.A39E mutant showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2. These findings suggest that the p.A39E mutant could impair galanin signaling in the hippocampus, leading to increased glutamatergic excitation and ultimately to TLE. In a cohort of 582 cases, we did not observe any pathogenic mutations indicating that mutations in GAL are a rare cause of TLE. The identification of a novel de novo mutation in a biologically-relevant candidate gene, coupled with functional evidence that the mutant protein disrupts galanin signaling, strongly supports GAL as the causal gene for the temporal lobe epilepsy in this family. Given the availability of galanin agonists which inhibit seizures, our findings could potentially have direct implications for the development of anti-epileptic treatment.
    Human Molecular Genetics 02/2015;
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    ABSTRACT: There are two known mRNA degradation pathways, 3' to 5' and 5' to 3'. We identified likely pathogenic variants in two genes involved in these two pathways in individuals with intellectual disability. In a large family with multiple branches we identified bi-allelic variants in DCPS in three affected individuals; a splice-site variant (c.636+1G>A) that results in an in-frame insertion of 45 nucleotides and a missense variant (c.947C>T; p.Thr316Met). DCPS decaps the cap structure generated by 3' to 5' exonucleolytic degradation of mRNA. In vitro decapping assays showed an ablation of decapping function for both variants in DCPS. In another family we identified a homozygous mutation (c.161T>C; p.Phe54Ser) in EDC3 in two affected children. EDC3 stimulates DCP2, which decaps mRNAs at the beginning of the 5' to 3' degradation pathway. In vitro decapping assays showed that altered EDC3 is unable to enhance DCP2 decapping at low concentrations, and even inhibits DCP2 decapping at high concentration. We show that individuals with bi-allelic mutations in these genes of seemingly central functions are viable and that these possibly lead to impairment of neurological functions linking mRNA decapping to normal cognition. Our results further affirm an emerging theme linking aberrant mRNA metabolism to neurological defects. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email:
    Human Molecular Genetics 02/2015; 24(11). DOI:10.1093/hmg/ddv069
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    ABSTRACT: Current estimates indicate that approximately one third of all disease-causing mutations are expected to disrupt splicing. Abnormal splicing often leads to disruption of the reading frame with introduction of a premature termination codon that targets the mRNA for degradation in the cytoplasm by nonsense mediated decay (NMD). In addition to NMD there are RNA surveillance mechanisms that act in the nucleus while transcripts are still associated with the chromatin template. However, the significance of nuclear RNA quality control in the context of human genetic diseases is unknown. Here we used patient-derived lymphoblastoid cell lines as disease models to address how biogenesis of mRNAs is affected by splice site mutations. We observed that most of the mutations analyzed introduce premature termination codons and trigger mRNA degradation in the cytoplasm. However, for some mutant transcripts, RNA levels associated with chromatin were found down-regulated. Quantification of nascent transcripts further revealed that a subset of genes containing splicing mutations have reduced transcriptional activity. Following treatment with the translation inhibitor cycloheximide the cytoplasmic levels of mutant RNAs increased, while the levels of chromatin-associated transcripts remained unaltered. These results suggest that transcription-coupled surveillance mechanisms operate independently from NMD to reduce cellular levels of abnormal RNAs caused by splicing mutations. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email:
    Human Molecular Genetics 02/2015; 24(10):2784-95. DOI:10.1093/hmg/ddv039
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    ABSTRACT: Exposure of a developing fetus to maternal gestational diabetes (GDM) has been shown to programme future risk of diabetes and obesity. Epigenetic variation in fetal tissue may have a mechanistic role in metabolic disease programming through interaction of the pregnancy environment with gene function. We aimed to identify genome-wide DNA methylation variation in cord blood and placenta from offspring born to mothers with and without GDM. Pregnant women of South Asian origin were studied and fetal tissues sampled at term delivery. The Illumina HumanMethylation450 BeadChip was used to assay genome-wide DNA methylation in placenta and cord blood from 27 GDM exposed and 21 unexposed offspring. We identified 1485 cord blood and 1708 placenta methylation variable positions (MVPs) achieving genome-wide significance (adjusted P-value <0.05) with methylation differences of >5%. MVPs were disproportionately located within 1st exons. A bioinformatic co-methylation algorithm was used to detect consistent directionality of methylation in 1000bp window around each MVP was observed at 74% of placenta and 59% of cord blood MVPs. KEGG pathway analysis showed enrichment of pathways involved in endocytosis, MAPK signalling and extracellular triggers to intracellular metabolic processes. Replication studies should integrate genomics and transcriptomics with longitudinal sampling to elucidate stability, determine causality for translation into biomarker and prevention studies. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email:
    Human Molecular Genetics 01/2015; 24(11). DOI:10.1093/hmg/ddv013
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    ABSTRACT: High-risk mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas cutaneous types (e.g. HPV8 and 77) are suspected to be involved in non-melanoma skin cancer. The antibody response to HPVs is a key determinant of protective immunity, but not all infected individuals seroconvert. Genetic variability of the host may have large impact on seroconversion. A previous genome-wide association study (GWAS) has identified a susceptibility locus (rs41270488) for HPV8 seropositivity within the major histocompatibility complex (MHC) region. To further study this locus, we imputed alleles at classical leukocyte antigen (HLA) loci using HLA*IMP:02 with a reference panel from the HapMap Project and the 1958 Birth Cohort, and conducted an integrated analysis among 4,811 central European subjects to assess the contribution of classical HLA alleles and gene copy number variation (CNV) at the hypervariable DRB locus within the MHC region to HPV seropositivity at both the individual HPV type level and the phylogenetic species level. Our study provides evidence that the association noted between rs41270488 and HPV8 seropositivity is driven by two independent variants, namely DQB1*0301 (odds ratio [OR]=1.51, 95% confidence interval [CI]=1.36-1.68, P=1.0×10(-14)) and DRB1*1101 (OR=1.89, 95%CI=1.57-2.28, P=1.5×10(-11)) within the HLA class II region. Additionally, we identified two correlated alleles DRB1*0701 (OR=1.67, 95%CI= 1.41-1.98, P=2.6×10(-9)) and DQA1*0201 (OR=1.67, 95%CI=1.38-1.93, P=1.7×10(-8)), to be associated with HPV77 seropositivity. Comparable results were observed through imputation using SNP2HLA with another reference panel from the Type 1 diabetes Genetics Consortium. This study provides support for an important role of HLA class II alleles in antibody response to HPV infection. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email:
    Human Molecular Genetics 01/2015; 24(9). DOI:10.1093/hmg/ddv015