Searching Online Mendelian Inheritance in Man (OMIM): A Knowledgebase of Human Genes and Genetic Phenotypes

Joanna S. Amberger; Ada Hamosh

doi:10.1002/cpbi.27

Curr Protoc Bioinformatics. Author manuscript; available in PMC 2018 Jun 27.

Published in final edited form as:

Curr Protoc Bioinformatics. 2017 Jun 27; 58: 1.2.1–1.2.12.

Published online 2017 Jun 27. doi: 10.1002/cpbi.27

PMCID: PMC5662200

NIHMSID: NIHMS887086

PMID: 28654725

Searching Online Mendelian Inheritance in Man (OMIM): A Knowledgebase of Human Genes and Genetic Phenotypes

Joanna S. Amberger¹ and Ada Hamosh

Author information Copyright and License information PMC Disclaimer

Abstract

Online Mendelian Inheritance in Man (OMIM) at OMIM.org is the primary repository of comprehensive, curated information on genes and genetic phenotypes and the relationships between them. This unit provides an overview of the types of information in OMIM and optimal strategies for searching and retrieving the information. OMIM.org has links to many related and complementary databases providing easy access to exploring more information on a topic. The relationship between genes and genetic disorders is highlighted in this unit. The basic protocol explains searching OMIM both from a gene then clinical features perspective. Two alternate protocols provide strategies for viewing gene-phenotype relationships as a gene map table and clinical features as a Quick View or Side-by-Side format. OMIM.org is updated nightly and the MIMmatch service, described in the Support Protocol, provides a convenient way to follow updates to entries, gene-phenotype relationships, and collaborate with other researchers.

Keywords: OMIM, human genetic disorders, molecular genetics, disease gene discovery

INTRODUCTION

Online Mendelian Inheritance in Man (OMIM®) is a continuation of Dr. Victor McKusick's Mendelian Inheritance in Man (MIM) (McKusick, 1998), a seminal medical genetics resource used primarily by physicians and other professionals interested in genetic disorders, by genetics researchers, and by advanced students in science and medicine. It provides concise textual information based on the peer-reviewed biomedical literature on over 15,500 genes, 26,200 allelic variants, and 7,800 genetic phenotypes. In addition, OMIM.org provides tabular views of phenotype-gene relationships (gene map), overviews of clinical features of phenotypes (clinical synopses), phenotypic series, and a convenient way to follow updates and collaborate (MIMmatch). All entries in OMIM contain extensive targeted links to external data resources. The overall structure of OMIM is shown in Figure 1.2.1 and illustrates the intersections of gene and phenotype information.

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Figure 1.2.1

Diagram of OMIM content. Dashed lines indicate that not all genes have allelic variants; not all phenotypes are mapped; and mapped phenotypes are not necessarily part of a Phenotypic Series.

The Basic Protocol describes a basic text search and overview of the layout of search results. Alternate Protocol 1 explains searching the Gene Map to reveal unique displays of the intersection between gene and phenotype. Alternate Protocol 2 explains searching clinical information to display the Quick View and Side-by-Side views of the Clinical Synopses. The Support Protocol describes how to register for MIMmatch alerts.

BASIC PROTOCOL: SEARCHING OMIM

OMIM.org is the official website for OMIM information. It has been optimized to retrieve and display information from OMIM in a straightforward and clear manner. OMIM.org supports free-text and field-directed searches. Detailed help, example searches, and tips are available from every screen. The top of the OMIM home page (https://omim.org) shows the black menu bar that is common across all OMIM.org web pages. From this menu a user can always access Statistics, Download/API registration, Contact Us, MIMmatch access, Help/FAQ, and Tips specific for the page (?). Statistics include the Update List of new and added entries, number of entries in OMIM, and number of phenotype-gene relationships cataloged by OMIM. Below the search box is access to advanced search pages, example searches, search help, and a tutorial.

Necessary Resources

Hardware

Any Internet-connected computer, tablet, or mobile device

Software

Up-to-date Web browsers such as Chrome, FireFox, Safari, Microsoft Explorer or Edge

Performing an OMIM search for genes

If, for example, you are interested in potassium channel genes, you can enter your search in a number of ways. For example, +potassium +channel (352 entries retrieved), KCN* (333 entries retrieved), or “potassium channel” (with quotes potassium and channel must appear as a phrase, 276 entries retrieved). Of note, entering potassium channel without qualifiers applies both Boolean AND and OR to the search. Entries satisfying the AND operator are given higher relevance (1,334 entries retrieved). OMIM searches are vocabulary enhanced to accommodate synonyms, British spelling, and user-selected thesaurus terms. Figure 1.2.2 shows an entry retrieval page for a search on +potassium +channel and is described below.
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Figure 1.2.2
Search result page from a search of +potassium +channel at OMIM.org. Targeted links for entry 600937 are displayed by clicking the “Links” button below the entry title. The mouse-over explanation of the MIM number prefix (in this case “Gene description”) is also displayed.
1. Blue buttons “Gene Map Table” and “Clinical Synopsis” to the right of the search box navigate the search results to the Gene Map display and Clinical Synopsis (see Alternate Protocols 1 and 2). If thesaurus terms are available for the search, they will be displayed below the search box.
2. The text below the green line shows the total number of entries retrieved with that search; an option to expand the number of titles displayed; an option to download the search results, and retrieval navigation buttons.
3. Each entry in OMIM has a unique and stable MIM number. The MIM number has a prefix denoting whether the entry represents a gene or phenotype. A mouse-over reminds the user what they mean. The number is followed by the preferred MIM title and symbol. Clicking on the title brings up the full display of that entry. Below the title is the cytogenetic location and genomic coordinates; clicking on either of them takes the user to that gene/locus in OMIM’s gene map or in UCSCs Genome Browser.
4. Colored triangles precede links to reveal on-page information and access to Gene-phenotype/Phenotype-gene Relationships, ICD+ codes, Phenotypic series, and Links (opened for entry 600937). ICD+ and Phenotypic series links will not appear in gene entries. Access to this information is also present on the entry full view.
Clicking on the title for 176260 opens the entry full view for this gene (Figure 3). Note that the search terms are highlighted, and there is a green bar next to the Description paragraph denoting information that has been changed or added in the last 3 month. Highlights and change bars can be toggled off by selecting the option to the right of the search box.
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Figure 1.2.3
Entry full view for 176260 displaying highlighted search terms, green entry change bar (left of description paragraph), and Reference Plus link.
1. Following the number and preferred title are alternative names that may have been given to the entry. The HGNC-approved gene symbol display and link are above the mapping information links and Gene-Phenotype relationship table.
2. Left of the title is the entry navigation Table of Contents. Selecting the heading takes the user directly to that section in the entry. Note that Allelic Variants are listed in a gene entry and can be viewed as descriptive text or in a Table View (Figure 1.2.4). Both versions have links, when available, to dbSNP, ExAC, and ClinVar.
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  Figure 1.2.4
  Allelic variant table view showing dbSNP, ExAC, and ClinVar links
3. To the right of the title are External Links. The topically organized pull-down menus in this stack contain links to over 55 resources including genome browsers, DNA and protein sequence databases, model organism databases, pathway database, etc. Each link takes the user directly to the relevant information in that resource.
4. The plus sign at the end of text paragraphs takes the user to articles in PubMed that are related to the citation(s) in the MIM entry paragraph. This is an easy way to find additional articles that may be available on a specific topic.

Performing an OMIM search for phenotypes (including disorders) or clinical features

Information in a phenotype entry is different from that in a gene entry. Organizationally, each phenotype in a unique phenotype-gene relationship has its own OMIM entry and number. Clinical features in an entry are specific to that phenotype-gene relationship. To show how a class of related phenotypes lies across the genome, OMIM has Phenotypic Series. Users can search by disorder name or clinical features. For example, starting at the OMIM.org home page, search on hypogonadism and microcornea. Optional thesaurus terms related to hypogonadism (e.g., hypogenitalism, micropenis, small testis, etc.) are displayed under the search box that could be selected to further broaden a search. For the purposes of this protocol, select 600118 by clicking on the title, Warburg Micro syndrome 1 (Figure 1.2.5).
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Figure 1.2.5
Full view of entry 600118 showing the ICD+ coding numbers, in-page view of the clinical synopsis, and MIMmatch information.
1. The ICD+ link shows the available disease identifiers. The External Links have robust Clinical Resources (shown), Animal Model, and Cell Lines sections. These links appear only if there is information in the external resource that is relevant to the MIM entry.
2. The Clinical Synopsis (a feature-based list) and Phenotypic Series links can display contents in-page (down triangle, shown here) or in a new page (main button).
3. If the user is a MIMmatch member, MIMmatch options will be displayed below the Table of Contents to the left of the entry. The user has options to follow updates to the entry or share interest. This entry has 15 individuals sharing their interest. The link provides details and a way to share contact information.
4. The Phenotypic Series shows the genetic heterogeneity of Warburg Micro syndrome (Figure 1.2.6).
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  Figure 1.2.6
  Phenotype Series for Warburg micro syndrome. The sort can be changed by clicking on the triangle links in the table headers. Explanation of the Inheritance and Phenotype mapping keys are available through a mouse-over pop-up.

GUIDELINES FOR UNDERSTANDING ENTRY STRUCTURE AND CONTENT

[Copy Editor: Rather than having one Guidelines section following the last protocol, the authors have included protocol-specific guidelines after each protocol. CP style can accommodate this.]

Number

Each OMIM entry is given a unique and stable six-digit number based on the chromosomal location. Autosomal entries start with a 1, 2 or 6, X-linked entries start with a 3, Y-linked with a 4, and mitochondrial with a 5. Numbers that start with a 1 or 2 do not refer to a mode of inheritance.

MIM numbers are preceded by a prefix:

An asterisk (*) before an entry number indicates a gene.

A number symbol (#) before an entry number indicates that it is a descriptive entry, usually of a phenotype, and does not represent a unique locus. The reason for the use of the number symbol is given in the first paragraph of the entry. Discussion of any gene(s) related to the phenotype resides in another entry(ies) as described in the first paragraph.

A plus sign (+) before an entry number indicates that the entry contains the description of a gene of known sequence and a phenotype.

A percent sign (%) before an entry number indicates that the entry describes a confirmed mendelian phenotype or phenotypic locus for which the underlying molecular basis is not known.

No symbol before an entry number generally indicates a description of a phenotype for which the mendelian basis, although suspected, has not been clearly established or that the separateness of this phenotype from that in another entry is unclear.

A caret (^) before an entry number means the entry was removed from the database or moved to another entry as indicated.

Title

Each entry has a “Preferred title” with symbol. Synonymous names and symbols that have been used in the literature are included as “Alternative title(s)”. “Included titles” mark placement of information on a topic that does not warrant a separate entry (e.g., fusion genes).

Text

Information in the main text of an OMIM entry is put under standard headings (e.g., Description, Clinical Features, Cloning and Expression, etc.) that can be targeted in fielded searches (see online search help 1.5; https://omim.org/help/search#1_5).

Allelic Variants

This section reports mutations and variations in the gene that are found to underlie a phenotype. OMIM includes only select variants. Criteria for inclusion include the first mutation to be discovered, high population frequency, distinctive phenotype, historic significance, unusual mechanism of mutation, unusual pathogenetic mechanism, and distinctive inheritance (e.g., dominant with some mutations, recessive with other mutations in the same gene). Most of the allelic variants represent disease-causing mutations. A few polymorphisms are included, many of which show a positive correlation with particular common disorders. Effective January 2013, based on a rigorous assessment of published reports, OMIM creates phenotype-gene relationships that are "established," "provisional," or of "unknown significance." An established relationship may be based on (1) the existence of multiple, unrelated individuals with pathogenic variants in the same gene; (2) variants that segregate with the phenotype in multiplex families; and/or (3) variants that occur de novo in a statistically significant number of individuals. Functional data and/or animal models support the causality but are not required. A provisional relationship may be based on (1) only one multiplex family reported to have variants in a single gene and the variants segregate with the phenotype in the family, and (2) there is supportive functional data such as in vitro enzyme activity, a comparable phenotype in a model organism experiment, or an animal model. In this case the gene-phenotype relationship is qualified by noting that the variant has been identified in only 1 family. In rare instances, a similar gene-phenotype relationship may be established on the basis of a single patient if there is robust supporting phenotype and functional data. A variant of unknown significance may be created if a report identifies only 1 patient or family and provides no supporting functional data.

References

All information in an OMIM entry is cited. The references are listed in alphabetical order in this section. There are links to PubMed and to the full text of the article, when available.

ALTERNATE PROTOCOL 1: SEARCHING OMIM’S GENE MAP

OMIM’s Gene Map is a table of the genes and loci in OMIM organized by chromosome. OMIM currently has entries for over 15,500 genes and focuses on gene-phenotype relationships. The tabular format provides easy access to multiple gene-phenotype relationships in a single view. The table includes the cytogenetic location, genomic coordinates, gene/locus symbol and title, gene/locus MIM#, comments, and homologous mouse gene. If there is a phenotype(s) associated with a gene/locus, there is a column for phenotype, the phenotype MIM#, the inheritance mode, and the phenotype mapping key. Mousing over the number will display the definition of the key. A summary of the definitions are the following: (1) the disorder was positioned by mapping of the wildtype gene; (2) the disease phenotype itself was mapped; (3) the molecular basis of the disorder is known; (4) the disorder is a chromosome deletion or duplication syndrome. The following describes accessing the gene map table view of a standard search OMIM then restricting the view to genes with phenotypes and then a direct search of the gene map by genomic coordinates to show the phenotypes within a region.