Online Mendelian Inheritance in Humans (OMIM) (2023)

Cytogenetic location: 15q23 Genomic coordinates (GRCh38): 15:71096894-71783383 (by NCBI)



Microfibrils are multifunctional fibrillar extracellular matrices that contribute to the elastic properties of connective tissue and control the bioavailability of growth factors. THSD4 promotes microfibril assembly (Tsutsui et al., 2010).

Cloning and Expression

Tsutsui et al. (2010) cloned two mouse Thsd4 splice variants, which they named Adamtsl6-alpha and Adamtsl6-beta. The derived proteins contain 1,018 and 658 amino acids, respectively. Full-length Adamtsl6-alpha has an N-terminal signal sequence followed by an atypical thrombospondin type 1 repeat (TSR), a cysteine-rich domain, an ADAMTS spacer, 6 tandem TSRs, and a C-terminal PLAC domain. The atypical N-terminal TSR is bisected by an insertion of approximately 200 amino acids. This TSR contains a consensus tryptophan motif (WxxWxxW) and 6 conserved cysteines, and the insert contains 2 heparin binding motifs (RRxR). Adamtsl6-beta lacks the atypical N-terminal TSR and cysteine-rich domain of Adamtsl6-alpha and instead has the N-terminal signal sequence directly fused to the ADAMTS spacer. Both Adamts16 isoforms contain N-glycosylation sites. RT-PCR of mouse tissues showed ubiquitous and almost uniform expression of Adamtsl6-alpha. In contrast, Adamtsl6-beta was differentially expressed in selected tissues including brain, spinal cord, eye, kidney, stomach and uterus and was not expressed in heart, liver, lymph nodes, submandibular gland and spleen. Both variants were expressed in mouse embryos at all developmental stages tested. Immunohistochemical analysis and immunological gold microscopy of embryonic and adult mice revealed the expression of Adamtsl6 in fibrillar structures of various elastic tissues, where it was colocalized with fibrillin-1 (FBN1; 134797). Gel electrophoresis performed under reducing and non-reducing conditions suggested that Adamtsl6 could form both intramolecular and intermolecular disulfide bonds. After transfection of human osteosarcoma cells, both Adamtsl6 isoforms were recovered in the extracellular matrix, but unlike Adamtsl6-alpha, Adamtsl6-beta was also found in the conditioned medium. Adamtsl6 secretion was dependent on its N-glycosylation.

Saito et al. (2011) studied the expression of Adamtsl6 during the development of embryonic tooth germs in mice. They found that Adamtsl6-beta is specifically regulated during the formation of the periodontal ligament, which consists of elastic fibers composed of fibrillin-1 microfibrils. Adamtsl6-beta expression was downregulated in the adult periodontal ligament. Adamtsl6-alpha was only expressed in odontoblasts.

Gene structure

Elbitar et al. (2021) stated that the THSD4 gene contains 17 coding exons.

(Video) Online Mendelian Inheritance in Man (OMIM): A Genetic Disorder Database


Hartz (2011) assigned the THSD4 gene to chromosome 15q23 based on an alignment of the THSD4 sequence (GenBank AK023772) with the genomic sequence (GRCh37).

Tsutsui et al. (2010) found that the mouse Thsd4 gene maps to chromosome 9.

Gene function

Tsutsui et al. (2010) found that recombinant mouse Adamtsl6-beta interacted with the N-terminal half of fibrillin-1 in a dose-dependent manner. When transfected into human osteosarcoma cells, both Adamtsl6-alpha and -beta promoted fibrillin-1 microfibril formation in a dose-dependent manner that was independent of fibrillin-1 synthesis. Fibrillin-1 deposition in the ECM was increased in transgenic mice overexpressing Adamtsl6-beta in cartilage. Tsutsui et al. (2010) concluded that ADAMTSL6 promotes assembly of fibrillin-1 microfibrils.

Marfan syndrome (MFS; 154700) is a connective tissue disease caused by defective formation of fibrillin-1 microfibrils. MFS is associated with overactivation of TGF-beta (TGFB1; 190180) signaling due to increased release of active TGF-beta from disrupted fibrillin-1 microfibrils. Using a mouse model of MFS, Saito et al. (2011) showed that expression of Adamtsl6-beta rescued the formation of fibrillin-1 microfibrils in the periodontal ligament, one of several affected tissues in MFS. Adamtsl6 expression also attenuated overactivation of TGF-beta signaling in MFS mice. Using various in vitro, in vivo, and culture models, Saito et al. (2011) confirmed that Adamtsl6 is required for assembly of fibrillin-1 microfibrils.

(Video) |OMIM|Online Mendelian inheritance in man|omim

Molecular genetics

Using exome sequencing in 35 French families with familial thoracic aortic aneurysms and a set of next-generation sequencing capture genes in 1114 unrelated patients with thoracic aneurysms and dissection, Elbitar et al. (2021) identified 5 families with a pathological heterozygous variant in the THSD4 gene (614476.0001-614476.0005). The mutations included two 1 bp deletions, one duplication and two nonsense mutations. In the 4 families with a positive family history, the mutation split with the disease. Functional studies showed that the variants resulted in haploinsufficiency, or an abnormal arrangement of fibrillin-1 microfibrils.

animal model

Elbitar et al. (2021) created a Thsd4 +/- mouse model and showed that heterozygous mice exhibited progressive dilatation of the thoracic aorta. Histological analysis showed normal elastic fiber formation from 0 to 5 months of age; However, patchy accumulation of Alcian blue positive areas in the aorta was observed at 6 and 9 months, suggesting the presence of proteoglycans.

ALLELIC VARIANTS 5 selected examples):


ClinVar: RCV002210954

Using exome sequencing, Elbitar et al. (2021) identified a 1 bp deletion (c.740del, NM_024817.2) in exon 4 of the THSD4 gene, resulting in a leu247 to ter (L247X) substitution in a mother and son (family 1, TAA- 1889) resulted in familial thoracic aortic aneurysm-12 (AAT12; 619825). Subject had a type A aortic dissection at age 43 and his mother had her ascending aorta replaced for a dissection at age 75. Other findings observed in the subject included a slight pectus excavatum, dolicostomelia, and a high arch of the palate.

(Video) OMIM (Online Mendelian Inheritance in Man) - GANL 401, MUST.


THSD4, 1-BP DEL, 1402G
ClinVar: RCV002210955

In a family (Family 2, TAA-1839) with familial thoracic aortic aneurysm-12 (AAT12; 619825), Elbitar et al. (2021) identified a 1 bp deletion of a guanine in a 3-guanine repeat (c.1402delG, NM_024817.2) in exon 8 of the THSD4 gene, resulting in image shift and premature termination (Ala468GlnfsTer45). The female subject and her daughter had dilatation of the ascending aorta with diameters of 42 mm at the aortic root and 47 mm at the ascending aorta in the mother (age 48 years) and 28 mm at the aortic root and 32 mm at the ascending aorta. Aorta for daughter (age 16 years). Subject's sister had an aortic root diameter of 33 mm with 36 mm in the ascending aorta (age 46 years). The father (80 years old) who was a carrier of the variant was not known to be affected and was unavailable for study. The subject was also found to have dolicostomelia, hypertelorism, and arthritis.


THSD4, 9-BP DUP, NT137
ClinVar: RCV002210956

In a family (Family 3, TAA-1850) with familial thoracic aortic aneurysm-12 (AAT12; 619825), Elbitar et al. (2021) identified a 9 bp in-frame duplication in the THSD4 gene (c.137_145dup, NM_024817.2) that would likely result in a 3 amino acid residue duplication (Asp46_Gly48dup). The subject had an enlarged aortic root (48 mm) after a myocardial infarction at the age of 39 years. His brother also carried the duplication and underwent surgery for an aortic dissection at the age of 42, noting a dilatation of the ascending aorta prior to the dissection. The subject's father also carried the duplication and underwent aortic dilatation surgery of the ascending and abdominal aorta at age 68. No other clinical manifestations of connective tissue disorders were observed in the family.

(Video) OMIM Database


ClinVar: RCV002210957

In a patient (family 4; TAA-1817) with familial thoracic aortic aneurysm-12 (AAT12; 619825), Elbitar et al. (2021) identified a c.961T-A transversion (c.961T-A, NM_024817.2) in exon 5 of the THSD4 gene, resulting in a tyr321 to asn (Y321N) substitution. The subject required Bentall surgery for aortic regurgitation at the age of 61. The aortic root size was 44 mm (Z = 3.9 SD). The patient also had a spontaneous pneumothorax. His daughter was also a carrier of the variant and had an aortic root diameter of 30 mm and an ascending aortic diameter of 29 mm. This variant has not been reported in population databases.


THSD4, ARG781TRP ({dbSNP rs767807136})
ClinVar: RCV002204561

In a patient (family 5; TAA-1819) with familial thoracic aortic aneurysm-12 (AAT12; 619825), Elbitar et al. (2021) identified a transition c.2341C-T (c.2341C-T, NM_024817.2) in exon 13 of the THSD4 gene that resulted in a substitution of arg781 to trp (R781W). The subject underwent elective surgery at the age of 57 for an aortic root diameter of 50 mm. The subject also had Raynaud's syndrome and a bicuspid aortic valve. No other family members were affected. The variant had a frequency of 0.000035 among non-Finnish Europeans in the gnomAD database.

(Video) Online Mendelian Inheritance in Man (ClinGen Biocurator Working Group)


What information does the OMIM online mendelian inheritance in man database provide? ›

OMIM® - Online Mendelian Inheritance in Man. ®

The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 16,000 genes. OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries contain copious links to other genetics resources.

What is online Mendelian inheritance in man? ›

Online Mendelian Inheritance in Man (OMIM™) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics.

Who funds OMIM? ›

OMIM is supported by a grant from NHGRI, licensing fees, and generous contributions from people like you.

What are the Mendelian inheritance patterns of human disorders? ›

There are five basic modes of inheritance for single-gene diseases: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial. Genetic heterogeneity is a common phenomenon with both single-gene diseases and complex multi-factorial diseases.

What does OMIM tell you? ›

Online Mendelian Inheritance in Man (OMIM®) is a continuously updated catalog of human genes and genetic disorders and traits, with particular focus on the molecular relationship between genetic variation and phenotypic expression.

Why is OMIM important? ›

OMIM ENTRIES. Throughout its history, the primary mission of OMIM has been to collect and curate knowledge on human genes and genetic disorders and traits.

Do humans follow Mendelian inheritance? ›

Characteristics that are encoded in DNA are called genetic traits. Different types of human traits are inherited in different ways. Some human traits have simple inheritance patterns like the traits that Gregor Mendel studied in pea plants.

Is OMIM a primary database? ›

Online Mendelian Inheritance in Man (OMIM), a continuation of Dr Victor A. McKusick's Mendelian Inheritance in Man (MIM) (1), is the primary repository of comprehensive, curated information on genes and genetic phenotypes and the relationships between them.

What is the best example of a Mendelian trait in humans? ›

An example of the mendelian trait in humans is Phenylketonuria: It is an example of a Mendelian trait, this disorder is transmitted from parents to the offspring when both parents are heterozygous (Aa) and both are homozygous (aa) conditions.

Who writes OMIM? ›

OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, under the direction of Dr. Ada Hamosh. The OMIM database is made available to the general public subject to certain restrictions.

Does the government fund gene therapy? ›

Federal law prohibits the use of federal funds for research on human germline gene therapy.

Who owns my genome? ›

Every cell in your body contains your complete genetic code, or genome, which comprises all of your DNA and thus all of your genes. Some portions of the genome are essential for life, so they are shared between all people.

Do humans have Mendelian traits? ›

Mendelian Traits are those traits which follow Mendel's rules of only 2 possible versions of a gene (1 dominant, 1 recessive). There are only a few examples of this in humans. 1. Use the chart below to determine your phenotype (observable characteristic) and possible genotype(s) (a pair or pairs of alleles).

What are 3 examples of Mendelian genetics? ›

Three major patterns of Mendelian inheritance for disease traits are described: autosomal dominant, autosomal recessive, and X-linked (Figure 1.1).

What are the 3 Mendelian genetics? ›

The three laws of inheritance proposed by Mendel include: Law of Dominance. Law of Segregation. Law of Independent Assortment.

Does my genome determine everything about me? ›

Does my genome determine everything about me? Not entirely. Genomes are complicated, and while a small number of your traits are mainly controlled by one gene, most traits are influenced by multiple genes.

Is OMIM a secondary database? ›

OMIM is a secondary database consists of data derived from the analysis of primary data such as sequences, active site residue of proteins and so on. Thus the correct answer is option C.

What is OMIM 167000? ›

Entry - #167000 - OVARIAN CANCER - OMIM.

Which database contains information on mendelian disorders? ›

OMIM is a comprehensive, authoritative database that features catalogs of autosomal dominant, autosomal recessive, x-linked, y-linked, and mitochondrial phenotypes. Includes information on human genes and genetic disorders.

How many genes with known sequence and phenotype are currently present in OMIM? ›

The phenotype–gene relationships are tabulated in OMIM's Morbid Map of the Human Genome (Morbid Map). Currently, over 6200 phenotypes have been attributed to molecular alterations in over 3900 genes (Figure ​

Why is it important for us to study the human genome? ›

It enables us to: search for genes linked to different types of disease. understand inherited disorders and their treatment. trace human migration patterns from the past.

Why is Mendelian inheritance important? ›

The study of Mendelian inheritance is important for students of childhood development because it provides the essential building blocks for understanding more complex patterns of inheritance.

What human traits do not follow Mendelian genetics? ›

The 4 non-Mendelian inheritance examples include multiple allele traits, co-dominance, polygenic traits, sex-linked inheritance, and incomplete dominance.

Is OMIM part of ncbi? ›

Distribution of OMIM and software development are provided by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM).

What is the source material for OMIM? ›

The primary source material for OMIM is the published literature. The scientific staff review sev- eral leading journals that publish major articles in clinical and molecular genetics.

What is phenotype mapping key in OMIM? ›

Phenotype map key 1: the disorder has been placed on the map based on its association with a gene, but the underlying defect is not known. Phenotype map key 2: the disorder has been placed on the map by linkage; no mutation has been found.

Why are humans not used to study Mendelian genetics? ›

However, modern studies have revealed that most traits in humans are controlled by multiple genes as well as environmental influences and do not necessarily exhibit a simple Mendelian pattern of inheritance(see “Mendel's Experimental Results”).

What human character is not Mendelian? ›

An example of a non-Mendelian trait is skin color. Skin color is a polygenic trait and is coded for by three genes, each of which has two alleles.

Are Mendelian traits rare? ›

Discrete traits (as opposed to continuously varying traits such as height) with simple Mendelian inheritance patterns are relatively rare in nature, and many of the clearest examples in humans cause disorders.

Is OMIM curated? ›

Genome databases for vertebrates and other eukaryotic species. A curated repository of published and unpublished data on human mitochondrial DNA variation.

Why are people against gene therapy? ›

Arguments Against Gene Therapy

Three arguments sometimes raised against gene therapy are that it is technically too dangerous, that it discriminates or invites discrimination against persons with disabilities, and that it may be becoming increasingly irrelevant in some cases.

Why is gene therapy controversial? ›

This approach is known as germline gene therapy. The idea of these germline alterations is controversial. While it could spare future generations in a family from having a particular genetic disorder, it might affect the development of a fetus in unexpected ways or have long-term side effects that are not yet known.

Has the FDA approved gene therapy? ›

The FDA has approved the first gene therapy for a treatment called Vijuvek by Krystal Biotech. "I am definitely very excited. It means that I will be in a lot less pain," said Rafi, who was in school when she got word of the FDA's action.

Do I own my own DNA? ›

The interpretation of the courts is that once the DNA/tissue leaves the body, it is no longer the property of the individual. The courts seem to be relying on the informed consent contracts that patients sign prior to any procedure, which establishes clear guidelines for the future ownership of said materials.

Is your DNA yours? ›

Each parent passed down half of their DNA to you. This means that there's half of their DNA that you didn't inherit. Your ethnicity inheritance only shows the parts of their DNA that you inherited.

Who owns my DNA on Ancestry? ›

Access to test results: If you are the person who activates a test for yourself on our website, then you will be the Owner of that test, and you will have control over who has access to the DNA results of that test. As the Owner of a DNA test, you can share your ethnicity results with other users.

Is autism a Mendelian trait? ›

Although the underlying genetic architecture of ASD's is not yet known, the literature demonstrates that it is not, writ large, a monogenic disorder with Mendelian inheritance, but rather a group of complex genetic syndromes with risk deriving from genetic variations in multiple genes.

Is eye color a Mendelian trait? ›

Abstract. Although eye color is usually modeled as a simple, Mendelian trait, further research and observation has indicated that eye color does not follow the classical paths of inheritance. Eye color phenotypes demonstrate both epistasis and incomplete dominance.

Is blood type Mendelian? ›

Blood groups are hereditary. They have a Mendelian pattern, in other words, they are the product of a single gene. The ABO gene has three types of alleles: A, B, and O.

Is Down syndrome a Mendelian disorder? ›

Down syndrome (DS) is a genetic disorder appeared due to the presence of trisomy in chromosome 21 in the G-group of the acrocentric region. DS is also known as non-Mendelian inheritance, due to the lack of Mendel's laws.

What genes are inherited from father only? ›

All men inherit a Y chromosome from their father, which means all traits that are only found on the Y chromosome come from dad, not mom. The Supporting Evidence: Y-linked traits follow a clear paternal lineage.

Is shortness of fingers a Mendelian trait? ›

Yes, Albinism and Brachydactyly (shortness of fingers and toes) are some of the Mendelian traits found in humans.

What is the most common mode of Mendelian inheritance? ›

Autosomal Dominant Inheritance - Most common mode ...

What is the first law of inheritance? ›

The first law of inheritance is the law of dominance. The law states that hybrid offspring will only inherit the dominant characteristics in the phenotype. The alleles that suppress a trait are recessive traits, whereas the alleles that define a trait are known as dominant traits.

What are the six different modes of Mendelian inheritance in humans? ›

Autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, multifactorial, and mitochondrial inheritance are examples. Each mode of inheritance results in a characteristic pattern of affected and unaffected family members.

What is the main idea Mendel's data revealed patterns of inheritance? ›

Answer and Explanation: Mendel's data revealed the inheritance pattern of traits controlled by single genes. Traits which are controlled by a single gene are called Mendelian traits because of this. Albinism is an example of a Mendelian trait in human beings.

What valuable information does gene mapping provide about inheritance? ›

Genetic mapping provides a powerful approach to identify genes and biological processes underlying any trait influenced by inheritance, including human diseases.

What useful information can you find about a gene in NCBI's genome data viewer? ›

The GDV browser displays biological information mapped to a genome, including gene annotation, variation data, BLAST alignments, and experimental study data from the NCBI GEO and dbGaP databases.

What is the best database to be used in research about genetic diseases? ›

The Ensembl genome database project. This one of the largest resources available for all genomic and genetic studies, it provides a centralized resource for geneticists, molecular biologists and other researchers studying the genomes of our own species and other vertebrates and model disease organisms.

What database do I need to find genes? ›

GenBank ® is the NIH genetic sequence database, an annotated collection of all publicly available DNA sequences (Nucleic Acids Research, 2013 Jan;41(D1):D36-42).

Which type of disorders is the most common of the mendelian inherited disorders? ›

Most (67.7%) are autosomal dominant disorders.

What are the three Mendel's law of inheritance in details? ›

Answer: Mendel proposed the law of inheritance of traits from the first generation to the next generation. Law of inheritance is made up of three laws: Law of segregation, law of independent assortment and law of dominance.

What were Mendel's two main conclusions about inheritance of traits? ›

Key Points on Mendel's Laws

The law of segregation states that every individual possesses two alleles and only one allele is passed on to the offspring. The law of independent assortment states that the inheritance of one pair of genes is independent of inheritance of another pair.

What controls the inheritance of traits according to present interpretation of Mendel's experiments? ›

Mendel's work revealed two fundamental truths: that physical traits are determined by factors (now called genes) passed on by both parents, and that these factors are passed in a predictable pattern from one generation to the next (Figure 1).

Which two genes are most likely to be inherited together? ›

The closer two genes were to one another on a chromosome, the greater their chance of being inherited together. In contrast, genes located farther away from one another on the same chromosome were more likely to be separated during recombination.

Why is it important to recognize genetic inheritance? ›

Understanding genetic factors and genetic disorders is important in learning more about promoting health and preventing disease. Some genetic changes have been associated with an increased risk of having a child with a birth defect or developmental disability or developing diseases such as cancer or heart disease.

How did you inherit your genetic information? ›

One copy is inherited from their mother (via the egg) and the other from their father (via the sperm). A sperm and an egg each contain one set of 23 chromosomes. When the sperm fertilises the egg, two copies of each chromosome are present (and therefore two copies of each gene), and so an embryo forms.

What method was used to identify the gene in Human Genome Project? ›

Ultimately, the project used one particular method for DNA sequencing, called Sanger DNA sequencing, but first greatly advanced this basic method through a series of major technical innovations.

What information can your genome reveal? ›

The Human Genome Project was designed to generate a resource that could be used for a broad range of biomedical studies. One such use is to look for the genetic variations that increase risk of specific diseases, such as cancer, or to look for the type of genetic mutations frequently seen in cancerous cells.

What information can be found in the human genome? ›

The genome is the entire set of DNA instructions found in a cell. In humans, the genome consists of 23 pairs of chromosomes located in the cell's nucleus, as well as a small chromosome in the cell's mitochondria. A genome contains all the information needed for an individual to develop and function.


(Joseph Ross)
2. Database of Mendelian traits in humans and animals | OMIM and OMIA
(Genomics Boot Camp)
3. OMIM Presentation
(JSU Bioinformatics)
4. GeneScout Tutorial
5. OMIM part 1
(Kelvin Ex Machina)


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