NRAS gene related symptoms and diseases

All the information presented here about the NRAS gene and its related diseases, symptoms, and test panels has been aggregated from the following public sources: ORPHANET,NCBIGENE,OMIM,HGNC, Mendelian Rare Disease Search Engine.

Table of contents:

Main symptoms and clinical features
Other symptoms and clinical features
Related Diseases
Current trends
Suitable testing panels

Top 5 symptoms and clinical features associated to NRAS gene

Symptoms // Phenotype	% Cases
Neoplasm	Uncommon - Between 30% and 50% cases
Melanocytic nevus	Uncommon - Between 30% and 50% cases
Leukemia	Uncommon - Between 30% and 50% cases
Global developmental delay	Uncommon - Between 30% and 50% cases
Intellectual disability	Uncommon - Between 30% and 50% cases

Other less frequent symptoms and clinical features

Patients with NRAS gene alterations may also develop some of the following symptoms and phenotypes:

Not very common - Between 30% and 50% cases
Carcinoma
Nevus
Rarely - Less than 30% cases
Generalized hypotonia
Melanoma
Hepatomegaly
Broad forehead
Curly hair
Hypertelorism

And 363 more phenotypes, you can get all of them using our tools for rare diseases.

Rare diseases associated to NRAS gene

Here you will find a list of rare diseases related to the NRAS. You can also use our tool to get a more accurate diagnosis based on your current symptoms.

JUVENILE MYELOMONOCYTIC LEUKEMIA

Alternate names

JUVENILE MYELOMONOCYTIC LEUKEMIA Is also known as juvenile chronic myelomonocytic leukemia, jmml, leukemia, juvenile myelomonocytic

Description

Juvenile myelomonocytic leukemia is an aggressive pediatric myelodysplastic syndrome (MDS)/myeloproliferative disorder (MPD) characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny (Loh et al., 2009). JMML constitutes approximately 30% of childhood cases of myelodysplastic syndrome and 2% of leukemia (Hasle et al., 1999). Although JMML is a progressive and often rapidly fatal disease without hematopoietic stem cell transplantation (HSCT), some patients have been shown to have a prolonged and stable clinical course without HSCT (Niemeyer et al., 1997). Chronic myelomonocytic leukemia (CMML) is a similar disorder with later onset. Both JMML and CMML have a high frequency of mutations affecting the RAS signaling pathway and show hypersensitivity to stimulation with GM-CSF, which causes STAT5 (OMIM ) hyperphosphorylation (Loh et al., 2009). Genetic Heterogeneity of Juvenile Myelomonocytic LeukemiaIn up to 60% of cases of JMML, the RAS/MAPK pathway is deregulated due to somatic mutations in the PTPN11 (OMIM ), KRAS (OMIM ), and NRAS (OMIM ) genes. Additionally, both germline and somatic mutations in the CBL gene have been found in patients with JMML, indicating a frequency of 10 to 15% of JMML patients overall (Loh et al., 2009). Somatic disruptions of the GRAF gene (ARHGAP26 ) have also been found in patients with JMML.About 10 to 15% of JMML cases arise in children with neurofibromatosis type I (NF1 ) due to germline mutations in the NF1 gene (OMIM ). In addition, patients with Noonan syndrome (NS1, {163950}; NS3, {609942}) or Noonan syndrome-like disorder (NSLL ) due to germline mutations in the PTPN11, KRAS2, and CBL genes, respectively, also have an increased risk of developing JMML. Genetic Heterogeneity of Chronic Myelomonocytic LeukemiaSomatic mutations in the CBL, ASXL1 (OMIM ), TET2 (OMIM ), and SF3B1 (OMIM ) genes have been found in patients with CMML.

Most common symptoms of JUVENILE MYELOMONOCYTIC LEUKEMIA

Generalized hypotonia
Abnormal facial shape
Anemia
Anteverted nares
Splenomegaly

More info about JUVENILE MYELOMONOCYTIC LEUKEMIA

SOURCES: ORPHANET MESH OMIM

ACUTE PROMYELOCYTIC LEUKEMIA

Alternate names

ACUTE PROMYELOCYTIC LEUKEMIA Is also known as acute myeloid leukemia with t(15;17)(q22;q12);(pml/raralpha) and variants, acute myeloblastic leukemia 3, apml, aml m3, aml with t(15;17)(q22;q12);(pml/raralpha) and variants, leukemia, acute promyelocytic

Description

Acute promyelocytic leukemia (APL) is an aggressive form of acute myeloid leukemia (AML; see this term), characterized by arrest of leukocyte differentiation at the promyelocyte stage, due to a specific chromosomal translocation t(15;17) in myeloid cells. APL manifests with easy bruising, hemorrhagic diathesis and fatigue.

Most common symptoms of ACUTE PROMYELOCYTIC LEUKEMIA

Leukemia
Acute promyelocytic leukemia
Abnormal granulocytopoietic cell morphology

More info about ACUTE PROMYELOCYTIC LEUKEMIA

SOURCES: OMIM ORPHANET MESH

NOONAN SYNDROME

Description

Noonan Syndrome (NS) is characterised by short stature, typical facial dysmorphism and congenital heart defects.

Most common symptoms of NOONAN SYNDROME

Intellectual disability
Short stature
Hearing impairment
Scoliosis
Growth delay

More info about NOONAN SYNDROME

SOURCES: ORPHANET

NOONAN SYNDROME 6; NS6

Most common symptoms of NOONAN SYNDROME 6; NS6

Intellectual disability
Global developmental delay
Short stature
Generalized hypotonia
Hearing impairment

More info about NOONAN SYNDROME 6; NS6

SOURCES: OMIM MESH

RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISEASE

Alternate names

RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISEASE Is also known as alps4, rald, autoimmune lymphoproliferative syndrome, type iv

Description

RAS-associated autoimmune leukoproliferative disease (RALD) is a rare genetic disorder characterized by monocytosis, autoimmune cytopenias, lymphoproliferation, hepatosplenomegaly, and hypergammaglobulinemia.

Most common symptoms of RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISEASE

Anemia
Hepatomegaly
Fever
Splenomegaly
Recurrent infections

More info about RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISEASE

SOURCES: ORPHANET OMIM

LARGE CONGENITAL MELANOCYTIC NEVUS

Alternate names

LARGE CONGENITAL MELANOCYTIC NEVUS Is also known as gphn, pigmented moles, lcmn, giant congenital pigmented nevus, giant congenital melanocytic nevus, congenital pigmented nevus, giant pigmented hairy nevus, gmn

Description

A large, or giant, congenital melanocytic nevus (LCMN or GCMN) is a pigmented skin lesion of more than 20 cm - or 40 cm- respectively, projected adult diameter, composed of melanocytes, and presenting with an elevated risk of malignant transformation.

Most common symptoms of LARGE CONGENITAL MELANOCYTIC NEVUS

Seizures
Hypertelorism
Neoplasm
Failure to thrive
Hydrocephalus

More info about LARGE CONGENITAL MELANOCYTIC NEVUS

SOURCES: ORPHANET OMIM

THYROID CANCER, NONMEDULLARY, 2; NMTC2

Description

Nonmedullary thyroid cancer (NMTC) comprises thyroid cancers of follicular cell origin and accounts for more than 95% of all thyroid cancer cases. The remaining cancers originate from parafollicular cells (medullary thyroid cancer, MTC; {155240}). NMTC is classified into 4 groups: papillary, follicular, Hurthle cell (OMIM ), and anaplastic. Approximately 5% of NMTC is hereditary, occurring as a minor component of a familial cancer syndrome (e.g., familial adenomatous polyposis, {175100}, Carney complex, {160980}) or as a primary feature (familial NMTC or FNMTC). Papillary thyroid cancer (PTC) is the most common histologic subtype of FNMTC, accounting for approximately 85% of cases (summary by Vriens et al., 2009).Follicular thyroid cancer (FTC) accounts for approximately 15% of NMTC and is defined by invasive features that result in infiltration of blood vessels and/or full penetration of the tumor capsule, in the absence of the nuclear alterations that characterize papillary carcinoma. FTC is rarely multifocal and usually does not metastasize to the regional lymph nodes but tends to spread via the bloodstream to the lung and bones. An important histologic variant of FTC is the oncocytic (Hurthle cell, oxyphilic) follicular carcinoma composed of eosinophilic cells replete with mitochondria (summary by Bonora et al., 2010).For a general phenotypic description and a discussion of genetic heterogeneity of NMTC, see NMTC1 (OMIM ).

Most common symptoms of THYROID CANCER, NONMEDULLARY, 2; NMTC2

Neoplasm
Abnormality of metabolism/homeostasis
Carcinoma
Medullary thyroid carcinoma
Follicular thyroid carcinoma

More info about THYROID CANCER, NONMEDULLARY, 2; NMTC2

SOURCES: MESH OMIM

NEUROCUTANEOUS MELANOCYTOSIS

Alternate names

NEUROCUTANEOUS MELANOCYTOSIS Is also known as neurocutaneous melanosis, neuromelanosis, ncm

Description

Neurocutaneous melanocytosis (NCM) is a rare congenital neurological disorder characterized by abnormal aggregations of nevomelanocytes within the central nervous system (leptomeningeal melanocytosis) associated with large or giant congenital melanocytic nevi (CMN; see this term). NCM can be asymptomatic or present as variably severe and progressive neurological impairment, sometimes resulting in death.

Most common symptoms of NEUROCUTANEOUS MELANOCYTOSIS

Intellectual disability
Seizures
Global developmental delay
Generalized hypotonia
Ataxia

More info about NEUROCUTANEOUS MELANOCYTOSIS

SOURCES: MESH OMIM ORPHANET

COLORECTAL CANCER; CRC

Alternate names

COLORECTAL CANCER; CRC Is also known as colon cancer

Description

Colorectal cancer is a heterogeneous disease that is common in both men and women. In addition to lifestyle and environmental risk factors, gene defects can contribute to an inherited predisposition to CRC. CRC is caused by changes in different molecular pathogenic pathways, such as chromosomal instability, CpG island methylator phenotype, and microsatellite instability. Chromosome instability is the most common alteration and is present in almost 85% of all cases (review by Schweiger et al., 2013). Genetic Heterogeneity of Colorectal CancerMutations in a single gene result in a marked predisposition to colorectal cancer in 2 distinct syndromes: familial adenomatous polyposis (FAP ) and hereditary nonpolyposis colorectal cancer (HNPCC; see {120435}). FAP is caused by mutations in the APC gene (OMIM ), whereas HNPCC is caused by mutations in several genes, including MSH2 (OMIM ), MLH1 (OMIM ), PMS1 (OMIM ), PMS2 (OMIM ), MSH6 (OMIM ), TGFBR2 (OMIM ), and MLH3 (OMIM ). Epigenetic silencing of MSH2 results in a form of HNPCC (see HNPCC8, {613244}). Other colorectal cancer syndromes include autosomal recessive adenomatous polyposis (OMIM ), which is caused by mutations in the MUTYH gene (OMIM ), and oligodontia-colorectal cancer syndrome (OMIM ), which is caused by mutations in the AXIN2 gene (OMIM ).The CHEK2 gene (OMIM ) has been implicated in susceptibility to colorectal cancer in Finnish patients. A germline mutation in the PLA2G2A gene (OMIM ) was identified in a patient with colorectal cancer.Germline susceptibility loci for colorectal cancer have also been identified. CRCS1 (OMIM ) is conferred by mutation in the GALNT12 gene (OMIM ) on chromosome 9q22; CRCS2 (OMIM ) maps to chromosome 8q24; CRCS3 (OMIM ) is conferred by variation in the SMAD7 gene (OMIM ) on chromosome 18; CRCS4 (OMIM ) is conferred by variation on 15q that causes increased and ectopic expression of the GREM1 gene (OMIM ); CRCS5 (OMIM ) maps to chromosome 10p14; CRCS6 (OMIM ) maps to chromosome 8q23; CRCS7 (OMIM ) maps to chromosome 11q23; CRCS8 (OMIM ) maps to chromosome 14q22; CRCS9 (OMIM ) maps to 16q22; CRCS10 (OMIM ) is conferred by mutation in the POLD1 gene (OMIM ) on chromosome 19q13; CRCS11 (OMIM ) maps to chromosome 20p12; and CRCS12 (OMIM ) is conferred by mutation in the POLE gene (OMIM ) on chromosome 12q24.Somatic mutations in many different genes, including KRAS (OMIM ), PIK3CA (OMIM ), BRAF (OMIM ), CTNNB1 (OMIM ), FGFR3 (OMIM ), AXIN2 (OMIM ), AKT1 (OMIM ), MCC (OMIM ), MYH11 (OMIM ), PARK2 (OMIM ), and RNF43 (OMIM ), have been identified in colorectal cancer.

Most common symptoms of COLORECTAL CANCER; CRC

Neoplasm
Carcinoma
Oligodontia
Colon cancer
Colitis

More info about COLORECTAL CANCER; CRC

SOURCES: OMIM

LINEAR NEVUS SEBACEUS SYNDROME

Alternate names

LINEAR NEVUS SEBACEUS SYNDROME Is also known as linear sebaceous nevus syndrome, jnp, sfm syndrome, solomon syndrome, epidermal nevus syndrome, formerly, sebaceous nevus syndrome, linear, nevus sebaceus of jadassohn, jadassohn nevus phakomatosis, nevus sebaceus syndrome, schimmelpenning syndrome, organoid nevus

Description

Linear nevus sebaceous syndrome (LNSS) is characterized by the association of a large sebaceous nevus, usually appearing on the face or on the scalp, with a broad spectrum of abnormalities that may affect every organ system, including the central nervous system (brain neoplasms, hemimegalencephaly and lateral ventricle enlargement).

Most common symptoms of LINEAR NEVUS SEBACEUS SYNDROME

Intellectual disability
Seizures
Global developmental delay
Short stature
Growth delay

More info about LINEAR NEVUS SEBACEUS SYNDROME

SOURCES: ORPHANET OMIM

NEVUS, EPIDERMAL

Alternate names

NEVUS, EPIDERMAL Is also known as nevus, keratinocytic, nonepidermolytic

Description

Epidermal nevi are congenital lesions that affect about 1 in 1,000 people. They appear at or shortly after birth as localized epidermal thickening with hyperpigmentation that frequently follow the lines of Blaschko, suggesting that they result from postzygotic somatic mutation in the skin (Paller et al., 1994).A rare subgroup of epidermal nevi is clinically indistinguishable from other epidermal nevi, but displays histopathologic features typical of epidermolytic hyperkeratosis (see EHK, {113800}), and patients with this type of epidermal nevi sometimes have offspring with generalized EHK (Paller et al., 1994).Woolly hair nevus is a rare condition characterized by the development of woolly hair in a restricted area on the scalp, either present at birth or becoming evident later in life when scalp hair begins to grow. Woolly hair nevus can be an isolated finding or can occur in association with additional ectodermal defects; epidermal nevi have been reported in association with woolly hair nevi (summary by Ramot and Zlotogorski, 2015).Nevus sebaceous, a benign congenital skin lesion that preferentially affects the scalp and face, is characterized by hairless, yellow-orange plaques of various size and shape. Histology shows that nevus sebaceous is a hamartoma consisting of epidermal, sebaceous, and apocrine elements. About 24% of nevi develop secondary tumors, some of which may be malignant (summary by Groesser et al., 2012).Also see giant pigmented hairy nevus (OMIM ) and malignant melanoma (OMIM ).

Most common symptoms of NEVUS, EPIDERMAL

Global developmental delay
Hyperkeratosis
Palmoplantar keratoderma
Nevus
Epidermal acanthosis

More info about NEVUS, EPIDERMAL

SOURCES: OMIM

DIFFERENTIATED THYROID CARCINOMA

Alternate names

DIFFERENTIATED THYROID CARCINOMA Is also known as well-differentiated thyroid carcinoma, pact, tpc, nonmedullary thyroid carcinoma, papillary, papillary or follicular thyroid carcinoma, papillary carcinoma of thyroid, familial nonmedullary thyroid cancer, papillary, ptc

Description

Differentiated thyroid carcinoma (DTC), also known as papillary or follicular thyroid carcinoma, is a slow-growing malignancy usually presenting in adults as an asymptomatic thyroid mass.

Most common symptoms of DIFFERENTIATED THYROID CARCINOMA

Neoplasm
Pain
Carcinoma
Hoarse voice
Goiter

More info about DIFFERENTIATED THYROID CARCINOMA

SOURCES: ORPHANET OMIM

Search interest in NRAS

Potential gene panels for NRAS gene

NRAS Sequence Analysis Panel

United States.

By Baylor Miraca Genetics Laboratories

This panel specifically test the NRAS gene.

NRAS gene related symptoms and diseases

Top 5 symptoms and clinical features associated to NRAS gene

Other less frequent symptoms and clinical features

Not very common - Between 30% and 50% cases

Rarely - Less than 30% cases

Rare diseases associated to NRAS gene

JUVENILE MYELOMONOCYTIC LEUKEMIA

Alternate names

Description

Most common symptoms of JUVENILE MYELOMONOCYTIC LEUKEMIA

ACUTE PROMYELOCYTIC LEUKEMIA

Alternate names

Description

Most common symptoms of ACUTE PROMYELOCYTIC LEUKEMIA

NOONAN SYNDROME

Description

Most common symptoms of NOONAN SYNDROME

NOONAN SYNDROME 6; NS6

Most common symptoms of NOONAN SYNDROME 6; NS6

RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISEASE

Alternate names

Description

Most common symptoms of RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISEASE

LARGE CONGENITAL MELANOCYTIC NEVUS

Alternate names

Description

Most common symptoms of LARGE CONGENITAL MELANOCYTIC NEVUS

THYROID CANCER, NONMEDULLARY, 2; NMTC2

Description

Most common symptoms of THYROID CANCER, NONMEDULLARY, 2; NMTC2

NEUROCUTANEOUS MELANOCYTOSIS

Alternate names

Description

Most common symptoms of NEUROCUTANEOUS MELANOCYTOSIS

COLORECTAL CANCER; CRC

Alternate names

Description

Most common symptoms of COLORECTAL CANCER; CRC

LINEAR NEVUS SEBACEUS SYNDROME

Alternate names

Description

Most common symptoms of LINEAR NEVUS SEBACEUS SYNDROME

NEVUS, EPIDERMAL

Alternate names

Description

Most common symptoms of NEVUS, EPIDERMAL

DIFFERENTIATED THYROID CARCINOMA

Alternate names

Description

Most common symptoms of DIFFERENTIATED THYROID CARCINOMA

Search interest in NRAS

Potential gene panels for NRAS gene

NRAS Sequence Analysis Panel

NRAS Sequence Analysis (Familial Mutation/Variant Analysis) Panel

NRAS Sequence Analysis (Prenatal Diagnosis) Panel

PreSeek Non-invasive Prenatal Gene Sequencing Screen Panel

Non-immune Hydrops Panel Panel

NGS RASopathy Panel Panel

Comprehensive Cardiac Panel Panel

Noonan syndrome 6 (NRAS) Panel

Noonan Syndrome 11-Gene Sequencing Panel Panel

Noonan Spectrum Disorders Panel Panel

Rasopathy NextGen Panel Panel

Juvenile Myelomonocytic Leukemia Panel

Cardiomyopathy Panel Panel

Noonan Syndrome Panel Panel

NRAS Mutation Analysis Panel

MyeloidDx by NGS Panel

MyeloidDx by NGS Panel

NRAS-Related Noonan syndrome Panel

Noonan Spectrum Panel Panel

Autoimmune Lymphoproliferative Syndrome Panel by next-generation sequencing (NGS) Panel

Autoimmune Lymphoproliferative Syndrome Deletion/Duplication Panel Panel

NRAS Sequencing Panel

NRAS Deletion/duplication analysis Panel

Prenatal Noonan Spectrum Panel Panel

Noonan Syndrome Sequencing Panel Panel

Noonan Syndrome Deletion/Duplication Panel Panel

Expanded RASopathy Panel (14 Genes) Panel

Noonan Spectrum Disorders Panel, Sequencing Panel