NDRG1

N-myc downstream regulated 1, the group of NDRG family

Basic information

Region (hg38): 8:133237175-133302022

Previous symbols: [ "CAP43" ]

Links

ENSG00000104419 ∙ NCBI:10397 ∙ OMIM:605262 ∙ HGNC:7679 ∙ Uniprot:Q92597 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease type 4D (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4D (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4D (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, type 4D	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Musculoskeletal; Neurologic	10831399; 22978647; 23163601; 24136616

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDRG1 gene.

• Charcot-Marie-Tooth disease type 4 (14 variants)
• Charcot-Marie-Tooth disease type 4D (5 variants)
• not provided (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDRG1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				181	1	182
missense			196			196
nonsense	9	1	1			11
start loss			1	1		2
frameshift	5	1	2			8
inframe indel			10	1		11
splice donor/acceptor (+/-2bp)	3	16		1		20
splice region			16	49	4	69
non coding	1		34	159	67	261
Total	18	18	244	343	68

Highest pathogenic variant AF is 0.00000657

Variants in NDRG1

This is a list of pathogenic ClinVar variants found in the NDRG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-133237256-A-C		Charcot-Marie-Tooth disease type 4D	Likely benign (Apr 27, 2017)
8-133237257-G-A		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 12, 2018)
8-133237405-C-T		Charcot-Marie-Tooth disease type 4D	Likely benign (Jan 12, 2018)
8-133237517-G-T		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Apr 20, 2018)
8-133237538-C-T		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 13, 2018)
8-133237539-G-A		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 12, 2018)
8-133237578-C-G		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 13, 2018)
8-133237579-G-A		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 12, 2018)
8-133237582-G-A		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 13, 2018)
8-133237584-A-G		Charcot-Marie-Tooth disease type 4D	Benign (Jan 12, 2018)
8-133237683-C-A		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 12, 2018)
8-133237699-C-G		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 12, 2018)
8-133237743-C-T		Charcot-Marie-Tooth disease type 4D	Benign (Jan 13, 2018)
8-133237922-A-G		Charcot-Marie-Tooth disease type 4D	Benign (Jan 13, 2018)
8-133238012-T-A		Charcot-Marie-Tooth disease type 4D	Benign (Jan 12, 2018)
8-133238024-C-T		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 13, 2018)
8-133238044-A-T		Charcot-Marie-Tooth disease type 4D	Benign (Jan 13, 2018)
8-133238087-G-A		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 13, 2018)
8-133238167-G-A		Charcot-Marie-Tooth disease type 4D	Benign (Jan 13, 2018)
8-133238187-C-T		Charcot-Marie-Tooth disease type 4D	Benign (Jan 13, 2018)
8-133238201-G-A		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 13, 2018)
8-133238225-A-G		Charcot-Marie-Tooth disease type 4D	Likely benign (Apr 27, 2017)
8-133238260-A-C		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 12, 2018)
8-133238353-C-T		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 13, 2018)
8-133238475-C-T		Charcot-Marie-Tooth disease type 4D	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDRG1	protein_coding	protein_coding	ENST00000414097	15	64852

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0113	0.988	125718	1	29	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.651	226	255	0.885	0.0000168	2579
Missense in Polyphen		88	109.67	0.80238		1081
Synonymous	-0.664	110	101	1.08	0.00000744	763
Loss of Function	3.14	8	24.9	0.322	0.00000127	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000109	0.000109
Finnish	0.000787	0.000647
European (Non-Finnish)	0.0000967	0.0000791
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53- mediated caspase activation and apoptosis. Has a role in cell trafficking, notably of the Schwann cell, and is necessary for the maintenance and development of the peripheral nerve myelin sheath. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy. {ECO:0000269|PubMed:15247272, ECO:0000269|PubMed:15377670, ECO:0000269|PubMed:17786215, ECO:0000269|PubMed:9766676}.
• Disease: DISEASE: Charcot-Marie-Tooth disease 4D (CMT4D) [MIM:601455]: A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot- Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. {ECO:0000269|PubMed:10831399}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Androgen Receptor Network in Prostate Cancer;TP53 Regulates Transcription of Cell Death Genes;VEGFA-VEGFR2 Signaling Pathway;Gene expression (Transcription);Generic Transcription Pathway;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain;Transcriptional Regulation by TP53;Direct p53 effectors;Validated targets of C-MYC transcriptional repression;HIF-1-alpha transcription factor network (Consensus)

Recessive Scores

• pRec: 0.381

Intolerance Scores

• loftool: 0.732
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.71

Haploinsufficiency Scores

• pHI: 0.366
• hipred: Y
• hipred_score: 0.554
• ghis: 0.508

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ndrg1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); muscle phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: ndrg1b
• Affected structure: thymus
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: signal transduction;negative regulation of cell population proliferation;response to metal ion;DNA damage response, signal transduction by p53 class mediator;peripheral nervous system myelin maintenance;regulation of apoptotic process;mast cell activation;cellular response to hypoxia;postsynapse organization
• Cellular component: nucleus;cytoplasm;centrosome;cytosol;microtubule;plasma membrane;cell-cell adherens junction;microtubule cytoskeleton;myelin sheath;perinuclear region of cytoplasm;recycling endosome membrane;extracellular exosome;glutamatergic synapse
• Molecular function: protein binding;microtubule binding;Rab GTPase binding;gamma-tubulin binding;cadherin binding