NTF4

neurotrophin 4, the group of Neurotrophins

Basic information

Region (hg38): 19:49061065-49065076

Previous symbols: [ "NTF5" ]

Links

ENSG00000225950 ∙ NCBI:4909 ∙ OMIM:162662 ∙ HGNC:8024 ∙ Uniprot:P34130 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glaucoma 1, open angle, O (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glaucoma 1, open angle, O	AD	Ophthalmologic; Pharmacogenomic	Open-angle glaucoma is typically asymptomatic until late stages, when irreversible nerve damage has already taken place; Agents that may contribute to glaucoma should be avoided	Ophthalmologic	19765683; 20215012

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NTF4 gene.

• Inborn genetic diseases (10 variants)
• not provided (4 variants)
• Glaucoma 1, open angle, O (1 variants)
• Intellectual disability, X-linked 99 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NTF4 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						0
missense		1	9	1	1	12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				2	1	3
Total	0	1	9	3	2

Variants in NTF4

This is a list of pathogenic ClinVar variants found in the NTF4 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-49061255-T-C			Benign (Nov 08, 2018)
19-49061372-C-T		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
19-49061373-G-A		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
19-49061381-C-T		Glaucoma 1, open angle, O	Pathogenic (Oct 01, 2009)
19-49061382-G-A		Glaucoma 1, open angle, O	Conflicting classifications of pathogenicity (Jan 06, 2020)
19-49061477-T-C		Inborn genetic diseases	Likely pathogenic (Jul 08, 2014)
19-49061484-C-T		Inborn genetic diseases	Uncertain significance (Jul 13, 2022)
19-49061520-C-T		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
19-49061545-C-T		NTF4-related disorder	Likely benign (Jul 01, 2019)
19-49061601-G-A		Inborn genetic diseases	Uncertain significance (Sep 26, 2022)
19-49061619-C-A		Inborn genetic diseases	Uncertain significance (Jun 21, 2023)
19-49061675-C-T		Inborn genetic diseases	Uncertain significance (Apr 06, 2023)
19-49061676-G-A		Inborn genetic diseases	Uncertain significance (Aug 23, 2021)
19-49061735-G-A		Glaucoma 1, open angle, O • Intellectual disability, X-linked 99	Likely benign (-)
19-49061795-C-T		NTF4-related disorder	Benign (Apr 26, 2019)
19-49061838-C-T		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
19-49061841-G-A		Inborn genetic diseases	Uncertain significance (Dec 05, 2022)
19-49062073-G-A			Likely benign (May 22, 2021)
19-49062161-G-A			Likely benign (May 10, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NTF4	protein_coding	protein_coding	ENST00000301411	1	9284

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0120	0.660	125561	0	4	125565	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.194	133	139	0.954	0.00000964	1287
Missense in Polyphen		47	48.695	0.96519		458
Synonymous	0.163	54	55.5	0.972	0.00000340	499
Loss of Function	0.492	3	4.07	0.737	2.23e-7	45

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000922	0.00000881
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Target-derived survival factor for peripheral sensory sympathetic neurons.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Differentiation Pathway;MAPK Signaling Pathway;PI3K-Akt Signaling Pathway;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;NTF4 activates NTRK2 (TRKB) signaling;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;Activated NTRK2 signals through RAS;Activated NTRK2 signals through PLCG1;Signaling by NTRK2 (TRKB);Signaling by NTRKs;SHP2 signaling;Activated NTRK2 signals through FRS2 and FRS3;GPCR signaling-G alpha i;Signaling by Receptor Tyrosine Kinases;Neurotrophic factor-mediated Trk receptor signaling;p75(NTR)-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.242

Haploinsufficiency Scores

• pHI: 0.296
• hipred: N
• hipred_score: 0.285
• ghis: 0.489

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ntf5
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; 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); 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); limbs/digits/tail phenotype

Gene ontology

• Biological process: transmembrane receptor protein tyrosine kinase signaling pathway;activation of phospholipase C activity;ganglion mother cell fate determination;peripheral nervous system development;memory;long-term memory;sensory organ boundary specification;adult locomotory behavior;epidermis development;regulation of signaling receptor activity;nerve development;nerve growth factor signaling pathway;mechanoreceptor differentiation;negative regulation of neuron apoptotic process;regulation of neuron differentiation;neurotrophin TRK receptor signaling pathway;neuron projection morphogenesis;modulation of chemical synaptic transmission;innervation;taste bud development
• Cellular component: extracellular region;extracellular space;synaptic vesicle;axon;dendrite;cytoplasmic vesicle
• Molecular function: protein binding;growth factor activity