NDNF

neuron derived neurotrophic factor

Basic information

Region (hg38): 4:121035613-121073021

Previous symbols: [ "C4orf31" ]

Links

ENSG00000173376

∙ NCBI:79625 ∙ OMIM:616506 ∙ HGNC:26256 ∙ Uniprot:Q8TB73 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Kallmann syndrome (Supportive), mode of inheritance: AD
hypogonadotropic hypogonadism 25 with anosmia (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 25 with anosmia	AD	Endocrine	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	Endocrine; Genitourinary; Neurologic	20301509; 31883645

ClinVar

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

not_specified (51 variants)
Hypogonadotropic_hypogonadism_25_with_anosmia (8 variants)
not_provided (1 variants)
NDNF-related_condition (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDNF gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024574.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			50 clinvar	4 clinvar		54
nonsense	2 clinvar	1 clinvar				3
start loss						0
frameshift	1 clinvar	1 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	3	2	51	4	0

Highest pathogenic variant AF is 0.0000034203983

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDNF	protein_coding	protein_coding	ENST00000379692	3	37409

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.380	0.619	125725	0	9	125734	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.483	275	298	0.921	0.0000153	3731
Missense in Polyphen		60	78.36	0.76569		957
Synonymous	-0.104	119	118	1.01	0.00000630	1103
Loss of Function	3.04	4	17.9	0.224	8.22e-7	250

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000126	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000444	0.0000440
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Promotes matrix assembly and cell adhesiveness (By similarity). Promotes neuron migration, growth and survival as well as neurite outgrowth (PubMed:20969804). Promotes endothelial cell survival, vessel formation and plays an important role in the process of revascularization through NOS3-dependent mechanisms (PubMed:24706764). {ECO:0000250|UniProtKB:Q8C119, ECO:0000269|PubMed:20969804, ECO:0000269|PubMed:24706764}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

loftool
rvis_EVS: -0.67
rvis_percentile_EVS: 15.86

Haploinsufficiency Scores

pHI: 0.615
hipred: Y
hipred_score: 0.544
ghis: 0.522

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ndnf
Phenotype

Zebrafish Information Network

Gene name: ndnf
Affected structure: neurocranium
Phenotype tag: abnormal
Phenotype quality: morphology

Gene ontology

Biological process: angiogenesis;neuron migration;response to ischemia;nitric oxide mediated signal transduction;positive regulation of cell-substrate adhesion;positive regulation of neuron projection development;peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan;extracellular matrix organization;negative regulation of neuron apoptotic process;vascular wound healing;cellular response to hypoxia;negative regulation of endothelial cell apoptotic process
Cellular component: extracellular region;extracellular matrix
Molecular function: glycosaminoglycan binding;heparin binding