NDNF

neuron derived neurotrophic factor

Basic information

Region (hg38): 4:121035612-121073021

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.

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.

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					5	5
missense			19	2		21
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	1	19	2	5

Variants in NDNF

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

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

Position	Type	Phenotype	Significance	ClinVar
4-121036278-T-C		not specified	Uncertain significance (Dec 17, 2023)
4-121036286-A-G		not specified	Uncertain significance (Feb 28, 2023)
4-121036404-G-A		Hypogonadotropic hypogonadism 25 with anosmia	Benign (Sep 05, 2021)
4-121036509-T-C		not specified	Uncertain significance (Jun 11, 2024)
4-121036565-C-T		Hypogonadotropic hypogonadism 25 with anosmia	Pathogenic (Apr 07, 2020)
4-121036579-T-C		Hypogonadotropic hypogonadism 25 with anosmia	Benign (Sep 05, 2021)
4-121036716-C-T		not specified	Likely benign (Oct 18, 2021)
4-121036734-G-A		not specified	Uncertain significance (May 01, 2022)
4-121036749-G-C		not specified	Uncertain significance (Aug 19, 2023)
4-121036811-AT-A		Hypogonadotropic hypogonadism 25 with anosmia	Likely pathogenic (Aug 13, 2021)
4-121036936-T-G		Hypogonadotropic hypogonadism 25 with anosmia	Benign (Sep 05, 2021)
4-121036950-T-C		not specified	Uncertain significance (Jan 09, 2024)
4-121036995-C-T		not specified	Uncertain significance (Nov 01, 2022)
4-121037016-T-C		not specified	Likely benign (Apr 23, 2024)
4-121037032-A-G		Hypogonadotropic hypogonadism 25 with anosmia	Benign (Sep 05, 2021)
4-121037048-G-A		not specified	Uncertain significance (Apr 19, 2023)
4-121037070-C-T		not specified	Uncertain significance (Jun 09, 2022)
4-121037075-A-G		not specified	Uncertain significance (Mar 07, 2024)
4-121037092-T-C		not specified	Uncertain significance (Mar 15, 2024)
4-121037129-T-A		not specified	Uncertain significance (May 28, 2024)
4-121037146-T-G		Hypogonadotropic hypogonadism 25 with anosmia	Uncertain significance (Jul 16, 2023)
4-121037198-G-A		not specified	Uncertain significance (Oct 27, 2021)
4-121037201-A-G		not specified	Uncertain significance (Dec 02, 2022)
4-121037318-T-C		not specified	Uncertain significance (Jun 03, 2022)
4-121037321-T-A		not specified	Uncertain significance (Nov 27, 2023)

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

• 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

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