NDNF
protein-codingneuron derived neurotrophic factor
Gene summary
Predicted to enable heparin binding activity. Involved in several processes, including cellular response to hypoxia; negative regulation of apoptotic process; and nitric oxide mediated signal transduction. Located in extracellular region. Is active in obsolete extracellular space. Implicated in hypogonadotropic hypogonadism. [provided by Alliance of Genome Resources, Jun 2026]
- C4orf31
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~37.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0030010
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0030010
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0030010
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0018800
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Endocrine; Genitourinary; Neurologic
Intervention: Endocrine
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NDNF variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024574.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 1 | 4 | |||
| missense | 58 | 4 | 62 | |||
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 1 | 2 | 1 | 4 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 3 | 3 | 62 | 5 | 0 | 73 |
Highest pathogenic variant AF is 0.0000034203983
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_078850.3 | 3 | MANE Select | |
| Ensembl | ENSP00000369014.4 | 3 | MANE Select | |
| Ensembl | ENSP00000426723.1 | 3 | Standard | |
| Ensembl | ENSP00000423352.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ndnf | Danio rerio | Structure: neurocranium Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- angiogenesis
- neuron migration
- response to ischemia
- nitric oxide mediated signal transduction
- positive regulation of cell-substrate adhesion
Molecular Function
- glycosaminoglycan binding
- heparin binding
Cellular Component
- extracellular region
- extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379692
- Coding exons
- 3
- Length
- 37409
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125734
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.483 | 275 | 298 | 0.921 | 0.0000153 | 3731 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |