NDNF neuron derived neurotrophic factor [Homo sapiens (human)] - Gene

Summary

Official Symbol: NDNFprovided by HGNC
Official Full Name: neuron derived neurotrophic factorprovided by HGNC
Primary source: HGNC:HGNC:26256
See related: Ensembl:ENSG00000173376 MIM:616506; AllianceGenome:HGNC:26256
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HH25; NORD; C4orf31
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 extracellular space. Implicated in hypogonadotropic hypogonadism. [provided by Alliance of Genome Resources, Jul 2025]
Expression: Biased expression in lung (RPKM 64.4), placenta (RPKM 31.0) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q27

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (121035613..121072535, complement)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (124339896..124376833, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (121956768..121993690, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Overexpression of NDNF Improves the Cytoprotective Effects of Aged Human Bone Marrow Mesenchymal Stem Cells by Modulating Oxidative Stress and Apoptosis.
Title: Overexpression of NDNF Improves the Cytoprotective Effects of Aged Human Bone Marrow Mesenchymal Stem Cells by Modulating Oxidative Stress and Apoptosis.
Secretome profiling identifies neuron-derived neurotrophic factor as a tumor-suppressive factor in lung cancer.
Title: Secretome profiling identifies neuron-derived neurotrophic factor as a tumor-suppressive factor in lung cancer.
Neuron-Derived Neurotrophic Factor Is Mutated in Congenital Hypogonadotropic Hypogonadism.
Title: Neuron-Derived Neurotrophic Factor Is Mutated in Congenital Hypogonadotropic Hypogonadism.
NDNF acts as an endogenous modulator that promotes endothelial cell function and ischemia-induced revascularization through eNOS-dependent mechanisms
Title: Neuron-derived neurotrophic factor functions as a novel modulator that enhances endothelial cell function and revascularization processes.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Observational study of gene-disease association. (HuGE Navigator)
Title: A systematic gene-based screen of chr4q22-q32 identifies association of a novel susceptibility gene, DKK2, with the quantitative trait of alcohol dependence symptom counts.
direct duplication of chromosome 4q27q31.3 de novo results in partial trisomy of its long arm.
Title: Mosaicism for terminal deletion of 4q.

Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hypogonadotropic hypogonadism 25 with anosmia MedGen: C5394246 OMIM: 618841 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Protein	Gene	Interaction	Pubs
Tat	tat	Microarray analysis indicates HIV-1 Tat-induced upregulation of neuron-derived neurotrophic factor (NDNF; C4orf31) in primary human brain microvascular endothelial cells	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH93971 (e-PCR)
- UniSTS:92610

D4S276 (e-PCR)
- UniSTS:27631

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables glycosaminoglycan binding	IEA Inferred from Electronic Annotation more info
enables glycosaminoglycan binding	ISS Inferred from Sequence or Structural Similarity more info
enables heparin binding	IBA Inferred from Biological aspect of Ancestor more info
enables heparin binding	IEA Inferred from Electronic Annotation more info
enables heparin binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to fibroblast growth factor stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to hypoxia	IDA Inferred from Direct Assay more info	PubMed
involved_in extracellular matrix organization	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within extracellular matrix organization	IEA Inferred from Electronic Annotation more info
involved_in extracellular matrix organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in gonadotrophin-releasing hormone neuronal migration to the hypothalamus	IEA Inferred from Electronic Annotation more info
involved_in gonadotrophin-releasing hormone neuronal migration to the hypothalamus	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of endothelial cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of neuron apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in nervous system development	IEA Inferred from Electronic Annotation more info
involved_in neuron migration	IDA Inferred from Direct Assay more info	PubMed
involved_in nitric oxide mediated signal transduction	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of cell-substrate adhesion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell-substrate adhesion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of neuron projection development	IDA Inferred from Direct Assay more info	PubMed
involved_in response to ischemia	IEA Inferred from Electronic Annotation more info
involved_in vascular wound healing	IEA Inferred from Electronic Annotation more info
involved_in vascular wound healing	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in extracellular matrix	IEA Inferred from Electronic Annotation more info
located_in extracellular matrix	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info
is_active_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: protein NDNF

Names: fibronectin type-III domain-containing protein C4orf31

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_024574.4 → NP_078850.3 protein NDNF precursor

See identical proteins and their annotated locations for NP_078850.3

Status: VALIDATED

Source sequence(s)

AC105254, AK026844, AY358821, BC019351, BX359842, DA807168

Consensus CDS

CCDS3717.2

UniProtKB/Swiss-Prot

A8K0Q0, Q6UWE5, Q8TB73, Q9H5P7

Related

ENSP00000369014.4, ENST00000379692.9

Conserved Domains (1) summary

pfam10179
Location:291 → 383

DUF2369; Uncharacterized conserved protein (DUF2369)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

121035613..121072535 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024454212.2 → XP_024309980.1 protein NDNF isoform X1

UniProtKB/Swiss-Prot

A8K0Q0, Q6UWE5, Q8TB73, Q9H5P7

Related

ENSP00000541834.1, ENST00000871775.1

Conserved Domains (1) summary

pfam10179
Location:291 → 383

DUF2369; Uncharacterized conserved protein (DUF2369)
XM_024454213.2 → XP_024309981.1 protein NDNF isoform X1

UniProtKB/Swiss-Prot

A8K0Q0, Q6UWE5, Q8TB73, Q9H5P7

Related

ENSP00000541835.1, ENST00000871776.1

Conserved Domains (1) summary

pfam10179
Location:291 → 383

DUF2369; Uncharacterized conserved protein (DUF2369)