NTF3

Chr 12

neurotrophin 3

Also known as: HDNF, NGF-2, NGF2, NT-3, NT3

NCBI Gene: 4908 ENSG00000185652 UniProt: P20783

This gene encodes neurotrophin-3, a growth factor that promotes survival of sensory neurons including proprioceptive and visceral neurons and controls neuronal survival and differentiation during development. Mutations cause autosomal dominant congenital insensitivity to pain with anhidrosis and peripheral neuropathy affecting sensory and autonomic function. The gene is highly constrained against loss-of-function variants (pLI 0.93, LOEUF 0.37), indicating intolerance to protein-truncating mutations.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the neurotrophin family, that controls survival and differentiation of mammalian neurons. This protein is closely related to both nerve growth factor and brain-derived neurotrophic factor. It may be involved in the maintenance of the adult nervous system, and may affect development of neurons in the embryo when it is expressed in human placenta. NTF3-deficient mice generated by gene targeting display severe movement defects of the limbs. The mature peptide of this protein is identical in all mammals examined including human, pig, rat and mouse. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.37

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.37LOEUF

pLI 0.932

Z-score 3.08

OE 0.08 (0.03–0.37)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.74Z-score

OE missense 0.63 (0.54–0.74)

108 obs / 172.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.37)

0≤0.351.4

Missense OE?0.63 (0.54–0.74)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 1 / 13.0Missense obs/exp: 108 / 172.1Syn Z: 0.42

Background carrier burden — how many people carry a rare variant somewhere in NTF3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

302 rare PASS variants

Rare truncating (LoF)

1 in 14,000

19 rare PASS variants

Rare synonymous (reference)

1 in 160

159 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NTF3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 500	1 in 13,000
South Asian	~43k	1 in 380	1 in 4,700
Remaining (unassigned)	~30k	1 in 170	none seen
European (Finnish)	~27k	1 in 1,900	≈ 1 in 8,000
Admixed American	~22k	1 in 300	≈ 1 in 22,000
African / African American	~21k	1 in 350	≈ 1 in 17,000
East Asian	~20k	1 in 430	≈ 1 in 19,000
Ashkenazi Jewish	~13k	≈ 1 in 6,500	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 170	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓