CNTF

protein-coding

ciliary neurotrophic factor, the group of Interleukin 6 type cytokine family

Gene summary

The protein encoded by this gene is a polypeptide hormone whose actions appear to be restricted to the nervous system where it promotes neurotransmitter synthesis and neurite outgrowth in certain neuronal populations. The protein is a potent survival factor for neurons and oligodendrocytes and may be relevant in reducing tissue destruction during inflammatory attacks. A mutation in this gene, which results in aberrant splicing, leads to ciliary neurotrophic factor deficiency, but this phenotype is not causally related to neurologic disease. A read-through transcript variant composed of the upstream ZFP91 gene and CNTF sequence has been identified, but it is thought to be non-coding. Read-through transcription of ZFP91 and CNTF has also been observed in mouse. [provided by RefSeq, Oct 2010]

MANE transcript

NM_000614.4

Inheritance

—

ClinVar variants

U:42B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1

Max pathogenic AF

—

Genomic locus

chr11:58,622,665-58,625,733

External References & Databases

Ensembl (ENSG00000242689)

Transcript & Mutation Effects

hg38 • Region Span ~3.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CNTF variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 44

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000614.4. 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						0
missense			42 clinvar	3 clinvar	1 clinvar	46
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	42	3	1	46

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000614.4	RefSeq	NP_000605.1	2	MANE Select
ENST00000361987.6	Ensembl	ENSP00000355370.4	2	MANE Select
ENST00001143598.1	Ensembl	ENSP00000809060.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Jak-STAT signaling pathway - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)
JAK-STAT-Core
Differentiation Pathway
Signaling by Interleukins

Biological Process

signal transduction
positive regulation of cell population proliferation
regulation of signaling receptor activity
positive regulation of gene expression
cytokine-mediated signaling pathway

Molecular Function

cytokine activity
ciliary neurotrophic factor receptor binding
interleukin-6 receptor binding
protein binding
growth factor activity

Cellular Component

extracellular region
extracellular space
cytoplasm
axon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361987
Coding exons: 2
Length: 3053
Individuals with no LoFs: 125684
Homozygous LoFs: 1
Heterozygous LoFs: 28
Defined: 125713
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.653	139	119	1.17	0.00000694	1312
Missense (PolyPhen)		50	43.452	1.1507		524
Synonymous	-0.168	45	43.6	1.03	0.00000230	401
Loss of Function	0.00877	7	7.03	0.996	3.84e-7	73

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00043	0.00039	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: CNTF is a survival factor for various neuronal cell types. Seems to prevent the degeneration of motor axons after axotomy.;

Recessive Scores

pRec: 0.281

Intolerance Scores

LoFtool: 0.791
RVIS EVS: 0.42
RVIS percentile EVS: 76.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.914

Gene Damage Prediction

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