FEZF1

Chr 7AR

FEZ family zinc finger 1

Also known as: FEZ, HH22, ZNF312B

NCBI Gene: 389549ENSG00000128610UniProt: A0PJY2

This gene encodes a transcriptional repressor that belongs to the zinc finger double domain protein family. The encoded protein is thought to play a role in the embryonic migration of gonadotropin-releasing hormone neurons into the brain. Mutations in this gene are associated with hypogonadotropic hypogonadism-22 with anosmia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

Primary Disease Associations & Inheritance

Hypogonadotropic hypogonadism 22, with or without anosmiaMIM #616030
AR
161
ClinVar variants
24
Pathogenic / LP
0.95
pLI score· haploinsufficient
0
Active trials
Clinical Summary— FEZF1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 75 VUS of 161 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.34LOEUF
pLI 0.950
Z-score 3.20
OE 0.07 (0.03–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.29Z-score
OE missense 0.78 (0.69–0.87)
210 obs / 269.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.69–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 1 / 13.9Missense obs/exp: 210 / 269.7Syn Z: 0.16

ClinVar Variant Classifications

161 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic1
VUS75
Likely Benign41
Benign21
23
Pathogenic
1
Likely Pathogenic
75
VUS
41
Likely Benign
21
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
21
0
23
Likely Pathogenic
0
0
1
0
1
VUS
1
71
3
0
75
Likely Benign
0
5
14
22
41
Benign
0
0
20
1
21
Total2775923161

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FEZF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

FEZF1-related hypogonadotropic hypogonadism with or without anosmia

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hypogonadotropic hypogonadism 22, with or without anosmia

MIM #616030

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — FEZF1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Long noncoding RNA FEZF1-AS1 in human cancers.
Zhou Y et al.·Clin Chim Acta
2019Review
Genetics of Hypogonadotropic Hypogonadism.
Topaloglu AK et al.·Endocr Dev
2016Review
[Progress in Role of FEZF1-AS1 in Non-small Cell Lung Cancer].
Chen J et al.·Zhongguo Fei Ai Za Zhi
2020Review
LncRNA FEZF1-AS1 accelerates multiple myeloma progression by regulating IGF2BP1/BZW2 signaling.
Long X et al.·Hematol Oncol
2023
Prognostic value of lncRNA FEZF1 antisense RNA 1 over-expression in oncologic outcomes of patients with solid tumors.
Zhang Y et al.·Medicine (Baltimore)
2019Meta-analysis
FEZF1-AS1/miR-107/ZNF312B axis facilitates progression and Warburg effect in pancreatic ductal adenocarcinoma.
Ye H et al.·Cell Death Dis
2018
Mechanism of lncRNA FEZF1-AS1 in promoting the occurrence and development of oral squamous cell carcinoma through targeting miR-196a.
Xu L et al.·Eur Rev Med Pharmacol Sci
2019Functional
LncRNA FEZF1-AS1 promotes non-small lung cancer cell migration and invasion through the up-regulation of NOTCH1 by serving as a sponge of miR-34a.
Huang S et al.·BMC Pulm Med
2020
LincRNAFEZF1-AS1 represses p21 expression to promote gastric cancer proliferation through LSD1-Mediated H3K4me2 demethylation.
Liu YW et al.·Mol Cancer
2017
Long non‑coding RNA FEZF1‑AS1 facilitates non‑small cell lung cancer progression via the ITGA11/miR‑516b‑5p axis.
Song H et al.·Int J Oncol
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools