GZF1

Chr 20AR

GDNF inducible zinc finger protein 1

Also known as: JLSM, ZBTB23, ZNF336

GZF1 encodes a transcriptional repressor that binds specific DNA sequences to negatively regulate RNA polymerase II-mediated transcription, including regulation of VSX2/HOX10 expression. Biallelic mutations cause an autosomal recessive disorder characterized by joint laxity, short stature, and myopia. The gene shows tolerance to loss-of-function variants in the general population (pLI 0.002, LOEUF 0.646).

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Joint laxity, short stature, and myopiaMIM #617662
AR
0
Active trials
1
Pubs (1 yr)
36
P/LP submissions
0%
P/LP missense
0.65
LOEUF
LOF
Mechanism· G2P
Clinical SummaryGZF1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 154 VUS of 318 total submissions
📖
GeneReview available — GZF1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.65LOEUF
pLI 0.002
Z-score 2.88
OE 0.37 (0.220.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.95Z-score
OE missense 0.74 (0.670.81)
323 obs / 437.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.220.65)
00.351.4
Missense OE0.74 (0.670.81)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 9 / 24.3Missense obs/exp: 323 / 437.6Syn Z: 0.43
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongGZF1-related joint laxity, short stature, and myopiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7034th %ile
GOF
0.5465th %ile
LOF
0.3940th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

318 submitted variants in ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic5
VUS154
Likely Benign101
Benign23
Conflicting2
28
Pathogenic
5
Likely Pathogenic
154
VUS
101
Likely Benign
23
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
20
0
28
Likely Pathogenic
1
0
4
0
5
VUS
6
136
12
0
154
Likely Benign
0
11
18
72
101
Benign
0
5
15
3
23
Conflicting
2
Total151526975313

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

View in ClinVar →

Protein Context — Lollipop Plot

GZF1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found