GZF1

GDNF inducible zinc finger protein 1, the group of Zinc fingers C2H2-type|BTB domain containing

Basic information

Region (hg38): 20:23362182-23373062

Previous symbols: [ "ZNF336" ]

Links

ENSG00000125812 ∙ NCBI:64412 ∙ OMIM:613842 ∙ HGNC:15808 ∙ Uniprot:Q9H116 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Larsen syndrome (Strong), mode of inheritance: AR
• joint laxity, short stature, and myopia (Strong), mode of inheritance: AR
• joint laxity, short stature, and myopia (Strong), mode of inheritance: AR
• joint laxity, short stature, and myopia (Supportive), mode of inheritance: AR
• joint laxity, short stature, and myopia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joint laxity, short stature, and myopia	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Musculoskeletal; Ophthalmologic	28475863
Individuals are at risk for ophthalmologic features such as retinal detachment

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GZF1 gene.

• not_provided (184 variants)
• Inborn_genetic_diseases (73 variants)
• Joint_laxity,_short_stature,_and_myopia (13 variants)
• GZF1-related_disorder (9 variants)
• Larsen_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GZF1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022482.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				68	1	69
missense			126	6	3	135
nonsense	2		1			3
start loss						0
frameshift	7	2	5			14
splice donor/acceptor (+/-2bp)						0
Total	9	2	132	74	4

Highest pathogenic variant AF is 0.00000309767

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GZF1	protein_coding	protein_coding	ENST00000338121	5	10914

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00178	0.997	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.95	323	438	0.738	0.0000271	4720
Missense in Polyphen		91	175.43	0.51874		1862
Synonymous	0.434	175	182	0.959	0.0000126	1337
Loss of Function	2.88	9	24.3	0.370	0.00000120	316

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000241	0.000241
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000170	0.000167
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional repressor that binds the GZF1 responsive element (GRE) (consensus: 5'-TGCGCN[TG][CA]TATA-3'). May be regulating VSX2/HOX10 expression. {ECO:0000269|PubMed:14522971, ECO:0000269|PubMed:16049025}.
• Disease: DISEASE: Joint laxity, short stature, and myopia (JLSM) [MIM:617662]: An autosomal recessive disease characterized by generalized joint laxity, joint dislocation, pectus carinatum, short stature, and severe myopia with retinal detachment. {ECO:0000269|PubMed:28475863}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.527
• rvis_EVS: -0.57
• rvis_percentile_EVS: 18.9

Haploinsufficiency Scores

• pHI: 0.147
• hipred: N
• hipred_score: 0.419
• ghis: 0.441

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.494

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gzf1

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;branching involved in ureteric bud morphogenesis;negative regulation of transcription, DNA-templated
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;sequence-specific DNA binding;metal ion binding