ZNF335

zinc finger protein 335, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 20:45948659-45972203

Links

ENSG00000198026 ∙ NCBI:63925 ∙ OMIM:610827 ∙ HGNC:15807 ∙ Uniprot:Q9H4Z2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephalic primordial dwarfism due to ZNF335 deficiency (Strong), mode of inheritance: AR
• microcephalic primordial dwarfism due to ZNF335 deficiency (Supportive), mode of inheritance: AR
• microcephalic primordial dwarfism due to ZNF335 deficiency (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly 10, primary, autosomal recessive	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	Neurologic	23178126

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZNF335 gene.

• not provided (423 variants)
• Inborn genetic diseases (72 variants)
• Microcephalic primordial dwarfism due to ZNF335 deficiency (57 variants)
• not specified (55 variants)
• Autosomal recessive primary microcephaly (1 variants)
• ZNF335-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZNF335 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	86	10	99
missense	1	2	214	17	5	239
nonsense	3		1	1		5
start loss						0
frameshift	3	3	2			8
inframe indel			5			5
splice donor/acceptor (+/-2bp)		3				3
splice region			8	20	7	35
non coding			6	46	35	87
Total	7	8	231	150	50

Highest pathogenic variant AF is 0.0000197

Variants in ZNF335

This is a list of pathogenic ClinVar variants found in the ZNF335 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-45948675-C-G			Likely benign (Dec 05, 2018)
20-45948675-C-T			Benign (Jul 27, 2018)
20-45948956-G-A			Likely benign (Nov 27, 2023)
20-45948962-G-A		ZNF335-related disorder	Likely benign (Feb 02, 2022)
20-45948976-C-T		not specified	Uncertain significance (Oct 04, 2022)
20-45948979-C-T		Inborn genetic diseases	Uncertain significance (Feb 01, 2023)
20-45948981-T-C			Uncertain significance (Sep 27, 2022)
20-45948984-T-C		Microcephalic primordial dwarfism due to ZNF335 deficiency	Uncertain significance (Mar 02, 2022)
20-45948998-C-G			Uncertain significance (Mar 20, 2023)
20-45949009-G-C		Inborn genetic diseases	Uncertain significance (Sep 20, 2022)
20-45949018-C-G			Uncertain significance (Jun 02, 2022)
20-45949018-C-T			Uncertain significance (Jan 15, 2022)
20-45949019-G-A		ZNF335-related disorder	Benign/Likely benign (Oct 22, 2023)
20-45949030-C-T			Uncertain significance (Jun 28, 2022)
20-45949031-G-A			Likely benign (Mar 18, 2022)
20-45949069-C-T		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)
20-45949070-A-T			Uncertain significance (Jun 20, 2022)
20-45949085-C-T			Uncertain significance (Dec 07, 2023)
20-45949163-T-G			Likely benign (Jun 13, 2022)
20-45949182-AGT-A		Microcephalic primordial dwarfism due to ZNF335 deficiency	Uncertain significance (Jan 13, 2021)
20-45949183-G-T			Uncertain significance (Dec 02, 2021)
20-45949186-T-C			Likely benign (Nov 27, 2023)
20-45949193-G-A			Uncertain significance (Aug 23, 2022)
20-45949203-G-A		Microcephalic primordial dwarfism due to ZNF335 deficiency	Likely benign (Aug 31, 2022)
20-45949213-G-A		not specified	Likely benign (Dec 29, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZNF335	protein_coding	protein_coding	ENST00000322927	27	23542

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.89e-7	1.00	125637	2	109	125748	0.000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.550	795	840	0.947	0.0000529	8673
Missense in Polyphen		280	326.9	0.85652		3389
Synonymous	-0.632	360	345	1.04	0.0000228	2771
Loss of Function	4.83	23	65.0	0.354	0.00000335	710

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000687	0.000685
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.000435	0.000416
European (Non-Finnish)	0.000546	0.000501
Middle Eastern	0.000544	0.000544
South Asian	0.000300	0.000294
Other	0.00115	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component or associated component of some histone methyltransferase complexes may regulate transcription through recruitment of those complexes on gene promoters. Enhances ligand- dependent transcriptional activation by nuclear hormone receptors. Plays an important role in neural progenitor cell proliferation and self-renewal through the regulation of specific genes involved brain development, including REST. Also controls the expression of genes involved in somatic development and regulates, for instance, lymphoblast proliferation. {ECO:0000269|PubMed:12215545, ECO:0000269|PubMed:18180299, ECO:0000269|PubMed:23178126}.
• Disease: DISEASE: Microcephaly 10, primary, autosomal recessive (MCPH10) [MIM:615095]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age- related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH10 is characterized by extremely small head size and death usually by 1 year of age. Neuropathologic examination shows severe loss of neurons as well as neuronal loss of polarity and abnormal dendritic maturation. {ECO:0000269|PubMed:23178126}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.625
• rvis_EVS: -1.12
• rvis_percentile_EVS: 6.62

Haploinsufficiency Scores

• pHI: 0.321
• hipred: N
• hipred_score: 0.476
• ghis: 0.619

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.972

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zfp335
• Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: in utero embryonic development;positive regulation of neuroblast proliferation;regulation of transcription by RNA polymerase II;brain development;regulation of gene expression;cerebral cortex neuron differentiation;regulation of gene expression, epigenetic;neuron projection morphogenesis;brain morphogenesis;positive regulation of lymphocyte proliferation;positive regulation of neurogenesis;regulation of histone H3-K4 methylation;histone H3-K4 trimethylation
• Cellular component: nucleus;nucleoplasm;histone methyltransferase complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II core promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;protein binding;transcription regulatory region DNA binding;metal ion binding