ZNF592

protein-coding

zinc finger protein 592, the group of Zinc fingers C2H2-type

Gene summary

This gene is thought to play a role in a complex developmental pathway and the regulation of genes involved in cerebellar development. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia. [provided by RefSeq, Jan 2011]

Previous symbols:

SCAR5

MANE transcript

NM_014630.3

Inheritance

ClinVar variants

U:191B:29

Top phenotype

Spinocerebellar ataxia, autosomal recessive 5

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr15:84,748,592-84,806,445

External References & Databases

Ensembl (ENSG00000166716)

Transcript & Mutation Effects

hg38 • Region Span ~57.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cerebellar ataxiaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0000437

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spinocerebellar ataxia, autosomal recessive 5AR

Manifestation: Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 12030328; 20531441

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNF592 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 199

ZNF592-related disorderTotal: 9

not providedTotal: 8

Galloway-Mowat syndrome 1Total: 3

Aganglionic megacolonTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014630.3. 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			2 clinvar	10 clinvar	1 clinvar	13
missense			186 clinvar	14 clinvar	4 clinvar	204
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	191	24	5	220

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014630.3	RefSeq	NP_055445.2	8	MANE Select
ENST00000560079.7	Ensembl	ENSP00000452877.2	8	MANE Select
ENST00000299927.4	Ensembl	ENSP00000299927.3	8	Standard
ENST00000299927.5	Ensembl	ENSP00000299927.3	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
protein binding
metal ion binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299927
Coding exons: 8
Length: 57794
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125748
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.804	651	711	0.915	0.0000437	8336
Missense (PolyPhen)		239	327.06	0.73076		3996
Synonymous	-1.44	324	293	1.11	0.0000190	2562
Loss of Function	5.37	1	35.6	0.0281	0.00000188	466

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in transcriptional regulation.;

Recessive Scores

pRec: 0.102

Intolerance Scores

LoFtool: 0.00930
RVIS EVS: -1.83
RVIS percentile EVS: 2.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: E
Indispensability score: 0.952

Gene Damage Prediction

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