ZFR

protein-coding

zinc finger RNA binding protein, the group of MicroRNA protein coding host genes

Gene summary

This gene encodes an RNA-binding protein characterized by its DZF (domain associated with zinc fingers) domain. The encoded protein may play a role in the nucleocytoplasmic shuttling of another RNA-binding protein, Staufen homolog 2, in neurons. Expression of this gene is regulated through alternative polyadenylation that mediates differential microRNA targeting. Elevated expression of this gene has been observed in human patients with pancreatic cancer and knockdown of this gene may result in reduced viability and invasion of pancreatic cancer cells. [provided by RefSeq, Sep 2016]

MANE transcript

NM_016107.5

Inheritance

ClinVar variants

U:155B:78

Top phenotype

autosomal recessive spastic paraplegia type 71

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr5:32,354,350-32,444,740

External References & Databases

Ensembl (ENSG00000056097)

Transcript & Mutation Effects

hg38 • Region Span ~90.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary spastic paraplegiaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019064

Submitter: Ambry Genetics

autosomal recessive spastic paraplegia type 71SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018423

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZFR variants in ClinVar

6 Conditions Cataloged

Pure or complex autosomal recessive spastic paraplegiaTotal: 222

not specifiedTotal: 77

not providedTotal: 11

ZFR-related disorderTotal: 11

Hereditary spastic paraplegiaTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016107.5. 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			1 clinvar	72 clinvar	3 clinvar	76
missense			147 clinvar	3 clinvar		150
nonsense			1 clinvar			1
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	155	75	3	233

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016107.5	RefSeq	NP_057191.2	20	MANE Select
ENST00000265069.13	Ensembl	ENSP00000265069.8	20	MANE Select
ENST00000507465.1	Ensembl	ENSP00000422300.1	5	Standard
ENST00000890167.1	Ensembl	ENSP00000560226.1	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Exercise-induced Circadian Regulation

Biological Process

multicellular organism development

Molecular Function

DNA binding
RNA binding
double-stranded RNA binding
single-stranded RNA binding
protein binding

Cellular Component

nucleus
chromosome
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265069
Coding exons: 20
Length: 90412
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125748
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.09	303	580	0.522	0.0000308	6924
Missense (PolyPhen)		14	46.461	0.30133		548
Synonymous	0.257	200	205	0.977	0.0000109	2159
Loss of Function	6.87	3	60.8	0.0493	0.00000364	673

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000036	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in postimplantation and gastrulation stages of development. Involved in the nucleocytoplasmic shuttling of STAU2. Binds to DNA and RNA (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.148

Intolerance Scores

LoFtool: 0.0979
RVIS EVS: -0.75
RVIS percentile EVS: 13.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.942

Gene Damage Prediction

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