ZPR1

protein-coding

ZPR1 zinc finger, the group of Zinc fingers

Gene summary

The protein encoded by this gene is found in the cytoplasm of quiescent cells but translocates to the nucleolus in proliferating cells. The encoded protein interacts with survival motor neuron protein (SMN1) to enhance pre-mRNA splicing and to induce neuronal differentiation and axonal growth. Defects in this gene or the SMN1 gene can cause spinal muscular atrophy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

Previous symbols:

ZNF259

MANE transcript

NM_003904.5

Inheritance

ClinVar variants

P:1U:78B:7

Top phenotype

Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr11:116,773,799-116,788,039

External References & Databases

Ensembl (ENSG00000109917)

Transcript & Mutation Effects

hg38 • Region Span ~14.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

growth restriction, hypoplastic kidneys, alopecia, and distinctive faciesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859146

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Growth restriction, hypoplastic kidneys, alopecia, and distinctive faciesAR

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Dental; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Renal

Intervention: Audiologic/Otolaryngologic; Renal

Rationale: Among other findings, the condition can involve hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; As the condition can include renal anomalies, with morbidity and mortality reported to involve uremia, awareness may allow early interventions related to these manifestations

Refs: 29851065

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZPR1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 4

Growth restriction, hypoplastic kidneys, alopecia, and distinctive faciesTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003904.5. 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			1
missense	1 clinvar		65 clinvar	6 clinvar	1 clinvar	73
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	1	0	78	6	1	86

Highest pathogenic variant AF is 0.000006156734

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003904.5	RefSeq	NP_003895.1	14	MANE Select
ENST00000227322.8	Ensembl	ENSP00000227322.3	14	MANE Select
NM_001317086.2	RefSeq	NP_001304015.1	13	Standard
ENST00000425791.1	Ensembl	ENSP00000410141.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGFR1

Biological Process

microtubule cytoskeleton organization
inner cell mass cell proliferation
trophectodermal cell proliferation
mRNA processing
signal transduction

Molecular Function

protein binding
zinc ion binding
receptor tyrosine kinase binding
translation initiation factor binding

Cellular Component

nucleus
nucleoplasm
nucleolus
cytoplasm
Cajal body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000227322
Coding exons: 14
Length: 10331
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125748
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.726	216	248	0.870	0.0000126	3004
Missense (PolyPhen)		73	89.037	0.81988		1088
Synonymous	0.763	83	92.3	0.899	0.00000463	863
Loss of Function	1.81	17	27.2	0.625	0.00000155	296

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00060	0.00060	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00020	0.00020	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a signaling molecule that communicates proliferative growth signals from the cytoplasm to the nucleus. Plays a role for the localization and accumulation of the survival motor neuron protein SMN1 in sub-nuclear bodies, including gems and Cajal bodies. Induces neuron differentiation and stimulates axonal growth and formation of growth cone in spinal cord motor neurons. Plays a role in the splicing of cellular pre-mRNAs. May be involved in H(2)O(2)-induced neuronal cell death. {ECO:0000269|PubMed:11283611, ECO:0000269|PubMed:17068332, ECO:0000269|PubMed:22422766}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

RVIS EVS: 0.24
RVIS percentile EVS: 69.37

Essentials

Essential (gene trap): E