SPZ1

protein-coding

spermatogenic leucine zipper 1, the group of Protein phosphatase 1 regulatory subunits

Gene summary

This gene encodes a bHLH-zip transcription factor which functions in the mitogen-activate protein kinase (MAPK) signaling pathway. Because of its role in the upregulation of cell proliferation and tumorigenesis, this gene may serve as a target for Ras-induced tumor treatments. [provided by RefSeq, Oct 2011]

MANE transcript

NM_032567.4

Inheritance

ClinVar variants

U:56B:16

Top phenotype

Ciliary dyskinesia, primary, 38

gnomAD constraint

pLI —, LoF o/e —

Max pathogenic AF

—

Genomic locus

chr5:80,319,625-80,321,842

External References & Databases

Ensembl (ENSG00000164299)

Transcript & Mutation Effects

hg38 • Region Span ~2.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Ciliary dyskinesia, primary, 38AR

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary

Intervention: Audiologic/Otolaryngologic; Pulmonary

Rationale: Among other findings, patients can manifest with early-onset respiratory disease, including upper respiratory infections, and awareness may allow early interventions related to these sequelae

Refs: 29727692; 29727693

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPZ1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032567.4. 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				3 clinvar	1 clinvar	4
missense			56 clinvar	8 clinvar	3 clinvar	67
nonsense						0
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)						0
Total	0	0	56	11	5	72

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032567.4	RefSeq	NP_115956.3	1	MANE Select
ENST00000296739.6	Ensembl	ENSP00000369611.3	1	MANE Select
ENST00000511881.1	Ensembl	ENSP00000426530.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription, DNA-templated

Molecular Function

DNA binding
DNA-binding transcription factor activity
protein binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296739
Coding exons: 1
Length: 2218

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.717	183	212	0.862	0.00000959	2882
Missense (PolyPhen)		37	41.01	0.90222		653
Synonymous	-0.273	80	77.0	1.04	0.00000379	742
Loss of Function

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	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor that binds to the DNA sequence 5'- CANNTG-3'(E box) and the G-box motif. May play an important role in the regulation of cell proliferation and differentiation during spermatogenesis (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0722

Intolerance Scores

LoFtool: 0.835
RVIS EVS: 1.57
RVIS percentile EVS: 95.71

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.499

Gene Damage Prediction

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