NANOS1

protein-coding

nanos C2HC-type zinc finger 1, the group of Zinc fingers C2HC-type

Gene summary

This gene encodes a CCHC-type zinc finger protein that is a member of the nanos family. This protein co-localizes with the RNA-binding protein pumilio RNA-binding family member 2 and may be involved in regulating translation as a post-transcriptional repressor. Mutations in this gene are associated with spermatogenic impairment. [provided by RefSeq, Sep 2015]

MANE transcript

NM_199461.4

Inheritance

ClinVar variants

U:73B:13

Top phenotype

Spermatogenic failure 12

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr10:119,029,714-119,033,730

External References & Databases

Ensembl (ENSG00000188613)

Transcript & Mutation Effects

hg38 • Region Span ~4.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 12LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014172

Submitter: Labcorp Genetics (formerly Invitae)

male infertility with azoospermia or oligozoospermia due to single gene mutationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018393

Submitter: Orphanet

Clinical Genomic Database (CGD)

Spermatogenic failure 12AD

Manifestation: Genitourinary

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: 23315541

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NANOS1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 81

not providedTotal: 11

NANOS1-related disorderTotal: 5

Spermatogenic failure 12Total: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_199461.4. 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				6 clinvar		6
missense			72 clinvar	6 clinvar	1 clinvar	79
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	73	12	1	86

Highest pathogenic variant AF is 0.0014545851

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_199461.4	RefSeq	NP_955631.1	1	MANE Select
ENST00000425699.3	Ensembl	ENSP00000393275.1	1	MANE Select
ENST00000340087.5	Ensembl	ENSP00000345924.5	1	Standard
ENST00001123141.1	Ensembl	ENSP00000792946.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of cell growth
tissue homeostasis
posttranscriptional regulation of gene expression
epithelial cell migration
cell migration

Molecular Function

RNA binding
protein binding
zinc ion binding
translation repressor activity

Cellular Component

cytoplasm
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000425699
Coding exons: 1
Length: 4627
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.20	52	82.6	0.629	0.00000393	1773
Missense (PolyPhen)		9	18.706	0.48112		260
Synonymous	-0.666	46	40.6	1.13	0.00000210	684
Loss of Function	1.41	0	2.31	0.00	9.90e-8	55

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: May act as a translational repressor which regulates translation of specific mRNAs by forming a complex with PUM2 that associates with the 3'-UTR of mRNA targets. Capable of interfering with the proadhesive and anti-invasive functions of E-cadherin. Up-regulates the production of MMP14 to promote tumor cell invasion. {ECO:0000269|PubMed:17047063, ECO:0000269|PubMed:18223680}.;
Disease: DISEASE: Spermatogenic failure 12 (SPGF12) [MIM:615413]: An infertility disorder caused by spermatogenesis defects. It results in decreased sperm motility, concentration, and multiple sperm structural defects. Non-obstructive azoospermia, oligozoospermia and oligo-astheno-teratozoospermia are features observed in SPGF12 patients. {ECO:0000269|PubMed:23315541}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.612

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.766

Gene Damage Prediction

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